Eye Surgery:

What is Cataract? definition

2011-09-26T04:38:00.000-07:00

The popular idea of a cataract is that it is a film which grows over the eye. In fact, a cataract is any opacity in the normally clear protein of the lens which lies behind the iris. The problem can be likened to white of egg when fresh this is clear protein, but when damaged (by heat, in the case of the egg) it becomes progressively more opaque. The same thing happens in a cooked fish lens. Worldwide, cataract is the most common cause of poor vision and is estimated to have blinded 20 million people who do not have access to surgery.

There are few well defined causes of cataract though many factors may contribute. Age is the most important and dehydration another, particularly in a hot climate. There is little evidence for light induced damage, though ionizing radiation can produce opacities. Long term systemic corticosteroid treatment can hasten the process. Congenital rubella or rare metabolic disorders can cause cataract in childhood and diabetics develop opacities earlier than age matched controls. Trauma to the eyeor inflammation inside it may hasten the ageing process.

The patient with cataract complains usually of blurring or misting of vision which is poorly corrected or even made worse with a pin hole. Symptoms are often worse in bright light (especially sunlight) as the opacity both scatters light and is more noticeable with a small pupil if it is central in the lens. The opacity may be visible to a bright light shone onto the pupil but early change can be detected as it causes blurring of the retinal view with the direct ophthalmoscope which cannot be corrected by altering the focusing lenses. With the ophthalmoscope backed off a little and the red reflex brought into focus (together with the pupil margin), the opacity shows as darker spokes, shadows or granular dots against the reflected light, like obscured glass. The pattern is seen better after dilating the pupil.

There are no known preventive measures or medical treatments for cataract. Long term aspirin has been debated as a retardant, but the results of studies are conflicting. The surgical management has been revolutionized by the development of artificial plastic lens implants, usually inserted into the same position that the natural lens occupied, behind the iris. Non-specialists often wonder when to refer a patient with lens opacity for surgery. Any patient who is troubled by the symptoms of cataract might be helped by surgery. Younger patients may be particularly bothered by glare from early cataract when driving at night. The elderly are particularly suitable for a lens implant, but this may be feasible in most younger patients. Surgery may be postponed until likely benefit exceeds risk. Children with cataract should be referred early for investigation and consideration for surgery.
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What is eye strain

2010-06-21T00:36:00.000-07:00

With this article inaugurated the section of glaucoma. Talk glaucoma in later articles, we will now lay the foundation for understanding how stress can affect eye vision.

What is eye strain?
Ocular pressure is the colloquial name of intraocular pressure, IOP, whose initials are. The eye is a roughly spherical body, but it is solid inside and the covers are too rigid, so to preserve the spherical shape using the same trick that we use to shape a ball or a balloon. We fill the interior of a fluid that is more than atmospheric pressure. If the internal fluid pressure is greater than what is on the outside, the cover is stretched and takes the form (approximate) sphere. The air we filled balloon, and must be under some pressure to maintain the shape and not deform. In the eye goes something like, except that in no air.

Therefore we have inside the eye has a pressure above atmospheric. Recalling the science classes of the school, the pressure is equal to the force between the surface and in the international system is measured in Pascal (Pascal is a Newton/m2 a). However, other measures are more popular, centimeters of water, bar (and its submultiple the millibars), atmospheres, and above all, millimeters of mercury (abbreviated in mmHg). The atmospheric pressure at sea level is usually around 760 millimeters of mercury. This would be the absolute value, but in medicine we measure the pressure relative to atmospheric pressure. When we measure blood pressure and gives us for example 12 / 8, really are 120 mmHg systolic pressure (when it's rush of blood the heart) and 80 mmHg diastolic (when the arteries are more empty of blood). Ie 120 mmHg and 80 mmHg above atmospheric pressure. Note that when we abbreviate blood pressure is very common to remove the zero from the right, it's as if we divide ten the result.

What eye strain values are normal?
The pressure inside the eye is usually around 15 mmHg, but there is much variability, so that it accepts a normal range of 5 mmHg up or down. Ie between 10 and 20 mmHg are considered normal stresses. High intraocular pressure is considered from 21 mmHg, and a low pressure below 6 mmHg. It is very important to understand the variability, patients often do not live this way. It is customary to compare with blood pressure, although they are not comparable. Intraocular pressure rise after another 14 to 16 is not very important (to be honest, none), because a difference of 2 mmHg being rigorous in normal ranges is not significant. An increase in systolic blood pressure ("high") of 14-16 it is significant because a change of 20 mmHg.

Moreover, and this is very important, no intraocular pressure is a constant and unchanging. Fluctuates throughout the day, and change for reasons as seemingly banal as holding your breath or straining with the lid when you measure intraocular pressure. Moreover, the pressure measurement is not accurate, and the best measurement system, including an ophthalmologist and one measures the difference can be of 2 mmHg. Therefore, it is important to several measures of intraocular pressure over Tiemo to make us a better idea.

How do we keep eye strain?
Well, let the numbers and get back to the eye. We have said that a balloon filled with air as to achieve the desired pressure in the interior. But what fills the eye?. It is certainly not air.
The part "noble" of the eye are covered, the internal cavity as such does not have an active role in the formation of the image. Therefore, what fills the eye has two basic functions: a) be transparent to let light through it, and b) maintain intraocular pressure. The two elements that fill the interior of the eye are the aqueous and vitreous humor. The vitreous, vitreous body, or simply vitreous fluid can hardly be called. Constitutes the bulk volume of the eye, and is basically a three-dimensional protein and sugar, with few cells, and have "caught" a good volume of water. No active sanquíneos vessels or nerves. In other words, is primarily a fairly homogeneous tissue that makes support, and that is (mostly) transparent. Just spare suffering, for practical purposes is considered stable, not formed or deleted. Because the vitreous is practically zero dynamics, in order to maintain eye pressure has almost no importance (except in a specific treatment for glaucoma, which is irrelevant now.) Therefore, the head of the intraocular pressure is not necessarily the other element, the aqueous humor. The aqueous humor occupies only the front of the eye from the cornea to the lens. The volume is less important than the vitreous. As its name suggests, the aqueous humor is basically water, filtering the blood forming cells, and it is mostly water, and dissolved in it are various food items, small proteins, oxygen, carbon dioxide, etc. This fluid is not sealed, but to be constantly refilled. It is generated in one part of the eye, circulates among structures, and is absorbed by the other side. This constant movement allows the aqueous humor is always rich in oxygen and nutrients, so that meets the needs of the tissues that have no blood supply, which are the cristalno and the inside of the cornea. The production of aqueous humor is balanced, so that the same amount that is formed, it is extracted. This balance depends on intraocular pressure. We do not know all the details of this balance, but in most cases is very effective. Because the density of the aqueous humor is almost equal to that of water, the pressure inside the aqueous and vitreous is transmitted to the back of the eye. Thus, although the aqueous volume represents a minority, global intraocular pressure conditions.

Aqueous production: the ciliary body.
The aqueous humor is generated in a structure called the ciliary body. I talked about it in this article as an introduction to cataract surgery. It is the natural continuation of the iris (really the uveal portion that lies between the choroid and iris, but not necessary to enter both the anatomy). Within the ciliary body is a muscle, but what concerns us now is the ciliary body parts in contact with the interior of the eye, creating what is called ciliary processes (for those who likes a name, also called pars plicata) . These ciliary processes are the most anterior and internal part of the ciliary body, and are training a "wrinkled" behind the iris, from where the tendons (those "cuerdecita") holding the lens.

How the aqueous humor circulates?
After leaving the ciliary processes, the aqueous is in contact with the lens and the anterior part of the vitreous. A normal vitreous is subject to the retina (and another structure called the pars plana, which now does not matter), so that does not let the watery. But if the vitreous is missing or detached, the watery hole has to go to the back of the eye. Therefore, even though no vitreous (or is detached), well fill the gap left by the aqueous. Therefore, the permanence of the vitreous in the eye is not necessary for vision.

Anyway, it is usual that the aqueous is directed forward. He goes through the space between the lens (especially in front of the anterior capsule) and the iris. Then passes over one of the narrowest sections of the route, which is the edge of the pupil. The pupil is the central hole in the iris, and the edge of this hole is very close to the lens. In fact, it is in contact many times, and only separated during short periods in which the aqueous humor flows. This "narrow passage" will be important in some glaucomatous eyes.

Once saved this step, the aqueous humor enters the anterior chamber (the space between the cornea and iris. Here the aqueous broadcasts from back to front and center to the sides.

Out of the aqueous humor of the eye: Trabeculum and Schlemm's canal
As mentioned before, the water must leave the eye. It does so through existing structures in a very special area, where the cornea meets the iris. This area is called the iridocorneal angle, and is very important. As I explain slowly and drawings, I prefer to leave it for another article, which I now it has become very dense.

Is it bad to have pressure in your eye?
As we have seen, is not bad. In fact it is necessary. Same thing happens with other things in medicine is not bad to have cholesterol, blood pressure or prostate. In fact is (except women who do not have prostate xD). The problem is that the figures for blood pressure or cholesterol are above normal, or that the prostate is enlarged. Cholesterol and blood pressure are necessary for life.

And in the same way, eyestrain is necessary for the functioning of the eye. The problem arises when intraocular pressure is above normal limits. In fact, it is problematic (in fact, is often more problematic) that the intraocular pressure is too low, but this usually happens almost never. When intraocular pressure is high there is greater risk of glaucoma. But beware, not all involve high ocular tension glaucoma, and not all have the high tension glaucoma.

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The most frequent diseases of the eyes

2010-06-21T00:25:00.000-07:00

We return to eyes. As promised last four articles, published today a post-short, where I talk about most common diseases of the visual system. Over the past twenty months we've taken a good look at the most common in my field, and I think it's a good idea to list and link to the article in which he developed the explanation. I will do so in areas of age, as in ophthalmology (as in most of medicine, for that matter) the most important factor that discriminates the frequency of disease is certainly age.

The two peaks of age

If we saw a graph the proportion of people who go to the ophthalmologist for the years we would see that the elderly and children are most going to the query. Graphically, we would see a profile of a camel, with "two humps" that indicate the areas of maximum impact: the child and the elderly patient. In fact, the second hump is higher, and it is normal for the population that needs most attention is the old eye.

Childhood

The child or pediatric ophthalmology is a fascinating field, and its demand has increased considerably in recent times. Most often we can find in a child is:

- A graduation defect (myopia, hyperopia or astigmatism): The child is graded quite differently than adults. In addition, an adult may have more "wide sleeve" as bad graduated glasses or goggles not be enough, rarely involves serious problems for the view. The child must be more careful in indicating the goggles, because compromise on visual quality for the rest of life.
- A strabismus: the most common age of onset is in childhood strabismus. In this issue I have not spoken, and that I like very much. But it is quite complex to explain and yet I'm very encouraged to include in the list of outstanding items.

One shortcoming of graduation (especially a diopter difference between an eye and another) or strabismus can lead to what I always have to watch the pediatric ophthalmologist: the lazy eye. The lazy eye, we have to resolve during infancy because later there is no cure, and we must be vigilant because these problems often cause no symptoms.

In addition to what is described, which covers most of the reasons for child ophthalmologists, there are other less common causes. There are a number of congenital diseases (ie, to be born with them) such as congenital cataracts, congenital toxoplasmosis coloboma (where the pupil is not round but elongated, like missing a part of the iris) and so on.

A more common congenital problem but little serious the tear duct obstruction. The tear duct is a "tube" that connects the eye to the nose, and is where the tears drain. It sometimes happens that the baby is born with the plugged duct, which still has not been opened. That eye (or both eyes, if it occurs in both) he cries all the time (not being able to drain the tear, it builds up until it falls down his cheek) and gummy occur (infection due to "jam"). Not every baby's tears is due to this, to do some simple test to check. And sometimes resolves spontaneously without having to dilate the duct.

And also as congenital anomaly, we would have color blindness and other defects of color vision (especially in men). Although born with it, until the child is not a little older do not usually detect it. Also I did not hurry to make the color test, because there is no curative treatment.

And no congenital diseases could highlight conjunctivitis and blepharitis (the latter can be cumbersome when complicated with styes), which rarely are of gravity for the vision.

Speaking and rare diseases, children may have uveitis, usually in connection with extraocular diseases such as juvenile chronic arthritis.

Adolescence

In adolescence, the most important anomaly is again the shortcomings of graduation. With puberty may occur as nearsightedness, or demonstrate some defects that had previously gone unnoticed, such as farsightedness or astigmatism. It is relatively rare for a strabismus appears at this age it is more common than one that is off and it was previously. In total, both defects graduation as strabismus often change during adolescence. At this time visual development is complete, therefore not going to develop a lazy eye, but we can not heal if you already have.

Apart from the issue of glasses, a teenager rarely happens by the ophthalmologists. If the case by some stroke of the eye (the typical balonazo, or rub the eye with a pencil), but usually not serious review. And also conjunctivitis, blepharitis or a sty. There may also be rare diseases (such as uveitis we said before.)

Young adult

Often spend little to our query. Between 18 and 25 can still change the ranking, especially myopia. But often handled in the optical (especially if you wear contact lenses).

And moreover, the most frequent reasons for consultation are:

- Foreign bodies in the eye: "Motes" to jump to the eye. Accidents usually are generally mild.
- Eye injuries. During the work, traffic accidents or other causes. Sometimes they are very serious.
- As always, conjunctivitis.
- Diabetic patients will do annual reviews of the fundus. If well controlled there is usually no problems.
- Retinal detachment: They occur in myopic patient, or by a sharp blow.
- In some cases, depends on the visual and environmental effort, you may receive eyestrain and dry eye (usually mild), often associated with blepharitis.

There may be some rare disease in the retina begins to show now, and uveitis may occur. And tooth that are relatively rare, inflammation of the optic nerve (retrobulbar neuritis in particular) are typical of the adult, particularly associated with neurological disease called multiple sclerosis.

But I say that most young adults do not pass through the eye.

The average age

Between 40 and 45 begin to appear the first signs of eye strain, and between 45-50 years almost everyone needs glasses to see up close (except for some short-sighted to simply remove their glasses to read.) And is that 100% of the population is old enough eyestrain.

It is true that now they can also manifest defects before graduation had passed desaparcibidos (mainly farsightedness, astigmatism and mild), and in the end you have to wear glasses for far and near.

Apart from the issues of glasses:

- We are already seeing more cases of dry eye.
- Glaucoma usually begins after this age, so there is more measured eye strain, especially when there is family history.
- Revisions fundus of diabetic patients, and retinal detachments in a similar way we see the previous paragraph.
- Although myopic appears sooner, during the Middle Ages we see much the typical "floaters"
- There are some problems in the retina (apart from the release) that occur in myopic patients, of whom speak in the future. May occur in young adults, but we see more in middle age and beyond. The optic nerve inflammation also seen at this age.
- And we began to see problems "irrigation" in patients with risk factors (hypertension, cholesterol, diabetes, smoking, etc). Both the retina and optic nerve can be affected ("stroke" or thrombosis)

Seniors

This is the stage where more is going to the ophthalmologist. Of course, there are cataracts, and although in the end everybody ends up having them, the speed with which they develop is very variable. It is increasingly common (and troubling) asocidada macular degeneration with age, which is the leading cause of blindness unrecoverable in this age group.

There are other common problems:

- Glaucoma appear many new cases of glaucoma, and others who are diagnosed between 40 and 60 years but to be treated on a daily basis and require periodic reviews
- Vascular Diseases: Everyone knows that the "irrigation" does not work well in the elderly. In the eye there are several structures that may be affected in the form of small "stroke" and what characteristics do not usually have an effective treatment to restore sight.
or thrombosis or infarcts in the retina. If we have the bad luck that is affected the central part of the retina as the eye can be left with poor vision.
or the optic nerve: in younger patients if we inflammation (optic neuritis), here we see the optic nerve infarctions [the technical name is AION, which stands for "anterior ischemic optic neuropathy"]
o There are other nerves to the eye area, who are the "move" the muscles of the eyes. By having a small vascular problem at this level, there is an acute strabismus (eyes are not parallel). In these strabismus, unlike those of children, it happens that the patient sees double.
- Also diagnose many "floaters" at this age. Interestingly, many patients associated with cataract and cataract surgery and the flies do not go away (in fact, the better view is often noted more), may be frustrated with the surgery performed.
- Retinal Detachment: We also see this problem in older people, with the added difficulty that it is sometimes difficult to do well after surgery (that to be several weeks with head down is much more uncomfortable in the elderly).

Finally, remember that only review the most common, and not even a detailed review of the most common, but simply what we see in consultation.

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Plugs for Occlusion of the Lacrimal Drainage System

2010-05-08T13:41:00.000-07:00

A stable tear film is a prerequisite to maintain an intact ocular surface and thus corneal transparency. Aqueous tear deficiency can be compensated by application of artificial tears or by reduction of lacrimal outflow. Next to medical therapy, blockage of the lacrimal drainage system is a commonly used modality to treat dry eye. The residence time of natural tears the fluid with the best lubricant and nutrient capacity for the ocular surface can be expanded by partial or complete blockage of the lacrimal drainage system. Implants to tamponade as well as a large number of surgical methods have been described to occlude the lacrimal drainage system. Implants are used in large quantity with an estimated total number of 200,000 plugs per year in the USA (approx. 10,000 plugs in Germany).

Considerations/Examinations Prior to Occlusion
A correct clinical diagnosis is mandatory to choose an adequate treatment from the multitude of modalities available to alleviate dry eye symptoms. It is of particular importance to carefully search for the cause and severity of the tear film disorder, since symptoms of dry eye are often unspecific. For example, chronic blepharitis should be excluded or treated first since it induces not aqueous deficiency but an evaporative form of dry eye, with over secretion of tears and the presence of proinflammatory cytokines in the tear film which may determinate if tear drainage is reduced.

A success rate (reduction of signs and symptoms) of 83.7% was reported in 80 eyes with isolated aqueous deficient dry eye, while this was reduced to 76.3% in 38 dry eyes with additional blepharitis.

The decision of when and how to occlude the drainage system depends on the severity of the aqueous deficiency. While mild degrees of discomfort resulting from aqueous deficiency can routinely be managed with pharmaceutical tear substitutes alone, moderate to severe disease is more likely to require punctual or canalicular occlusion. Therefore, the patient's medical history should be carefully reviewed and the frequency and type of medication used should be recorded.

Indications for Blocking the Lacrimal Drainage System
Blocking the drainage system can be beneficial for a number of indications, of which aqueous deficiency is certainly the commonest. Clinical studies have established objective and subjective benefit from permanent occlusion in moderate to severe forms of the disease. This approach is therefore well established in the stepwise management of dry eye where it has been found to improve tear volume, stability and symptoms in approximately 60%. Elevated tear film osmolarity decreases and rose bengal positive staining of the ocular surface improves in 75%, although impression cytologic abnormalities tend to persist for at least 6 weeks.

Kojima et al, reported that acrylic plug insertion improved the mean corneal fluorescein (pretreatment 4.8 ±2.3; 3 months 2.1 ± 1.3) and conjunctival rose bengal staining significantly in 18 eyes of 10 dry eye patients. While no statistical difference was observed for Schirmer test, tear clearance was significantly reduced by the treatment. As a general guideline, punctal plugs should be considered in patients with symptoms of dry eye, a Schirmer test of -5 mm and positive superficial punctate staining.

Punctal occlusion is also effective for contact lens induced symptoms of dry eye, where punctal plugs were shown to substantially increase the duration of daily contact lens wear. In a group of 9 contact lens wearers with bilateral mild to moderate aqueous tear deficiency (Schirmer test < 10mm in 5 min) and specific dry eye signs and symptoms, the lower canaliculus of the eye with the lower Schirmer test was occluded. Virtanen et al. found that at 1 month, (on a scale of 0 to 3) conjunctival hyperemia, rose bengal (treated eyes 0.6 ± 0.2, control eyes 1.1 ± 0.2) and fluorescein staining (treated eyes 0.2 ± 0.2, control eyes 0.9 ± 0.1) and symptoms were significantly lower in the plugged compared to the unplugged eye, although no significant difference in Schirmer test was found (treated eyes 8.8 ± 2.1, control eyes 7.2 ± 1.8).

Also, plasmin activity decreased significantly (p - 0.01) in the tear film of plugged eyes although however the positive effects were found to be lost again after 3 months. In summary, punctal occlusion of the lower canaliculus seems to induce only a relatively short lasting subjective and objective benefit for contact lens associated dry eyes. Becker found that punctal occlusion is also beneficial in aqueous-deficient dry eye patients undergoing lid surgery such as ptosis surgery or blepharoplasty which increases ocular surface exposure. This is also true for more severe dry eyes, which are often induced by an underlying immune disorder directed against mucous membrane or glandular tissue, such as Stevens-Johnson syndrome, toxic epidermal necrosis or mucous membrane pemphigoid. Inflammation and subsequent scarring of the tissues involved can lead to the aqueous-deficient as well as the evaporative form of dry eye, due to occlusion of the canaliculi, lacrimal or meibomian glands. If the lacrimal drainage system is not already blocked as a consequence of the disease - which may affect puncta or canaliculi - these eyes can benefit from prolonging the residence time of any remaining natural tears or applied substitute medication.

The same has been reported for trachoma-induced conjunctival cicatrization and dry eye. On the downside, extensive surgical manipulation as well as retention of proinflammatory cytokines or potentially cytotoxic medication on the ocular surface can also lead to acute exacerbation or chronic levels of conjunctival inflammation. In this special group of patients, systemic immunosuppression can be mandatory to control inflammation (see chapter 6). This simultaneously avoids preservative-induced toxicity of topically applied medication. It is also important that other contributing factors such as malposition of lid margin and resulting trichiasis are treated adequately. Refractive Surgery Refractive corneal surgery, such as PRK, LASIK or LASEK, all permanently alter corneal morphology including corneal innervation. If the sensitive corneal nerve fibers originating from the trigeminal nerve are severed, the afferent part of the lacrimal reflex loop is impaired and this can result in impaired epithelial wound healing. Huang et al. reported that temporary lacrimal drainage occlusion reduced postoperative symptoms and the need for lubricants. It also improved density of conjunctival goblet cells, corneal wound healing and visual acuity.

Topical Modulation of Pharmacological Effects Lacrimal plugs can be used as an adjunctive modality to modulate the effect or minimize potential side effects of other forms of topical treatment. For example, when tumors of the ocular surface are treated with topical mitomycin C, blocking the lacrimal drainage will not only expand the retention time and efficacy of the drug but also may reduce nasal mucosal irritation. This may also be important in medical glaucoma treatment, but clinical evidence supporting this hypothesis is still lacking. Types of Plugs The types of plugs available can be differentiated according to their material as well as their intended location or duration of placement. Dissolvable plugs are still available for temporary occlusion, but this is more a diagnostic than a therapeutic measure, which can be used to exclude that a patient will develop epiphora following permanent surgical occlusion. Most plugs are made of a polymer and are intended for either punctal or canahcular placement. Absorbable and non-absorbable plugs both have a similar efficacy in reducing tear drainage of dry eye in the short term. Punctal Plugs Punctal plugs are placed directly in the opening of the lacrimal punctum and extend into the lacrimal ampulla. In this position they prevent the active and passive drainage of tear fluid. Different shapes and materials are available.

Their position can easily be controlled and if required the plug can be removed even without the use of a slit-lamp. However, as a consequence of the superficial localization, the devices also more easily cause irritation of the ocular surface (feeling of itchiness or pressure) and may be extruded, e.g. due to patient manipulation. Infection or migration is more rarely encountered. Shape and Design. A flat cap, a slender cylindrical neck and a notably thicker, usually cone-shaped base are typical. After insertion into the lacrimal punctum, the volume of the base fills the ampulla and prevents extrusion of the plug, while the flat cap adapts to the surface of the lid, projects sideways from the lumen of the lacrimal punctum and thus not only occludes the punctum completely but also prevents dislocation further into the lacrimal drainage system. Sakamato et al. could show that the design has a significant impact on the retention time and the rate of complications of silicone plugs. Devices with a more flexible design can be inserted more easily but are also likely to be lost earlier.

Material for Punctum Plugs. At present, most the punctal plugs dominating the market are made of silicone material. Other materials tested are teflon, HEMA or PMMA, but none of these has shown significant advantages over silicone plugs. Intracanalicular Plugs A wider variety of materials and shapes exist for intracanalicular plugs. The available implants can be inserted into the ampulla or in the horizontal portion of the lacrimal canaliculi. Since they do not protrude onto the surface, such plugs avoid mechanical irritation of the ocular surface. Rarely is an initial discomfort reported. The lack of surface contact and the position in the predominantly collapsed canaliculus reduce the risk of contamination. However, due to their position, intracanalicular plugs are more difficult to follow up and if complications occur (most of all epiphora) - they are more difficult to remove. In principle the diameter of the device is more critical than the length in order to achieve total occlusion of the drainage system. Temporary Dissolvable Intracanalicular Plugs Shape and Design. Dissolvable intracanalicular plugs can be used for short-or medium-term closure of the lacrimal drainage system. The duration of the efficacy and residence of such plugs depends on the material.

Dissolvable intracanalicular plugs are rod-shaped. Some implants are available in several sizes. Material for Intracanalicular Plugs. Clinical reports exist for gelatin, catgut (no longer available), and hydroxypropyl cellulose. For short-term closure, collagen implants can be used, which reduce tear drainage - measured as reduced tear clearance - for 48h. However, all materials from animal sources carry a minute risk of prion transfer and induction of vC JD. Synthetic materials, such as polydioxanone, are recommended for medium term (of up to 6 months) occlusion of the lacrimal canaliculi. Permanent, Non-Absorbable Intracanalicular Plugs Shape and Design. At least three different implants for the permanent occlusion of the lacrimal canaliculi are currently available in Europe. The Herrick® lacrimal silicone plug has the shape of a golf tee. It is compressed and therefore sits firmly in the canaliculus. Modifications with dye (blue) or semi-radiopaque properties are meant to facilitate correct positioning and localization in case of any complications. The SmartPLUG® is made of an acrylic polymer and is rod-shaped (0.4 mm wide and 12 mm long). It can be inserted into the canaliculus without dilating the lacrimal punctum. Upon exposure to body temperature the plug spontaneously shortens to 1.5-2 mm, while the diameter simultaneously increases to well over 1 mm. This is thought to ensure complete occlusion of the canalicular tear drainage. Recently, expandable hydrogel rods (diameter 0.3 mm, length 3 mm) have become available, which are placed in the vertical portion of the canaliculus by means of an inserter. After 20min, the material fills the ampulla of the lacrimal canaliculus completely. Material for Intracanalicular Plugs. Extensive experience exists with silicons With this, occasional infections have been reported.

The new materials, such as thermodynamic acrylic polymers and hydrogel, are supposed to reduce bacterial adhesion and biofilm formation and may thus in the long term result in fewer infections. Insertion The method of insertion depends on the type of plug selected. Local anesthesia is not normally required, but in certain cases can increase patient comfort. Following a careful documentation of the case history, the following parameters should be defined: (1) intended duration of occlusion, i.e. temporary or permanent; (2) number of puncta/canaliculi to be occluded; (3) position of the plug in relation to the canahcular drainage system- punctum, ampulla or horizontal canaliculus, and (4) plug size, which is only variable (and important) with punctal plugs. Due to the potential complications, informed consent should be obtained for all implanted devices even for temporary occlusion with punctal plugs. Usually the lower canaliculus is occluded first, since access is easier and extrusion substantially lower than for the upper punctum. Often, closure of the lower lacrimal canaliculus is sufficient to reduce symptoms and artificial tear substitution substantially. In order to ensure complete and lasting occlusion, the punctal diameter can be measured with a specific instrument to select an appropriately sized plug. Technical Recommendations Technical recommendations include: Choice of anesthesia: A cotton wool tip soaked in topical anesthetic and directly applied onto the conjunctiva in the caruncular region/medial can-thus or a subconjunctival injection of 0.5 ml of a short-acting anesthetic are usually sufficient. Preparations to insert to plug: If required, place the plug on an inserter, which releases the device upon pressure. This is often a double-ended instrument with an additional lacrimal dilator. Evert the lid margin, including the lacrimal punctum and lateralize the punctum in order to stabilize its position. Dilate the punctum while avoiding to overstretch the annulus! Insertion of a punctal plug: Place the plug by means of the inserter and release it with gentle pressure.

Minor corrections of the position can still be made. It is important to instruct the patient not to rub or press the medial canthus. To improve patient compliance, he should be warned that the irritation may persist for several days or weeks! Insertion of intracanalicular plug: Herrick® lacrimal plugs are preloaded to an inserter. The plug is compressed while it is inserted and the carrier can be removed by slowly turning and pulling it. The final position of the plug in the horizontal canaliculus is influenced by the constant blinking and peristaltic motion. Plugs made from acrylic polymer should be inserted either with special forceps provided by the manufacturer or sterile tying forceps covered with silicon sleeves in order to avoid any mechanical damage to the sensitive material. Two-thirds of the plugs are inserted into the lacrimal punc-tum/canaliculus and the thermodynamic acrylic polymer then contracts upon contact with body heat. The material then becomes gelatinous. To avoid chronic inflammation, contamination of the plug from touching the lid lashes or margin should be avoided. If the local body temperature is reduced due to stress or reduced vascular perfusión, for example in older patients, the rod may not contract rapidly until a warm, sterile cotton wool tip is applied to the medial lid margin. Tai et al, reported a mean retention time of 85.1 ± 7.3 weeks. Prospective investigations indicate a stabilization of objective functional parameters of the tear film and ocular surface (tear volume, tear film stability, rose bengal staining). However, it should be remembered that temporary lacrimal plugs made of collagen only effectively occlude the canaliculi for <48h, reduce the outflow of tears only by 60-80% and may be insufficient to improve symptoms and mimic full occlusion. Among the permanent devices, punctal or intracanalicular plugs show the same degree of objective and subjective improvement, such as reduced artificial tear substitute application or punctate surface staining and increased break-up time as goblet cell density in impression cytology. Success of treatment is often difficult to quantify in dry eye, since evaluation of symptoms and signs, such as surface staining, remain predominantly subjective on both the patient's and the doctor's side.

In a randomized controlled trial of 44 patients with severe dry eye due to inactive trachoma, patient satisfaction was significantly higher if artificial tear substitution and lacrimal drainage occlusion were combined compared to artificial tears only. Unilateral lacrimal drainage occlusion in severe dry eye due to Sjógren's syndrome was found to significantly improve scores of ocular discomfort, rose bengal staining compared with the non-occluded fellow eye (pretreatment rose bengal staining (mean ± SD) 7.3 ± 1.1, posttreatment 6.2 ± 1.9; control: pretreatment 7.3 ± 1.2, posttreatment 7.00 ± 1.15). Punctal plugs are easy to follow up. Due to their superficial placement, they can be observed conveniently with a slit-lamp. If the implant is no longer visible, extrusion can be assumed to be the likely cause. Migration into the lacrimal drainage system has been reported, but seems to be a rare event. If in doubt, high-frequency ultrasonography can be helpful to check the lacrimal drainage system for any foreign body. The same modality can also be employed to locate intracanalicular plugs. The need to inspect the position of an intracanalicular plug only arises if signs or symptoms of dry eye recur or if a chronic inflammatory process in the canaliculi is suspected. Slit-lamp biomicroscopy, assessment of the tear meniscus and spontaneous lacrimal outflow provide some evidence of adequate function or dysfunction of the lacrimal plugs. Herrick plugs with blue staining can be more easily localized by transillumination of the medial canthal area. Semi-radiopaque lacrimal plugs have not found wide application in clinical practice, due to unnecessary financial and medical burden. If an acrylic thermodynamic plug is positioned in the vertical ampulla of the canaliculus it can be visualized through the lacrimal punctum. Placing the in plant in the horizontal part of the canaliculus probably reduces extrusion and impede the formation of biofilm. In this position the implant cannot be visualized directly by slit-lamp microscopy. High-frequency ultrasound can be successfully used for long-term controls and has confirmed a stable placement in the horizontal canaliculus for up to 2 years in 100%. Due to their shape, volume and material characteristics, differentiation of a plug from the tissues of the lid is easier with acrylic than silicone implants.

Removal of Lacrimal Plugs While absorbable plugs may not require mechanical removal, if they dissolve within days or weeks, slowly-absorbing or even non-absorbable plugs sometimes need to be removed because of symptoms or signs or irritation or epiphora. Given careful patient selection, this is a rare problem and can be done under topical anesthesia. After everting, the plug can simply be grasped with a pair of forceps around its collar, loosened and removed carefully. This may be more difficult where a scar or a hyperplastic tissue reaction has evolved. If the plug's material has become brittle it may break into parts. Since any plug remnants can cause inflammation in the canaliculus, they should be removed. This may require retrograde manipulation via the opposite canaliculus with a pigtail type probe under an operating microscope and local or even general anesthesia. Extensive granuloma formation is rare but may require a canaliculotomy for plug removal and ablation of the hyperplastic mucosa. Due to its form a golf tee-shaped plug can only be removed via the naso-lacrimal duct by probing and irrigation of the lacrimal drainage system. Since the plug is very rarely recovered from the nose, reduction of epiphora, improved fluorescein clearance and patency of the system upon irrigation can be used as indicators of successful removal. Ultrasonography may helpful identify plug material in the drainage system, but is not commonly available. Plugs which initially remain in the lacrimal sac may be eliminated spontaneously, as has been reported for fragments of irrigation cannulas or lacrimal probes. However, if signs of impaired flow or even dacryocystitis are observed, retention of plug material in the lacrimal drainage system, usually in the lacrimal sac, should be suspected and surgical removal attempted. Where instruments for endoscopic endocanalicular manipulation (e.g. a microdrill system) are not available, routine dacryocystorhinostomy remains an excellent method to remove the foreign material and to cure any secondary obstruction of tear drainage.

Contraindications, Side Effects and Complications Contraindications include allergy to plug materials, punctal ectropion and pre-existing canalicular obstruction. As discussed above, obviously severe inflammatory changes of the lids and ocular surface should also be treated to reduce the load of proinflammatory cytokines, since reduced tear clearance may otherwise exacerbate chronic surface disease. Due to improvements of shape and material of the devices and provided that patient selection is adequate, lacrimal drainage obstruction by means of plugs is a low-risk procedure. If both the upper and lower lacrimal punctum/ canaliculus are to be blocked, a trial of complete blockage with absorbable plugs prior to insertion of permanent, i.e. polymeric plugs is mandatory to avoid epiphora or tear meniscus-induced visual impairment. If complications do occur, they relate either to subjective symptoms or objective clinical signs. Although plugs are implanted in large quantities, complications have only been reported rarely. However, these can be severe and the use of plugs should therefore always be considered carefully. In particular, multiple insertion of plugs must be avoided. Up to 7 lacrimal plugs in one lacrimal drainage system have been reported. After plug implantation probing, flushing or endoscopic examination of the lacrimal drainage system should not be performed, since they are likely to induce displacement of the plug themselves. Careful case history, tear clearance rate as a measure of spontaneous tear outflow, tear meniscus height and, high-frequency ultrasound examination (20-MHz probe) should be sufficient to decide upon diagnosis and further management. Signs and Symptoms of Irritation Provided patient selection was adequate and a preliminary trial with temporary plugs was performed, epiphora should be a very rare problem.

However, retention of cytotoxic substances and inflammatory mediators at the ocular surface can cause signs and symptoms of irritation, which may require plug removal. In a retrospective study by Tai et al., on 203 eyes lacrimal plugs had to be removed in 6.9% due to severe itching, a sensation of pressure and mechanical irritation. These were more commonly reported for punctum plugs than intracanalicular plugs. The high rate of spontaneously lost punctal plugs may be a consequence of these problems. Loss or Migration of Plugs Spontaneous loss of punctal plugs has been described by various authors to occur in 29-51% and this is more common in patients with horizontal lid laxity and dilated puncta . In Tai et study the estimated probability of plug retention was 49% with a mean survival time of 85.1 ± 7.3 weeks. Most of the extruded implants (50%) are lost within 4 weeks. Retention is better in the lower than in the upper punctum . Dislocation into the deeper segments of the lacrimal drainage system is very rare, but can result in more severe consequences . It can occur if too small a plug was chosen, implantation was too deep and or the lacrimal punctum was overstretched. If the plug is still visible through the ostium it can be repositioned using a 27/4-gauge cannula. The tip of the cannula is introduced in the central hole of the plug (the former link to the inserter) and the plug lifted, so that its flat top rests again on the lid margin. If canaliculitis or dacryocystitis evolve, canaliculotomy, external dacryocystorhinostomy or endoscopic-microsurgical management are required. If a plug is lost spontaneously, punctal devices can be anchored by placing a non-absorbable suture through its collar and to the lid margin. Alternatively an intracanalicular plug may be used, since 20-MHz ultrasonography has shown that all of 40 implanted thermodynamic acrylic plugs remained in their original position over a period of 2 years.

To reduce patient discomfort and costs due to repeated device insertion and if permanent outflow obstruction is required, we however prefer to block the lacrimal drainage surgically. Biofllm Formation and Infection The formation of biofilm and bacterial overgrowth are general problems of artificial materials in medical use. Due to their direct exposure to the surface of the eye and their complex shape, punctum plugs are easily contaminated by microbes. Cultures of punctum plugs removed because of symptoms of irritation showed bacterial colonization by various species of Staphylococcus, in more than 50%. The risk of bacterial colonization increased with the retention time. Although the central hole of a punctal plug -required for coupling the device to the inserter - acts as an additional reservoir for bacteria, only few clinical reports of acute or chronic infection or inflammation exist. Bacterial adhesion not only depends on the time but the retention material of the plug and its surface as well as. In-vitro studies have shown that acrylic plugs are much less likely to be colonized by bacteria than silicone devices. Chronic Inflammation and Scarring Chronic inflammation, mucosal hyperplasia and scarring can result from the constant mechanical stress and irritation of the intracanalicular epithelial surface by punctal or intracanalicular plugs.

Formation of pyogenic granuloma or papilloma has been reported with the use of both. If this occurs the plug should be removed, although this may be difficult or even impossible. Sometimes - despite removal of all artificial material - subjective complaints persist. The proximal position in the vertical portion of the canahculus, i.e. the ampulla, can result in a partial extrusion of acrylic intracanalicular plugs. If the implant cannot be advanced into the drainage system, the part of the protruding implant can be simply removed with Vanna's scissors. Conclusions Iatrogenic occlusion of the lacrimal drainage system with plugs is the second most frequent method of treating the dry eye. It preserves natural tears or prolongs the retention time of artificial tears on the ocular surface and can substantially improve the quality of life of patients with moderate/severe dry eye. Before blocking a lacrimal drainage system a pre-existing blepharitis or other forms of ocular surface inflammation must be treated in order to reduce the load of proinflammatory cytokines on the ocular surface. The patient's consent should be obtained. The effect of lacrimal canalicular closure can be simulated with absorbable plugs. A stepwise approach is recommended, occluding the lower lacrimal canahculus first. Implants differ in terms of material, design, place of application and time of retention. Punctal plugs are easy to insert and monitor. Discomfort and a high rate of spontaneous loss due to extrusion are a relevant disadvantage.

If a punctal plug is sufficient to control signs and symptoms of dry eye and is spontaneously lost, implantation of intracanalicular plugs or surgical measures to reduce tear drainage should be considered. Compared with punctal silicone plugs, intracanalicular plugs of acrylic polymer or hydrogel result in less discomfort and are well tolerated, but are more difficult to remove. If patients with a history of dry eye and iatrogenic canalicular occlusion present with signs of inflammation of the lacrimal drainage system, the presence of artificial material in the lacrimal canaliculi should be excluded, for example by means of 20-MHz ultrasonography. Multiple simultaneous or sequential implantation of polymeric devices increases the risk of inflammation and complication. Occlusion of the lacrimal drainage system with plugs is usually easier to reverse than surgical approaches.

Eyelid Botulinum Toxin Injections for the Dry Eye

2010-05-08T13:23:00.000-07:00

The symptoms of dry eye can be reduced by adding lubricants to the tear film or stimulating tear secretion. Another strategy is to reduce the drainage of tears. A reduced drainage causes the natural tears as well as added lubricants to remain in the eye for a longer period of time. Punctum plugs are a well established method to block the lacrimal passages but this technique has a significant number of side effects including discomfort, abrasion of the conjunctiva and cornea, epiphora, canaliculitis, dacryocystitis, granuloma formation, extrusion or intrusion of the plug, fragmentation of punctal plugs and canalicular stenosis. The puncti can also be closed surgically with cautery or more sophisticated procedures. However, blocking the lacrimal passages can cause epiphora even in patients with Sjogren's syndrome and with permanent surgical occlusion of the tear drainage system this complication may also become irreversible.

In 1855, Arlt observed that epiphora is a constant phenomenon in facial palsy and further that epiphora may exist in facial palsy without punctal eversión or ectropion. He reported that epiphora was the first symptom making him suspect facial palsy in one patient.

It is also our clinical experience that sometimes epiphora is the only sequel in facial palsy. The observation of Arlt was a strong argument for the hypothesis of a lacrimal pump, an active lacrimal drainage coupled to blinking, an idea proposed already in the 18th century. The type of coupling between blinking and lacrimal drainage has been widely debated. The conjunctival sac, the canaliculi, the lacrimal sac or the nasolacrimal duct, alone or in combination, have been proposed as the lacrimal pump. However, when dacryocystorhinostomy was introduced to treat dacryocystitis, it became evident that the lacrimal sac and the nasolacrimal duct were not necessary for an adequate lacrimal drainage and that the canaliculi have a major role in lacrimal drainage. The importance of the canaliculi was experimentally confirmed by pressure and flow recordings by Rosengren . The preseptal and pretarsal deep (Homer's muscle) and superficial heads of the orbicularis oculi muscle are thought to be the main muscles acting on the canaliculi. There are also suggestions that the valve mechanism directing the flow of tear fluid towards the nasal cavity is a muscle dependent mechanism, either by a sphincter mechanism or by apposition of the upper and lower lid during blinking. In addition, lacrimal drainage has a passive component driven by gravity.

Blinking not only has a major role in the lacrimal drainage, but also with each blink the tear film is re-established and thus blinking is also responsible for wetting the ocular surface.

Botulinum toxin was introduced in 1980 in the treatment of strabismus. It is one of the most lethal naturally occurring neurotoxins, and is produced by Clostridium botulinum bacteria. Different strains produce different types of toxin, but botulinum toxin A is the type used clinically. There are two commercially available botulinum toxin A products, Botox (Allergan Botox Ltd, Ireland) and Dysport® (Ipsen Biopharm, UK). The nature of effects and side effects of both preparations is similar but the efficacy per unit of toxin differs. In general, the efficacy of Botox is 2-5 times the efficacy of Dysport. The toxin acts by rapid and strong binding to presynaptic cholinergic nerve terminals with subsequent intemalization of toxin and reduction in the output of acetylcholine. This leads to a down regulation of post junctional acetylcholine receptors. The effect is a weakening of the involved muscle, skeletal or smooth. Recovery of muscle function usually requires 2-4 months and occurs through several mechanisms most importantly, neural sprouting and reinnervation.

Botulinum toxin, especially type B toxin, also has autonomic effects, due to the alterations in peripheral cholinergic parasympathetic nerves. This effect can be used to reduce tear production in lacrimal hypersecretion. In ophthalmology the main use of botulinum toxin is in the treatment of blepharospasm but also to induce ptosis in patients with lagophthalmus or keratitis and in patients with squint problems. In recent years the use of botulinum toxin for cosmetic purposes has become widespread. The side effects are typically reversible and of short duration. In blepharospasm, side effects are caused by toxin effects on adjacent muscles, for example causing ptosis or diplopia or overdosage with impaired blinking causing dry eyes and keratitis. Epiphora is also described as a complication in the treatment of blepharospasm.

With this background, we initiated a series of experiments to investigate whether an injection of botulinum toxin could cause a situation similar to facial palsy with a reduction of tear drainage and a beneficial effect to patients with dry eyes.

Method
The anatomical basis for the lacrimal pump is thought to be the deep and superficial heads of the pretarsal and preseptal orbicularis oculi muscle. Therefore, in a previous study, a subcutaneous injection of botulinum toxin was given in the area between the punctum and the medial canthus in the lower and sometimes also the upper lid. The aim was to temporarily denervate the orbicularis fibers adjacent to the canaliculus. Botulinum toxin A (Botox®, Allergan Botox Ltd, Ireland) was used in a concentration of 2.5IU/0.1 ml. A volume of 0.1 ml to both the upper and lower eyelid or 0.15 ml (3.75IU) to the lower lid was used.

Injection of botulinum toxin to the medial lower lid reduces the horizontal sliding of the lower lid when blinking and injection to the medial upper lid causes a discrete retraction and a slightly weaker vertical movement of the upper lid.

In the study it was shown that the blink output (volume expelled with each blink) was reduced to 64-70% of baseline values with lower lid injections and to 38% with both upper and lower lid injections.

The lacrimal drainage capacity (drained volume per unit time), including both active drainage by blinking and passive drainage by gravity, was reduced to 52% with one injection and to 42% with injections to both upper and lower lid. The subjective experience of the injections was a more comfortable eye in 6/9 with one injection. With injections to both upper and lower lids, 9/10 patients experienced a wetter eye but 2 of these did not feel more comfortable. We had the impression therefore that injections to both upper and lower lid had a more pronounced effect, however when injections were given to the upper lid some side effects appeared, although they were judged to be tolerable and of short duration. Notably 1 patient complained of increased foreign body sensation for a couple of weeks probably related to a decreased blinking associated with injections to the upper lid. With isolated lower lid injections no side effects were noted. The effect of the injections lasted for approximately 3 months, when blink output and lacrimal drainage values also had returned to baseline.

A small number of patients have had repeated injections over the last 5 years with no side effects and no signs of damage to the eyelid.

Recently, a randomized prospective controlled study (unpublished) was started to further investigate the suggested treatment. The study is still open and includes only well-documented cases of primary or secondary Sjógren's syndrome with dry eyes. Botulinum toxin (3.75 IU) is given subcutaneously in the medial part of the lower eyelid. One eye receives the toxin and the other placebo (saline) in each patient. The patient is unaware of which side is treated with toxin. Three weeks after treatment the patients found the toxin-treated eye 'better' (6/10) or 'similar' (4/10) to the eye treated with placebo. No patient found the placebo-treated eye better. Three months after treatment the patients reported no difference between the toxin-treated and the placebo-treated eye. The most common side effect was epiphora (3/10), no ptosis or lagophthalmus was observed and no diplopia reported. The overall impression was 'positive' in 6/10 patients.

Conclusion
The treatment of dry eyes with botulinum toxin A injections to the lower lid is safe with few and temporary side effects. Our clinical experience is that the botulinum toxin injections have a success rate of 60-70%. The duration of the effect of the injection is about 3 months. The technique is simple.

The orbicularis muscle and the eyelids are responsible both for establishing and removing the tear film, therefore a change in the function of the orbicularis muscle can result in both a dry eye when blinking is impaired and a wet eye when the tear pump is blocked. In facial palsy, sometimes lagophthalmus and corneal drying dominates whereas epiphora in this situation may result from lacrimal pump failure, punctal eversión or paralytic ectropion. Further, the tear production can possibly be impaired by injections of botulinum toxin close to the lacrimal gland. These factors may cause varying results on the tear film of botulinum toxin injections into the eyelids in patients treated for ble-pharospasm.

Botulinum toxin injections are not recommended in patients where impaired blinking is a factor causing the dry eye symptoms. In our experience, patients with minor as well as serious dry eye problems have benefited from the treatment. If the effect is unsatisfactory, punctal temporary or permanent punctual occlusion should be considered.

Keratoprosthesis Surgery

2010-05-08T13:17:00.000-07:00

When Is There a Need for Keratoprostheses?
A keratoprosthesis (artificial cornea) needs to be considered when there is little or no prospect of success with conventional cadaveric corneal transplantation or limbal stem cell transplantation. This may be due to a hostile environment such as a dry keratinised ocular surface, lid deficiency, a highly vascularised cornea, or multiple previous corneal graft failure.

Classification of Keratoprostheses
There are a number of ways to classify keratoprostheses, based on the type of fixation (nut and bolt, intrastromal, epicorneal with tissue covering, supra-Descemetic) or the material of the haptic {PMMA e.g. Choyce and Boston (previously known as Dohlman Doane) devices, Dacron (Pintucci), titanium, ceramics, hydrogel (AlphaCor), silicone, expanded PTFE (Legeais), biological materials and analogue such as tooth and bone (Strampelli, Falcinelli), tibial bone.

To our knowledge, at present only the Boston keratoprosthesis, the Pintucci device, the Worst Singh device and the AlphaCor artificial cornea are commercially available, while the haptics of the osteo-odonto-keratoprosthesis (OOKP) and the tibia bone prosthesis are made usually from the patients' own tissue by the surgeon himself. This article focuses on the use of two distinctly different devices, the OOKP and AlphaCor artificial cornea.

The Osteo-Odonto-Keratoprosthesis
OOKP was first described by Strampelli in the early 1960s. Basically, a single rooted tooth root and surrounding jaw bone is fashioned into a plate measuring some 12-15 mm long and 3 mm thick, through which a PMMA optical cylinder is cemented into a hole previously drilled through this plate. The anterior surface of the plate is entirely bony, and the posterior surface mostly dentine. The osteo-odonto-acrylic plate is buried in a submuscular pocket to acquire soft tissue investment. At the same time as fashioning the plate or lamina, the ocular surface is cleared down to Bowman's membrane and exposed to the level of insertion of the recti muscles. The bare area is covered with buccal mucous membrane harvested from the inside of the cheek. Two to four months later, at stage 2 surgery, the lamina is retrieved and placed on the surface of the cornea, having trephined a corneal opening for the posterior part of the optical cylinder to protrude intraocularly. The iris, lens and anterior vitreous will also have been removed.

There was an initial international enthusiasm, but it was mostly forgotten after poor results were reported by some authors. The current technique is that of Falcinelli, who made stepwise improvement of the original technique from the 1970s to the 1990s. Falcinelli's excellent long term visual and retention results were independently surveyed and his modified technique began to spread after he took on three initial international students in the mid-1990s. The initial spread to Austria, Germany and England has propagated further to Egypt, Japan, Singapore, India and Hong Kong through the efforts of the OOKP teaching group.

The strength of the OOKP lies in its ability to be retained even in the dry eye situation. It is not entirely understood as to why the retention rate should be so good, but there are at least three factors. Firstly, there is gradation of materials from non living rigid PMMA to previously living rigid dentine, which in turn is interfaced with living porous jaw bone through living flexible alveolar ligament. Secondly, the jaw bone is interfaced with buccal mucous membrane which not only provides a blood supply to the bone, but also a biological seal against infection. Finally, the buccal mucous membrane is mechanically strong and biologically resilient, thus restraining (shrink wrapping) the OOKP complex even in a hostile ocular environment such as the dry eye.

Indications
The OOKP can be used to rehabilitate all cases of corneal blindness, but because of the gravity of the surgical programme, should be limited to end stage ocular surface diseases such as severe Stevens Johnson syndrome, ocular cicatricial pemphigoid, trachoma, other forms of cicatrising conjunctivitides, chemical injury, uncorrectable loss of eyelid, and absolute/severe dry eye states. It is not to be used in unilateral corneal blindness because of the severity of the surgical programme, the possibility of severe complications, the requirement for lifelong follow up, and because of the difference of image size the OOKP optics would cause, compared to a phakic or pseudophakic eye. In cases of bilateral corneal blindness, only one eye should be rehabilitated although attention should be given to the fellow eye for any glaucoma present. The fellow eye is kept as a spare eye.

Contraindications
The lower age limit is 18 or 19 years of age. Obviously, in eyes with no light perception, there is no hope for visual amelioration. Eyes with severe damage to the posterior segment, i.e. persistent retinal detachment, advanced glaucoma or damage to the optic nerve, should not be operated on either.

Patient Assessment
The patient and their family need to be assessed as a unit, to determine if they are committed to a severe surgical programme and lifelong follow up at the OOKP centre. The patient's psychological state and wish for regaining sight needs to be assessed. Prolonged blindness and onset of blindness can lead to depression and various states of dependence on spouse and family. Some patients are happily blind. Some can lead an independent life despite becoming blind, especially if the onset of blindness was at a young age. Some carers cherish the dependence of the blind relative they are caring for, and may subconsciously resent to their regaining independence. Others may push the patient towards surgery when the patient is not seeking surgery. All in all, it is important that it is the patient who wants to have surgery to restore sight, but both the patient and relatives must understand the severity of the surgery, the possibility of serious complications and thus the possibility of further surgery, and the requirement of lifelong follow up.

Ocular assessment consists of full history and examination, concentrating on ascertaining retinal and optic nerve integrity. Previous surgery (especially lid, cornea, lens) and ocular perforation should be noted. Attention should be paid to the possibility of glaucoma, which may be worsened following OOKP surgery due to unintended additional surgical alterations of the anterior chamber angle and the inefficacy of topically applied glaucoma drugs, which will not be absorbed into the anterior chamber through the buccal mucosa covering the haptic. The axial length needs to be measured to determine the optical power of the optical cylinder to be used. Typically, ocular examination includes assessment of relative afferent pupil defect, projection of light in quadrants (patients usually have PL, HM or at best CF vision by the time they come for OOKP surgery), slit-lamp examination, digital palpation of intraocular pressure (the corneae are usually too dry and scarred for applanation tonometry), B-scan to exclude and assess retinal detachment, peripheral anterior synechiae, lens status, and pre-phthisis presenting as a short eye, and A-scan for biometry. Very few cases require electrodiagnostic tests which also cannot be entirely relied upon.

Oral assessment is best done by an oral surgeon, who will also be working on harvesting the tooth together with root and surrounding jaw bone, and buccal mucous membrane. Oral hygiene is assessed. The presence of canine teeth as well as gum and bone recession is assessed, followed by imaging of relevant teeth and their juxtaposition to adjacent teeth with orthopantomography (a form of dental panoramic radiography), individual canine teeth x-rays, and even a spiral CT scan. A single-rooted tooth, usually a canine, with a straight long root of good girth, good bone quality as close to the base of the crown, and good separation from its two adjacent teeth is selected. Buccal mucous membrane is also assessed for area available, quality and whether previous harvesting has taken place and if so on which side. Sometimes, it is necessary to harvest lower labial mucous membrane for lining the upper and lower eyelids.

Results of OOKP
The performance of any keratoprosthesis can be measured in terms of a number of parameters including retention (long-term anatomical success), vision (visual acuity, visual field, quality of vision include glare, etc.), patient satisfaction including cosmesis, and sight-threatening complications such as glaucoma, retinal detachment, etc. The size of the visual field depends on the geometry of the optical cylinder and therefore on the size of the available tooth. But often it is much less than its theoretically calculated value. With a classical PMMA cylinder it varies between 30 and 50° and can be enlarged by a larger or conical posterior part of the optic. The visual acuity may be as good as 1.5 (20/12 = 6/4) depending only on retinal status.

Falcinelli et al. reported an anatomic success rate of 96.5% after a follow-up of approximately 5 years, 94.1% in 10 years and 88.8% in about 20 years with a maximum of follow-up of 27 years In patients with dry eyes, which represent 41.5% of all of Falcinelli et al.'s patients, an improvement of visual acuity at long-term follow-up was found in over 90%of cases.

In a smaller German series of 25 patients, one-third had excellent visual acuity of 0.9 or better, two-thirds reading vision (-0.5 or 6/12) and 80% ambulatory vision (>0.05 or 1/20). To compare the results of OOKP with other keratoprostheses, figure 4 shows the Kaplan-Meier anatomic survival analysis of K.H.'s series (Homburg) of different keratoprostheses (25 patients with an OOKP, 4 with a tibial-bone KPro, 5 with a Pintucci KPro, and 1 with Legeais keratoprosthesis). Figure underlines the superiority of OOKP (and the biologic support tibial bone) over other alloplastic haptics.

At the Sussex Eye Hospital in Brighton, we have operated on 35 cases since 1996 (21 male, 14 female, with a mean age of 50.6 years at stage 2). Presenting diagnoses were: 15 Stevens-Johnson syndrome, 5 chemical injury, 6 ocular cicatricial pemphigoid, 4 miscellaneous dry eye diseases, 1 trachoma, 1 linear IgA disease, 1 ectodermal dysplasia, 1 post-bomb blast, and 1 congenital trigeminal nerve hyoplasia. 34/35 proceeded through stage 1 and stage 2 (1 developed a total retinal detachment between stage 1 and stage 2). Mean time interval between stages 1 and 2 was 19.8 weeks (range 9-84). Preoperative visual acuity was: PL (15), HM (15), CF (5). Postoperative visual acuity at last follow-up was: 6/5 (4), 6/6 (2), 6/9 (5), 6/18 (3), 6/24 (1), 6/36 (2), <6/60 (2), HM (4), CF (1), PL (3), andNPL (6) (2 patients required subsequent evisceration). Mean follow-up was: 34.7 months (range 1-96). There were 3 allografts. 7 exhibited clinical resorption of OOKP lamina. 2 subsequently required repeat OOKP surgery. Postoperative complications (episodes, not eyes) were: 5 retro-prosthetic membranes, 4 retinal detachments (including the 2 secondary to laminar resorption and endophthalmitis: see below), 3 vitreous haemorrhages, 3 extrusions of lamina, 2 infections of buccal membrane graft, 2 endophthalmitis, 1 expulsive haemorrhage and 1 epiretinal membrane. OOKP surgery is usually carried out in two stages. In the first stage a monoradicular tooth is harvested to prepare an osteo-odonto-lamina.

The root and surrounding jaw bone is sliced sagittally, whilst the crown is grasped with extraction forceps, to expose pulp which is removed. A hole is drilled through dentine through which the anterior part of a PMMA optical cylinder is cemented in place (there are various designs and sources of OOKP optical cylinder, the Brighton school uses cylinders from Lamda Polytech Ltd, Brackley, Northants., UK, the cylinders implanted in Germany had been fabricated by Morcher GmbH, Stuttgart, Germany). The crown is removed prior to drying with filtered oxygen and cementing of the optical cylinder. The saw, flywheel and drill and burr tips are constantly irrigated with balanced salt solution to provide cooling. Where periosteum has been detached, it is glued back with fibrin glue. The KPro is then implanted into a submuscular pouch (often the lower eyelid of the fellow eye) for a period of 2-4 months. A tooth allograft can be considered in edentulous patients, but HLA-matching, screening for blood-borne infections, and long-term immunosuppression with cyclosporin will be required. An allograft may be more rapidly resorbed compared with an autograft. One of us (K.H.) prefers using tibial bone in edentulous patients, but it is known that a tibial bone haptic is resorbed three times as fast as the osteo-odontolamina.

A buccal mucous membrane graft of about 3 cm diameter is used to cover the OOKP lamina, as there are stem cells present, it has proliferating capability and is adapted to high bacterial load. It will be vascularised by the time of stage 2 surgery and will provide the blood supply to the bone part of the OOKP lamina. Once harvested the fat from the buccal mucous membrane graft is removed with curved scissors and the graft soaked in an antibiotic solution until required. The eye is prepared by isolating the recti with stay sutures, a 360° per-itomy performed and the conjunctiva and tenons separated from underlying sclera. Corneal epithelium and Bowman's membrane are removed. The buccal mucosa is then trimmed to obtain an oval piece of adequate size to fit snugly on the front of the eye. The mucous membrane graft is sutured onto the side of the insertion of the four recti muscles and to the sclera with interrupted 6-0 vicryl. If possible, the cut edge of the graft should also be sutured to the conjunctiva.

When Not to Do Ocular Surface Reconstruction and Tooth Harvesting Together If the eye is very dry or there is a risk of the mucous membrane graft not taking, it may be better to perform stage 1 surgery in two steps. The mucous membrane graft to the eye is done first, and it is only when the graft has been shown to be well established before the patient is readmitted for tooth harvesting and preparing an OOKP lamina. Otherwise if there is a significant delay in mucous membrane healing, or if further partial or full repeat mucosal grafting proves necessary, the lamina may be resorbed whilst buried in the lid for an excessively long time. Stage 2 surgery is carried out 2-4 months after stage 1 in order for soft tissue to become integrated into the bone pores of the lamina. The interval also allows the lamina to recover from thermal damage, and any infection introduced from the oral cavity can be treated whilst the lamina is in the submuscular rather than on the eye. If the lamina is implanted submuscularly for a longer period of time, there may be significant resorption of the lamina. The first step in stage 2 surgery is to retrieve the buried lamina for inspection. It is only if this is of adequate size that the surgeon proceeds to prepare the eye for receiving the device.

After the OOKP lamina is retrieved from its submuscular pocket, soft tissue is excised from the posterior surface and the pseudocapsule that has grown around the OOKP is opened in the corners to form four pentagonal-shaped flaps of fibrovascular tissue which are used to fix it to the recipient sclera. Excess tissue is also trimmed from the anterior surface of the implant. A template is made of the lamina in order to plan placement of a Flieringa ring, and preplaced sutures for securing the lamina. The lamina is temporarily returned to its submuscular pocket until the cornea is about to be trephined. Traction sutures are applied to the lids for access to the eye. A superior rectus stay suture is placed and a buccal graft flap is fashioned by making an arcuate incision from 3 to 9 o'clock under constant irrigation with BSS and adrenaline. The flap is reflected and the cornea exposed. The buccal mucous flap is then reflected and a Flieringa ring sutured in place with sutures left long at 3 and 9 o'clock for traction. The centre of the cornea is marked and the template placed on the cornea and cardinal sutures are preplaced. Intravenous mannitol has by then been administered to reduce the intraocular pressure before trephination.

The cornea is partially trephined, the size depending on the diameter of the posterior part of the optical cylinder. This is completed with scissors or a blade. The iris is then completely removed using forceps. If the patient is phakic the lens is removed either by ICCE or ECCE (Falcinelli advocates an ICCE as he fears a capsular rim may occlude the trabecular meshwork. The Brighton school favours ECCE to avoid traction on the vitreous base). A posterior capsulotomy is made (if an ECCE has been used) and an anterior vitrectomy performed, with adequate traction provided by the surgical assistant on the two Flieringa ring sutures. The lamina is then sutured to the cornea with the posterior part of the optical cylinder traversing the corneal opening. Sterile air is then injected to reinflate the eye and indirect fundoscopy performed to ascertain adequate centration, to take note of the appearance of the posterior pole of the eye, and any presence of blood in the vitreous. Further interrupted sutures are applied to secure the lamina onto the sclera. The Flieringa ring is then removed, the buccal mucous membrane is repositioned and sutured in place, with a hole cut through the membrane to allow the anterior part of the optical cylinder to protrude.

Complications - Diagnosis and Management Complications can be divided into operative and postoperative complications. Significant damage to adjacent teeth is uncommon. Very occasionally, the maxillary sinus space may be breached. Facial and jaw fractures are also possible. Overheating of the OOKP lamina can take place without adequate irrigation. Buttonholing the buccal mucous membrane can also take place and requires suture repair. Vitreous haemorrhage can take place, especially if the surgeon does not wait long enough for the iris root bleeding to stop following total iridodialysis. Expulsive choroidal haemorrhage is possible. Mannitol infusion before opening the eye, and hypotensive anaesthesia help to prevent this catastrophic complication. The optical cylinder may become tilted if suture tensioning of the OOKP lamina is not done correctly. Among the most common postoperative complications is ulceration or necrosis of the mucous membrane graft. This is less common with a vascularised cornea, otherwise tenons tissue should be mobilised to lie over the cornea and to help supply the central part of the buccal mucous membrane graft with blood.

When the mucous membrane should thin or ulcerate, it is important to exclude infection and treat with prophylactic topical and systemic antibiotic. The thinned or ulcerated area, if not healed, will necessitate a bipedicular flap from the peripheral part of the graft, followed by a new graft to the peripheral bare area thus created. The periphery often has a better blood supply. Occasionally it is necessary to repeat the buccal mucous membrane graft altogether. If this has to be done following stage 2, then it will be necessary to remove the device and close the corneal opening with a small corneal graft whilst the device is returned to a submuscular pocket usually under the lower lid of the contralateral eye. It is also possible to use lid skin as cover as a last resort, having removed muscle and fat from the skin first. Glaucoma may be pre-existent or secondary to OOKP surgery. This needs to be tackled, otherwise continued field loss and finally loss of central vision will ensue despite technical success and retention of the device. Assessment of glaucoma is difficult but it is possible to estimate intraocular pressure with digital palpation through the upper lid, with the patient looking down to avoid the rigid OOKP lamina.

Other parameters which can be assessed include optic disc appearance, visual field examination and electrodiagnostic tests. Treatment is limited to systemic carbonic anhydrase inhibitor and surgery (cyclode-struction or drainage tube) which has not yet been worked out fully. It is not known how the OOKP lamina is absorbed, but it is in an ectopic situation, and the fact that it no longer bears a load (it previously did with mastication) may be responsible for increased osteoclastic activity. Bacterial action around the area bound by the mucous membrane graft opening may also play a part. The strategy has been to insert an adequately sized lamina of a minimum thickness of 3 mm throughout to allow for loss. The diameter of the cylindrical opening through the lamina is dictated by the diameter of the anterior part of the optical cylinder. For a thin root, a narrower optical cylinder needs to be used. When there is inadequate bone and dentine, the lamina (or the optical cylinder) can extrude through the overlying buccal mucous membrane. The subsequent entry of microorganisms can lead to the permanent loss of the eye. Thus the laminar dimensions are assessed at each clinic visit, using a cotton bud, the stability of the optical cylinder ascertained, including measuring the refraction, since any change in refraction is most likely to have been caused by an axial shift or tilt of the optical cylinder.

Serial photography from the side will also document and demonstrate protrusion of the anterior optical cylinder using the buccal mucous membrane as a reference point. In the absence of a change of refraction, such a protrusion may be due to thinning of the mucous membrane or the OOKP lamina, or a combination of both. Even though imaging will be at the limits of resolution, spiral CT and electron beam tomography have been useful in confirming clinical suspicion, leading to fashioning of a new lamina ready for lamina exchange after 2-3 months, in anticipation of device failure. Retinal detachment is a distinct possibility, especially in a young person following disturbing vitreous. Patients are warned of symptoms of posterior vitreous detachment, and each clinic follow-up is accompanied by a B-scan of the fundal periphery which cannot be viewed through the optical cylinder. Repair is now usually done with the BIOM system, although the endoscopio vitrectomy approach is sometimes called for. Neither technique requires the removal of the OOKP device.

AlphaCor The Device An alternative to rigid KPro technology is the AlphaCor™ artificial cornea (Addition Technology Inc., Des Planies, 111., USA) which has been described previously and surgical techniques discussed]. It is a flexible poly(2-hydroxyethyl methacrylate) (PHEMA) core-and-skirt keratoprosthesis with a peripheral macroporous skirt region that biointegrates through tissue ingrowth surrounding an effectively non-porous transparent optic. It is implanted within a lamellar pocket of which the central 3.5 mm posterior to the optic is removed, with the optic becoming a full-thickness corneal replacement 3 months later at stage 2 of the procedure, when tissue anterior to the optic is removed. A typical postoperative appearance of the device in the eye before and after stage 2 opening is seen in figure. A Gunderson flap, as pictured in figure, was originally felt a necessary adjunct to AlphaCor implantation, but it is now rarely performed. The device is designed for use as a corneal replacement in an eye with a reasonable corneal tear film, but may be used in mild-moderate dry eye states (if appropriately managed, for example with artificial tears, lateral tarsorrha-phy, bandage lens and some surgeons believe, with restasis), and in eyes with limbal stem cell abnormality.

Although a specially modified earlier prototype was evaluated in animals for a severely dry eye situation, this has not been developed for human application to date. The hydrophilic nature of PHEMA requires it to be positioned in a wet environment such that it retains a tear film to provide a good quality refractive surface. An inadequate or inflammatory tear film could increase the risk of postoperative stromal melting around the device, and of contact-lens type deposition on the optic. AlphaCor's conservative design, which lacks protuberant parts so as to minimise mechanical stresses, does entail the optic being recessed in relation to surround corneal tissue, and this impacts adversely on optic wetting and refractive performance in some cases. Indications AlphaCor has gained widespread regulatory clearance for use in adults with corneal opacity unsuited to a corneal graft due to a high risk of failure. Nearly 90% patients to date had previous graft failures (1-13, mean 2.4). Glaucoma affected 56.0% cases preoperatively and 24.9% had a drainage tube in situ. A history of chemical injury was reported in 12.6% of the series, and aniridics represented 6.9%. Detailed data concerning patient profiles and outcomes are voluntarily compiled and updated in the manufacturer's anonymous database, and available to user surgeons. Outcomes 300 AlphaCors have been implanted to date, with a maximum of just over 7 years follow-up, mean over 1 year.

Protocol cases have a better chance of 1-year retention in situ than a donor graft in similar preoperative conditions, as has been discussed previously, and risk and protective factors for the device have been described elsewhere. Risk factors for graft survival, such as vascularisation, number previous failed grafts, and glaucoma tubes, do not appear to impact adversely on AlphaCor outcomes, A system for evaluating risk of graft or AlphaCor success preoperatively has been suggested but requires more data to validate. Postoperative best corrected visual acuity outcomes for AlphaCor range between Light Perception and 6/6, with patients demonstrating a mean gain of 2.5 lines visual acuity. The best corrected visual acuity achieved with AlphaCor matches that (paired t-test) of patients achieved from their previous donor tissue graft prior to its failure. Discussion The choice of keratoprosthesis in the severely dry eye is straightforward, as only one device the OOKP will work. With careful assessment, adequate technique, regular follow up and early recognition and management of complications, most patients can look forward to many years of sight with an OOKP.

The surgery is complex and requires extensive support including long general anaesthesia, as well as input from oral surgical, oculoplastic, glaucoma, vitreoretinal and radiological colleagues. OOKP surgery should be confined to specialist centres. Shared care with the referring ophthalmologist is only appropriate if the referring ophthalmologist is willing to be rapidly available and is capable of recognising and treating complications of OOKP surgery. In the appropriately managed marginally dry eye, an AlphaCor keratopros-thesis may be considered, although the device should be seen as an alternative to high-risk keratoplasty in multiple graft rejection and vascularised corneae. Despite encouraging results from AlphaCor in eyes that would be high risk for penetrating keratoplasty and falling incidences of complications as described previously as risk and protective factors have been learned and management improved, this is clearly a device still very much on the learning curve and there is room for continued development and improvement of techniques and postoperative management to optimise outcomes.

Current data support the concept that patient selection is critical for success and suggest that AlphaCor outcomes result in higher probabilities of success at 1 and 2 years than is achieved by high-risk cases undergoing conventional donor penetrating keratoplasty. However, ongoing data collection and analysis will be critical in determining definitively which patients should have AlphaCor and which should have a further graft or other procedure in order to achieve the best possible outcome. KPro surgery is a complex and growing field. Those interested are invited to join the KPro Study Group (www.kpro.org), to add their contribution to the ongoing research and device evaluation.

Surgery of the Cornea: Corneal, Limbal Stem Cell and Amniotic Membrane Transplantation

2010-05-08T11:35:00.000-07:00

Corneal Surgery in the Treatment of Dry Eye
Severe forms of dry eye can lead to scarring of the cornea. Persistent defects in the precorneal tear film and associated degenerations of the corneal epithelium can cause apoptosis of stromal keratocytes. There is now ample evidence for an intensive cross talk between epithelial and stromal cells in the cornea.A good example is neurotrophic keratopathy early after penetrating keratoplasty where loss of sensory innervation leads to a reduced autonomous stimulation of tear secretion. If these eyes are not lubricated sufficiently after keratoplasty, superficial stromal scarring can be observed. Luckily, these opacifications often resolve if intensive topical lubrication is initiated early enough. In case of permanent scarring, surgical treatment options come into play.

For persistent superficial stromal scarring, lamellar corneal transplantation offers a relatively safer treatment option compared to full thickness grafting. In this situation we prefer the deep anterior lamellar keratoplasty (DALK) technique initially described by Melles et al. After preparation of a scleral tunnel at the 12-o'clock position and injection of air into the anterior chamber via a paracentesis, a custom made knife is used to dissect into a deep stromal plane immediately anterior to Descemet's membrane. The depth of incision is judged by the shadow surrounding the tip of the knife. A second and then a third specialized instrument is used to dissect within that deep stromal plane all around the cornea up to the limbal border. Thereafter, air is removed from the anterior chamber and a viscoelastic material is injected into the deep stromal pocket.

A conventional trephine (e.g. Barron) is then used to trephine with a diameter of e.g. 7 mm until viscoelastic material evades from the deep stromal pocket. After a circular excision of the anterior stromal tissue, special care has to be taken to thoroughly rinse the stromal bed and remove all remaining viscoelastic material since this later can cause interface haze. Thereafter, the lamellar donor tissue is placed into the stromal bed and immediately fixed with two continuous double running 10-0 nylon sutures. The donor tissue has to be prepared prior to this step by placing a donor corneoscleral tissue upside down (epithelial side down) and punching out an equally sized circle from the corneal center. Endothelial cells are then removed using fine dry sponges. Thereafter, trypan blue is gently placed onto remaining Descemet's membrane for better visualization and Descemet's membrane is then gently removed from the underlying stroma using fine forceps. Alternatively, for very superficial stromal scars, excimer laser phototherapeutic keratectomy can be used.

In case of deep stromal scarring, conventional full thickness penetrating keratoplasty is performed. We prefer the non mechanical trephination of donor and host tissue to reduce postoperative astigmatism and improve visual results. Trephination of donor tissue is performed in an artificial anterior chamber with a defined pressure of 22 mm Hg. After placing a metallic protection mask onto the center of the cornea, the donor tissue is excised using the 193-nm excimer laser. The recipient is prepared by marking the center of the cornea using a radial keratometry marker. Then again, a metallic protection mask is placed onto the recipient and the center of the cornea is excised along the metallic mask using the excimer laser. After removal of the central host tissue, a small iridotomy is performed in the peripheral iris at 12 o'clock. Then the donor tissue is fixed in the recipient using eight interrupted 10-0 nylon cardinal sutures. Finally, a double running diagonal continuous suturing technique according to Hoffmann is used to fix the donor tissue permanently into the recipient rim. The cardinal sutures are removed and a placido ring is used to detect potential corneal astigmatism. The latter is then corrected as far as possible by manipulating the suture material.
In case of spontaneous perforation of ulcerations associated with severe forms of dry eye, e.g. in the context of chronic graft versus host disease, a penetrating keratoplasty a chaud has to be performed. To reduce corneal inflammation, we combine an amniotic membrane patch graft.

Special care has to be taken to provide sufficient lubrication of the graft after transplantation in eyes with reduced tear film. The surgical procedure itself exacerbates tear film deficiency by interrupting the sensory innervation and thereby autonomic stimulation of tear production. Sufficient lubrication of the graft after transplantation also seems to reduce the risk of corneal graft rejection. This may be due to the fact that dry eye causes ocular surface inflammation, which in turn activates antigen presenting cells and promotes graft rejection. In cases of severe dry eye, we perform a simultaneous amniotic membrane patch graft. Surgery for persistent epithelial defects itself using amniotic membrane transplantation is discussed below.

Limbal Stem Cell Surgery in the Treatment of Dry Eye
If severe forms of dry eye lead to limbal stem cell deficiency or if limbal stem cells are affected, e.g. in chemical burns causing dry eye due to meibo-mian gland deficiency together with stem cell deficiency, limbal stem cell surgery comes into play. There are several options when stem cells are deficient, unilateral and incomplete: (a) limbal autograft (from the ipsilateral or the contralateral eye) and (b) sequential keratectomy when the deficiency is localized. The latter can be combined with amniotic membrane transplantation. When unilateral stem cell deficiency is complete, tissue has to be obtained from the other healthy eye either by limbal autograft or by transplantation of ex-vivo cultivated limbal stem cells. These can be grafted on amniotic membrane or e.g. on fibrin gels. Transplantation of ex-vivo cultivated limbal stem cells has the advantage that only a small amount of healthy limbal tissue from the contralateral eye needs to be excised. In cases where bilateral stem cell deficiency occurs, stem cells have to be obtained from donor tissue, again either for ex-vivo amplification or direct surgical transplantation. In these cases, long term immunosuppression is mandatory to enable survival of grafted tissue.

Amniotic Membrane Transplantation in the Treatment of Dry Eye
Persistent epithelial defects and stromal ulcerations are a common problem in patients with severe dry eye, most commonly associated with neurotrophic keratopathy, rheumatoid diseases or chronic forms of graft-versus-host disease. Conservative measures include lubrication of the ocular surface, occlusion of the draining canaliculi, serum eyedrops and bandage contact lenses. If these measures fail, transplantation of amniotic membrane usually as a patch graft is a simple, reliable, fast and cost-effective measure to promote surface healing despite tear film deficiencies. Amniotic membrane acts in several ways to promote repair of the ocular surface. First, amniotic membrane can act as a new basement membrane for epithelial cells to grow on. Second, amniotic membrane exerts an anti-inflammatory milieu, e.g. by releasing IL-1 receptor antagonist. Thereby, inflammation of the ocular surface, which in itself causes dry eye, can be inhibited. Third, amniotic membrane contains growth factors (such as neurotropic growth factor (NGF)) which directly address the pathophysiology of dry eye in neurotrophic keratopathy.

Finally, amniotic membrane integrates into the cornea, either subepithelially, intraepithelially or intrastromally, and thereby smoothes surface defects in case of corneal ulceration. Amniotic membrane can be used in three different forms in the context of erosions and ulcerations of the cornea in severe dry eye: in case of pure epithelial defects, a patch of amniotic membrane is placed over the cornea and acts as a biologic contact lens. The size of the tissue can either be defined using conventional trephines or excised manually. The amniotic membrane is usually fixed using 10-0 nylon sutures with a bandage contact lens on top of it. In case of corneal ulcerations, one up to several layers of amniotic membrane can be placed in the ulcer. The most superficial layer is then sutured to the cornea. Both approaches can be combined in severe surface defect sandwich approach. Dry Eye Associated with Neurotrophic Keratopathy Neurotrophic keratopathy is characterized by a combination of severe to moderate dry eye with a reduced healing capacity of the corneal epithelium.

Causativ
e for a neurotrophic keratopathy is a defect in the sensory innervation of the cornea, i.e. the first branch of the trigeminal nerve. The reduced sensory information from the cornea leads to a reduced stimulation of the autonomic innervation of the basal and reflex tear production. Clinically, neurotrophic dry eye in the first stage appears as a normal keratoconjunctivitis sicca, i.e. epithelial surface irregularities, dot-like flu-orescein and rose bengal staining. Especially in the first stage of neurotrophic keratopathy it is very easy to miss the diagnosis and confuse a stage I neurotrophic keratopathy with a dry eye of other origin. Therefore, it is imperative to perform aesthesiometry of the corneal surface in all patients with unilateral or asymmetric or abnormal dry eye disease. Neurotrophic keratopathy then progresses to stage II, which is characterized by a persisting epithelial defect and may eventually lead to stage III disease, which is a corneal ulcer with the danger of progressive corneal melting and perforation. In all three stages, corneal aesthesiometry is a decisive step in making the correct diagnosis. Treatment of stage I—III primarily consists of topical unpreserved lubricants. Additional lid malpositions and other exacerbating factors should be minimized. Other treatment options in stage I and II include punctum plugs, bandage contact lenses and a temporary tarsorrhaphy.

Causal treatment options include the topical administration of NGFs or pro-NGF (currently in preclinical evaluation) which are essential for maintenance of normal epithelial wound healing, topical application of serum eyedrops (which also contain NGFs), and amniotic membrane transplantation (which also contains NGF). Amniotic membrane transplantation in neurotrophic keratopathy has two different indications with respect to the stage of neurotrophic keratopathy. In stage I (keratopathia punctate superficialis) and stage II (persisting epithelial defect), the purpose of amniotic membrane transplantation is to provide a natural bandage lens in addition to providing NGFs. This means that in stage I and stage II disease a 'patch' of amniotic membrane will be sutured onto the cornea (diameter up to 10 mm), usually with eight 10-0 nylon sutures, to keep the patch in place. Alternatively a larger patch, e.g. 16 mm, can be fixed onto the cornea and adjacent conjunctiva using eight 8-0 absorbable vicryl sutures. To provide a longer survival of the amniotic membrane on the corneal surface, we usually add a 17-mm bandage contact lens with prophylactic antibiotic topical drops on the amniotic membrane.

The strategy shifts in stage III neurotrophic keratopathy with ulceration where amniotic membrane grafts are placed in the ulcer and the most superficial layer sutured to the adjacent corneal stroma, again with usually eight 10-0 nylon sutures. In addition, one can place a patch on top of the cornea and the conjunctiva again sutured with eight single stitches with a 10-0 nylon sutures ('sandwich'). Again, a 17-mm bandage lens is added on top of this. The sutures and the bandage contact lens are left in place for 4 weeks with prophylactic topical antibiotic eyedrops and tear replacement. After 4 weeks the sutures are carefully removed without damaging the amniotic membrane. In summary, amniotic membrane transplantation either as a patch in stage I or II or as a graft (or sandwich) in stage III is a very reliable, easy to perform and helpful strategy to treat epithelial surface disorders or ulcers associated with the dry eye in neurotrophic keratopathy.

Treatment for Dry Eye Associated with Chronic Polyarthritis Chronic polyarthritis leads to several pathologies of the ocular surface. These include severe dry eye along with corneal melting and immune mediated inflammatory diseases of the sclera and the posterior pole of the eye. Amniotic membrane transplantation presents a useful adjunct treatment option for persistent epithelial defects associated with severe dry eye disease associated with chronic polyarthritis, which is resistant to topical treatment with tear replacement drops and punctum plugs, temporal tarsorrhaphy and serum eyedrops. In case of persisting epithelial defects, amniotic membrane transplantation is usually performed as patch graft as described above and prophylactic topical antibiotic applied. An additional bandage contact lens and the sutures are only carefully removed after 4 weeks. Amniotic membrane transplantation provides a useful and reliable strategy to relieve symptoms associated with epithelial defects associated with severe dry eye in patients with chronic polyarthritis.

Conclusions
To conclude: (1) severe forms of dry eye can cause persistent corneal epithelial defects, corneal ulcerations and consequently corneal scarring; (2) a very useful instrument in the surgical management of persistent epithelial defects is the transplantation of amniotic membrane (either as patch, graft or sandwich); (3) persistent corneal scars secondary to dry eye can be treated either by lamellar or - if deep in the stroma - by penetrating keratoplasty; (4) limbal stem cell transplantation offers a new opportunity to restore limbal barrier function and corneal surface integrity in diseases associated with severe dry eye and limbal stem cell deficiency (such as chemical burns), and finally (5) the possibility to transplant ex-vivo cultivated limbal stem cells on fibrin gels as carriers greatly improves the management of patients with unilateral limbal stem cell deficiency.

Surgery of the Conjunctiva

2010-05-08T11:22:00.000-07:00

Dry eye is a multifactorial disease characterized by the development of a chronic vicious cycle between the tear film and ocular surface epithelium, resulting in tear film instability as well as ocular surface epithelial damage that are respectively observed as shorter fluorescein breakup time and punctate flu-orescein staining of the ocular surface epithelium. The vicious cycle may be related to the other dry eye mechanisms, such as the well known hyperosmolarity or the more recently emphasized inflammation, yet the exact relationship between the three mechanisms (tear film instability, hyperosmolarity, and inflammation) remains unclear. However, numerous risk factors may be related to the three central mechanisms of dry eye mentioned above, and these risk factors may result in or exacerbate the clinically evident dry eye. The conjunctival abnormalities described in this chapter may all be regarded as risk factors for dry eye, and they include: conjunctivochalasis (CCh); superior limbic keratoconjunctivitis (SLK); pterygium and pinguecula, and cicatricial changes associated with severe ocular surface disease, such as in Stevens Johnson syndrome and ocular cicatricial pemphigoid.

CCh, also known as lip like folds, conjunctival pleating , and lid parallel conjunctival folds (LIPCOF), can be both a diagnostic sign and a risk factor for dry eye. From the etiological viewpoint, CCh exacerbates dry eye via the dysfunction of the tear meniscus and mechanical action. CCh is generally located along the lower tear meniscus where it may interfere with the tear meniscus which is known to serve three important functions including: (1) retention of tears (75-90% of the total tear volume rests in the tear meniscus); (2) distribution of tears to the ocular surface, and (3) ocular surface tear routing due to its connection to the lacrimal drainage system. CCh may result in tear film instability and the disruption of tear flow leading to delayed tear clearance, which then in turn may exacerbate dry eye associated inflammation.

A paradoxical consequence of CCh associated tear meniscus dysfunction in mild cases of dry eye is pseudo epiphora. In more severe cases, CCh will not only reduce the retention and distribution of tears but also of tear substitutes applied. Another mechanism exacerbating dry eye or dry eye associated symptoms is CCh related mechanical friction. This occurs between the lax conjunctiva and the lid margin and/or cornea. Ocular surface epithelial damage and conjunctival hyperemia are frequently seen in cases with CCh combined with aqueous tear deficient (ATD) dry eye, and may be attributed to this friction associated mechanical trauma to the ocular surface. This mechanism is also involved in SLK, where there is friction between the lax upper bulbar and palpebral conjunctiva, limbus, and upper part of the cornea. Interestingly, the characteristic changes of advanced SLK include inflammation and inflammation-related focal dry eye, and these can be successfully treated surgically.

Next, when investigating the mechanism that prompts the pinguecula or pterygium to cause or exacerbate dry eye, ectopic menisci formed around pinguecula or pterygium head which invade the cornea should be considered. These ectopic menisci are known to cause thinning of the adjacent tear film resulting in local tear-film instability and focal evaporative dry eye. This mechanism may help explain the superficial punctate keratopathy (SPK) or Dellen found adjacent to the pinguecula or a pterygium head which are often medically uncontrollable; this is especially true in cases with a background of ATD.

Finally, the cicatricial change in conjunctiva seen in severe ocular surface diseases such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid is associated with chronic subconjunctival immunological inflammation. This inflammation involves lacrimal gland ducts and conjunctival epithelium, resulting in ATD and inhibition of the normal differentiation of conjunctival epithelium. This leads to the pathological keratinizationl which transforms hydrophilic surfaces into hydrophobic ones. These mechanisms are found in the severe form of dry eye that is often accompanied by severe ocular surface diseases and is a result of a combination of ATD and evaporative dry eye.

Based on the conjunctiva-associated mechanisms in dry eye described above, several surgical strategies can be considered. For the treatment of CCh, conjunctival resection should be designed to reconstruct the normal tear meniscus to the greatest possible length along the lower lid margin. Ideally, this resection would extend from the lateral canthus to the punctum in order to restore normal tear meniscus function, rather than just a simple resection of the lax conjunctiva. In contrast, in cases of pinguecula or pterygium, resection of the protruding conjunctival lesion, which is thought to induce SPK, should be designed to remove the ectopic meniscus which is the causative factor of focal dry eye. This is usually indicated in cases with ATD.

In cases with severe ocular surface disorders with conjunctival cicatrization associated with dry eye, mitomycin C and/or amniotic membrane can be used at the time of resection of subconjunctival fibrovascular tissues to reduce conjunctival inflammation when anti-inflammatory medical treatment was unsuccessful. However, those cases are sometimes accompanied by corneal stem cell disorders which often necessitate additional reconstruction of ocular surface epithelium.

The previously described treatment modalities are sometimes applied simultaneously, and at other times in a more stepwise approach. The following sections will describe the practical aspects of conjunctival surgery for dry eye, including indications, surgical techniques, and complications.

Surgery of Conjunctivochalasis

Background of the Disease
CCh is a very common ocular disorder that is characterized by a redundancy of bulbar conjunctiva. Although there are two etiological theories associated with this disease (age-related and subconjunctival inflammation-related), our research has demonstrated the breakdown of elastic fibers in the redundant conjunctiva without any inflammatory cell infiltrates , thus supporting the age-related theory. However, it is often clinically experienced that CCh may cause non-specific inflammation, possibly via the redundant CCh-induced mechanical action during blinking and/or eye movement, or an exacerbation of dry eye-related inflammation via the CCh-induced delayed tear clearance.

CCh is unique in that it may induce tear meniscus dysfunction which is a risk factor for both watering eyes and dry eyes. Symptoms of dry eye discomfort and/or corneal epithelial damage may be exacerbated not only as a result of tear meniscus dysfunction, but also because of the mechanical friction created between the redundant conjunctiva and the ocular surface. It has also been reported that LIPCOF can potentially be used as a diagnostic marker for dry eye. Historically, surgery of CCh has been little practiced, yet numerous recent reports support the efficacy of a surgical approach for improving ocular symptoms and ocular surface epithelial damage in cases with or without dry eye.

Concept of Surgery
Although numerous surgical methods for CC have been reported , such as a crescent resection, resection combined with inferior peritomy and radial relaxing incision, and excision with amniotic membrane transplantation (AMT) and scleral fixation, all previous methods involved no firm strategy for tear meniscus reconstruction and most procedures only targeted the redundant conjunctiva inferior to the cornea while redundant conjunctiva in the nasal and temporal areas were ignored. Therefore, the ideal surgical method must be applicable to all variations of CCh and should achieve reconstruction of the entire lower tear meniscus and eliminate ocular surface undulations.

Indication for Surgery
First, surgery for CCh is only indicated when the disorder is symptomatic. Asymptomatic CCh, even if there is excess tissue, is not an indication for surgery. Second, surgery should only be performed if the reported symptoms can be explained by clinically established signs of tear meniscus dysfunction and/or the mechanical action of redundant conjunctiva.

In cases of dry eye combined with CCh, surgery should be performed when medical treatment is found to be ineffective. However, in cases of CCh with unstable tear film and no SPK (often diagnosed as dry eye and ineffectively treated with eyedrops alone), surgery can be expected to produce positive results. Traditionally, punctal occlusion with plugs has been the initial method for treating patients with moderate dry eye and prominent CCh. However, recent results now indicate that CCh surgery should be considered prior to punctal occlusion.

Surgical Procedure
The operation includes the following steps: (1) topical anesthetic eyedrops with epinephrine are applied; (2) planned incision lines are marked using a newly developed marker (Chalasis marker, M-1405; Inami Co., Ltd, Tokyo, Japan). Small eyes require forced bilateral eye movement for correct marking; (3) subconjunctival anesthesia is performed, and an arc-shaped incision is made to the anesthesia-ballooned conjunctiva using scissors (Chalasis scissors, M-1406; Inami Co., Ltd) along the line created by the marker on the lower half of the bulbar conjunctiva; (4) subconjunctival tissues are dissected distal to this arc incision in order to easily stretch the redundant conjunctiva and to obtain firm attachment of the conjunctiva directly to the sclera; (5) radial incisions are then made with the Chalasis scissors in the redundant conjunctiva in order to create three conjunctival sections distal to the arc incision. The conjunctiva in the lower section is then pulled upwards, and any tissue that can be overlaid on the limbal conjunctiva resected and fixed using approximately five 9-0 silk stitches.

For the treatment of the lateral sections, forced bilateral eye movement, henceforth referred to as the 'eye rotation step', are performed when judging the amount of excess tissue to avoid suture breaks due to postoperative eye movement. It is important to resect all redundant conjunctiva of the temporal conjunctiva while less resection is required of the nasal side due to the subsequent resection of the plica semilunaris; (6) the temporal and nasal conjunctival flaps are then sutured with interrupted 9-0 silk; (7) excision of the plica semilunaris and minor temporal adjustment is then performed. The plica semilunaris should be excised at the base and no sutures are necessary. Using these procedures, complete reconstruction of the lower tear meniscus and elimination of conjunctival surface-related undulations associated with CCh can be obtained.

Postoperative Follow-Up, Complications, and Management Postoperatively, patients are advised to wear an eyepatch for 1 week at bedtime to prevent any possible wound dehiscence. Sutures are removed 2 weeks after surgery. During the 2-week postoperative period, 0.1% betamethasone and antibiotic eyedrops should be instilled 4 times daily. Following removal of the sutures, betamethasone should be replaced by 0.1%fluorometholone instilled 4 times daily together with antibiotic eyedrops. Instillation times of the 0.1%fluorometholone should be reduced according to the extent of postoperative inflammation, and fully discontinued within 2 months postoperatively. Dry-eye patients should additionally receive artificial tears (ideally preservative-free) in combination with the above-mentioned postoperative eyedrops. That combination is then substituted with the eyedrops that the patients were using for dry-eye treatment prior to surgery once postoperative inflammation subsides.

Without the 'eye rotation' step, early postoperative complications in our previous study of 168 eyes included secondary lymphangiectasia in 6 eyes (3.5%), dehiscence in 11 eyes (6.5%), and pyogenic granuloma due to a reaction to the 9-0 silk suture in 2 eyes (1.1%). Lymphangiectasia can be managed by needling or excision, and pyogenic granuloma can be managed with topical steroids or surgical removal.

Surgery for Superior Limbic Keratoconjunctivitis

Background of the Disease
SLK is a unique inflammatory disease, first reported by Theodore in 1963, of the superior bulbar conjunctiva, limbus, and upper part of the cornea. The condition may be associated with corneal filaments, SPK, edema hyperemia and papillary hypertrophy of the superior bulbar and palpebral conjunctiva and limbus. The etiology of SLK is not clearly understood, however, there is a mechanical theory which suggests that in SLK the superior bulbar conjunctiva is lax due to congenital or age-related factors. In addition, blink-associated mechanical friction could lead to chronic inflammation of the lax conjunctiva. SLK is reportedly associated with ATD dry eye and thyroid disease, and is accompanied by severe symptoms of irritation. Many non-surgical treatments have been attempted, such as the application of silver nitrate, vitamin A eyedrops, N-acetylcysteine and autologous serum, bandage soft contact lenses, and punctal plugs. Effective surgical treatments include simple resection, thermocauterization, and recession of the abnormal conjunctiva.

Indications for Surgery
Artificial teardrops or low concentration topical steroids, such as 0.1% fluorometholone, should be tried. However, for SLK combined with moderate to severe dry eye, punctal occlusion with punctal plugs is the best method of treatment. SLK cases with myopia are most effectively treated with soft contact lenses in combination with frequent instillation of preservative-free artificial tears. Surgery should only be considered for cases that are unresponsive to medical treatment.

Concept of Surgery
Based on the concept that SLK-associated abnormal findings, such as con-junctival hyperemia, limbal thickening, and SPK, are the result of the friction between the redundant upper bulbar conjunctiva at and around the SLK lesion and the upper palpebral conjunctiva, surgery should aim to eliminate lax conjunctiva without leaving any redundant tissue at the SLK lesion by a crescent excision of the conjunctiva superior to the SLK lesion. Conjunctival redundancy is located mainly at - but not limited to - the SLK lesion. Therefore, we resect the perilesional conjunctiva but not the SLK lesion itself, and leaving intact conjunctiva close to the cornea may be helpful for future cataract or glaucoma surgery. As a result of this procedure, diseased conjunctiva within the SLK lesion is successfully stretched, conjunctival inflammation and positive rose bengal (RB) improve in as late as 1 month, and the amount of goblet cells within the SLK lesion is restored to the normal level.

Surgical Procedure
Our surgical method involves four steps: (1) Prior to surgery, a topical anesthetic with epinephrine and RB staining are applied to determine the localization of the abnormal conjunctival area in SLK. (2) After the administration of subconjunctival local anesthesia, an arc-shaped conjunctival incision is placed from the 2 o'clock to the 10 o'clock position adjacent and distal to the RB-stained lesion. (3) After excision of the subconjunctival connective tissue from the superior conjunctiva to the arc incision, the extent of resection is determined by the amount of redundant conjunctiva with the distal conjunctiva overlaid onto the RB-stained proximal conjunctiva. In accordance with the determined extent of resection, the conjunctiva is resected to form a crescent using the arc incision as the base. (4) The crescent incision of the conjunctiva is closed with interrupted stitches using 9-0 silk suture. Throughout the procedure, it is important that the patient is asked to look down as far as possible. This procedure usually results in complete resolution of SLK-associated hyperemia.

Postoperative Follow-Up, Complications, and Management Postoperative treatment consists of antibiotic eyedrops and 0.1% fluo-rometholone eyedrops, both instilled 4 times daily for 2 weeks and twice daily over the following 2-6 weeks. In cases involving a more invasive removal of subconjunctival tissue, the 0.1 %fluorometholone should be replaced with 0.1% betamethasone. The sutures should be removed 1-2 weeks postoperatively. To date, no early or late postoperative complications have been observed. Our success rate was 100%in 6 eyes of 5 patients.

Surgery for Pterygium
Background of the Disease
Severe progression or recurrence of pterygium sometimes leads to clinical problems such as corneal scarring and irregular astigmatism. Advanced scarring may extend close to the optical zone and extraocular muscles, resulting in visual loss and restriction of ocular mobility, respectively. Rarely does pterygium relate to or coexist with the condition of dry eye, but when thick and irregular pterygium tissue invades the corneal surface it can lead to uneven tear distribution which is responsible for the focal evaporative form of dry eye. Early pterygium and pinguecula are commonly not problematic in normal eyes and should not be considered for surgery.

However, both have the potential to induce epithelial damage in cases of dry eye and during contact lens wear, because the irregular protrusion of these surfaces is insufficiently covered with tear film under the low tear volume. It is common to observe chronic inflammation in pinguecula of hard contact lens wearers because of physical stimulation and unstable tear-film coverage. When an ectopic tear meniscus is formed along the pterygium head, tear-film thinning will result next to it. This can cause tear-film instability which may lead to SPK around the pterygium head. Tear-film thinning is also notable over the prominent parts of the pterygium, and this may result in symptoms of irritation and dry-eye sensation as well as conjunctival hyperemia. Coincidental dry eye magnifies these symptoms, and the chronic epithelial damage caused by the tear evaporation results in chronic non-specific inflammation and may promote the progression of pterygium and pseudo-pterygium.

Indications
There are numerous reports that explore the surgical treatment of pterygium, yet medical treatment should be tried before resorting to surgery. Frequent use of artificial teardrops and hyaluronic acid instillation can improve apical surface damage in pterygium and focal inflammation should be treated with a low dose of fluorometholone unless steroid-induced complications are observed. The indication for surgery is not clearly defined, and sometimes includes the cosmetic and social requirements of the patient. The most important point of pterygium surgery is to inhibit recurrence of the disease, because the need for reoperation substantially reduces the prognosis and increases the risk of complications due to cicatrization. Indication, selection, and timing of the surgical procedure based on the clinical picture (e.g. chronic injection, bilateral pterygium, and thickening of the Tenon's tissue) determine the success of surgery. In dry eyes, corneal epithelial damage resistant to conventional management with artificial teardrops and punctal plugs is a clear indication for surgery.

Concept of Surgery
The purpose of surgery in primary pterygium is to remove hyperproliferat-ing subconjunctival tissue and the abnormal pterygium head and to minimize the risk of recurrence. Attention should focus on the: (1) area of excision; (2) use of intraoperative chemicals; (3) technique of wound closure, and (4) transplantation of tissue to the area of excision to inhibit recurrence.

For advanced and recurrent pterygium, in order to prevent further recurrences and/or to reconstruct surgically induced conjunctival cicatrization, additional concepts have been proposed. These include: (1) reconstruction of the limbal barrier to block pterygium re-invasion, and (2) reconstruction of conjunctival area lost by excessive surgical resection and scarring.

The concept of an autologous limboconjunctival graft taken from the patient's healthy eye has been reported, however this procedure carries the risk of inducing partial limbal deficiency at the donor site. Therefore, keratoep-ithelioplasty using a preserved corneal graft is an alternative procedure that eliminates the risk of damage for the other eye.

Surgical Procedures
Previously, simple resection with bare scleral closure has been used in early or small pterygia. However, a variety of studies have shown a high rate of recurrence for that technique when not accompanied by adjunctive therapy. Slow epithelial wound healing and prolonged postoperative inflammation may activate fibroblasts, resulting in recurrence. It is now widely accepted that adjunctive therapy and creation of a physical barrier dramatically reduces the risk of pterygium recurrence.

The adjunctive intraoperative application of mito-mycin C (MMC) has been commonly used and is found to improve the clinical outcome even in mild cases.MMC is an alkaloid agent capable of suppressing the proliferation of fibroblasts which are thought to be responsible for the etiology of pterygium. The commonly used concentration of MMC ranges between 0.02 and 0.04%, and the duration of application between 1 and 3 min (compared to postoperative topical use). The intraoperative application of MMC is relatively safe, however postoperative complications such as scleroma-lacia and persistent epithelial defects can result from an excessive MMC effect. Therefore, it is important that MMC is not applied to surgically damaged or thin sclera, and that the ocular surface is thoroughly rinsed with 0.9% saline afterwards.

Conjunctival rotational flaps and conjunctival transplantation are commonly used surgical methods to prevent recurrence. Technically, both approaches are relatively simple and do not require the use of any special materials. However, folding of the conjunctiva after rotation can sometimes cause cosmetic problems. Transplantation of a free conjunctival graft is more complicated and time-consuming, yet superior to conjunctival flap rotation in achieving a smooth conjunctival surface. The technique is especially useful in recurrent pterygia, where a large epithelial defect may result from resection. Free conjunctival autografts not only promote epithelial healing, but also act as an epithelial barrier to inhibit recurrence and were found to be superior to AMT in a comparative randomized trial. On the downside, it results in additional scarring of normal conjunctiva.

Amniotic membrane (AM) is now widely accepted as an effective biological tool to inhibit pterygium recurrence. AM promotes epithelial wound healing and prevents inflammation. AMT was first introduced in pterygium surgery in 1997 by Tseng et al, and several reviews have summarized the proposed basic mechanisms of AM. Although the precise biological effects of AM are still unclear, clinical results have indicated that fibroblast growth under the AM is suppressed and that postoperative complications such as persistent epithelial defect and scleromalacia, even after a large-sized resection, are reduced. AMT appears to successfully improve the prognosis of severely recurrent pterygium.

Postoperative Follow-Up, Complications, and Management Complications are subdivided into two categories: intraoperative and postoperative.

Intraoperative complications are rare. The most serious complication is damage to the medial rectus. Sufficient caution should therefore be paid during the removal of subconjunctival tissue, especially in recurrent pterygia with severe scarring and excessive bleeding, and squint hooks or silk threads should be used to simplify the separation. Corneal perforation is a very rare complication, but excessive thinning of the cornea during excision should be avoided. Intraoperative surgical slit-lamp examination is a useful tool for examining the corneal thickness at the time of pterygium removal.

Major postoperative complications of pterygium surgery include infection, corneal ulcers, and scleromalacia. Infection is rare, yet it should be noted that wearing bandage contact lenses after large-area resections dramatically increases the risk of infection.

Appropriate antibiotic instillations should be used until the wound is fully healed. Persistent epithelial defects and Dellen formation are not common, but they may progress to corneal melting. Frequent instillation of artificial tears and ointments are usually sufficient for treatment. Severe cases occasionally require additional treatment using punctal plugs or bandage contact lenses to increase the stability of tear film and promote epithelial healing. Scleromalacia is the most undesirable complication, because it may appear even after years of intra- or postoperative MMC and (3-irradiation. Since scleromalacia is difficult to stop and may require surgical treatment such as scleral patching or lamellar keratoplasty, MMC should always be applied with great care. Although topical instillation of MMC or 5-fluorouracil in the postoperative period have been reported to be efficient, it is wise to remember that these treatments are associated with an increased risk of severe complications such as persistent epithelial damage and scleromalacia.

Surgery for Cicatricial Ocular Surface Disease

Background of the Disease
The majority of cicatrizing diseases of the ocular surface are associated with dry eye. Obstruction of lacrimal ducts opening onto the conjunctival surface due to progressed cicatrization, as well as conjunctival sac shortening and symblepharon formation, all lead to reduced secretion, pooling, and abnormal distribution of tears and tear meniscus. Extensive scar formation and symblepharon also interfere with normal eye-blinking and cause trachiasis and entro-pion which further degrade the ocular surface environment.

Dry-eye patients in need of conjunctival reconstruction can be divided into two groups: (1) cicatrization caused by exogenous reasons such as thermal or chemical injury, or (2) cicatrization caused by endogenous disease such as Stevens-Johnson syndrome and ocular pemphigoid. Although the pathogenesis of cicatrization varies, excessive proliferation of fibroblasts and conjunctival epithelium and the loss of goblet cells are commonly observed in these disorders. Active autoimmune-related inflammation is thought to be the primary reason for the pathogenesis. Therefore, removal of inflamed tissue and activated fibroblasts helps to inhibit the progression of these diseases and stabilizes the ocular surface. Medical treatment using steroids and other immuno-suppressive medications is essential for controlling chronic inflammation and stabilizes the ocular surface. Intensive medical treatment is first considered to reduce inflammation and to inhibit the progression of cicatrization. Although the surgical indication is controversial, the recent advance of ocular surface reconstruction utilizing the intraoperative application of MMC and AMT notably improves the prognosis of severe cases in both the acute and chronic phases.

Concept of Surgery
Reconstruction of the conjunctival sac and removal of scar tissue is the primary rationale for conjunctival surgery when attempting to reestablish a healthy ocular surface. In addition, reduction of chronic inflammation in the subconjunc-tival tissue also helps to prevent progression of cicatrization and dry eye and subsequent corneal complications such as persistent epithelial defect and stem cell deficiency. Thus, concepts of surgery include not only reconstruction of conjunctival tissue, but also removal of activated fibrotic tissue and immunoantigens.

Indications and Surgical Procedures
The surgical procedures, including intraoperative use of MMC and AMT, are identical for upper and lower conjunctival fornix reconstruction. First, conjunctival dissection is performed 2-3 mm from the limbus. After removal of fibrovascular tissue in the subconjunctival area and symblepharolysis, 0.04% intraoperative MMC is applied using a surgical microsponge for 5min. The MMC is then carefully washed out using 200-300ml of 0.9% saline. It is important to coagulate any bleeders to prevent dilution of the MMC and detachment of the AMT. Preserved AM is applied with the epithelial side up to cover the bare scleral area. The AM is then tightly sutured to the scleral surface using 10-0 nylon. If a case requires full coverage with AM, the edge of the AM should be sutured to the lid margin and the fornix should be reconstructed with anchoring nylon sutures. Additional keratoepithelioplasty and transplantation of free conjunctiva should be considered for severe cases.

Recently, cultivated oral mucosal epithelial transplantation (COMET) has been applied as an alternative method. This ex vivo expanded epithelial sheet provides rapid epithelialization and prevents cicatrization without converting to the original oral buccal mucosal tissue structure. Although no comparative studies have yet been performed, our preliminary clinical results indicate that the viable oral mucosal epithelial lining was able to maintain the reconstructed conjunctival space even in cases with recurrent severe cicatrizing ocular surface diseases after conventional AMT. COMET is a newly developed cell-sheet transplantation procedure which uses cultivation technology and AM as a substrate. A small amount of oral mucosa is excised, and from this epithelial cells are isolated by EDTA and enzymatic treatment. The cell suspension obtained is cultured on AM using a co-culture system with 3T3 fibroblasts to generate a stratified epithelial sheet suitable for transplantation. The advantage of this procedure is that it uses autologous epithelium and is independent of the presence of ocular donor tissue, which may be unavailable in severe bilateral disease. Compared to simple tissue transplantation of full-thickness oral buccal mucosa, the oral mucosal epithelium cultivated on AM is composed of 5-7 stratified epithelial layers, similar to corneal and conjunctival epithelium. This epithelial structure is also maintained after transplantation onto the ocular surface without converting to the original tissue structure.

Concepts for Conjunctival Fornix Reconstruction
The concepts include: (1) reconstruction of conjunctival area; (2) prevention of cicatrization through inactivation of conjunctival fibroblasts and inflammatory cells using intraoperative MMC; (3) AMT; and (4) epithelial transplantation, i.e. (a) limbal transplantation, (b) conjunctival transplantation, and (c) cultivated mucosal epithelial transplantation.

Postoperative Follow-Up, Complications, and Management The appropriate use of postoperative medication is mandatory to achieve and maintain a successful surgical result. Since the primary pathogenesis is frequently exacerbated by the surgical procedure, it is important to limit any inflammatory response during the early phase. Systemic steroids and topical cyclosporin are effective for most cases. Epithelial healing should be promoted for rapid stabilization of the ocular surface using artificial tears and punctal plugs. Effective long-term immunosuppression is required to maintain the reconstructed conjunctival fornix, and this is most important in ocular cicatricial pemphigoid.

In summary, management of cicatrizing ocular surface disorders is extremely challenging. Recent advances in ocular surface reconstruction techniques have dramatically changed the indication and strategy of surgical treatment. The application of intraoperative MMC and AMT are especially effective for reducing recurrent fibrosis and chronic inflammation. The introduction of new techniques based on regenerative medicine may potentially bring a future shift in paradigm. However, severe tear volume deficiency resulting from cicatrization has yet to be overcome. Since a minimum of tear secretion is essential for the survival of surface epithelia, every case should be considered carefully to decide whether the indication and time are right for surgical intervention. Appropriate medical management and surgery are required to improve the prognosis in the long term.

Lacrimal Drainag e Surgery in a Patient with Dry Eyes

2010-05-08T11:07:00.000-07:00

Although incorrect, it is a commonly held view that the patient with true dry eye that is, a lack of aqueous tear production should never require surgery to the lacrimal drainage pathway, apart from canalicular or punctal occlusion to preserve fluid on the ocular surface.

Ocular surface health particularly that of the hydrophobic corneal epithelium is dependent upon two main factors: First, an adequate precorneal tear film that requires not only secretion of the correct proportions of surface water, mucus and oil, but also the regular downward sweep of the upper lid that evenly spreads these various components across the upwardly moving cornea during the blink cycle.

Secondly, the removal of ocular surface debris that is achieved by the continuous flow of tears from lateral to medial across the ocular surface, by the dilution of the tear lake with new secretion, and by removal of debris through tear drainage.

Failure of lacrimal drainage will prevent this physiological cleansing of the ocular surface and thereby lead to an accumulation of noxious substances within the tear film; this failure of clearance being exacerbated by concentration of retained surface debris by evaporation from the stagnant tear lake.

The noxious substances may be extrinsic or intrinsic: Extrinsic factors include external allergens (such as pollens or dust mites) and external physical or chemical irritants, such as irritant fumes or dusts. Intrinsic factors include the antigens from commensal bacteria (especially staphylococci) on the lid margins or in meibomian secretions, and the inflammatory mediators that spill onto the ocular surface from the chronically inflamed conjunctiva of the dry eye. The inflammatory load on the ocular surface is particularly great in a dry eye without tear drainage not only because of their lack of removal and their concentration by tear film evaporation, but also because the poor environment is easily exploited by periocular commensal bacteria which, in turn, proliferate and markedly exacerbate the already significant chronic conjunctivitis.

A much more severe inflammatory and infective load often with unusual bacterial flora can arise where nasolacrimal duct occlusion is present, with transcanalicular wash back of debris from the lacrimal sac into the tear film (a so called volume sign). Although canahcular occlusion alone will stop wash back of this infective and inflammatory debris, such occlusion risks a severe dacryocystitis unless occlusion is preceded by dacryocystectomy or dacryocystorhinostomy (DCR).

Rational Management of the Lacrimal Drainage System in Dry Eyed Patients

Where occlusion of the lacrimal drainage puncta or canaliculi occurs as part of the underlying disease causing dry eye (for example, with mucous membrane pemphigoid or after Stevens Johnson syndrome), lacrimal surgery is required only rarely. However, despite intensive treatment with preservative free anti inflammatory and antibacterial drops, some of these patients develop such a severe toxic response that the ocular surface is improved only by establishing free drainage of the inflammatory mediators. This type of patient typically requires external DCR with retrograde canaliculostomy or with primary or secondary placement of a glass Jones canalicular bypass tube.

Where the patient with a dry eye and patent tear drainage pathways needs preservation of ocular surface fluids, consideration should be given to canalicular occlusion. Whilst there are many commercially available plastic plugs for occluding either the puncta or canaliculi, the foreign surface of such devices inevitably gathers a gross biofilm (particularly in the already disadvantaged ocular environment of the dry eye) that can only exacerbate the toxic changes on the diseased ocular surface. If such patients require occlusion of outflow, this should first be tested by a reversible occlusion of both the upper and lower canaliculi with punctal plugs or self dissolving (collagen) canahcular plugs to check that the ocular surface disease is not worsened by the loss of tear film outflow: where all is well, canahcular occlusion by thermal cautery will succeed in almost all patients, but excision of the canahcular ampulla may be needed where this fails. To reduce wash back of toxic debris from the lacrimal sac into the tear lake, patients with nasolacrimal duct occlusion should all undergo DCR; the absolute cure of wash back being in practical terms achievable with external DCR and anterior ethmoidectomy. Although dacryocystectomy would also eliminate wash back, with the apparent benefit of occluding outflow, a complete absence of fluid drainage from the ocular surface might as already discussed above actually worsen the dry eye. Rather than primary dacryocystectomy, it is best to perform external DCR with later canahcular occlusion.

Surgical Techniques

External Dacryocystorhinostomy
DCR is designed to widely open the lacrimal sac into the nasal space, thereby eliminating the lacrimal sac and opening the common canaliculus directly into the nose and the wide soft tissue anastomosis required is possible only with an external approach incorporating a limited anterior ethmoidectomy.

The procedure can be performed under either general or local anaesthesia, typically as a day case procedure: Local anaesthesia with intravenous sedation tends to provide an excellent operative field, although it can be associated with rather more postoperative nasal oozing than that after general anaesthesia. Local anaesthesia is readily achieved by spraying the anterior nasal cavity with lidocaine 4% spray and infiltrating the medial one third of the lower eyelid and paranasal area with a solution of 0.5%bupivacaine with 1:100,000 to 1:200,000 epinephrine. Anterior ethmoidal nerve block, using 2-3 ml of the same solution, is achieved by passing a 23-gauge needle along the medial orbital wall from just above the medial canthus and angulated about 20° below the axial plane (to avoid injury to the anterior ethmoidal vessels). The anterosuperior nasal cavity is packed with about 80-100 cm of 1-cm packing gauze soaked in 2 ml of cocaine solution (4 or 10%) and the packing left in place until the silicone intubation is passed through the nasal cavity. Topical ocular anaesthesia, such as 0.5% amethocaine, is also required during the surgical procedure. Maximum vasoconstriction is obtained if the local anaesthetic is given at least 10 min before surgery commences and is most conveniently given prior to surgical gowning.

Where general anaesthesia is the preferred choice of the patient or surgeon, controlled hypotensive anaesthesia suitable for day case admissions is readily achieved with modern techniques such as either total intravenous anaesthesia (TIVA) using Propofol and Remifentanyl, or the combination of a volatile inhalation anaesthetic (such as isofluorane) with titrated small doses of a (3-blocker to prevent the compensatory tachycardia. For patients under general anaesthesia, nasal vasoconstriction is readily achieved, after sterile preparation and draping, by placing 3 cotton-tips - moistened in 1:1,000 epinephrine - as far superiorly and anteriorly as possible within the nasal space. Whether under local or general anaesthesia, the head-end of the operating table should always be raised during surgery, to decrease the cephalic venous pressure.

A 12- to 15-mm straight skin incision should be placed on the flat paranasal area, starting just above and about 1 cm in front of the medial canthal tendon - this type of incision only rarely leaving a noticeable scar, whereas more posterior incisions tend to bowstring across the inner canthal concavity. The skin is then undermined posteriorly to the anterior limb of the medial can-thai tendon, leaving the orbicularis muscle and angular vessels undisturbed. The pretarsal and preseptal orbicularis fibres are separated by blunt dissection along the line of the fibres, this revealing the anterior lacrimal crest along which the paranasal periosteum is widely divided using a Rollet's rougine; damage to the vascular preseptal orbicularis muscle and the angular vessels may be avoided by retracting them medially with a squint hook, or (where under general anaesthesia) by placement of 2/0 silk traction sutures through the anterior periosteal edge, encircling the angular vessels and orbicularis, with the sutures clipped under tension to the surgical drapes. The rougine is used to displace the lacrimal sac from its fossa and the maxillolacrimal suture line entered using an angled (e.g. Traquaire's) periosteal elevator, this being worked up and down along the bony suture; should the bone be too thick to breach, at this point, it is possible to enter the ethmoid sinus through the lamina papyracea (behind the posterior lacrimal crest), or the bone of the anterior lacrimal crest may be thinned down using a burr, or hammer and chisel.

A large rhinostomy is fashioned by first crossing the anterior lacrimal crest as far superiorly as possible (where the crest is thinnest), and the directing bone removal inferiorly and in front of the crest (to give an L-shaped rhinostomy). Every few bites, the periosteal elevator should be swept around the bone edge to separate the underlying nasal mucosa from the bone and, where cotton-tips have been placed within the nose, these should be withdrawn sufficiently to allow the rhinostomy to be fashioned. The remaining spur of thick bone of the frontal process of the maxilla is then removed and the thin bone between the upper duct and nose is removed using a Jensen bone nibbler. Further bone should be removed up to the skull base, to ensure there is none alongside the common canalicular opening, and posteriorly to include a partial ethmoidectomy - removal of the bone fragments and mucosa facilitating the sutured anastomosis of posterior mucosal flaps.

A '00' lacrimal probe is passed, through the lower canaliculus, into the lacrimal sac to tent its medial wall and a No. 11 blade used to enter the lumen of the lacrimal system at the anteromedial face of the sac-duct junction (thereby avoiding damage to the internal opening of the common canahculus). Once the lumen has been identified, the medial wall of the sac and upper duct are opened completely with Westcott spring scissors; occasionally it will be found that only the relatively thick lacrimal sac fascia has been opened, and the thin sac mucosa remains intact. Where there is a membranous block of the internal opening of the common canahculus, this should be carefully excised using a No. 11 blade or fine scissors. With the nasal packing or cotton-tips in place to avoid damaging the septal mucosa, the nasal mucosa is incised vertically with a No. 11 blade to create anterior and posterior flaps; this incision should be about 3-4mm in front of the arch formed by the anterior end of the middle turbinate attachment - this arch generally being evident after partial ethmoidectomy. Relieving horizontal incisions are made at the superior and inferior bone edges to mobilise both flaps.

The anterior flap is held away from the operative field by passing a 6/0 absorbable suture (on an 8-mm diameter half-circle needle) through the middle of preseptal orbicularis fibres - that is, those that have been retracted medially by the assistant - and then through the middle of the anterior nasal flap, the two ends clipped (with the needle still attached) and hung aside across the nasal bridge. The posterior flaps are sutured - from the fundus of the sac to the entrance to the duct - with a 6/0 absorbable suture placed in a locked continuous suture; to facilitate this suturing in a recess, it is best to use the whole needle length, with it reverse-mounted in a non-locking angled needle holder. The lacrimal probe, kept in place during suture of the posterior flaps, is removed and silicone intubation placed. The preplaced anterior suture is passed through the anterior sac flap, opposite the internal opening - this effectively suspending the mucosal anastomosis from the orbicularis fibres. Two other suspended anterior sutures are passed: the upper one is passed through preseptal orbicularis above the first suture, then through the upper end of the anterior nasal flap, through the upper anterior sac mucosa and finally through the stump of medial canthal tendon; the lower suture is passed through orbicularis, through the lower end of the anterior nasal mucosa, through the anterior sac flap near the nasolacrimal duct, and finally through the subdermal tissues lateral to the lower part of the skin incision. Skin closure is achieved with a 6/0 nylon continuous mattress suture and a firm dressing applied to the operative site for 12 h.

With a sutured primary mucosal anastomosis, nasal packing is not required routinely although ribbon gauze, moistened with 1:1,000 epinephrine, may be placed if major primary haemorrhage occurs and this pack left undisturbed for 5 days. The patient should be nursed semi-erect on bed rest after surgery, to reduce nasal venous congestion and oozing, and hot drinks avoided for 12-24 h. A topical combined antibiotic and anti-inflammatory medication is prescribed for a few weeks and, unless systemic antibiotics have been given during surgery, a short course of oral antibiotics is recommended to reduce postoperative infection. The dressing is removed on the day after surgery and nose blowing discouraged for the first week, to reduce the risk of epistaxis or subcutaneous emphysema. Skin sutures are removed at about 1 week and the intubation at about 4 weeks after surgery, by which time epithelialisation of the surgical fistula has been completed.

Dacryocystorhinostomy with Retrograde Canaliculostomy
Retrograde canaliculostomy is designed to open - at the lid margin next to the medial tear lake - canaliculi that are blocked within their first 7 mm or so, but have a patent common canahculus. As the extent of canahcular block can only be established at the time of surgery, the patient should be warned that they might require primary or secondary placement of a Jones canahcular bypass tube.

External DCR (see above) is completed to the stage of having sutured the posterior mucosal anastomosis and the internal common canahcular opening is entered retrogradely using a '0' gauge lacrimal probe, bent perpendicularly on itself at about 8-9 mm from the end. The probe is passed as far laterally as possible along each canahculus (if possible), a 1-2 mm cut-down made to expose the probe on the lid margin, the pseudo-puncta intubated and the DCR completed in a standard fashion. If solely the common canahculus is available, its lateral end should be opened into a carunculectomy site and - in this and other such cases where only a single canahculus is available - the returning end of the silicone intubation passed through one of the punctal annuli and forced medially through the lid tissues; this manoeuvre returning the intubation to the nasal space at a site remote from the common canalicular opening. Monocanalicular stenting is unlikely to stay in place because of the absence of a normal annulus at the pseudo-punctum.

The intubation can be removed when the conjunctival and canalicular epithelium have united - typically within 2-3 weeks - and they should not be left for much longer or cheese wiring will cause a cross union between the lids. Closed placement of a canalicular bypass tube is required if the pseudo-puncta fail to control symptoms.

Closed Placement of Jones Canalicular Bypass Tubes
The canalicular bypass tube (most commonly a Lester Jones Pyrex tube), is designed to allow free tear flow from the medial tear lake into the nose, by way of a false conduit. Closed placement is indicated where watering continues after canaliculo-DCR, after retrograde canaliculostomy or, exceptionally, after a functioning standard DCR (for example, in patients with facial nerve palsy). Although requiring continued maintenance and associated with various long-term problems, the majority of people with these drainage devices consider them to be of benefit.

The nasal end of a bypass tube needs to be free within the nasal space, somewhat in front of the middle turbinate, and intranasal examination is required - best with rigid endoscopy, although a good headlight and nasal speculum are often adequate. As nasal local anaesthesia (with vasoconstriction) creates an inappropriately capacious nasal space, optimum positioning of the tube is achieved under general anaesthesia - when the nasal cavity is closest to normality.

The ocular end of the tube should be positioned hard behind the medial end of the lower limb of the canthal tendon: this is best accomplished by using a Nettleship dilator to pierce the epithelium at the desired position and a track then forced through to the nose using the smallest end of the double-ended (bullhorn) dilators supplied with the commercial sets; this track should typically run about 30° downhill and in, or slightly forward from, the coronal plane. The position of entry into the nasal space is checked for suitability, an appropriate tube (commonly 11mm, with a 3.5-mm flange) slipped onto a T gauge lacrimal probe that is passed along the dilated track, and the tube forced along the track and into the nose using the end of the thumbnails; the use of any form of instrument on the tube flange tends to shatter it, and this should be avoided at all costs. The position of the ocular and nasal ends of the tube should be checked after withdrawing the 1 probe, and spontaneous flow of saline from the ocular surface verified. Suture of the tube is unnecessary after secondary placement.

Dacryocystectomy
Dacryocystectomy is probably indicated only in patients with well-controlled ocular surface disease in the presence of longstanding canalicular occlusion, in whom there has been an episode of acute dacryocystitis or increasing dilation of the sac due to mucus secretion.

Using the same approach as external DCR, the anterior limb of the medial canthal tendon is detached from the nasal bone and peeled laterally from the underlying tissue before the sac is mobilised from its fossa. Once peeled about 1 cm laterally, the underlying common canaliculus is transected and the sac mobilised medially from the underlying orbital tissues by careful dissection medially across the posterior lacrimal fascia. The tightly bound fundus and medial face of the sac is separated from the lacrimal sac fossa, the isolated sac drawn upwards whilst the superior part of the nasolacrimal duct is freed from its canal, and the duct transected as low as possible. The remaining stump of nasolacrimal duct should be thoroughly cauterised to encourage fibrosis and, after haemostasis, the medial canthal tendon reattached to the neighbouring orbicu-laris oculi muscle and the skin incision closed.

Permanent Punctal Occlusion
Before performing permanent punctal occlusion, it is imperative to verify the benefit of occlusion by a temporary canalicular plugging: This may be achieved by insertion of collagen plugs, under topical anaesthesia, into the horizontal portion of the upper and lower canaliculi. If the patient develops watering or an exacerbation of ocular surface inflammation, the original diagnosis of dry eye - and advisability of permanent occlusion - should be questioned. Likewise, it is unwise to occlude the canaliculi in the presence of a lacrimal sac mucocoele or pyocoele - conditions in which DCR should be first performed. Techniques for punctal and canalicular occlusion are presented in another chapter.

Correction of Lid Retraction and Exophthalmos

2010-05-08T10:52:00.000-07:00

Pathogenesis of Exophthalmos and Eyelid Retraction
Graves orbitopathy (GO) is the commonest orbital disease accounting for greater than 85% of bilateral exophthalmos and up to 50%of unilateral exophthalmos as documented in several large series of patients. In addition, 91% of patients with GO presents eyelid retraction at some point in the clinical course of the disease.

Exophthalmos and eyelid retraction although typical are not exclusive of GO: many other orbital and systemic disorders can originate these signs. Because of the fixed volume of the orbit determined by its bony boundary, any orbital space-occupying lesion leads to forward displacement of the eye; however, this condition which is referred to as exophthalmos can also be caused by non space occupying lesions such as third nerve palsy.

In the presence of a globe of normal size and position and with the gaze directed in primary position, eyelid retraction exists when white sclera is visible above (upper lid retraction) and/or underneath (lower lid retraction) the sclero corneal limbus. In GO eyelid retraction and eyelid displacement consecutive to exophthalmos coexist. In addition to GO, eyelid retraction can have a neurologic, myogenic, mechanistic or a miscellaneous number of other aetiologies. Whatever the cause of exophthalmos or eyelid retraction is, both make possible an increased evaporation of tears with drying of the ocular surfaces resulting in pain, reflex tearing and photophobia; the structural integrity of the cornea may also be damaged with possible compromise of the visual function.

Independently from the aetiology, acute onset of exophthalmos and/or eyelid retraction deserve maximum attention. In order to avoid corneal decompensation and waiting for a more definitive treatment, eye lubricants, moisture chambers, swimming goggles, temporary tarsorrhaphies or blepharorrhaphies represent the measures of choice.

Depending on neoplastic, vascular, infectious, inflammatory or malformative causes, exophthalmos is, in the majority of cases, amenable of medical or surgical causative treatment while for endocrine exophthalmos the commonest treatment is surgical and symptomatic and consists in orbital bone decompressions.

Eyelid retraction due to active inflammatory processes such as allergic or contact dermatitis, psoriasic erythrodermatitis, ichthyosis, bullous pemphigoid, iatrogenic or posttraumatic scars and other similar conditions can benefit from medical therapy ranging from topical treatments to systemic antimetabolite and immunosuppressive agents. Dermatitis can be treated with topical corticosteroids; ichthyosis, psoriasis and pemphigoid with topical transxstmoic acid or, when not responding to topical measures, with oral 13 cw retinoic acid or systemic metotrexate, cyclophosfamide, or cyclosporine. Massages and steroid injections can be beneficial in the treatment of recent iatrogenic or posttraumatic scars causing eyelid retraction. The treatment of stable eyelid retraction is basically surgical and mostly consists in lengthening of upper or lower lid retractors complexes. Multiple Z plasty, grafts, or flaps may also be required in order to increase the vertical length of the anterior eyelid lamella.

Owing to their high incidence, and considering that the scarce literature that links exophthalmos and eyelid retraction to ocular surface disorders almost exclusively regards GO, only dysthyroid exophthalmos and dysthyroid eyelid retraction, their influence on alterations of ocular surface and the treatment of these two conditions will be specifically analysed here.

Tear Film Profile in Graves Orbitopathy
In GO, increased palpebral fissure width, exophthalmos, blink rate, lid lag, lagophthalmos, deficit of elevation and poor Bell's phenomenon can all be potentially connected with drying of the ocular surface. Bartley et al. found a high incidence of various signs and symptoms of ocular surface disease in a cohort of 120 patients with GO during a 10-year follow-up. These included conjunctival hyperaemia (34.5%), pain or discomfort (30%), epiphora (20.9%), chemosis (23.3%), corneal staining (10.1%) and non-optic neuropathy-related loss of vision (7.2%). Although some of these findings may regress when the inflammatory component of the disease is well controlled with medical treatment, those resulting from increased exposure of the ocular surface are likely to persist.

According to the findings of Gilbard and Farris, in GO the damage to the ocular surface depends principally on a widened palpebral fissure which leads to increased ocular surface evaporations resulting in an elevated tear film osmolarity similar to that of keratoconjunctivitis sicca. In their series of GO patients, exophthalmos, lid lag and lagophthalmos did not correlate with ocular surface damage, and tear secretion measured by Schirmer test was not abnormal. Increased and not decreased blinking rate was found to be connected with significant ocular surface damage, but this finding was thought to be secondary to damage of the ocular surface. In Gilbard and Farris' series it was not specified whether the included patients were in the inflammatory or in the chronic phase of GO. More recently however, Khurana et al. presented similar results by comparing a population of 30 patients with GO, 15 presenting a short duration and 15 a long duration of their disease, with 30 controls.

Although it was not clear if the 15 patients presenting short duration of GO were or were not active, tear film pH, fluorescein staining, marginal tear strips and Schirmer test values were not different in patients and controls, in fact suggesting not abnormal tear secretion GO. Rose bengal and lissamine green staining intensity scores were significantly higher in patients as compared to controls, indicating the presence of drying epithelial cells in early as well as in late GO patients. Also in this series, an increased blink frequency was noted in patients which was interpreted as a mechanism of incomplete compensation for decreased break-up time, although a significantly low break-up time was found only in late GO patients.

When active GO has been specifically studied, ocular surface damage correlated significantly with a reduced tear secretion, but not with increased exposure of the ocular surface or impaired up gaze. The lacrimal gland physiologically expresses the TSH receptor which, in active GO, can bind with circulating anti TSH receptor autoantibodies contributing in fact to lacrimal gland impairment. Other studies, however, have shown that also in long-lasting GO, the orbital inflammatory process has an effect on the lacrimal gland and this ultimately reflects on its function and, in turn, on tear composition.

Although the literature concerning the ocular surface alteration occurring in GO is not extensive and far from being conclusive, the multifaceted nature of the problem is not disputed. Lacking a specific medical therapy for GO, the functional alterations of the lacrimal gland, which are subsequent to the autoimmune process affecting the whole orbit, can not be specifically cured and artificial tears remain the only medical means for relieving patients' discomfort. On the other hand, an increased palpebral fissure width, which resulted in being mainly responsible for exposure keratopathy and which depends on eyelid retraction and eyelid displacement secondary to exophthalmos, is amenable of effective surgical correction.

Surgical reduction of exophthalmos and widened palpebral fissure, which are the key steps in the surgical treatment of the 'dry eye' in patients with GO, will be discussed below.

Timing of Exophthalmos and Widened Palpebral Fissure Correction in Graves Orbitopathy

The natural course of GO is known to consist in an early dynamic inflammatory phase followed by a static postinflammatory phase, by the contrary the aetiopathogenesis of the disease remains obscure. As a consequence, a specific medical therapy does not exist. Systemic glucocorticoids and orbital radiation therapy, although effective on the inflammatory component of the disease, remain of little efficacy on exophthalmos or increased palpebral fissure width. Prompt restoration of stable euthyroidism and immunosuppression, when necessary, may decrease the duration of the dynamic phase and reverse its tendency to progress towards a more severe symptomatology. Nevertheless, a consistent amount of patients need surgery for functional reasons or aesthetic rehabilitation.

During the inflammatory phase, excluding minor procedures, such as temporary tarsorraphies or blepharorrhaphies, surgery consists in decompressions and it is required when systemic steroids or orbital radiotherapy fail to effectively treat two potentially blinding conditions: optic neuropathy or severe exposure keratopathy. During the post inflammatory phase, after a 6 to 8 month period of stable thyroid metabolism and stable orbitopathy, surgery is indicated for aesthetic, psycho-social rehabilitation and for the treatment of symptoms, such as persisting retro ocular tension or exposure keratopathy, even in presence of minimal aesthetic alterations. Depending on the severity of the symptoms, surgical rehabilitation can be more or less extensive, the full treatment consisting in decompression surgery, squint surgery, eyelid-lengthening and aesthetic eyelid and periorbital procedures.

Decompression surgery causes reduction of exophthalmos as well as reduction of upper and lower eyelid displacement. It may positively influence extraocular muscle restriction, but the displacement of the soft orbital tissues caused by decompression surgery may also induce or worsen strabismus. Eventual squint surgery should therefore follow orbital decompressions but considering that vertical tropias may influence eyelid position, squint surgery should precede an y eyelid lengthening procedure. Finally, when necessary, the finishing touch can be given by aesthetic eyelid and/or periorbital surgery.

In short, surgical rehabilitation needs to respect the given order since the preceding step may influence the step that follows. In particular circumstances, exceptions are possible and the rehabilitation can be favourably sped up by carrying out more than one procedure at the same time.

Correction of Exophthalmos in Graves Orbitopathy

The autoimmune process at the basis of GO leads to accumulation of glucosaminoglycans and collagen within extraocular muscles and orbital fat. The consequent oedema and fibrosis lead to marked swelling of the soft tissues confined within the boundary of the bony orbit with increase of intraorbital pressure leading to venous congestion, exophthalmos and other typical signs and symptoms of GO. Any surgical procedure aimed at decreasing the raised intra orbital pressure and its effects, by means of enlargement of the bony orbit and/or removal of the orbital fat is defined orbital decompression.

Orbital fat decompression was first described by Moore in 1920.A mean exophthalmos reduction of 6 mm and an improvement of extraocular eye motility have been reported by Olivari on a large series of patients, but the same results were not confirmed by other authors. Orbital fat decompression has never reached the popularity of bone decompression due to the feared complications that may be connected with this surgical approach and which may encompass damages to oculomotor ciliary and lacrimal nerves, orbital vas-culature, extraocular eye muscles, optic nerve and the eyeball itself. Recently, however, bone and fat decompression are no longer considered alternatives but had became complementary approaches concurring in tailoring the most adequate treatment to the specific patient's needs.

The history of orbital bone decompression surgery can be dated back to 1911 when Dollinger first proposed orbital enlargement by removing the lateral wall for the cure of exophthalmos. Since then, various osteotomies performed via different routes and involving one or more of the other orbital walls have been proposed. Also in the case of bone orbital decompression, in spite of theoretical expectations, severe complications are rare in clinical practice. The most common complication of this surgical approach is consecutive strabismus, although infraorbital hypoesthesia, sinusitis, lower lid entropion, eyeball dystopia, or more rarely leakage of cerebro spinal fluid, infections involving the central nervous system, damages to the eye and optic nerve or their vasculature, cerebral vasospasm, ischemia and infarction, can occur. Reactivation of GO after rehabilitative bony orbital decompression is another, recently described, rare complication.

In the 1980s, when the number of orbital decompression procedures being performed began to rise, as surgery started to be undertaken not only for functional reasons but also for the aesthetic/psychosocial rehabilitation of Graves patients, the antralethmoidal decompression by a transantral approach, as described by Walsh and Ogura in 1957, was the mainstay technique. The major disadvantage reported with transantral surgery was motility imbalance as high as 52% and therefore alternative procedures were sought in an attempt to decrease the risk of decompression-induced diplopia. In cases of mild exophthalmos, translid antral-ethmoidal decompression appeared to be a valid alternative, with a risk of iatrogenic diplopia in only 4.6% of patients. For more severe exophthalmos, inferomedial decompression was used in combination with lateral decompression. Such procedures, whether performed with separate periorbital incisions or via a coronal approach, were also related with a low incidence of consecutive diplopia.

In 1989, Leone et al, in an attempt to further reduce the effect of decompression surgery on extraocular muscle motility, proposed balancing the decompression by removing the medial and lateral orbital walls while sparing the floor. This technique, which theoretically should have minimised the risk of iatrogenic diplopia, later appeared to be connected with a higher risk for such a complication as compared with removal of the lateral orbital wall alone or with studies in which inferomedial and three-wall techniques were described.

Recently the lateral wall, and in particular its deeper portion, has been described as an elective zone of possible orbital volume expansion, especially if combined with fat decompression. Such a large number of variations illustrates that no single one can be considered the best. An analysis of the current literature on the argument is highly complicated due to the extreme heterogeneity of the patients included in each series, the variation applied to surgical techniques, the use of perioperative glucocorticoids, the difference in timing and modality of assessment of surgical results.

Many variables can affect the results of orbital decompression: volume and location of the osteotomy, amplitude of removal or incision of the periorbita, stage of the orbitopathy at the time of surgery, orbital compliance which refers to distensibility and plasticity of the soft orbital tissues, and preoperative Hertel readings, can all play a role.

At present the removal of the orbital roof is no longer used: minimal is in fact its contribution to orbital decompression and its removal establishes a direct communication between the anterior cranial fossa and the orbital content, making possible the transmission of the pulsation of the internal carotids to the latter including the eyeball. The orbital floor, the medial and the lateral orbital walls are currently removed in the course of decompression surgery, the extension of the osteotomy being dependent on the amount of exophthalmos reduction which is to be achieved.

Traditionally the removal of the medial wall and the floor, known as inferomedial decompression, is used to cure mild to moderate degree of exophthalmos and the lateral wall removal is added when more severe degrees of exophthalmos impose a greater decompression effect. Recently, in a further attempt to minimize the risk of iatrogenic strabismus, it was proposed to start decompression surgery by removing the lateral orbital wall and eventually to increase the effect of decompression by removing the orbital fat or the medial orbital wall leaving the removal of the floor as the very last option.

A number of different surgical routes can be used for decompression purposes, hidden incisions are to be preferred to visible trans-cutaneous approaches, such as Lynch or the mid lower lid incisions which produce exposed scars. Typical ophthalmological routes to inferomedial decompression, are the transcaruncular and the transinferior fornix. The latter also permits lateral decompression, which however is easier if the fornix incision, is coupled with an incision at the lateral canthus. That in fact permits the lower lid to swing outwards and gives a wide access to the lateral wall. This approach first described by McCord in 1981 and known as swinging eyelid is at present widely adopted it gives an excellent exposure of medial inferior and lateral orbital walls and leaves an inconspicuous scar at the lateral canthus. As an alternative the lateral orbital wall can also be approached by means of a separate upper skin crease incision.

The coronal incision implies a more extensive surgical dissection if compared with the swinging eyelid approach or other periorbital incisions but, in turn, provides access to all the orbital walls and the best exposure of the deep lateral orbital wall, which represents an elective zone for orbital expansion. The coronal approach can be performed also in those patients with GO presenting remarkable periorbital swelling or conjunctival chemosis, which may adversely interfere with periorbital incisions. It is the elective approach for minimising the number of periorbital incisions which are necessary to accomplish the full rehabilitation and this can be particularly advantageous in young or black patients.

In addition to this, the coronal incision is to be used when the lateral wall including the lateral orbital rim is completely removed. The coronal approach implies the elevation of a subpe-riosteal plane which, differently than with direct periorbital incision, does not disrupt the anatomical planes of the periorbital region: depressed disfiguring iatrogenic scars due to adhesions between deep and more superficial layers are consequently infrequent. The swinging eyelid approach is to be preferred to the coronal approach in unilateral cases or in male patients with impairing baldness. The swinging eyelid or the transinferior fornix approach can be associated with transconjunctival lower lid blepharoplasty or with lower lid-lengthening procedures speeding up the surgical rehabilitation of GO.

Orbital Decompression by Coronal Approach: Surgical Technique A coronal incision is made with a No. 10 blade from ear to ear, 3 cm behind the hairline. Bleeding from the wound edges is controlled with Raney scalp clips. In the central portion of the skull a subperiosteal plane is created by blunt dissection and laterally a surgical plane is bluntly developed between the deep and the superficial temporalis fascia. Laterally and inferiorly, where the deep temporalis fascia divides into a deeper and a more superficial layer to enclose Yasargil's superficial temporal fat pad, the surgical dissection is carried out directly against the deeper division of the fascia. The forehead flap thus created is then turned down in order to expose the superior and lateral orbital rims.

The supraorbital nerve is set free by chiselling its bony foramen when present and the periorbita, including the trochlea, is dissected off the orbital bones. After this, the temporalis muscle is dissected from its anterior origin with a No. 10 blade and periosteal elevators, leaving sufficient tissue for suturing at the end of surgery. In this way the lateral orbital wall is exposed. A small osteotomy is chiselled behind the lateral orbital rim, then it is extended inferiorly up to the inferior orbital fissure, superiorly and posteriorly up to the dura of the middle cranial fossa by means of bone-nibbling rongeurs and a surgical high-speed drill equipped with a cutting-burr or a diamond-burr tip. During surgical manoeuvres the soft orbital tissues and the temporalis muscle are retracted and protected with malleable orbital retractors.

When small spots of dura are exposed through the thin inner cortical bone of the greater wing of the sphenoid, bone removal is stopped as any further removal may increase the risk of complications without substantially contributing in creating space for orbital expansion. After this a Frazier suction tip is used to fracture the delicate bone of the medial orbital wall and the floor and Blakesly forceps No. 1 and No. 2 are used to remove bony fragments and mucosa of the sinuses.

The bulla ethmoidalis beneath the frontoethmoidal suture is opened towards the orbit from the posterior lacrimal crest up to the orbital apex, and then the orbital floor medial to the infraorbital canal is removed from 0.5 cm behind the inferior orbital rim up to the posterior wall of the maxillary sinus. The posterior two thirds of the maxillary ethmoidal strut are removed creating a wide antrostomy, while the anterior one third of the strut is left intact in order to prevent globe displacement and the possibility of medial entropion or hypoglobus. The removal of the most posterior portion of the maxillary ethmoidal strut together with the orbital process of the palatine bone give access to the sphe-noidal sinus increasing the possibility of apex decompression when necessary.

Finally, the periorbita is incised in order to promote maximal prolapse of the soft orbital tissues into the newly created spaces, the temporalis muscle is sutured back into position with 4-5 interrupted 2/0 Mersilene sutures and, after the insertion of a 3.3 mm diameter end perforated wound drain into each temporalis fossa, the scalp incision is closed with iron staples.

Orbital Decompression by Transinfenor Fornix/Trans Caruncular Swinging Eyelid/Upper Skin Crease Approach: Surgical Technique After the exposure of the inferior fornix by mean of a Desmarres retractor and a malleable órbita retractor, the conjunctiva and lower lid retractor complex are transsected en bloc with a Colorado needle and the inferior orbital rim is exposed.

At that level the periorbit is incised and the medial and inferior orbital walls exposed by developing a subperorbital plane and the bony orbit. In order to obtain the best possible exposure of the medial wall, the bony insertion of the inferior oblique muscle may be detached without consequences, and the con-junctival incision extended upwards, laterally to the caruncle. A separate incision lateral to the caruncle (trans caruncular approach) can possibly be used to address the medical orbital wall when the floor is not to be removed. After this the medial orbital wall and the orbital floor are addressed as for orbital decompression through a coronal approach. With the transinferior fornix approach, however the wide exposure of the orbital floor permits an easy removal of the bony infraorbital canal and the floor lateral to it.

If more decompression is needed the lateral wall can be removed starting the osteotomy from the anterior portion of the inferior orbital fissure by means of bone nibbling rongeurs and by means of a surgical high-speed drill equipped with a cutting-burr or a diamond-burr tip. In order to aid the removal of the upper part of the lateral orbital wall and in particular its anterior superior portion, a lateral canthotomy and lysing of the inferior limb of the lateral canthal tendon can be performed converting, infact, the pure transinferior fornix approach into a swinging eyelid approach. An upper skin crease incision can also be used in combination with the pure inferior fornix or with the swinging eyelid approach if a wider exposure of the lateral orbital wall is to be attained.

The removal of the lateral orbital wall can be carried out up to the dura as described for the coronal approach and as for coronal approach at the end of the procedure the periorbita is incised in order to promote maximal prolapse of the orbital tissues into the newly created spaces. The canthotomy is closed in layers as for a regular canthopexy procedure, the upper lid crease incision only needs approximation of the skin edges while the inferior fornix incision does not need any suturing. Transinferior fornix, swinging eyelid, trans caruncular, and upper skin crease approaches can all be used to remove orbital fat too.

Correction of Lid Retraction in Graves Orbitopathy
In GO, upper and lower lid retraction are due to a combination of inflammation, fibrosis, adrenergic stimulation and restriction of vertical recti muscles. Exophthalmos also contributes in increasing the eyelid aperture by displacing either the upper or the lower lid. Recently the influence of decompressive surgery which leaves the lower lid retractors undisturbed has been reported to similarly contribute to the reduction of upper and lower lid displacemen. Correction of upper or lower lid retraction implies recession of the lid retractors. Spacers are not essential for upper lid lengthening procedures or for the treatment of mild degrees of lower lid retraction that can benefit from free recession of lower lid retractors and lateral canthoplasty.

The surgical correction of more severe forms of lower lid retraction requires interposition of spacer grafts between the tarsus and the recessed retractors to provide height and the necessary stiffness to support the lower lid against gravity. A number of autologous, homologous, xenogenic and synthetic materials have been used but the optimum spacer remains controversial. Among biological materials, ethanol preserved donor sclera has been widely used, but it is of limited availability, carries a risk of transmission of infections and it is associated with recurrent retraction due to graft absorption and fibrosis. Upper lid tarsus is an optimal material but its use is limited by the scarce possibility of harvesting at the donor site.

The stiffness of cartilage grafts may alter eyelid contour and adversely interfere with eyelid motility and down-gaze, the same applies to porous polyethylene sheets. Other synthetic materials such as polytetrafluoroethylene or polyester mesh carry the risk of extrusion. An autogenous hard palate mucosal graft is relatively easy to obtain, is similar to lower lid tarsus in terms of contour, thickness and stiffness, has a mucosal surface, has no risk of rejection and undergoes minimal shrinkage following grafting. Ophthalmic complications of hard palate mucosal grafting are uncommon and usually limited to transient corneal abrasion; morbidity at the donor site encompasses secondary haemorrhages, retarded healing due to oral infections, pain, and rarely oronasal fistula.

Homologous acellular dermal matrix is a processed donor tissue with appropriate consistency for posterior lamella augmentation. One surface is cut through the dermis, the other has an intact basement membrane which provides a structural template that guides conjunctival epithelial migration and repopulation. Homologous acellular dermal matrix represents a valid alternative to hard palate mucosal graft, its use reduces surgical time and eliminates the problem of donor site morbidity, but currently is not available in Europe.

In short, at present, hard palate mucosal graft providing structural and epithelial elements represents the best choice for posterior lamella augmentation in lower lid lengthening, although it may be associated with the disadvantage of not negligible donor site morbidity. In light of this and considering that donor site morbidity may be minimised by meticulous surgical technique and appropriate postoperative care, harvesting and implantation techniques will be given and commented below.

The treatment of persistent upper eyelid retraction is surgical and by far less predictable than that of lower lid. The medical therapy of upper lid retraction with a-blockers eye drops is scantly effective and topical or systemic therapy with post-ganglial adrenergic blocker drugs such as guanethidine is connected with several undesirable side effects. Botulinum toxin can also be an option, its effect however is limited in time and multiple injections are required. With botulinum toxin temporary under or over correction can occur. Deficit of elevation and paralysis of the orbicularis muscle may also be possible, undesirable complications in GO patients who are at risk for corneal exposure.

Considering that upper eyelid lengthening is one of the last steps of the long-lasting and somewhat exhausting surgical rehabilitation of patients with GO and that, although several surgical techniques for its cure have been proposed, an elective method is lacking, it is strongly advisable to use the quickest and simplest possible technique.

In keeping with this, a quick, systematic approach suitable for every degree of upper eyelid retraction with or without alteration of eyelid contour such as lateral or medial peaks is given in table 3 and the related surgical techniques will be described and commented below.

Lower Lid Lengthening Surgical Procedure

Hard Palate Mucosal Graft Harvesting
Prior to surgery a careful in office inspection of the donor site is mandatory for a correct selection of candidates, and at surgery the location of the donor site is fundamental in order not to bare the periosteum or being obliged to apply excessive diathermy as this may cause bone necrosis. Prior to surgery, any lesion suspected for malignancy should be biopsied; oral candidiasis in immunocom promised patients should be cured since postoperative granulation at the donor site can be delayed; the presence of exostosis such as torus palatinus or prominent palatal roots of teeth should be considered since the thin overlying mucosa of these areas may lead to unwanted periosteal or root damage at surgery.

The presence of a bifid uvula or a muscular diastasis of the soft palate can be an important clue to an underlying bony palatal cleft that is not otherwise evident and which represents an absolute contraindication for mucosal harvesting. However, the presence of small isolated clefts of the bony palate may escape clinical detection due to the presence of an overlying intact mucosa and to their asymptomatic nature. Besides iatrogenic damage to the bone and periosteum and infectious causes, fistulas may also develop from such a malformation.

At surgery the donor site should be placed between the median raphe and the alveolar process and not extended posteriorly behind the first molar. At this level the submucosa is well defined and partial thickness mucosal dissection can be easily carried out anteriorly to the neurovascular bundle emerging from the greater palatine foramen. The latter can in fact be located medially to the third or to the second molar. Areas close to the gingival border or to the median raphe are not suitable as donor sites since the risk of bone necrosis secondary to periosteal damage is much higher here: at these levels the mucosa is in fact directly attached to the periosteum without interposition of the submucosa.

Although hard palate mucosal grafts can be harvested under local anaesthesia, general anaesthesia is to be preferred for the patient's comfort. The mouth is open with a Jonson mouth spreader. The hard palate is dried and a dermographic pen is used to mark the graft size that should be about twice the degree of lower lid retraction in width. Submucosal infiltration with lidocaine 2% with epineph-rine 1:80,000 is then carried out to aid haemostasis and dissection.

The harvesting is carried out first using a No. 15 Bard-Parker blade to incise the marked area, then with a disposable angled keratotome and surgical forceps to dissect the submucosal plane and elevate the graft. The use of suction and of a tongue depressor by the surgical assistant will greatly aid in this phase. Excessive diathermy should be avoided at all times, and at the end of surgery, in order to control oozing at the donor site a rolled vaseline or haemostatic gauze can be inserted into the mucosal defect and kept in place with a previously prepared palatal shell, digital pressure on the shell can also be applied for some time and fibrin glue used if necessary. Bleeding from major vessels can be controlled with injections of local anaesthetic within the bleeding area or into the palatine foramen or with ligation if necessary.

The mucosa of the graft consisting of epithelium and thick collagenous lamina propria is then prepared for the recipient site by removing the fatty submucosa.

Large spectrum systemic antibiotics and antiseptic mouthwashes are recommended for 1 week after surgery. Soreness at the donor site for a few days after surgery is common especially during eating; custom-made acrylic palatal stents which aids haemostasis and favourite granulation can increase the patient's comfort.

Lower Lid Lengthening
Topical oxybuprocaine HC1 0.4% drops are applied to eye, then 0.5-1 ml of lidocaine 2% with epinephrine 1:80,000 is administered subconjunctivally along the inferior margin of the tarsal plate and 0.25 ml of the same anaesthetic is administrated subcutaneously into the centre of the lower lid. A 5-0 silk traction suture is placed in the centre of the lower lid along the eyelid margin and the eyelid is everted over a Desmarres retractor. An infratarsal incision is done for the whole length of the tarsal plate with a No. 15 Bard-Parker blade and the conjunctiva lower lid retractor complex transsected en bloc.

A preseptal plane is then bluntly developed in order to adequately recess the lower lid retractors and conjunctiva. Bleeding is easily controlled with bipolar diathermy. After this a 6.0 absorbable suture is used to suture the hard palate mucosal graft into place, between the border of the conjunctiva lower lid retractors complex and the inferior border of the tarsal plate, the mucosal surface facing the eyeball. Multiple steri-strips are applied on the lid skin in order to immobilize lid and graft in a correct position for a few days after surgery. No bandage is applied, but ice compresses are recommended for a few hours after surgery. Artificial tears are also prescribed to implement patient's comfort.

Upper Lid Lengthening
Sutureless Transconjunctival Müllerectomy Topical oxybuprocaine HC1 0.4% drops are applied to the eye, then 0.25 ml of lidocaine 2% with epinephrine 1:80,000 is administered subcutaneously into the centre of the upper eyelid. A 5-0 silk traction suture is placed in the centre of the upper eyelid along the eyelid margin and the eyelid everted over a Desmarres retractor. Then 0.5 ml of lidocaine 2% with epinephrine 1:80,000 is injected close to the superior tarsal border subconjunctivally and between Müller's muscle and the levator aponeurosis over the whole length of the eyelid.

A high temperature battery-powered cautery is used to incise the conjunctiva along and just above the superior tarsal border. After this the conjunctiva is separated from Müller's muscle first with sharp then with blunt dissection. In this way the superior fornix is approached (fig. 7a). Müller's muscle is then grasped with fine-toothed forceps at the lateral aspect, the tension exerted with the Desmarres retractor is relieved, and a plane can easily be developed between Müller's muscle and the inferior surface of the levator aponeurosis by spreading the blade of blunt pointed straight scissors. The distal insertion of the muscle is gently cauterised, afterwards severed with scissors. The proximal insertion is then similarly addressed. At the end of the procedure the conjunctiva is not sutured.

Any possible lateral or medial alteration of the eyelid contour is treated by means of weakening the levator aponeurosis at the level of the peak. This is achieved by means of several small horizontal incisions which transform the aponeurosis under consideration in a kind of network increasing in fact its vertical length. At the end of the procedure the traction suture which was placed in the centre of the eyelid is removed. No bandage is applied but ice compresses are recommended for a few hours after surgery. Artificial tears are prescribed to implement the patient's comfort.

Sutureless transconjunctival Müllerectomy is an effective procedure for the cure of mild degree of upper eyelid retractions up to 2-3 mm. It does not interfere with the position of the skin crease since surgical dissection is carried out under the levator aponeurosis. It takes around lOmin/eyelid, reintervention for under- or overcorrection are rare and usually due to surgical mistakes as incomplete excision of Müller's muscle or damage to the aponeurosis of the levator muscle. Tear secretion may be reduced after Müllerectomy by the conjunctival approach. Nevertheless, the clinical risk of dry eye is low, and counterbalanced by the usually good functional and cosmetic results of the procedure.

Free En-Bloc Recession of Conjunctiva-Levator Complex by Anterior Approach (Blepharotomy)
This technique was developed by Leo Koornneef one of the most bright minded and talented surgeons in the field of orbit and ophthalmic plastic surgery of the 1980s and 1990s. Because of his untimely death he was unable to publish his idea, nevertheless he could present it at meetings and teach it to several of his fellows including myself.

Topical oxybuprocaine HC1 0.4% drops are applied to the eye, the skin crease is lined with a surgical skin marker. Then 0.5-1 ml of lidocaine 2%with epinephrine 1:80,000 is injected close to the superior tarsal border subcuta-neously and between the orbicularis muscle and levator aponeurosis over the whole length of the eyelid.

An incision is made along the line previously drawn at the level of the upper skin crease through the skin orbicularis layer using a No. 15 Bard Parker blade. Then further dissection is carried out with spring scissors in order to expose the levator aponeurosis and the orbital septum. The orbital septum is opened along the whole length of the eyelid. After this, an en bloc, full thickness levator aponeurosis-Müller's conjunctiva incision is carried out just above the upper border of the tarsal plate: the levator-conjunctiva complex is grasped with fine-toothed forceps in the central portion of the upper lid, and after a gentle localised cauterisation, spring scissors are used to start the incision as a buttonhole. Then the first incision is extended laterally and medially preceded by gentle cauterisation of the levator-conjunctival complex. If a lateral flare is present the deformity is corrected by means of a graded vertical cut through the levator-conjunctiva complex at the level of the lateral horn of the aponeurosis.

The desired degree of lengthening is checked, against gravity, by closing the skin with a temporary suture positioned in the centre of the lid and bringing the patient to a sitting position. At surgery, a couple of millimetres of over-correction are advisable at surgery in order to compensate for postoperative retraction. When the desired level is obtained, a careful inspection of the wound is carried out and any bleeding point cauterised. Finally, the blepharotomy is closed by carefully suturing the skin only, with a running interlocked 6-0 Dermalon suture which should stay in place for 1 week. No bandage is applied but ice compresses are recommended for a few hours after surgery.

Free En-Bloc Recession of Conjunctiva Levator Complex by Sutureless Posterior Approach
Topical oxybuprocaine HC10.4% drops are applied to the eye, then 0.25ml of lidocaine 2% with epinephrine 1:80.000 is administered subcutaneously into the centre of the upper eyelid. A 5-0 silk traction suture is placed in the centre of the upper eyelid along the eyelid margin and the eyelid everted over a Desmarres retractor. Then 0.5 ml of lidocaine 2%with epinephrine 1:80,000 is injected close to the superior tarsal border between levator aponeurosis and orbicularis muscle along the whole length of the eyelid. After a gentle localised cauterisation, spring scissors are used to start a buttonhole incision through the conjunctiva-levator complex in the central portion of the everted eyelid.

Through the buttonhole incision, by spreading the blades of blunt spring scissors, a plane is easily developed between the orbicularis muscle and the anterior surface of the levator aponeurosis. Then the buttonhole incision is extended laterally and medially; in order to minimize bleeding, gentle cauterisation of the conjunctiva-levator complex that is to be severed always goes before any extension of the incision. The incision is carried out just above the upper margin of the tarsal plate in bilateral cases or at a higher level in monolateral upper lid retraction. In this way, in monolateral cases, the skin insertion of the levator aponeurosis is left undisturbed, the skin crease does not rise after surgery and symmetry with the contralateral side is preserved.

The levator aponeurosis and orbital septum are bluntly separated from the orbicularis muscle in order to promote recession of the conjunctiva-levator complex. If a lateral flare is present, the deformity is addressed as for the anterior approach. Also with the posterior approach, eyelid level and contour are repeatedly checked, against gravity, by bringing the patient to a sitting position since when the desired lengthening is achieved. A couple of millimetres of overcorrection at surgery are again advisable in order to compensate for the expected postoperative retraction.

Before the end of the procedure a careful inspection of the wound is carried out and eventual bleeding point cauterised. Finally, the traction suture which was placed in the centre of the eyelid is removed. No bandage is applied but ice compresses are recommended for a few hours after surgery. Artificial tears are prescribed to implement the patient's comfort.

Free en-bloc resection of conjunctiva levator complex performed via an anterior or a sutureless posterior approach is an effective technique for the treatment of medium to severe degrees of upper lid retraction. The results are however not always predictable and reintervention may be necessary. Several intraoperative factors may affect the setting of the upper eyelid height, their consideration may aid in increasing success. Intravenous sedatives interfere with the alertness of the patient and with his collaboration in setting eyelid position, thus these drugs should be used only when it is strictly necessary.

Povidone iodine is an adrenergic-blocking agent. Preoperative irrigation of the conjunctival sac with this solution will result in a paralysis of Miiller's muscle and should therefore be avoided. Paralysis of levator and orbicularis muscle induced by local anaesthetic and the contraction of Miiller's muscle induced by local anaesthetics containing epinephrine are variables that may interfere with the position of the upper eyelid. These variables can be partially controlled if the dose of anaesthetic, its concentration of epinephrine, the sites and the pressure of injection are maintained constant. In order to include the effect of gravity on eyelid height, this should be set by bringing the patient to a sitting position.

The anterior approach may be more desirable to many surgeons since it is the more common technique for ptosis surgery. With this approach, particular attention should be paid to the suture of the skin in order to avoid the risk of postoperative fistulas. The posterior approach cannot be performed in extreme degrees of retraction in which the tarsus cannot be everted, but it is the elective treatment in dark skinned patients in which an unpleasant scar may result from an anterior approach.

A full-thickness incision of conjunctiva levator complex may easily create a flat eyelid contour, if dissection is carried out too far medially. Careful medial dissection also prevents possible nasal droops that are often difficult to be corrected. The graded incision of the lateral horn of the aponeurosis in the case of lateral flare should be vertical or rather parallel to the ductules of the lacrimal gland to avoid any damage to these structures.

In none of the three aforementioned techniques is the conjunctiva sutured at the end of surgery. This prevents possible suture related corneal erosions and leaves a natural drainage with reduction of postoperative ecchymosis. As previously mentioned, pressure bandages are not applied after surgery and no particular treatments except ice compresses and elevation of the head at sleeping time are required in the immediate postoperative period. In the case that after surgery the operated eyelid or a part of it begins to retract, the patient should be instructed to massage the lid downward while looking upward in order to maintain the eyelid at the physiological position. In the case of posterior approaches, vigorous massages may be started soon after surgery while in the case of anterior approach they must be delayed for at least 2 weeks, in order to avoid dehis cence of the surgical wound and possible fistulas.

Conclusions
GO is the commonest cause of exophthalmos and eyelid retraction. These two aesthetic and functional disabling conditions are amenable to effective surgical treatment. Relatively simple techniques can be used to correct eyelid retraction while more elaborated procedures are required to treat exophthalmos and any possible associated alteration of the ocular surface.

Correction of Entropion and Ectropion

2010-05-08T09:56:00.000-07:00

The eyelids protect the eye and keep the ocular surface moist. Eyelid malpositions can cause ocular surface disease (OSD) and threaten sight. This is in particular true for any eyelid entropion, which probably is the most common eyelid malposition, but is also true for the different forms of ectropion. This short chapter deals with the various forms of entropion and ectropion and their adequate therapies.

Entropion
Entropion is defined as an eyelid malposition, where the lid margin is inverted and directed towards the globe. The lid margin with or without lashes rubbing against the conjunctiva and the cornea causes foreign body sensation, pain and leads eventually to epithelial defects and finally to corneal scarring. Entropion should be distinguished from trichiasis and distichiasis, which present with similar symptoms, but usually need different therapy. Trichiasis is a common, acquired misdirection of eyelashes arising from their normal site of origin.

Distichiasis
is a rare, congenital condition with growth of abnormal lashes from an extra row, usually from the meibomian gland orifices. Under certain conditions, like inflammation in Stevens-Johnson syndrome, metaplastic changes in the meibomian gland orifices can induce 'acquired' distichiasis. In both trichiasis and distichiasis, the position of the lid margin is normal. If there is entropion of the lid margin this must be treated first before treatment of eyelash abnormality. Different types of entropion can be distinguished, according to the underlying etiology: (1) congenital entropion: (a) entropion and (b) epiblepharon, and (2) acquired entropion: (a) involutional entropion; (b) cicatricial entropion, and (c) acute spastic entropion.

Congenital Entropion
Congenital entropion is rare and should not be confused with epiblepharon. In congenital entropion the eyelid in its whole horizontal extension is involved and the eyelashes are directed towards the eye, but in epiblepharon the lashes are orientated more vertically. Congenital entropion tends to persist and cause keratopathy, whereas epiblepharon often resolves spontaneously.

Epiblepharon is characterized by an apparent overriding of the pretarsal orbicularis muscle and skin over the eyelid margin, causing the eyelashes to assume a vertical position. It most commonly occurs in Asians and affects the medial part of the lower eyelids. Not every child presenting with an epiblepharon, even when the lashes come into contact with the cornea, has to be operated. Often it resolves spontaneously during the first years of life.

If it fails to resolve, or if corneal irritation occurs, surgery is indicated. Recurrent attacks of conjunctivitis and persistent photophobia in children are indicators for symptomatic OSD. Surgical repair consists of circumscribed anterior eyelid lamellar shortening and tarsal fixation. An elliptical strip of skin and underlying orbicularis muscle is excised below and lateral the inferior punctum. The skin edges are sutured to the lower border of the tarsal plate or the eyelid retractors with absorbable sutures to prevent the orbicularis from overriding the lid margin. The cosmetic results are better, when the procedure is performed symmetrically on both sides. The vertical amount of skin excision should be moderate enough to prevent iatrogenic medial lower eyelid retraction causing an eversión of the lacrimal punctum.

Acquired Entropion
Acquired entropion can be either cicatricial or involutional. In addition, a form of acute spastic entropion can be defined in susceptible individuals with blepharospasm that has been induced by ocular irritation. Cicatricial entropion is due to contraction of the posterior lid lamella, involutional entropion caused by changes in the tissue structures with ageing. It is mandatory to distinguish involutional entropion from cicatricial entropion. Therefore, cicatricial changes in the conjunctiva have to be sought after. When examining a patient with entropion, the everted tarsal conjunctiva of both lower and upper eyelid should be investigated under the slit-lamp. Conjunctival and subconjunctival scar formation with or without shortening of the fornices and symblepharon formation are clinical signs for a cicatricial entropion. Severe posterior lamellar cicatrization causes in addition lid retraction.

Any condition that causes contracture of the conjunctiva can result in a cicatricial entropion. Such conditions include mechanical and chemical trauma, burns, trachoma infection (particularly in the upper eyelid) and cicatrizing conjunctivitis like topical glaucoma medication, herpes infection, Stevens-Johnson syndrome and ocular cicatricial pemphigoid. If cicatricial changes are present their cause should be established before considering surgery.

Involutional Entropion
Involutional entropion is the most common form of all entropia, and it is probably the most common eyelid malformation. Since involutional changes of the eyelid anatomy are responsible for this kind of entropion, it is therefore seen in the elderly patient. A combination of factors has been advocated to account for this kind of eyelid malposition [Jones, 1960; Collin and Rathburn, 1978]. This includes the following features: (1) horizontal eyelid laxity (desinsertion of lateral and medial canthus and/or tarsal plate laxity); (2) laxity and/or desinsertion of lower lid retractor complex, and (3) overriding of the preseptal orbic-ularis muscle over the pretarsal orbicularis. Enophthalmos due to orbital fat atrophy might aggravate the pathogenesis of involutional lower eyelid entropion, but is no longer considered a significant factor in its etiology. Any surgical treatment should address these factors.

Patient Assessment
In order to select an adequate surgical procedure for lower eyelid entropion repair, the patient has to be assessed carefully. This includes an assessment of the eyelid position and the condition of the lower eyelid. For this purpose, the simple 'snap-back' test is very useful. The lower eyelid is gently pulled downwards and away from the globe, which normally should not exceed approximately 3 mm. After releasing it, the eyelid should then spontaneously return in its normal position without an additional blink.

Therapy
The use of tape or therapeutic contact lenses temporarily can help to reduce bulbar irritation. Eventually, surgical intervention is the only effective way to correct this eyelid malposition. To achieve a long-lasting effect, the pathogenic features should be addressed. This includes horizontal lid laxity, vertical lid laxity and eyelid lamella dissociation. In the following a small number of procedures are described, which will allow one to correct the majority of involutional entropia.

Transverse/Everting Sutures
This simple, quick and everywhere (e.g. at the bedside) applicable procedure can correct any involutional entropion, if no marked lower lid laxity is present. A temporary cure for usually about 6 months is available and is particularly helpful in geriatric patients, when more invasive surgery is not indicated [Wright et al, 1999].

Transverse sutures prevent the preseptal orbicularis muscle from overriding the pretarsal part and are placed horizontally through the lid just underneath the tarsal plate [Schópfer, 1949]. Everting sutures are placed more obliquely through the lid to tighten the lower lid retractors and transfer their pull to the lid margin.

Three 5-0 Vicryl sutures are passed through the lid from the conjunctiva to the skin in the lateral two-thirds of the lid, starting from just below the border of the tarsal plate with transverse sutures and emerging through the skin just above that level in a distance of about 2mm from each other. Everting sutures run more obliquely and start lower in the fornix and emerge nearer to the lashes. The sutures are tied tightly and can be removed, if an overcorrection is present. Usually they are left for spontaneous resorption.

Wies Procedure. The Wies procedure is a transverse lid split combined with everting sutures [Wies, 1954]. By performing a horizontal full-thickness lid split, a fibrous tissue scar is induced, which permanently prevents an overriding of the preseptal orbicularis muscle. This is combined with everting sutures to tighten the lower eyelid retractors and increase their pull to the lid margin. This procedure gives good long-term results, if no horizontal lid laxity is present.

The technique consists of a horizontal full-thickness transsection of the whole of the lower eyelid about 4-5 mm below the lash line. The cut should be as horizontal as possible, and should not reach the lower punctum. Surgery is continued by passing three double-armed 5-0 Vicryl® sutures from the conjunctiva (and with it the lower lid retractors) below the lid transsection through the pretarsal orbicularis muscle to the skin above the transsection. The needles should start 1-2 mm from the conjunctival cut and emerge through the skin 1-2 mm below the lash line and about 2 mm apart. Before tying the everting sutures, the horizontal skin incision can be closed with a running 6-0 silk suture. Skin sutures are removed after 6-7 days. The everting sutures usually are left for spontaneous resorption, unless there is marked overcorrection, which in most cases is due to preexisting horizontal laxity.

Quicken Procedure. In most cases of involutional entropion a horizontal lid laxity is present. In these cases an additional full-thickness shortening is indicated. This is easiest performed by a Quickert procedure [Quickert and Rathburn, 1971], which is a Wies procedure combined with a horizontal lid shortening. The horizontal full-thickness lid split induces a fibrous tissue barrier to prevent the preseptal orbicularis muscle from overriding, the everting sutures tighten the lower eyelid retractors and increase their pull to the lid margin, and the horizontal lid shortening corrects lower lid laxity and stabilizes the lid.

A horizontal skin incision is made 4 - 5 mm from the lash line in the whole of the lower lid. Then a vertical transsection through the lid is made 5 mm medial to the lateral canthus, down to the horizontal skin incision, followed by the horizontal full-thickness transsection as in a Wies procedure, medially and laterally to the vertical incision. Finally, a full-thickness resection of excess lid margin is performed. The amount of excess tissue is estimated by overlapping the medial and the lateral end of the lid margin under slight tension. Three double-armed 5-0 Vicryl sutures are positioned in the lower conjunctival wound edge (as in the Wies procedure) before readapting the two ends of the lid margin with tarsal (6-0 Vicryl) and lid margin (6-0 silk) sutures. Surgery is continued and completed as in the Wies procedure. All silk sutures are removed after 1 week, the everting sutures left for spontaneous resorption.

The results after a Quickert procedure are usually good, the recurrence rate is as low as 3.7%.

Jones Procedure. Particularly in recurrences of lower eyelid entropion after one or more previous surgeries without horizontal laxity, and in cases where surgical trauma to the conjunctiva should be avoided, plication of the lower lid retractors through an anterior skin approach is indicated. This is in particularly helpful in lower eyelid cicatricial entropion due to ocular mucous membrane pemphigoid, when any surgical trauma to the conjunctiva should be avoided to prevent exacerbation of the disease.

With the Jones procedure the lower eyelid retractors are exposed via a skin approach, shortened, and sutures used to create a barrier to prevent the presep-tal orbicularis from overriding the pretarsal part. In the presence of additional lower eyelid laxity, particularly in the lateral canthal tendon, this procedure can be combined with a lateral tarsal strip procedure to tighten and shorten the lower eyelid.

The Jones procedure needs more dissection in the lower lid and more detailed knowledge of the anatomy.

Cicatricial Entropion
This is due to scarring of the conjunctiva and tarsal plate with shortening of the posterior lamella. Any condition that causes contracture, like chemical burns, mechanical trauma, topical glaucoma medication, ocular cicatricial mucous membrane pemphigoid and others, can induce scarring. It occurs commonly in upper and lower eyelids.

The choice of surgical procedures to correct lower eyelid cicatricial entropion is dictated by the severity of the entropion and the retraction and by the underlying cause. In ocular cicatricial pemphigoid, surgery should be confined to the anterior lamella whenever possible to avoid exacerbating the conjunctival disease. A retractor tightening procedure like the Jones procedure (see above) would be the method of choice.

Circumscribed conjunctival scars can be excised and corrected with a Z-plasty. Moderate degrees of cicatricial entropion with a minor degree of lid retraction can be managed with a tarsal fracture procedure. A horizontal incision is made through the whole length of the tarsus just below its centre down to the orbicularis muscle. Three double-armed 5-0 Vicryl sutures are passed from the lower fragment just below the incision and out through the skin immediately below the lash line. The sutures are tied to produce a mild overcorrection and removed after 2 weeks.

In severe cicatricial lower lid entropion with more severe degree of lid retraction, a posterior lamellar graft is indicated. The tarsoconjunctiva is lengthened with a graft, which is inserted near the lid margin to allow eversión. A piece of full-thickness buccal mucosa, tarsal plate, hard palate, ear cartilage or donor sclera is sutured with running 6-0 Vicryl sutures between the superior and inferior fragment of the horizontally divided lower tarsal plate. The lid margin is hold everted and the graft firmly apposed to its bed with everting sutures passed through the graft and tied on the skin just below the lashes.

Acute Spastic Entropion
Topical therapy of the underlying cause of ocular irritation may reverse the eyelid malposition. If this is not the case, a permanent entropion with usually involutional components may ensue, which will require surgical intervention according to the guidelines given before.

Upper Eyelid Entropion
Upper eyelid entropion is an eyelid malposition in which the upper eyelid margin is turned inwards against the globe. It can be responsible for severe OSD and ocular morbidity. It is relatively uncommon in the northern hemisphere in contrast to a number of countries in more arid areas of the world, where trachoma is endemic.

The condition can be congenital, which is rather rare, but is mainly caused by cicatricial changes of the posterior upper eyelid lamella. Any trauma, either mechanical or chemical, and infection to the conjunctiva can cause an upper eyelid entropion. Worldwide, trachoma is the most common cause of this upper eyelid malposition, other causes are listed in table. In addition to taking a careful history, a complete ocular examination with eversión of the posterior lamella and the superior fornix is essential to determine the etiology.

Upper eyelid trachoma may be further classified according to its severity as mild, moderate or severe. This is essential for choosing the most appropriate surgical procedure. However, first it is important to establish the diagnosis of upper eyelid entropion and differentiate this from simple trichiasis. This helps to avoid unnecessary and often useless epilation efforts.

Therapy

Anterior Lamellar Repositioning
This procedure is indicated in mild to moderate forms of upper eyelid entropion. It is easy to perform, safe and corrects the majority of upper lid entropia in the northern hemisphere [Hintschich, 1997]. The surgery divides the anterior from the posterior lamella of the upper eyelid, repositions the anterior lamella superiorly and sutures it to the tarsal plate at a higher level. This is often combined with a lid split at the grey line of the lid margin, which enhances the everting effect to the lid margin. This procedure requires a stable upper tarsal plate.

The superior tarsal plate is completely freed from the overlying orbicularis muscle down to the roots of the lashes through a skin crease incision. The entire length of the lid margin is split in the grey line, just anteriorly to the orifices of the meibomian glands, to a depth of 1-2 mm. Five to six 6-0 double-armed Vicryl sutures are anchored in the upper third of the anterior tarsal plate and then passed out through orbicularis and skin, just above the lash line. By closing these sutures, the anterior lamella is lifted and the lash-bearing part of the lid margin is everted. The split is allowed to granulate and the sutures can be left for spontaneous resorption.

In more severe forms of upper eyelid entropion a tarsal wedge resection or a rotation of the terminal tarsus can be performed. In cases of post-traumatic upper eyelid entropion, particularly after severe burns, the tarsal plate tends to be thin and unstable. This situation is often combined with upper lid retraction, conjunctival scarring and an upper fornix shortening. Under such conditions, none of the aforementioned techniques are applicable. A posterior lamellar graft is then indicated to stabilize and lengthen the upper eyelid. An autologous graft is put between the upper eyelid margin or the remnant of the tarsal plate and the recessed upper lid retractors.

A graft from the hard palate is favorable because it combines some stiffness with mucous membrane lining and is ideal for this kind of upper eyelid correction. Sutures and knots always should be covered by tissue to avoid corneal damage. Any aberrant or misdirected lashes and lid margin malpositions can be corrected at the same time, if necessary, by a full-thickness wedge excision.

It is important to correct cicatricial upper eyelid entropium before starting with any visual rehabilitative procedures, such as keratoplasty. Otherwise the continuing mechanical stress to the ocular surface caused by the lid malposition will jeopardize the result of any of these procedures. In consequence, one might be forced to perform lid surgery earlier than 6 months after the trauma in order to prevent ongoing damage to the ocular surface, although this can be associated with a higher failure rate of the surgery. Usually one waits for at least 6 months until healing and scarring is completed before corrective and reconstructive procedures are performed.

Ectropion
Lower eyelid ectropion is an eyelid malposition in which the lower eyelid margin is turned away from the globe. This condition can be classified into five categories according to the underlying etiology: (1) congenital ectropion and (2) acquired ectropion: (a) involutional ectropion; (b) cicatricial ectropion; (c) paralytic ectropion, and (d) mechanical ectropion.

Any severe ectropion with secondary lagophthalmos cannot only cause continuing epihora, but also OSD with exposure keratopathy and finally corneal ulceration. For therapy, it is important to be able to classify the actual type of ectropion so that the correct management is chosen based on the underlying cause. However, more than one etiological factor in one individual patient may be present, e.g. ongoing epiphora in a neglected involutional ectropion may lead to secondary cicatricial changes in the skin. This induces a vicious circle, which is increasingly difficult to reverse the longer the surgery is delayed. One should always look for cicatricial changes in the skin - either a general tightness, which is accentuated by asking the patient to look up and open the mouth, or a linear scar. Failure to recognize a cicatricial component is a common cause of surgical failure. Horizontal lid laxity and lateral or medial tendon weakness is assessed as for involutional entropion. Lower eyelid ectropion in facial nerve palsy mostly is associated with other abnormalities of facial nerve function, e.g. inability to lift the forehead or other signs of facial muscular weakness.

Congenital Ectropion
The majority of patients with congenital ectropion suffer from cicatricial ectropion due to a generalized shortage of the periorbital skin. Singular congenital ectropion is rare; it is mainly associated with additional abnormalities as in blepharophimosis syndrome, Down syndrome or ichthyosis. A congenital facial palsy like in a Moebius syndrome causes a paralytic ectropion.

Patients with shortage of skin require full-thickness skin grafting (see below). This surgery is purely functional and the aesthetic results are less favorable in comparison to the results in adults. However, in cases of severe cicatricial ectropion with lagophthalmos causing keratopathy in young children, skin grafting procedures should not be delayed to prevent them from sight-threatening complications. Tarsorrhaphies never work sufficiently in these cases and will only complicate the situation and delay a definite correction.

Acquired Ectropion

Involutional Ectropion
The most common type of ectropion is the involutional ectropion with its variety of involutional tissue changes including horizontal lid laxity, weakness of the retractors and a dissociation between the lamellae. The surgical procedure should address the underlying etiological factors, as mentioned above. In general, the surgery of an involutional ectropion, particularly of the medial eyelid with punctual eversión, medial tendon laxity, chronic conjunctival exposure and lacrimal pump insufficiency is difficult and the results often are less favorable compared to other lid malformations.

The treatment of involutional lower eyelid ectropion is to correct the lower lid laxity by shortening the lid in the area of maximum laxity. This can be carried out centrally or laterally, under a blepharoplasty flap which allows excess skin and fat to be removed for improved aesthetics, at the lateral canthus or medially just lateral to the punctum. Inverting sutures can support the correction of an everted lid margin. Inversion can be further helped if the posterior lamella of the lid is shortened and the lower lid retractors tightened with the excision of a diamond of tarsoconjunctiva and lower lid retractor plication. If the lid laxity is maximum in the medial canthal tendon this can be tightened with a medial canthal suture or a medial canthal full-thickness resection. Such a medial canthal resection involves cutting the inferior canaliculus that can be marsupialized into the conjunctival sac without necessarily causing epiphora.

Full-Thickness Wedge Excision
A full-thickness pentagon of lid is resected from the area of maximum lid laxity. If there is general lid laxity, the excision is performed in the lateral third of the lower eyelid. The amount of excision, which is necessary for correction, is assessed by overlapping the medial and the lateral portion of the lid gently. The lid transsection has to be perpendicular to the lid margin. Once the pentagon is excised, small vessels are cauterized, and the lid defect is repaired.

Lid Margin Repair
Two or three 6-0 Vicryl sutures on a half circle needle are passed with a horizontal partial-thickness bite into the tarsal plate of one wound edge and then into the tarsal plate of the other wound edge at the corresponding height entering from its conjunctival side. Before closing the sutures, the alignment of the lid margin is checked. Then a silk suture is passed through the grey line and in line with it and closed, leaving its ends long. An additional silk suture is passed in the lash line, some more in the skin to close it. The long ends of the grey line suture are caught and knotted with the skin sutures to prevent the grey line suture from rubbing against the globe. The silk sutures can be removed after 1 week.

Lazy T Procedure
This procedure corrects a medial ectropion with horizontal lid laxity. A medial full-thickness lid resection is combined with an excision of a diamond-shaped part of conjunctiva and subconjunctival tissue, which is closed with an inverting suture. The diamond excision is carried out in the conjunctiva immediately below the lower punctum. One needle of a double-armed 6-0 absorbable suture is passed through the superior apex of the diamond, the other through the conjunctiva below its inferior apex. With this needle, parts of the lower lid retractors are picked up, which are best found lateral to the diamond. Both needles are passed through orbicularis and skin and tied anteriorly. This suture not only closes the diamond excision, but also increases the inversion of the punctum, particularly on down-gaze.

Lateral Tarsal Strip Procedure
This procedure is an excellent method to correct any horizontal lower lid laxity and can be used for both entropion and ectropion repair [Anderson and Gordy, 1979]. It can be combined either with inverting or everting procedures, depending on the underlying pathology. If there is significant medial canthal laxity and the procedure would cause an unacceptable lateral displacement of the punctum, a lateral tarsal strip procedure should not be used (or only in combination with a medial tendon reinforcement).

The principle of this procedure is based on a (re)attachment of the lateral part of the tarsal plate to the periorbital tissue adjacent to the bony orbital rim inside the zygomatic arch. To attain a good result it is mandatory to free the lateral part of the tarsal plate from any epithelial tissues and to suture it as posterior as possible inside the orbital rim. This is necessary to firstly avoid the complication of inclusion cysts and secondly to reach the best alignment of the lid margin to the globe.

Usually monofile non-absorbable sutures, like 6-0 Prolene, are used, but long-acting absorbable sutures, like 5-0 Vicryl, also will work. The lateral canthal area and the bone is approached by an approximately 10 mm horizontal skin incision starting from the lateral canthus. The lower limb of the lateral canthal tendon is cut. The lateral part of the lower lid tarsal plate is completely denuded by removing the lid margin with all lash roots, the orbicularis muscle and the conjunctiva. In cases of a stretched tarsal plate causing marked laxity, a piece of tarsus can be resected. If the tarsal plate is too short to form a lateral canthal tendon, which reaches the periorbit, a periosteal flap can be formed. Such a flap can easily be dissected by incising the periosteum at the outer surface of the zygomatic bone, leaving the junction in the inner part of the arch intact. The lateral tarsal strip is sutured with a double-armed suture to either the periorbital tissue or the periosteal flap. The lateral canthus is restored with a hidden simple suture and the skin is closed.

Cicatricial Ectropion
Cicatricial ectropion is due to a shortage of skin. This can be either congenital or acquired. If the skin shortage is local it can be corrected with a Z-plasty and if it is general it should be corrected by the addition of skin either as a flap or a free graft. The treatment of cicatricial ectropion with tarsorrhaphy is useless and a waste of time. However, any additional lid laxity can be corrected with a lid shortening procedure.

Skin Grafting. In the periorbital area, full-thickness grafts are preferable to split-thickness grafts. Suitable donor sites are the upper eyelid (ipsi- or contralateral), the pre-or retroauricular site, and the inner side of the upper arm or the supra-clavicular fossa.

The recipient site must be prepared carefully, any subcutaneous scar tissue causing traction be excised and bleeding stopped. Traction sutures help to keep the bed stretched. The graft should be as thin as possible and not oversized, but just fitted into the defect to prevent it from developing a wrinkled surface. The graft should be left undisturbed for at least 2-3 days with a moist pressure dressing applying continuous pressure onto the stretched graft.

Paralytic Ectropion
A paralytic ectropion is caused by a seventh nerve palsy and due to a lack of normal innervation of the orbicularis muscle. Failure of normal lid closure with lower lid laxity and ectropion, upper eyelid retraction and brow ptosis are the clinical signs.

Lagophthalmos can cause severe OSD with corneal epithelial defects. The risk of significant morbidity is higher in patients with peripheral seventh nerve palsy, severe lagophthalmos, missing Bell's phenomenon and reduced corneal sensibility. In these patients, if no early spontaneous restoration of facial nerve function can be observed, an early surgical intervention to improve the lid closure is indicated. This can be either a temporary tarsorrhaphy or a botulinus toxin injection. The lower eyelid primarily requires support to hold the lid up against gravity. Lower eyelid ectropion repair is best performed by a lateral tarsal strip procedure. This can by combined with a medial canthoplasty (Otis-Lee procedure) [Lee, 1951]. With this simple procedure the upper and lower lid margins medial to the lacrimal puncta are sutured together permanently. This reduces the interpalpebral distance at the medial canthus and brings the lacrimal puncta into the tear film. Lid laxity can be corrected medially with medial can-thai sutures or in long-standing cases with a medial canthal resection.

Before putting weights into the upper eyelid, it is important to correct any lower lid ectropion and upper eyelid retraction first. Lid loading should be the last and not the first surgical procedure!

Floppy Eyelid Syndrome
Upper eyelid ectropion can be part of the 'floppy eyelid syndrome' [Culbertson and Ostler, 1981] which includes easily everted upper eyelids, chronic papillary conjunctivitis, and non-specific irritation. The typical patient with FES is male and obese with symptoms of foreign body sensation, morning tearing, mattering and redness, photophobia, and awakening with an everted eyelid. 70% of the patients present corneal involvement. The pathophysiology of FES is probably multifactorial with systemic mechanisms (obstructive sleep apnea) and mechanical mechanisms (sleeping preference).

Regardless of the cause, most patients benefit from surgical eyelid tightening after conservative measures such as shields, lubrication, and weight loss have failed to provide relief. To date, the literature on the surgical treatment of FES recommends pentagonal wedge resection beginning at the lateral third of the eyelid or a lateral tarsal strip procedure. These simple approaches are extremely helpful in treating OSD in such patients [Culbertson and Tseng, 1994]. In addition, a number of modifications have been described recently -including medial upper eyelid shortening - for which the reader is directed to the primary literature [Moore et al, 1996; Periman and Sires, 2002; Valenzuela and Sullivan, 2005].

Anti Inflammatory and Immunosuppressive Concepts

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Ocular surface disorders do not have to be treated routinely by systemic immunosuppression, as various local treatment options are available and sufficiently effective in many patients. These are: (1) lid closure, enable or improve it surgically; (2) local corticosteroids, they suppress local inflammation, but may deteriorate dry eye symptoms and increase risk of local infections; (3) topical cyclosporin A (CsA) acts as an anti inflammatory with rare side effects; (4) local lubricants, apply them frequently, but be aware of local toxicity resulting in intolerance to components of these drops (mostly preservatives); (5) vitamin A containing substances, they improve superficial epithelial cell layers; (6) autologous serum, it contains various cytokines and growth factors as useful adjunct for healing of epithelial defects; (7) therapeutic contact lens, apply it for superficial epithelial defects, but take care of infectious complications; (8) punctum plugs, insert them or obliterate nasolacrimal duct, and (9) amniotic membrane transplantation for reconstruction of superficial layers of the cornea and conjunctiva.

The use of the various local treatment options were recently recommended by an international expert panel. There is increasing evidence that dry eye problems beside other pathophysiological disturbances also show increased inflammatory cells and proinflammatory cytokines in the conjunctiva, lacrimal glands and tear fluid. Topical anti inflammatory substances are therefore a logical therapeutical adjunct. Glucocorticosteroids should be applied only for short time period as they are effective within several days, but severe side effects are probable in long term use.

Topical CsA is an anti inflammatory substance with a slowly acting effect increasing within weeks to 6 months; this substance can be applied topically for a long time, as side effects are very rare.

However, there are some systemic disorders with involvement of the ocular surface and adnexa, where the above-mentioned local treatment options are not sufficiently working. Among these systemic inflammatory disorders are atopic disorders, bullous mucocutaneous disorders with ocular involvement or inflammatory disorders due to collagenous or vasculitic systemic diseases. These systemic disorders may show heavy inflammatory involvement of the ocular surfaces and adnexa, therefore systemic anti inflammatory treatment regimens are reasonable.

The main indications for any systemic immunosuppression are (1) to prevent eyes from becoming blind by inflammation, (2) to maintain the integrity of the eye, and (3) to reduce mortality caused by systemic inflammation. A prerequisite for any immunosuppression is to rule out infection as the possible cause of inflammation. Immunosuppressive treatment regimens are sometimes shown to be effective in randomized controlled studies, but quite often only uncontrolled case series are available to justify the treatment.

In addition, the relative efficacy of different treatment regimens is not determined and interindividual variations of the effectiveness for the same substance is well known for various drugs. Therefore, at present each patient will be best treated with an individualized treatment regimen. In general, the use of alkylating substances often results in long term drug free remissions, but treatment with other substances needs to be continued long term or even indefinitely. A guideline gives advice how to manage this topic.

First line anti inflammatory treatment consists of corticosteroids, which can be applied topically, periocularly or systemically. Their anti inflammatory capacity becomes evident within a few days. However, side effects, possible complications, or sometimes ineffectivity limit their application. Usually, in patients with liver insufficiency about lmg/kg/day prednisolone is applied, and in severe inflammation pulses of 1 g/day for 3-5 days are possible.

The dose should be reduced stepwise (lOmg every 1-2 weeks, at the level of 40mg/day reduce in 5-mg steps, at 20mg/day in 2.5-mg steps, at lOmg in 1-mg steps), reduction intervals can be prolonged from 1 to 4 weeks depending on the clinical course. During glucocorticosteroid treatment, monitoring of hypertension, body weight, blood glucose (every 3 months), serum lipids, density of bones (once a year) should be performed. Important and frequent side effects are (a) increased risk of infection, (b) fluid retention, (c) diabetes mellitus, (d) hyperlipidemia, (e) osteoporosis, (f) atherosclerosis, (g) glaucoma, (h) cataract, (i) anxiety, (j) sleepiness, (k) mood changes, (1) easy bruising, and (m) poor wound healing. As supplements to steroids, calcium l,500mg/day, vitamin D 800IU/day, estrogens, if decreased or postmenopausal, and antiabsorbants should be added.

Adverse effects of glucocorticosteroids are cushingoid changes (weight gain, moon facies, fat redistribution, acne) for doses >5-10mg/day prednisone, suppression of adrenal glands, and delay of pubertal growth in children. Sometimes severe side effects such as pancreatitis, aseptic bone necrosis, IDDM, myopathy, or psychosis require immediate reduction of corticosteroids. In cases of concomitant use of NSAID, the risk of gastric ulceration increases. Long term corticosteroid therapy is associated with an increase in mortality. If corticosteroids fail to induce improvement of the inflammation within 2-4 weeks or if a continuous dose of > 10 mg/day is needed, then additional systemic immunosuppression with alternative drugs should be performed. The immunosuppressive substances frequently applied in such human disorders are outlined in table.

Cyclophosphamide (Cyc) is a cytotoxic alkylating drug. It effects resting and dividing lymphocytes and results in a broad T and B cell impairment. The drug is well absorbed and metabolized in the liver. It is eliminated via the kidneys and therefore some metabolites can cause bladder toxicity. The main indications for Cyc are as antineoplastic drug in oncology, in autoimmune disorders especially SLE and Wegener's granulomatosis, uveitis and ocular cicatricial pemphigoid. Usually a dose of Cyc of 1-3 mg/kg/day is given. Pulse treatment every 3-6 weeks of about 600-1,500mg is a possible alternative. The main side effects are bone marrow depression, rarely myelodysplasia, hemorrhagic cystitis, teratogenicity, ovarian suppression, testicular atrophy, azospermia, alopecia, nausea, vomiting, and opportunistic infections due to lymphopenia. Routine monitoring of blood cell count, platelets, urinalysis, every week initially and later every month is recommended.

Chlorambucil is a cytotoxic alkylating drug inducing crosslinking of DNA to proteins. It is metabolized in the liver to phenylacetic acid mustard. Inactive compounds will be eliminated in the urine. Indications are as antineoplastic drugs in oncology, Behcet's disease, uveitis especially due to Behcet's syndrome and sympathetic ophthalmia. The dosage should be 0.1-0.2 mg/kg/day for about 1 year. Alternatively a short-term (3-6 months) treatment is possible with initiation of 2 mg/day and an increase every week by 2 mg until complete suppression of inflammation or white blood cells are <2,400/|xl or platelets <100,000/|xl are reached. The side effects are bone marrow suppression, mostly reversible, but often prolonged, opportunistic infections (e.g., herpes zoster, Pneumocystis carinií), permanent sterility in men and amenorrhea in women, teratogenicity, increased risk of malignancy in the long term. Monitoring of blood cell counts every week initially, later monthly, in cases of short-term regimen every week is advised.Azathioprine (Aza) interferes with adenine and guanine ribonucleotides resulting in reduced numbers of lymphocytes, mixed lymphocytes reactivity, IL-2 synthesis and IgM production. The substance is orally well absorbed; metabolism of Aza needs activity of xanthine oxidase, which can be inhibited by allopurinol. The main general indications are rheumatoid arthritis, organ transplantation, psoriasis, Reiter's syndrome, or systemic lupus erythematosus; in ophthalmology, chronic uveitis, uveitis in Behcet's syndrome and intermediate uveitis are frequent indications. The dosage ranges between 1 and 3 mg/kg/day, reduction is recommended when allopurinol is applied. The main side effects are reversible bone marrow suppression, increased risk of non-Hodgkin's lym-phoma, hepatotoxicity 2%, and gastrointestinal intolerance 25%. Monitoring of blood cell counts and platelets at 4- to 6-week intervals and liver enzymes every 12 weeks is recommended. The dosage should be reduced if liver enzymes increase > 1.5-fold, stop Aza application if the rise is >5 times of normal.

Mycophenolate mofetil (MMF) selectively inhibits inosine monophosphate dehydrogenase, it reduces lymphocyte proliferation, suppresses antibody synthesis, reduces cellular adhesion to vascular endothelium, and inflammatory cell recruitment. MMF shows renal elimination and has a high oral bioavailabihty. The main indications are transplantation of solid organs, uveitis, and scleritis. However, no controlled studies are available. In most cases, MMF reduces ocular inflammation if applied with other immunomodulating substances. The recommended dosage is 2 X 1 g/day. The main side effects are gastrointestinal pain, nausea, vomiting, and diarrhea in up to one third, rarely infections, and neoplas-tic disorders. One should monitor blood cell counts every week for the first month, later at 2-month intervals, and liver enzymes at 3-month intervals.

Methotrexate (Mtx) is a folie acid agonist inhibiting dihydrofolate reduc-tase. It inhibits rapidly dividing cells. Oral absorption is reduced by metaboliza-tion of the drug by intestinal flora in up to one third, parenteral application is therefore much safer. Addition of lmg/day folate reduces nausea. Patients should abstain from alcohol consumption during treatment. The substance is eliminated by the kidneys. The main indications for Mtx are rheumatoid arthritis, juvenile chronic arthritis, psoriasis arthritis, systemic lupus erythematosus, several neoplastic disorders, uveitis, scleritis, orbital pseudotumor. Major side effects are cytopenia, hepatotoxicitiy, interstitial pneumonia, stomatitis, and nausea. Mtx is contraindicated during pregnancy. During treatment one should monitor blood cell counts and liver enzymes at 1- to 2-month intervals.

CsA inhibits preferentially immunocompetent T lymphocytes. CsA is metabolized in the liver and excreted in the bile. Bioavailabihty of CsA shows a broad range. The main indications are solid-organ transplantation, treatment-resistant rheumatoid arthritis, severe plaque psoriasis, uveitis, and Behcet's syndrome. The currently recommended dosage is 2-5 mg/kg/day. Serious side effects include nephrotoxicity, hypertension, less common hepatotoxicity, gingival hyperplasia, myalgia, tremor, paresthesiae, hypomagnesemia, and hir-sutism. It is recommended to monitor blood pressure often, at least every month, serum creatinine every 2 weeks for 2 months, then monthly. Detection of CsA blood levels is not necessary.

Tacrolimus (FK-506) inhibits activation of T lymphocytes. The absorption of the drug from gastrointestinum varies. Tacrolimus is metabolized by the cytochrome P450 system and shows mainly fecal elimination. Indications for FK-506 are solid-organ transplantations, and uveitis, although only small numbers of patients have been reported. The dosage is usually 0.1-0.15 mg/kg/day for transplantation and 0.05 mg/kg/day for uveitis, respectively. During treatment, monitor drug blood concentration weekly for about 2 months, then monthly; test liver enzymes, bilirubin, blood urea nitrogen, creatinine, electrolytes including calcium, magnesium, phosphate; cholesterol, triglycerides, glucose, blood cell count; blood pressure. The main known side effects are nephrotoxicity, neurologic symptoms, gastrointestinal symptoms, hyperglycemia, hypomagne-semia, tremor, and hypertension.

Immunosuppressive drugs as outlined above have a broad range of effects; they interact with pathologic immune reactions and should block them effectively. However, a lack of specificity or evolving severe side effects sometimes prevents a therapeutic success. In these situations combination therapy with multiple immunosuppressive drugs is sometimes useful. But with regard to a more specific immune regulatory effect, a lot of monoclonal antibodies or sometimes fusion proteins have been developed which specifically block a receptor. This blockade can downregulate an immune reaction if the blocked molecule has a key function in the pathological immune process. An overview of the substances currently used in patients with autoimmune disorders or in studies is given in table.

Biological substances with specificity for TNF-a receptors are frequently used in chronic polyarthritis. It has been noted that TNF-a is one key molecule responsible for destruction of cartilage of joints and blocking of this cytokine receptor will stop inflammation and structural tissue disorganization highly effectively. But aside from joint inflammation, the blockade of TNF-a receptors is also effective in psoriasis, Bechterew's arthritis and inflammatory bowel diseases. Some authors also report beneficial effects of blocking TNF-a receptors in various inflammatory eye disorders.

TNF-a is a cytokine produced by various cells (i.e. monocytes, macro-phages, neutrophils, activated lymphocytes, endothelial cells, fibroblasts, and other cells). The main function of this proinflammatory cytokine is to induce cachexia and fever. In addition, inflammatory cells will immigrate locally. An increase in synovia cell apoptosis and expression of adhesion molecules takes place. There are two known receptors of TNF-a, one is p55 and the second p75. They are located in the cell membrane and can be cleaved by matrix metalloproteinases. With regard to the eye, we know that TNF-a is expressed in the cornea, especially during inflammation. TNF-a may induce corneal angiogenesis in vivo. There is an interaction between TNF-a and sVCAM-1. TNF-a may increase NOS2, fibroblast apoptosis, and various MMPs - 1, 3, 10, 11, 13. TNF-a is elevated in psoriatic skin lesions.

Infliximab is a chimeric monoclonal antibody specific for TNF-a with a humanized Fc part and Fab fragment from mouse. In man the usual dosage is 3-5mg/kg b.w intravenously. The interval of treatment should be 0, 2 and 6 weeks and then every 8 weeks afterwards. Etanercept is a fusion protein specific for the p75 receptor of TNF-a. The usual dosage is 25 mg subcutaneously applied twice a week. Adalimumab is another monoclonal antibody fully humanized and specific for TNF-a. The usual application dosage is 40mg given subcutaneously every 2 weeks. These inhibitors of TNF-a show a very rapid anti-inflammatory response and rare side effects. The clinical efficacy of infliximab is superior to adalimumab and etanercept (personal experience). One has to look for possible infections which may cause lethal complications, especially in cases of tuberculosis. Active tuberculosis has to be ruled out before application of these drugs. Skin reactions may sometimes develop in the area of local application. Possibly myocardial insufficiency may become worse, induction of functional autoanti-bodies and autoimmunity is very rare. The long-term side effects are unclear at present, but an increase in neoplastic disorders is suspected.

Inhibition of the cell surface molecule CD20 is frequently performed in treatment of lymphomas and leukemias. As B cells with CD20 molecules on their cell surface are also involved in a variety of autoimmune disorders, the effect of the monoclonal antibody rituximab, which is able to block the CD20 cell surface antigen, is currently being investigated. At present, favorable clinical results have been reported in the treatment of rheumatoid arthritis or treatment-resistant scleritis due to primary Sjógren's syndrome. However, another study showed no promising effects in Wegener's granulo-matosis with complicated longstanding orbital granulomas. At present it is not clear what medical indication is best for rituximab application.

Severe forms of ocular cicatricial pemphigoid are best treated by systemic Cyc. Local treatment with corticosteroids and CsA is not sufficient, data for a possible effect of subconjunctivally injected mitomycin have not been reported yet, but the risks of that treatment are known, i.e. reduction of limbal stem cells, necrosis of the sclera and ciliary body. Early cases of ocular pemphigoid with moderate activity can be successfully managed with dapsone or related sul-fapyridine substances. But new treatment options have the potential to reduce side effects and seem to be as effective as Cyc. Promising results show daclizumab (antibody against CD25), intravenous immunoglobulins and methotrexate. In addition, surgical treatment may include keratolim-bal allografts and amniotic membrane transplantation in combination with penetrating keratoplasty in cases with sufficient immunosuppression.

Presumably, similar drugs will be developed for other disorders in the near future. Although we have a few guidelines and recommendations for the use of immunosuppressive substances in general, a lack of controlled studies complicates recommendations, for example for the application of immunosuppressive substances in Sjógren's syndrome. Therefore, it is still a big challenge which substance or combinations should be applied at what dosages and for how long in an individual patient. This matter is still a difficult task for every physician, even for those experienced in that field. Therefore, further work is still needed on evaluation of objective data for optimal adjustment of treatment. Possibly new options will be available in the future, hopefully with a more specific interaction to correct specifically the immunopathology without changing the physiologic conditions elsewhere in the body.

Medical Management of Dry Eye Disease

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The initial management of dry eye disease relies on the use of artificial tear substitutes and the conservation of natural tears. Most artificial tears are lubricants with an electrolyte content that is only an approximation of normal tears. Viscosity agents are often added to artificial tears to increase the ocular surface residence time. An understanding of the complex interactions between aging, hormonal change, the environment, and the immune system has lead to new therapies to treat dry eye disease. Treatments that reduce associated con-junctival inflammation and stimulate the production of normal tear components may become increasingly important for the management of severe disease. An understanding of the behaviour of normal tears and the aetiology of dry eye is fundamental to the development of an effective treatment strategy.

Rational for Medical Management

Structure of the Tear Film
The tear film is part of a functional unit that comprises the tears, corneal and conjunctival epithelium, lacrimal glands, and lids. Disturbance of one or more of these interrelating structures can result in characteristic symptoms and signs of dry eye disease. This disease acts through the common disease mechanisms of hyperosmolar tears and surface drying that damages the epithelial cells, with associated inflammation and a susceptibility to infection. The terms dry eye disease, dysfunctional tear syndrome, and keratoconjunctivitis sicca are synonymous.

Tears are mechanically spread over the ocular surface by upper lid blinking, but the development of an effective tear film depends upon surfactant phospholipids in the surface layer and mucous in the basal layer that allows the fluid to adhere to the hydrophilic epithelial cells. The lubricating action of the tear film disperses the shearing forces on the epithelium caused by blinking. Finally, the tear film provides a smooth optical interface, transports metabolites, and freely transmits oxygen and carbon dioxide to the cornea.

The structure of the tear film consists of an outer lipid layer lying on an aqueous layer that contains mucus. The meibomian glands secrete the lipid, which is released from the glands by lid movement. The lipid layer is composed of two phases: (1) an outer surface non polar phase that contains waxes, cholesterol esters, and triglycerides and (2) an inner polar aqueous-mucin phase that has surfactant properties. The inner polar phospholipids are bound to protein lipocalins within the aqueous layer that bind hydrophobic molecules and contribute to tear viscosity. The lipid layer reduces evaporation from the aqueous layer and dysfunction may result in an evaporative dry eye state.

The aqueous layer is secreted by the main and accessory lacrimal glands and consists of water, electrolytes, dissolved mucins, and proteins. It has antibacterial properties due to the presence of IgA, lysozyme and lactoferrin, and it contains growth factors (EGF, TGF-a, HGF) secreted from the lacrimal gland in response to injury. It also contains leukocytes and pro-inflammatory cytokines that accumulate when tear production is reduced during sleep. The aqueous phase can physically wash away debris and toxic agents that may cause inflammation. Deficiency of this layer results in an aqueous deficiency dry eye.

Mucins are at their highest concentration internally in the aqueous phase and they serve to increase viscosity and anchor the aqueous phase to the glyco-calyx of the external cells of the epithelium. Each mucin is a high-molecular-weight glycoprotein containing a protein core with radially linked carbohydrate side chains. The protein core forms the basis of further classification (e.g. MUC1, MUC2, etc.). Human mucins are classified according to anatomical distribution as transmembrane or secretory, and the secretory mucins are further classified according to their physical properties as gel-forming or soluble. Secretory ocular mucins are principally produced by the conjunctival goblet cells (MUC5AC) but also by the lacrimal glands (MUC7).

The glycocalyx of the superficial epithelial cells of the cornea and conjunctiva is formed of trans-membrane mucins (MUC1, MUC2, and MUC4). MUC1 is essential to aid spreading of the secretory gel mucin produced by goblet cells and it also prevents pathogens binding to the ocular surface. Damage to the mucus-binding complex will change the cell membrane from a hydrophihc to a hydrophobic surface and prevent normal tear film adherence. Loss of goblet cells and ocular surface mucus is a feature of cicatrising conjunctivitis, vitamin A deficiency, and chemical burns. Almost all of this complexity of structure is absent from artificial tears.

Mechanical Behaviour of the Tear Film
Fluids can be classified according to the way they behave under sheer stress. A perfect fluid has no resistance to shear stress and therefore lacks viscosity. Fluids that are not perfect are classified as either newtonian if their viscosity is constant for different rates of shear, or non-newtonian if they become less viscous over time when a shear force is applied. This property of non-newtonian fluids is termed thixotropy - these are fluids that are both viscous and elastic. Tears have thixotropic properties but most artificial tears do not. The linear charged polymers (carboxymethylcellulose and hyaluronic acid) are the only agents used in artificial tears that have shear-thinning characteristics of non-newtonian fluids. It has been proposed that tears behave like a fluid during blinking but more like a gel between blinks.

Regulation of Tear Film Components
Regulation of the stability of the tear film is under hormonal and neuronal control. Androgen receptors have been identified in meibomian tissue, while oestrogen and progesterone receptors have been identified in conjunctiva and lacrimal gland. Postmenopausal women and the elderly may be relatively androgen-deficient and this may account for some of the involutional changes seen in periocular tissue. Androgens (testosterone) may also act as a natural suppressor of inflammation. Hormone treatments have been evaluated to treat some of the involutional changes associated with dry eye disease. Nerve fibres have been demonstrated adjacent to the lacrimal gland, goblet cells, and meibomian glands. The role of these fibres in maintaining the tear film is unclear although parasympathetic (acetylcholine- and VIP-dependent) fibres stimulate aqueous and protein secretion from the lacrimal gland, and VIP endings at the basement membrane may stimulate mucus secretion from the goblet cells.

Inflammation and Dry Eye Disease
A T-lymphocyte infiltrate is present in the conjunctiva and accessory glands of 80% of patients with dry eye disease. There is also an increased expression of HLA class II antigens, markers of apoptosis (Fas-Fas ligand), and inflammatory cytokines in the epithelium. Although this is thought to be a primary event in Sjógren's syndrome, secondary inflammation from surface friction during blinking is probably an aggravating factor in the majority of patients with dry eye disease. Inflammation may thus be both the cause and the result of dry eye, amplifying and perpetuating disease. The presence of inflammation is the rationale for the use of steroid and immunosuppression in the treatment of dry eye disease in patients with and without Sjógren's syndrome.

Guidelines for Clinical Management
Dry eye disease is generally not curable and management is structured around the control of symptoms and the prevention of surface damage. Clinical tests have a low sensitivity and specificity and they are not a reliable basis for management. Fortunately, in the great majority of patients the disease is not sight threatening. The choice of treatment depends on the severity of the disease, and one or more of the following measures may be used alone or in combination. Initial treatment is with artificial tears that lubricate the surface and reduce lid friction, although they usually only provide relief for a short time period after drop instillation. The goal of treatment is to improve eye comfort and vision at a frequency of treatment that can be reduced to a minimum. Guidelines have been produced to indicate the level of management that is appropriate according to the severity of disease. There is a placebo effect and some patients wish to continue using artificial tears without clinical signs of dry eye. A benefit with regard to patient symptoms is more difficult to achieve than a resolution of ocular signs.

General Measures

Patient education. Discuss the nature of the condition to establish a realistic expectation of outcome, provide reassurance, and encourage compliance with treatment.

Review of the home and work environment. Emphasize the importance of blinking when reading or using a video display unit. Eliminate dry air conditioning and wind if possible. A reduction in room temperature and central heating will minimize tear evaporation. Humidifiers are usually disappointing because they do not increase room humidity sufficiently. Working directives and open plan offices can limit the ability of employers to implement these recommendations. A local increase in humidity can be achieved with moist chamber goggles or side shields to glasses if this is cosmetically acceptable.

Discontinue toxic topical treatments if possible. Numerous systemic treatments have been associated with symptoms of dry eye, e.g. thiazide diuretics, anticholinergics, tricyclic antidepressants, (3-blockers, isotretinoin (13-cis-retinoic acid), and antihistaminines (loratadine, cetrizine). The excipients (e.g. benzalkonium chloride, EDTA) in drops used for other reasons, e.g. glaucoma medications, may aggravate surface damage. The preservative benzalkonium chloride can be particularly toxic to the epithelium.

Aids should be provided for patients with a loss of dexterity (e.g. rheumatoid arthritis). Single unit dose dispensers for preservative free drops may not be appropriate. Stiff plastic dropper bottles can be held and squeezed in a nutcracker or an eyedrop bottle squeezer (available commercially).

Identify and Treat Associated Conditions

Local Factors Associated with Dry Eye
These factors include: Posterior lid margin disease (blepharitis) may exacerbate evaporative dry eye. This may be associated with rosacea and allergic eye disease, Corneal exposure from lagophthalmos, lid margin defects, or seventh nerve palsy allows excessive evaporation. Abnormal globe position, lid retraction or exophthalmos from thyroid eye disease should be treated, Relative corneal anaesthesia with reduced reflex tearing following LASIK may precipitate dry eye symptoms.

Systemic Disease
A number of systemic conditions also cause ocular surface disease and severe dry eye, although dry eye disease is rarely the presenting symptom. These conditions should be investigated and treated appropriately, but the treatment of the associated dry eye disease is then usually still based on ocular signs rather than the underlying condition. These diseases include: (i) Sjógren's syndrome; (ii) rheumatoid arthritis; (iii) scleroderma (crest syndrome - calcinosis, Reynaud's phenomenon, oesophageal hypomotility, sclerodactyly, and telang-iectasia); (iv) systemic lupus erythematosis; (v) retroviral infection: infection with HTLV1, HIV, hepatitis C, or chronic Epstein-Barr virus (EBV) infection -EBV infection has been proposed as a trigger for the onset of Sjógren's syndrome, and (vi) cicatricial conjunctivitis (mucous membrane pemphigoid, Stevens-Johnson syndrome, atopic keratoconjunctivitis, graft-versus-host disease).

Tear Substitutes
These have a relatively simple formulation compared to normal tears and their delivery is periodic rather than continuous. Although continuous delivery pumps are available, they are usually restricted to the treatment of extreme dry eye. The relative contribution of their individual components to the overall desired effect - lubrication, replacing tear components, reducing osmolarity, or diluting inflammatory agents - is difficult to prove. Slightly alkaline pH drops are better tolerated than neutral or acidic drops.

Almost all artificial tears aim to replace the aqueous phase of the tear film. There are no mucus substitutes, and oils and lipids are only an approximation to the action of tear lipid layer. Simple electrolyte solutions and saline are rapidly lost from the ocular surface and attempts have therefore been made to increase the ocular surface residence time by adding macromolecules that increase the viscosity or gel properties of the solution, contribute a demulcent effect, and potentially combine with the mucus component of the tear film. These viscous or gel agents are otherwise inactive components of the drop. For example, the ocular surface residence time of carboxymethylcellulose is significantly longer than smaller molecule hydroxypropylmethylcellulose, although it is uncertain whether this fact fully explains the difference in effect. Because relative efficacy or artificial tear drops is difficult to compare the principal categories are listed in alphabetical order below and in table.

Acetylcysteine 5% drops are commercially available and are useful in patients with filamentary keratitis and mucous plaques secondary to dry eye. They are used 4 times daily and may cause stinging following instillation if there is epithelial disease. Acetylcysteine 10 and 20% is not available commercially and they have a limited bottle life even if kept refrigerated.

Cellulose based products have been the mainstay of artificial drop treatment for years. Except for carmellose they have a short ocular surface residence time.

Carbomers 974P and 980 make a relatively viscous solution, which increases ocular residence time.

Electrolyte solutions are marketed to treat the 'electrolyte toxicity' from hypertonic tears. Their constituents are usually not provided. They may have added w-3, flaxseed or evening primrose oil, and vitamins A or E of unknown effect. They are not CE marked and have not been evaluated by the FDA but are available on the Internet. Saline (0.9%) drops are effective but very short acting.

Hydroxypropyl (HP) guar is not listed in pharmacopeias. It is marketed as Systane® (Alcon), which also contains polyethylene glycol 400 and propy-lene glycol. It is proposed that HP-guar becomes a viscous gel on combination with the patient's tears and binds to the hydrophobic epithelial surface to form a protective layer.

Oils and ointments contain petrolatum mineral oil (paraffin) and wool fat. Castor oil emulsion is marketed as Refresh Endura™ (Allergan) in the USA. Ointments can be useful for extreme dry eye disease and they can be used at bedtime to supplement other treatments given during the day. They can blur vision, which limits their use in mild dry eye. Clarymist™ is a spray that contains soy lecithin 1.0% incorporated in liposomes. The phosphatidylcholine polar molecule consisting of a fatty acid component that is lipid-soluble and a charged phosphate group that is water-soluble. It is proposed that this mimics the function of the tear lipid layer.

Polyvinyl alcohol and povidone are viscous additions to a balanced saline solution. They are available as non-preserved drops.

Autologous serum (20-100%) contains surface-acting proteins, cytokines, and inhibitors of inflammation. They are effective in severe dry eye disease such as graft-versus-host disease or ocular cicatricial pemphigoid and for in the management of associated epithelial breakdown. Recent European legislation has limited the manufacture of blood products to accredited laboratories and blood banks. The manufacture is therefore expensive.

Sodium hyaluronate is available from several manufacturers as unit doses or as a spray (Hycosan®, Vismed®, Hyabak®, HyloVision HD®) with a sufficient amount to last several weeks. It has a relatively long surface residence time and is particularly effective in the management of severe dry eye states. Concerns have been raised that phosphate-buffered solutions of sodium hyaluronate can cause corneal calcium precipitation in severe dry eye disease.

The excipients (stabilizers, buffering systems, etc.) and preservatives in many formulations are a potential source of corneal toxicity, especially if there is delayed tear clearance after punctal occlusion. Preservative-free drops are essential if there is severe dry eye, and the intensive use of drops containing benzalkonium chloride in severe dry eye can cause central corneal melt. It is recommended that non-preserved drops be used whenever possible, particularly if treatment is required more than 4 times daily.

Management of Dry Eye with Contact Lenses
Contact lenses can be used as an aid to manage dry eye disease or ocular surface exposure by preventing or reducing surface evaporation. They can help reduce surface discomfort from keratinisation or filamentary keratitis, and rigid lenses can overcome the effects of irregular astigmatism. Their use is normally reserved for patients with moderate to severe dry eye liable to epithelial breakdown and unresponsive to topical treatment, and their use is supplemented with ocular lubricants. In patients with Stevens-Johnson syndrome and ocular cica-tricial pemphigoid, shallow fornices and symblepharon may mean that large diameter lenses cannot be used. Hydrogel, silicone hydrogel, and silicone rubber lenses have been evaluated, but there is an increasing interest in the use of rigid corneal and scleral lenses.

For each lens the potential benefit of a reservoir of fluid trapped behind the lens and the mechanical protection provided has to be weighed against the increased evaporation from the surface of the lens, reduced tear flow, and the risk of infection. The key properties of lens fit, the resistance to spoliation, and the oxygen transmission of the available contact lenses are listed below and in table. Oxygen transmission is measured as the Dk/t of the lens - where Dk is the oxygen permeability of the lens material and (t) the lens thickness. To limit overnight corneal swelling to <4%, it has been estimated that a lens should have a Dk/t of 87.0 ± 3.3 X 10~9 units, where the units are (cm/s) (ml 02/ml X mm Hg). Hydrogel Lenses These are available in a wide range of parameters. The use of a thin lens made of a high water content material increases the oxygen transmission, although they are not recommended for overnight wear as they do not achieve the required Dk/t.

The lens material may carry an electronic charge such that an ionic material attracts positively charged proteins, while non-ionic materials tend to attract lipids. If there is decreased tear production with a high concentration of protein and mucin in the tear film a non-ionic material may be preferable. Omafilcon A (Proclear, Coopervision) contact lenses have a high water content and incorporate phosphorylcholine that creates a biocom-patible layer of synthetic lipid on the surface that makes the lens hydrophilic, increases the surface wettability, and reduces the rate of protein adsorption. The Benz 3X lens material has similar properties (Igel®, Ultravision). High water content lenses can cause corneal dehydration by absorbing water from the tear film, and with a poor tear film the lens is prone to drying and discomfort. For more severe dry eye conditions a thin low water content lens should be considered although they carry a greater risk of epithelial hypoxia.

Silicone Hydrogel Lenses These have high oxygen transmissibility due to the silicone component of the lens material, and because the water content can be reduced the potential for lens dehydration is also reduced. They meet the minimum recommended oxygen transmission for overnight wear. The lens is less flexible than a hydrogel lens and sometimes may be less comfortable due to the higher modulus. Until recently, silicone hydrogel lenses were only available in a limited number of parameters. Second-generation silicone hydrogel materials such as Galyfilcon A (Acuvue® Advance™, Johnson & Johnson) and Iotrafilcon B (02 Optix™, CIBA Vision) have a higher water content and although they have a lower Dk/t their increased flexibility may increase comfort. These new lenses have a Dk/t of>130.

Silicone Rubber
Silicone rubber lenses have previously been used extensively for managing severe dry eye disease. They have an extremely high oxygen transmissibility of 200-400 and can be worn overnight without hypoxia. They do not contain water and cannot dehydrate but they are prone to surface spoliation. They can also tighten unpredictably after fitting, which can result in lens binding. They are semi-rigid and do not drape well over an irregular cornea. Two types of silicone rubber lenses have been marketed, Silflex (Wóhlk) and Silsoft (Elastofilcon A, Bausch & Lomb). Unfortunately, Silflex lenses have been withdrawn and Silsoft™ lenses are only available in high positive powers for aphakia or high hypermetropia.

Limbal Diameter Rigid Gas-Permeable Lenses (RGP)
Limbal diameter rigid lenses are particularly useful in cases of exposure or moderate to severe dry eye (e.g. Stevens-Johnson syndrome). They protect the entire corneal surface by retaining a tear reservoir. They flex less than silicone lenses so the chances of binding are reduced. The oxygen transmission is not as high as silicone rubber, but greater than hydrogels. Although they may not be as comfortable as hydrogel or silicone hydrogel lenses in mild dry eye, they do not dehydrate and may be more comfortable in severe dry eye.

Scleral Lenses
Scleral contact lenses have an important role in the management of severe dry eye disease, exposure, and trichiasis. With the introduction of RGP materials the first choice for fitting is with a non-ventilated design. They have a large diameter (typically between 16 and 23 mm) and the bearing surface for the lens is the sclera rather than the cornea. The lens retains a precorneal fluid reservoir of saline or non-preserved artificial tear solution that maintains corneal hydration and physically protects the entire ocular surface. They can be comfortable to wear without adaptation because there is little movement and thus minimal lid sensation. Although fitting sets are available, specialist knowledge of their use is necessary. Overnight wear is possible although there is significant hypoxia, and this is only indicated if there is nocturnal exposure.

Collagen Shields
These have been evaluated for dry eye but are now generally unavailable. They contain porcine or bovine collagen and are packed dry and hydrated with saline before inserting. They can help re-epithelialisation of the severe dry eye, although they are not licensed for the treatment of dry eye. They dissolve over time although the rate can vary. They can be uncomfortable, vision is usually reduced to at least 6/36 and corneal visualisation is difficult. The oxygen permeability of a new lens is similar to a hydrogel lens, but this increases dramatically as the lens dissolves.

Contact Lens Selection
The type of contact lens used is dependent on the severity of the ocular surface disease and the aetiology. Table summarises the different lens types and provides a guideline for lens selection dependent on the severity of dry eye. A silicone hydrogel lens can be used across the whole spectrum of disease as long as the fornices are not severely contracted. Table shows the compatibility between eyedrops and contact lenses. If treatment with topical medication is required the use of a non-fenestrated scleral lens may prevent effective drug penetration.

Tear Stimulation
Cholinergic agonists (secretogogues) such as oral pilocarpine (Salagen® 5 mg orally q.i.d.) and cevimeline (15 mg t.i.d.) that act on the exocrine glands have been shown to reduce the symptoms of dry eye and dry mouth in patients with Sjógren's syndrome, although side effects such as flu-like symptoms, blurred vision, nausea, and sweating in about 40% of patients limits their usefulness. Diquafosol 2%, a topical analogue for the nucleotide receptor P2Y2, has been shown to be capable of increasing the production of ocular surface aqueous and mucous, although it improves corneal signs better than symptoms. Other topical agents (rebamipide, ecebet sodium, gafar-nate) are being assessed as mucous production stimulators. Stimulated secretion of mucin MUC1 from corneal epithelium by topical eicosanoids (15(S)-HETE) has been demonstrated. Topically applied eledoisin (Alcon-Cusi, Spain), a extract from octopus venom glands, stimulates tear flow as a vasodilator and a contraction agent of extravascular smooth muscle and may be useful in volume-deficient dry eyes due to palsy of the major pet-rosal nerve.

Anti Inflammatory Agents

Low dose topical steroid is an effective supplementary treatment for the management of acute exacerbations of dry eye disease. However, the risks of long-term treatment must be balanced against the potential benefits of increased comfort. Intensive topical prednisolone 1% used 4 times daily for 6 weeks was reported to be helpful in severe dry eye associated with graft-versus-host disease.

Topical ciclosporine A 0.05%(Restasis®, Allergan) is a safe, well-tolerated agent that reduces T-cell-mediated inflammation of lacrimal tissue. Treatment is followed by a fall in indictors of inflammation (HLA-DR-positive cells, IL-6 levels, and apoptosis) in the tear film and conjunctiva. An increase in goblet cell numbers and reversal of squamous metaplasia has also been documented, with an improvement in tear flow as assessed by Schirmer's test.

Systemic tetracyclines (doxycycline 50-100mg daily) may help control any blepharitis associated with dry eye disease. It may act as an antibiotic to reduce lipase production that can break down meibomian lipids and exacerbate evaporative dry eye. They may also directly block some inflammatory cytokines and metalloproteinases in the tears.

Other Options

Retinoic acid 0.05% has no demonstrated beneficial effect on dry eye disease apart from reversing squamous metaplasia and keratinisation.

Zidovudine, an antiretroviral agent, has been reported to be effective in primary Sjógren's syndrome.

Postmenopausal women taking oestrogens are at increased risk of developing dry eye disease. Oral oestrogen replacement is not helpful and has potential systemic risks. Although no benefit effect has been demonstrated for topical oestrogens, there may be an effect for combined oral oestrogen and androgen. The role of topical androgens (e.g. testosterone 0.03%) on evaporative dry eye has not yet been fully evaluated.

The effect of flaxseed (w-3) oils taken orally or added to artificial tears is unproven.

Trehalose is a natural disaccharide that protects cells against desiccation. It appears to be clinically effective against signs of dry eye but it is not available commercially.

Patients following acupuncture feel better but lack any objective signs of improvement, suggesting a placebo effect.

Suggested Sequence for the Introduction of Medical Therapy

Symptoms but no signs: (a) environmental measures; (b) preserved artificial drops.

Mild conjunctival and corneal stain: (a) non-preserved drops of increased viscosity; (b) ointment at night.

Confluent central corneal stain: (a) intensive frequency of non-preserved drops; (b) trial of topical anti-inflammatory treatment (cyclosporine A or steroid); (c) temporary punctual occlusion.

Actual or potential epithelial breakdown: (a) intensive non-preserved drops; (b) topical anti-inflammatory treatment; (c) autologous serum (if available); (d) contact lens; (e) immunosuppression for autoimmune disease (rheumatoid arthritis, graft-versus-host disease, OCP, etc).

Conclusions

Medical treatment is central to the management of dry eye disease. Environmental control has an important role in prevention of symptoms.

Use non-preserved viscous preparations wherever possible for moderate to severe dry eye. As the ocular residence time of an agent is increased they tend to become more effective and the frequency of treatment can thus be reduced.

The role of anti-inflammatory agents and topical immunosuppression needs to be better defined.

Contact lenses have a role in the prevention of epithelial breakdown and visual rehabilitation in severely dry eyes.

Classification and Diagnosis of Dry Eye

2010-05-08T09:12:00.000-07:00

Classification of Keratoconjunctivitis Sicca
The condition of keratoconjunctivitis sicca (KCS) is synonymous with that of dry eye. According to the International Dry Eye Workshop (DEWS) the dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. It comprises two subgroups: tear or aqueous-deficient dry eye (aqueous tear deficiency) is due to a failure of lacrimal function while evaporative dry eye is due, predominantly but not entirely, to lipid tear deficiency.

Either form may cause damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort. A unifying mechanism is tear hyperosmolarity, which can directly cause damage to surface epithelial cells. However, an additional factor is the release of pro inflammatory cytokines in the lacrimal gland and tears, which can both initiate autoimmune lacrimal damage, as in Sjógren's syndrome, or perpetuate chronic conjunctival inflammation.

The commonest form of teardeficient KCS is non Sjógren's dry eye, whose age related form has a prevalence of about 15% in the older population. It is due to a T-cell infiltration of the lacrimal gland which reduces secretory function. Non-Sjógren's dry eye can be caused by other lacrimal diseases such as graft-versus host disease and sarcoidosis, by lacrimal obstruction in cicatricial conjunctival diseases (e.g. ocular pemphigoid, Stevens Johnson syndrome and trachoma) and also by reduced sensation at the ocular surface, leading to a loss of afferent reflex drive to the lacrimal gland. Sjógren's syndrome is a less common disorder, with a prevalence of about 0.2-0.5%.

It is an autoimmune exocrinopathy giving rise to dry eye and dry mouth and affects other mucous membranes and even the central nervous system. Primary Sjógren's syndrome occurs in the absence of a defined connective tissue disorder, whereas secondary Sjógren's syndrome is accompanied by such a condition, such as rheumatoid arthritis, systemic lupus or Wegener's disease. In general, the onset of Sjógren's syndrome dry eye is earlier than that of non Sjógren's dry eye and it evolves with greater severity.

The commonest form of evaporative dry eye is due to meibomian gland obstruction and this in turn has a strong association with skin disorders such as acne rosacea, atopic dermatitis (affecting the face) and seborrhoeic dermatitis. Evaporative dry eye can also result from lidglobe malposition (e.g. proptosis), contac-lens wear and occupational and environmental stresses. Thus it may be associated with low humidity due to air conditioning, with a reduction in blink rate while performing microscopy or with increased width of the palpebral aperture which occurs when working at a video display terminal. Such events may contribute to the office eye syndrome.

Diagnosis of Keratoconjunctivitis Sicca
The above definition of the dry eye accentuates the following features of the disease: (1) symptoms; (2) interpalpebral surface damage; (3) tear instability, and (4) tear hyperosmolarity. There are numerous tests for the diagnosis of dry eye and they vary with respect to their invasiveness. The selection and order of these tests is of paramount importance since each test may influence the outcome of the test which follows. In general it is recommended to start with the least invasive procedure and to end with the most invasive test. Occasionally it is necessary to perform some tests on a subsequent day. At the end of a battery of tests it should be possible to confirm the diagnosis, classify the form of dry eye, being conscious of its grade, and initiate appropriate therapy.

Symptoms and History
A record of clinical history and ocular symptoms is required. Several questionnaires have been developed for the assessment of dry eye. A special questionnaire for the detection of psychosomatic alterations exists and can be applied additionally.

Important aspects of the patient's history are: (a) symptoms: burning sensation, foreign body sensation, tired eye, photophobia, epiphora, swelling of the lids; (b) onset of the symptoms, duration; (c) circadian rhythm; (d) environmental conditions at home and in the office (smoke, wind, humidity); (e) contact lens associated problems; (f) cosmetics; (g) systemic diseases; (h) allergic diseases; (i) dermatologic diseases, and (j) drug history.

Examination of the Lids
The dynamics of blinking and of lid position should be observed whilst taking the history in order to prevent conscious alterations. Points of interest are: (a) frequency of blinking; (b) variation of blink intervals; (c) size of the palpebral aperture, and (d) adequacy of lid closure.

The position of the lids may influence the tear turnover, therefore care should be taken to identify the following malpositions: (a) entropion; (b) ectropion; (c) eversión of the lacrimal puncta; (d) cicatrical malposition; (e) dermatochalasis, and (f) swelling of the temporal aspect of the upper lid, implying enlargement of the lacrimal gland.

Slit-Lamp Examination
Slit-lamp biomicroscopy should evaluate the following anatomical structures and their alterations: (a) Lid margins: hyperaemia, telangiectasia, thickening, scarring, keratinization, ulceration, tear debris, abnormalities of the meibomian orifices, metaplasia, character of expressed meibomian secretions, (b) Eyelashes: misdirection, malposition, encrustations, collarettes, (c) Conjunctiva: erythema, swelling, keratinization, papillary/follicular reaction, pinguecula, lid parallel con junctival folds, (d) Cornea: infiltrates, scars, punctuate staining or ulcers, vascu-larization, pannus, and pterygium. (e) Additionally, the tear film should be analysed for: filaments, mucus, and cellular debris, meibomian foam.

Non-Invasive Break-Up Time
The non-invasive break-up time test was created to measure the stability of the precorneal tear film without any dye. It involves projection of a target onto the convex mirror surface of the tear film and recording the time taken for the image to break up after a blink. The test was originally performed with a custom-built 'Toposcope' but has also been performed over a limited zone of the exposed precorneal film, using a keratometer. It can also be measured with the TearscopePlus and is a non-invasive procedure.

Interferometry
Tear film interferometry is a non-invasive technique for grading the behaviour of the tear film lipid layer and estimating its thickness on the basis of the observed interference colours. It is useful for selecting dry eye candidates for punctal occlusion. Apparatus which have been used for this purpose include the TearscopePlus and the Kowa DR-1.

A colour scale which has been used is as follows: (a) greyish colours, uniform: normal; (b) greyish colours, non-uniform: normal; (c) yellow colours: dry eye; (d) brown colours: dry eye, and (e) blue colours: dry eye.

Reflective Meniscometry
Reflective meniscometry is a non-invasive method to measure the radius of the tear meniscus curvature. The radius is directly proportional to the tear meniscus volume and to the total tear volume of the tear sac. A radius <0.25 mm indicates a hyposecretory dry eye. Fluorescein Tests Fluorescein sodium is used for several dry eye tests. They all are mildly invasive tests. At a concentration around 0.1%, the dye is highly fluorescent, staining the tear film and epithelial defects. Once the surface layer of epithelial cells is lost, the dye spreads rapidly in the intercellular space.

Fluorescein is available in the form of fluorescein-impregnated paper strips or as a 1-2% solution in a sterile, unit dose sachet. Fluorescence is with the use of a blue exciter filter in combination with a yellow barrier filter. Most slit-lamps are provided with an adequate blue light source and it is well worth purchasing a suitable Kodak Wratten 12 or 15 barrier filter. To instil fluorescein from an impregnated strip, a drop of sterile saline is applied to the impregnated end and the excess discarded with a rapid flick. The moistened tip is then touched lightly onto the lower tarsal plate of the right and then the left eye, in sequence. Because 1-2% fluorescein is non-fluorescent, it is only appropriate to apply a small volume in order to achieve dilution and fluorescence. A suitable volume is 2-5 |xl applied with a micropipette.

The fluorescein tear film break-up time records the rupture of the tear film after a blink. The tear film should be evaluated after a few blinks. The average of three measurements provides a representative measure of the tear film stability. Evaluation: >10 s: normal; 5-10 s: marginal dry eye; <5 s: dry eye. Fluorescein staining of the interpalpebral surface of the eye has a characteristic pattern in KCS, initially affecting the lower part of the exposed eye and later affecting the cornea and conjunctiva more extensively. In meibomian gland dysfunction the staining pattern is often disposed over the lower cornea, closer to the lower lid margin. A number of suitable grading schemes exist. The Oxford grading scheme consists of a series of panels representing the cornea and the two zones of exposed conjunctiva, on which is displayed a pattern of dots representing increasing staining from grade 0 to 5. The number of dots increases sequentially in a log-linear scale: from grade 0 to 1 there is a 1-log step, which means that 10 dye spots are detected per 1 zone in grade 1. Between grade 1 and 5 there is a 0.5-log unit increase of spots, which equals 32 dye spots in grade 2, 100 dye spots in grade 3 and 316 dye spots in grade 4, always counted per 1 zone. Grade 5 is detected, when the number of dye spots exceeds 316 per 1 zone.

The individual scores for each of the 3 panels are added up to give the total score. The maximum staining score for the exposed conjunctiva and cornea is 15. An important point to note is that if the recommended filter combination is used then grading with fluorescein can be carried out on both the cornea and conjunctiva and use rose bengal can be avoided. This prevents patient discomfort, since in the absence of an anaesthetic, rose bengal causes intense stinging on instillation. Staining of the epithelium can occasionally be obscured by the fluorescence of the tear film. Asking the patient to blink several times allows the staining pattern to be viewed more clearly. The stained meniscus can be used to estimate the meniscus volume, either simply by measuring meniscus height using the width of the slit-lamp beam, or in a more sophisticated fashion, by reflective meniscometry or by assessing its profile photographically in slit section. A meniscus radius of curvatures <0.25 mm suggests a dry eye condition. Fluorescein can also be used for measurements of tear turnover and of the tear fluorescein clearance.

Meibometry Meibometry is a mildly invasive quantitative method for measurement of the basal level of meibomian lipid on the lid margin. In this test, lipid is blotted onto a loop of plastic tape, which produces a strip of increased transparency. The change in transparency is quantified photometrically and provides an index of the uptake of lipid. The system can be calibrated to provide approximate estimate of the amount of lipid on the lid margin, without giving information about chemical composition. An appropriate photometer is available at Courage & Khazaka Electronic GmbH (Cologne, Germany), together with the plastic tape for testing. Schirmer Test The Schirmer I test is one of the oldest tests available for dry eye diagnosis and is a measure of reflex tear secretion. It is performed in the unanaesthetised eye. It is highly invasive, and is therefore performed later in the diagnostic sequence. A standard filter paper is placed with its notched tip bent around the lower lid margin at the junction of the middle and outer third. With the eyes closed, the Schirmer paper is allowed to wet for a period of 5 minutes, after which the length of wetting is measured from the notch to the leading, wetted edge. Evaluation: <6 mm: in the dry eye range; 6-10 mm: dry eye suspect; > 10mm: normal.

The Schirmer test can also be performed after instillation of a topical anaesthetic when it has been said to represent a 'basal' measurement, since sensory reflex stimulation from the eye is suppressed. This is called the Jones test. Although the test value is usually lower than that recorded by the Schirmer I test, the test has not been adequately validated. If the Jones test is performed after nasal stimulation, it is named Schirmer II test. In Sjógren's syndrome in contrast to non-Sjógren's dry eye, it has been shown that the ability of nasal stimulation to increase the tear production of the anaesthetised eye is greatly reduced and is of diagnostic value.

Rose Bengal Staining
The rose bengal test is markedly invasive. Rose bengal is not a vital dye. It stains damaged cells which possess an abnormal mucin coat. It is intrinsically toxic and therefore causes marked stinging on instillation. If used in drop form, its use should be preceded by instillation a topical anaesthetic.
Rose bengal is available in drop form (1%) (Minims Rose Bengal, Chauvin) or as a dye-impregnated paper strip. Staining is a dose-dependent staining effect so that when the paper strip is used, and less dye is delivered, a weaker staining pattern is achieved.

Grading of staining using rose bengal uses the same approach as for staining and grading using fluorescein. The Oxford scale has been described above. The classic, van Bijsterveld schema is also based on an estimate of staining on the cornea and the nasal and temporal part of the exposed bulbar conjunctiva. Each zone is graded from 0 to 3, and the maximum total score is 9. A score >3 is regarded as indicative of dry eye according to the van Bijsterveld schema. It should be noted that the visibility of rose bengal staining is greatest over the white of the bulbar conjunctiva. For grading purposes visibility on the cornea is reasonable when the background is a blue iris, but is poor against a dark brown iris.

Lissamine Green
Lissamine green (Lissaver Plus, Contopharma, Interlaken, Switzerland) stains the eye in a similar way as rose bengal, but it is less toxic and is consequently well tolerated. It is therefore recommended as an alternate test to the rose bengal test. However, the contrast of the dye is less sharp and the detection of the stained areas more difficult. Lissamine green is used in a 1.0% concentration. The test is mildly invasive, similar to fluorescein. The Oxford grading system and the van Bijsterveld system can be applied as described above.

Meibography
Meibography involves the transillumination of the meibomian glands after eversión of the upper and lower lid. The glands are visible in silhouette and the absence of glands or 'drop-out' can be quantified. The manipulation of the lids stimulates reflex tearing and the test should be regarded as mildly invasive.

Ocular Fermng Test
If a tear sample taken from the lower tear meniscus is applied to a glass slide, a characteristic ferning pattern develops as the tears evaporate. This pattern can be viewed under the microscope at a 40-100X magnification and used as an index of dry eye. In dry eye states, the delicate fronded pattern becomes broken up and irregular and the appearances can be graded. Fern formation is influenced by the protein and electrolyte composition of the tears. Since only a small sample of tears is required for the test it is only mildly invasive. Grading is based on the regularity of arborization of the ferning pattern. Classes 1 and 2 are regarded as normal, and classes 3 and 4 represent increasing degrees of dry eye.

Impression Cytology
Impression cytology is a histological method of cytological examination without the disadvantages of an invasive excisional biopsy. The samples can be examined by light microscopical, electron-microscopical, immunological and molecular biological methods. Several methods of interpretation of the results exist. Important features of dry eye include squamous metaplasia, loss of goblet cells and accumulation of inflammatory cells. Ultrastructural signs include changes in the nuclear/cytoplasmic ratio and an increased frequency of 'snake-like' chromatin.

Osmolarity
The measurement of tear osmolarity (mosm/1) is regarded as a gold standard in the diagnosis of dry eye, however it is difficult to measure and no commercial instrument is currently available. Studies using the depression-of-freezing-point osmometer have suggested that a value of >312 mosm/1 is diagnostic of dry eye. Newer techniques for routine clinical use are in development.

General Information and Recommendations
Diagnostic tests of dry eye states are in general intended for two groups of patients: those who come for the first visit with a suspected dry eye and those who have already undergone therapy elsewhere and wish further advice. In the first group of patients the test series for dry eye can be started immediately. In the second group of patients it is recommended to stop the patients' preexisting therapy for 1 week and start the testing afterwards. This opens the pathway towards an exact diagnosis without any therapeutic interference.

For the routine diagnostic way of a suspected dry eye state it is advised to select a number of tests. Non-invasive procedures like questionnaires, symptoms and history and slit-lamp examination are among these and often are called low-tech diagnostic. Considering patients' comfort and economic aspects, simple tests should always be used. These tests provide already a reliable information of the dry eye condition. A questionnaire has a surprisingly high sensitivity of 77% with a specificity of 81%. In combination with data from other non-invasive methods, sensitivity and specificity can even be raised. Slit-lamp characteristics like an irregularity of the black line or hyper-aemia of the conjunctiva result in a sensitivity of 92% and a specificity of 81%. Simple low-tech diagnostic is therefore the basis of the dry eye testing.

Besides that, a battery of dry eye tests exist which are mildly or markedly invasive. The order of tests is of critical importance since one test may influence the result of the next. Therefore it is recommended to start with the least invasive test and to end with the most invasive procedure. Some tests are mutually exclusive, which means that in a certain patient only a selection of dry eye tests is performed.

Within this system of tests with increasing invasiveness, intervals of 5 min are recommended between invasive tests. This is the time necessary for restoration of the original meniscus height. For the routine dry eye patient a sequence of tests giving the essential information for the classification should be selected.

After having selected the appropriate combination of tests, the grading and interpretation of these tests gains importance. It is essential to know the information we can get from a certain test in order to classify our patient's dry eye form as tear-deficient or evaporative. If you suspect a hyperevaporative dry eye the non-invasive BUT and meibography should be measured. Meniscometry and Schirmer I test are specifically indicative for the hypovolemic dry eye. The same tests give us sufficient information about the severity of the ocular surface disease. Staining with Lissamine and fluorescein allow a more precise quantification of the severity and are therefore recommended. The interpretation is based on a grading system of the tests mentioned above. This system allows us to distinguish normal from marginal dry eyes or manifest dry eye patients.

Once the diagnosis is confirmed and the grade of the disease established the patients need follow-up examinations. The course of the KCS under therapy is documented. We get the best information from a repetition of the tests which have been selected initially. This pathway of examination provides reliable information about the course of the disease and forms the basis for longitudinal observations. However, we have to take into account that certain tests like fluorescein and rose bengal staining show limits with respect to their reliability at different times. Nevertheless, these tests are necessary to provide exact information about the localization of ocular surface defects, whereas the non-invasive tests give us broader information about the whole ocular surface. The diagnosis of dry eye is therefore based on the data of different tests with increasing invasiveness arranged in a way to minimize interference between the tests and on the grading of the results which permit a selection of the appropriate therapy and a long-term observation of the patient.

Functional Anatomy and Immunological Interactions of Ocular Surface and Adnexa

2010-05-08T08:17:00.000-07:00

Anatomy
The ocular surface and its adnexa comprise the cornea, the conjunctiva with bulbar, fornical and palpebral parts, the main lacrimal gland, the glands of the eyelids, i.e. meibomian, Moll's, and accessory lacrimal glands and the nasolacrimal system with the upper and lower puncta, the paired lacrimal canaliculi, the lacrimal sac and nasolacrimal duct. The nasolacrimal ducts collect the tear fluid from the ocular surface and convey it into the nasal cavity whereas all other structures contribute to formation of the preocular tear film. The tear film serves to protect and lubricate the ocular surface, as well as to provide the major refractive surface for the visual system.

The preocular tear film (see chapter 1 by J.M. Tiffany) contains water, protective antimicrobials, cytokines, lipids, and mucins and can be divided in three components: a lipid component, an aqueous component, and a mucus component. The lipid component is secreted by the meibomian glands in the eyelid and forms the superficial layer of the tear film. The aqueous component contains electrolytes, water, and a large variety of proteins, peptides and glycopeptides and is primarily secreted by the lacrimal gland as well as the accessory lacrimal glands (glands of Krause; glands of Wolfring) of the lids. The mucus component is the product of conjunctival goblet and epithelial cells, corneal epithelial cells and acinar as well as excretory duct cells of the lacrimal gland, which have recently been shown to produce mucins.

Ocular Surface
The apical surface of the ocular surface epithelia, both corneal and conjunctival, provide a specialized interface between the tear fluid and the epithelium that stabilizes the fluid layer. That interface includes the undulating membrane ridges on the apical cell's apical membrane, termed microplicae, and emanating from their apices, a layer termed the glycocalyx. Membrane-bound mucins of corneal and conjunctival epithelial cells are present in the glycocalyx layer; soluble mucins (MUC5AC) from conjunctival goblet cells (figs lb, 2b) as well as MUCs 5B and 7 from lacrimal glands are in solution in the tear film. Both MUC5B and MUC7 have been shown to bind bacteria and contribute to innate immunity of the tear film. Beside MUC5AC, conjunctival goblet cells secrete the trefoil factor family (TFF) peptides TFF1 and TFF3. TFF peptides are, together with mucins, typical constituents of mucus gels that influence the rheological properties of the tear film, promote migration of corneal epithelial cells, have antiapoptotic properties, and induce cell scattering. Conjunctival and corneal epithelial cells are able to react against pathogens by the production of inducible antimicrobial peptides. Moreover, in certain disease states the corneal cells are able to produce TFF3.

Lacrimal Gland
The lacrimal gland is anterior in the superolateral region of the orbit, and is divided into two parts by the levator palpebrae superioris muscle. The lacrimal gland consists of acini that are built of a luminar lining of columnar epithelial cells that are surrounded by a basal layer of myoepithelial cells and an enclosing basement membrane. The human lacrimal gland is a tubuloalveolar gland of serous type. Intercalated and 6-12 interlobular ducts drain the secretions into the conjunctival fornix beneath the temporal bone. The tubules discharge without any characteristic excretory duct system (histologic distinction from serous salivary glands) into the interlobular ducts. The connective tissue between the acini contains accumulations of lymphocytes as well as many plasma cells mainly secreting IgA and being part of the eye-associated lymphoid tissue (EALT). As already mentioned, the lacrimal gland produces electrolytes, water, and a large variety of proteins, peptides and glycopeptides. Of these, recent research regarding tear film rheology and innate immunity focus on production of different constitutively and inducible antimicrobial peptides, such as 3-defensins , surfactant proteins A and D as well as MUCs 4, 5AC, 5B and 7 that are secreted into the tear film.

Eyelid
The skeleton of the eyelid is a collagen plate called the tarsus. It contains a row of branched alveolar sebaceous glands, unrelated to the eyelashes. These tarsal or Meibomian glands have punctate openings along the free edge of the eyelid close to its posterior margin. They produce a lipid material whose synthesis is dependent on neuronal, hormonal, and vascular factors. This lipid material is fluid, spreads easily, is a surfactant as well as an aqueous barrier and must remain functional after a blink. To satisfy these requirements, the Meibomian lipids have a specific composition. Even after delivery it may be modified by lipases produced by ocular bacteria, and modifications in the lipid components can lead to unique disease states. Sexual hormones, especially androgens, seem to play a decisive role in Meibomian physiology.

Near the anterior margin of the eyelids there are two or three rows of stiff hairs - the eyelashes. In the middle of the lid is the cross-striated orbic-ularis oculi muscle, the fiber bundles of its palpebral part overlapping one another like tiles on a roof. The tendon of the cross-striated levator palpebral muscle is inserted into the tarsus; beneath it is the smooth tarsalis muscle. The tone of the latter is determined by autonomic nervous impulses and is supposed to adjust the width of the palpebral opening. The apocrine ciliary glands (Moll's glands) open close to the eyelashes. These apocrine glands are active from birth in producing agents against pathogenic microorganisms in the eyelid shaft and on the ocular surface, i.e. lysozyme, (3-defensin-2, adrenomedullin, lactoferrin, and IgA. In the conjunctival fornix the eyelid also contains small accessory lacrimal glands (Krause's glands, Wolfring's glands). Although much smaller, these glands are histologically comparable to the main lacrimal gland. However, only less is known about the secretions of these small glands and their contribution to tear film physiology.

Nasolacrimal Ducts
A lacrimal system consists of the upper and the lower lacrimal canaliculus, the lacrimal sac and the nasolacrimal duct. The structures are surrounded by a wide ranging cavernous system and are embedded in the osseous canal between the maxilla and the lacrimal bone. The internal wall of each lacrimal canaliculus is lined by a thick non-cornified epithelium resting on a basement membrane. The lacrimal sac and the nasolacrimal duct are lined by a double-layered epithelium with integrated goblet cells sometimes forming characteristic mucous glands. As a draining and secretory system, the nasolacrimal ducts play a role in tear transport by production of MUCs 2, 4, 5AC, 5B, and 7, TFF peptides TFF1 and TFF3 and non-specific immune defense [19]. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into the surrounding vascular system. This system is similar to a cavernous body that is subject to autonomic control and regulates tear outflow. Tear duct-associated lymphoid tissue (TALT) is present in the efferent tear ducts. Under normal conditions, tear fluid components are constantly absorbed into the blood vessels of the surrounding cavernous body. These vessels are connected to the blood vessels of the outer eye and could act as a feedback signal for tear fluid production, which ceases if these tear components are not absorbed.

Lacrimal Functiona
Unit and Host Defense at the Ocular Surface Lacrimal Functional Unit
The cornea possesses the richest sensory innervation of the body to detect noxious stimuli. The trigeminal sensory neurons (CN V) that innervate the eye vary in their chemical composition and electrophysiological properties, and can be classified according to the stimuli that activate them preferentially: mechanical forces, temperature, or irritant chemicals. Different classes of noxious stimuli (mechanical injuries, heat, extreme cold) activate to a different degree the various populations of sensory fibers of the ocular surface and evoke unpleasant sensations of distinct quality.

It is recognized today that the tear film is secreted reflexively from the 'lacrimal functional unit' that is composed of the ocular surface tissues (cornea and conjunctiva, including goblet cells and Meibomian glands), the lacrimal glands (main and accessory), and their interconnecting sensory (CN V) and autonomic (CN VII) innervation. This reflex secretion is initiated by subconscious stimulation of the highly innervated ocular surface epithelia. The human nasolacrimal ducts are integrated in this reflex arc, as shown by recent investigations.

Host Defense at the Ocular Surface
Some defense mechanisms of the innate immune system have already been mentioned above and it is beyond the scope of this chapter to deal with all of them. However, it should be mentioned that the defense of the ocular surfaces presents a unique challenge in that not only must integrity be maintained against microbial, inflammatory and physical assault, but it must be done while minimizing the risk of loss of corneal transparency. This puts severe limitations on the degree to which scarring or neovascularization can occur in the cornea secondary to any infectious, inflammatory, immunological or wound-healing process. The defense system must be equally effective under two extremes of conditions: those found in the open eye and the closed eye environments. Distinctly different defense strategies are utilized in both open and closed conditions. The extraordinary effectiveness of this system is evidenced by the fact that despite continued exposure to a microbe-rich environment, the external ocular surfaces maintain a very low microbial titer and are highly resistant to breaching by all but a few pathogens.

Eye-Associated Lymphoid Tissue as an Entrance Side for Immunological Events
EALT

The epithelia of the ocular surface, the corneal and conjunctival epithelia, the epithelium of the efferent tear ducts, the Meibomian glands, main and accessory lacrimal glands and lids make up a physiological system that was recently dubbed the lacrimal-ocular surface system. The LOS is organized to maintain the clarity of the cornea - a homeostatic set-point. Like the systems that represent epithelial interfaces between the internal and external environments, i.e., the gastrointestinal, integumentary and respiratory systems, the LOS system collaborates with the innate and adaptive immune system to respond to microbial invasion. The lacrimal glands, conjunctiva and efferent tear ducts constitute one venue of this collaboration area. These tissues are populated by IgA-producing plasma cells and their epithelia actively transport secretory IgA into the nascent tear fluid.

Specific secretory immunity depends on sophisticated cooperation between the mucosal B cell system and an epithelial glycoprotein called the secretory component. Initial stimulation of Ig-producing B cells is believed to take place mainly in organized mucosa-associated lymphoid tissue (MALT). It has become evident that MALT is characterized by considerable region-alization or compartmentalization, perhaps determined by the different cellular expression profiles of adhesion molecules and/or the local antigenic repertoire. Antigenic stimulation of B cells results in the generation of predominantly IgA-synthesizing blasts that leave the mucosae via efferent lymphatics, pass through the associated lymph nodes into the thoracic duct, and enter the circulation. The cells then return selectively to the lamina propria as plasma cells or memory B cells by means of homing mechanisms.

Organized lymphoid tissue in the conjunctiva (conjunctiva-associated lymphoid tissue - CALT) and efferent tear duct system TALT have recently been termed collectively EALT [41]. However, aggregated follicles that fulfill the criteria for designation as EALT occur only in somewhat less than a third of conjunctivae and nasolacrimal ducts from unselected cadavers with no known history of disease involving the eye, efferent tear ducts, or nose. In most cases, only lymphocytes and other defense cells are amply present subepithelially, i.e. inside the conjunctiva and efferent tear ducts that do not form aggregated follicles. It is as yet unclear whether special types of bacteria, viruses, allergic reactions, or other factors, such as some type of immune deviation, are responsible for the development of EALT in humans. However, when EALT is present, it can provide the basis from which primary low-grade B cell lymphoma of the MALT type may arise.

EALT as an Entrance Side for Immunological Events Some organs of the human body (anterior eye chamber, brain, placenta, testicle) have a special immunological state of reduced activation of the specific and non-specific immune system. This condition of local immune suppression, termed the immune privilege, is expressed in delayed or totally suppressed rejection of allogenic transplantations in these organs; this is illustrated by the maintenance of the immunophenotypic immature placenta in the maternal organism and in the survival of corneal and lens transplants in the anterior eye chamber. The biological functions of the immune privilege are evident: tolerance of a foreign antigen is obviously better in some organs than its rejection, and this can be achieved only at the expense of T-cell-mediated cytolysis of local cells. Such cell loss is not replaceable in poorly regenerative, postmitotic, or highly differentiated tissues. Therefore, some viruses survive in the central nervous system, as their elimination by T-effector cells would doubtlessly lead to neural cell death with subsequent severe neurological deficit or even individual death. A similar situation exists in the anterior eye chamber [44] and the testicle. Such immune suppression is not necessary in regenerative organs, like the liver or the skin, since all the cells needed for this process are able to proliferate and redifferentiate.

The mechanisms that maintain the immune privilege are non-uniform among different organs, and they are not understood in detail. Besides the classic concept of mechanical tissue barriers (i.e. the blood-brain, blood-testis and blood-retina barriers), we must consider the expression of so-called death ligands (CD95, TRAIL, TNF) that induce apoptosis of potentially dangerous T cells, as well as a special form of antigen presentation that produces immune tolerance. Such immune deviation was first described in the anterior eye chamber. There, injection of foreign antigen does not lead to a local T-cell reaction (type IV immune reaction) as it does at other body locations, but rather produces systemic tolerance against the inoculated antigen. In this way, antigens are not attacked in the anterior eye chamber, thus protecting the sensitive visual system against inflammatory damage. In this way, the immune privilege of the anterior eye chamber allows transplantation of allogenic lenses, artificial intraocular lenses, and corneae (although type IV immune reactions are possible after corneal transplantation in rare cases).

Such tolerance is known to be transferable by injection of splenocytes from an animal primed by inoculation of an antigen into a second animal, demonstrating that antigens from the anterior eye chamber receive a signal that produces immune deviation and that regulatory T cells have developed. In contrast to the spleen, the cervical lymph nodes do not play a critical role in the induction of immune deviation, as was shown in rats by Yamagami and Dana. Nevertheless, the drainage routes of the antigens from the anterior eye chamber and the location of their origin, as well as the passage of the belonging antigen-presenting cells, are unclear. In particular, it is not clear what role is played by the conjunctiva and the nasolacrimal ducts, as well as the lymphoid tissues associated with them, in the immune privilege of the anterior chamber of the eye.

Egan et al. demonstrated in mice that potent immunologic tolerance can be achieved by exposure of antigen (ovalbumin) via the conjunctival mucosa. They identified the submandibular lymph node as the principal lymph node in which antigen-bearing antigen-presenting cells are located and in which antigen-specific T-cell clonal expansion occurs following conjunctival application of antigen. Clonal expansion was maintained at an elevated level and the T cells were responsive in vitro during a 10-day period of daily ovalbumin application to the conjunctiva. However, despite continuous antigen application, the number of antigen-specific T cells steadily declined over the 10-day period, and by day 14, the remaining ovalbumin-specific T cells were refractory to secondary challenge with ovalbumin, indicating that they had become anergic in vivo. Egan et al. concluded that the fact that antigen-presenting cells presenting ovalbumin were found only in the submandibular lymph node - and not in other lymph nodes, spleen, or nasal associated lymphoid tissue (NALT) -rules out the possibility that tolerance in this system was due to drainage of antigen through the efferent tear ducts and association with NALT or gastrointestinal-associated lymphoid tissue (GALT).

However, one important point is lacking in the suggestions of Egan et al. It has not yet been appreciated that antigens drained by the tear fluid itself, and not applied intraconjunctivally, would be able to induce immune deviation via CALT and/or TALT. With regard to protection of the cornea against inflammatory destruction, this would be plausible and analogous to the process in the nervous system and the anterior eye chamber. In comparison with gastrointestinal tract MALT (GALT), it is not known as yet whether M cells occur in human CALT and TALT, although they probably do, as their presence has been demonstrated in several animal species. M cells are highly specialized epithelial cells that facilitate uptake and transcytosis of macromolecules and microorganisms. Following transcytosis, antigens to cells of the immune system in lymphoid aggregates are released beneath the epithelium, where antigen processing and presentation and stimulation of specific B and T lymphocytes take place.

According to a definition formulated by Isaacson for MALT of the gut wall (i.e., Peyer's patches), MALT comprises four components organized MALT, a lamina propria, intraepithelial lymphocytes, and an associated lymph node. Circulation of the lymphoid cells in these four components enables them to home to their original and other mucosal sites, where they exert the effector function. Such a response may be dominated by slgA release and may include cytotoxic T-lymphocyte action . In this regard, the submandibular lymph node found by Egan et al. might be the 'associated lymph node' of CALT and TALT, but not of NALT.

Activation of T lymphocytes has been observed in dry eye, which leads to the frequent occurrence of abnormal (pathological) apoptosis in terminally differentiated, acinar epithelial cells of the lacrimal gland [53]. Tears secreted to the ocular surface will then contain proinflammatory cytokines and will inflame the tissues of the ocular surface. Abnormal apoptosis has also been detected in the epithelial cells and lymphocytes of the ocular surface [53]. This ocular surface inflammatory response consists of inflammatory cell infiltration, activation of the ocular surface epithelium with increased expression of adhesion molecules, inflammatory cytokines and pro-apoptotic factors, increased concentrations of inflammatory cytokines in the tear fluid and increased activity of matrix-degrading enzymes in the tear fluid. It has been suggested that the reduction of circulating androgens plays a role in these processes. Treatment with locally applied cyclosporin A eye drops interferes with inter-leukin metabolism, especially of interleukin-6, thus creating a new treatment option that leads to remarkable improvement of the irritation symptoms and ocular surface signs in particular in severe cases of keratoconjunctivitis sicca.

Taken together, these findings support the conclusion that CALT and TALT play a role in the pathogenesis of dry eye. One can imagine that misdirected stimulation of EALT could result in a misguided form of immune deviation at the ocular surface. Within the scope of this event, T cells would no longer be hindered in inducing autoimmunity by apoptosis, finally resulting in the clinical picture of dry eye.
It should be mentioned, however, that a recently published article has placed our understanding of MALT in a different light concerning its functional significance. Alpan et al. demonstrated that a systemic immune response to orally administered soluble antigens does not depend on the presence of functional GALT, but more likely on initiation of immune response by gut-conditioned dendritic cells. This finding suggests that MALT is not required for initiation of a primary immune response to antigens that have entered the body. If present, however, it seems to act in two ways: It produces plasma cell precursors that later migrate into adjacent mucosa, mature to plasma cells, and produce slgA for mucosal protection. It allows uptake of antigens by M cells and presentation of these antigens to virgin T and B cells to initiate a primary immune response. Thus, MALT could represent a second pathway (a kind of safeguard of the adaptive immune system) for initiation of a immune response to antigens that have been incorporated into the mucus layer and, in the case of CALT or TALT, have entered the ocular surface and are drained with tear fluid.

It can be concluded that development of EALT is a common feature frequently observed in symptomatically normal nasolacrimal ducts. Whether special types of bacteria, viruses, or other factors, e.g., immune deviation, are responsible for the development of EALT in humans requires future investigation in prospective and experimental studies.

The Normal Tear Film

2010-05-08T08:02:00.000-07:00

Importance of Film
In the open eye, the exposed surfaces of cornea and sclera are covered with a very thin film of tear fluid. This has both protective and nutritional properties; its thickness changes due to evaporation while the eye is held open, and during prolonged eye-opening the film may break up to expose surface epithelial cells directly to the air. The tear break up time (TBUT) is an important clinical parameter in defining the normality of function of the eye. During normal life, break-up will perhaps occur only comparatively rarely, as blinking is very rapid and is a nearly automatic response to symptoms of drying. However, normal life for many people now includes prolonged periods of computer or other visual screen use, and it is known that the blink rate falls when paying close attention. Hence the tear film may break up between blinks. The Corneal Protection Index (CPI), defined as the ratio of TBUT to the length of the interblink, can be used to indicate the boundary between normal and dry eye.

Position and Extent of the Tear Film
The term tear film is normally used to describe the film of fluid covering the corneal surface and contained between the lid margins. In fact we should also include the film overlying the exposed bulbar sclera; however, because this surface is rough and irregular it is much harder to obtain information about its nature by the usual reflectance-based methods used for the cornea, so this area is often ignored. At present we cannot even say with certainty that a uniform and continuous tear film is present over all the exposed sclera. However this area is not negligible in upward gaze it may contribute 60% or more of the total exposed area. It is also neglected because it is of much lower importance than the cornea in the visual process, and because, having its own blood supply, it recovers more readily from injuries and infections.

The exposed area is quite closely dependent on interpalpebral height, which in turn is determined by the direction of gaze (exposure is considerably greater in upward than in downward gaze, as the upper lid follows the movement of the globe). Thus in downward gaze not all the cornea is exposed, along with a small area of sclera, while in upward gaze we may see all the cornea plus a variable amount of sclera both above and below the limbus as well as larger lateral areas. A rough linear relationship between area and palpebral height is often used: Area (cm2) = 0.28 X (height in mm) — 0.44. A more precise value can be obtained by computer analysis of images of the eye, allowing separate estimation of the areas of exposed cornea and sclera. Typical values for the area in normal level gaze are 2-3 cm2, of which 45-55% is cornea. These figures help to strengthen the recommendation to those doing much computer work, to keep the screen as low as possible to minimise ocular exposure and drying because of the reduced blink rate.

The total area of the human conjunctival sac has been estimated as 16 cm2. If all this is covered by a layer of gelatinous mucus with a water content of about 90%, say averaging 1 |xm thick, 1.44 |xl of fluid would be contained. Where the lids overlie the globe, it is possible that two such layers on the apposed surfaces will be in contact, giving an effective fluid thickness of 2 |xm. However, it seems unlikely that in this case there would be free flow of fluid (e.g. fresh tear fluid entering the upper conjunctival sac through the tear ductules) although fluid transport could occur through a 'squeegee' mechanism in blinking.

Formation of the Film
As the lids close during the blink, the upper and lower menisci are pushed ahead of them and sweep up the fluid forming the preocular film, rather like a windscreen wiper. In the opening phase of the blink, the viscosity of the tears causes fluid to be pulled out of both menisci to create a new film, but opposed to this is the negative pressure due to the concave tear meniscus. As long as the lids are moving, fluid is spread, but when the lids become stationary there is within 0.3-1 s a settling down or rearrangement whereby fluid is pulled back into the meniscus while the bulk of the spread film remains intact. The region closest to the meniscus is however considerably thinned and if fluorescein is instilled, a 'black line' can be seen around the rim of the tear film. This line is so thin that it contains too little dye to fluoresce, and it acts as a barrier to diffusion or flow of fluid into or out of the film in the interblink period. Hence the film is effectively isolated from the rest of the lacrimal system while the eye is open, and is subject to different influences such as evaporative loss at these times. The isolated film has been referred to as 'perched' because it covers the exposed eye but is in a sense independent of the ocular adnexa.

Volume of Various Compartments
We can distinguish three distinct components of the fluid in the lacrimal sac: the film itself, lying between the lid margins; the continuous line of meniscus around the lid margins, joining at the outer canthus and around the caruncle, and the fluid under the lids.

It is still not clear what volume of tears lies under the lids, or whether this should be included as part of the tear film. In the normal eye the lid margins glide in contact with the globe during a blink, and it is thought that there is a slight curvature inwards of the margin of the upper lid to give a 'windscreen wiper' action sweeping the film forward as the lids close. This would suggest that the exposed and the under-lid compartments remain separate; but King-Smith et al. discuss the possibility that the two compartments are connected but that during the blink the upper meniscus changes position, being swept down by the advancing lid margin.

Recent experiments on adding saline to severely dry eyes showed that fluid was absorbed (presumably under the lids) before any lid margin meniscus became visible, implying that the two compartments are connected. The mean under-lid volume was calculated to be 5-6 |xl. The volume of tears in the combined upper and lower menisci can be calculated from their total length (about 50 mm) and cross-sectional area, assuming that their profile is a quadrant of a circle; using a mean value of 0.365 mm for the radius of curvature, the normal meniscus volume is about 2.9 |xl. The volume of the preocular film clearly depends on its thickness (see below), but taking commonly-agreed limits of 3 and 10 |xm and an area of 2 cm2, the volume is 0.6-2.0 |xl with a mean probably about 1.0 |xl. Hence the total volume of tear fluid in the external eye is roughly 10 |xl. This does not include additional small amounts such as the fluid over the caruncle.

Clearly there is considerable personal variation in this figure - differences in form of the lid margins, slight inward or outward turning of the lids relative to the globe, positioning of the puncta and height of the palpebral opening can all affect the contained tear volume.

Thickness of Precorneal Film
Estimates of tear volume involve knowing the thickness of the film. This is not easy to measure, although several methods have been used over the years. Simple methods include isolating an area of tear film by pressing the end of a wide-mouthed syringe onto the eye and measuring the volume of fluid sucked off, absorbing fluid over a known area by placing a disc of absorbent paper on the eye, or measuring fluorescence intensity after adding a known amount of fluorescein to the film. More recently the variation of intensity of light reflection has been analysed in three ways (varying angle, frequency or wavelength). Ocular coherence tomography can measure corneal thickness with and without a contact lens and estimate the film thickness by difference. All these methods are summarised by King-Smith et al. Some estimates of tear film thickness by these methods are given in table 1. The film thickness over the anterior surface of a contact lens is generally thinner than the precorneal film, and less stable, although this varies with the contact lens material and depends on factors such as degree of contamination of the lens surface by tear components.

Volume Flow of Tears Into and From the Eye
The volume of tears in the external eye at any moment is a balance between the rate of inflow of fluid from the lacrimal gland, from the accessory lacrimal tissue and by permeation of water from the corneal epithelium through aquaporin-controlled channels. Removal of fluid is principally by drainage through the puncta following each blink, and by evaporation from the open eye. When the lids close, the upper and lower puncta press on each other and prevent outflow, but as the lids open there is a drop in canalicular pressure and fluid is sucked into the puncta from the marginal lacrimal lake [11]. Evidence for absorption of water by the corneal or conjunctival epithelium is lacking, although it is suggested that some or all of that passing down the canaliculi is absorbed before it reaches the nose.

There is considerable variation in the rate of inflow of tears. It has often been suggested that in the quiet eye there is a 'basal rate' of flow, augmented by different degrees of stimulation; one variant is that the basal secretion is produced by the accessory lacrimal tissue (about 10%of the total) and stimulated reflex or psychic tears by the main lacrimal gland, but there appears to be no firm evidence for this.

Another view is that all secretion is stimulated, that in the quiet eye being produced simply in response to opening of the eye. Most clinical estimates of tear flow rate are based on the Schirmer test and its variants; these are described below in 'Clinical Tests'. Published values of the 'unstimulated' flow rate are usually around 1.2|xl/min or roughly 1.2 ml/day (assuming a 16-hour waking cycle, since tear output is largely inhibited during sleep), with a turnover rate of 16%/min. However, using the Fluorotron Master instrument, a much lower value was found of 0.15|xl/min (about 0.15ml/day from each eye) with a turnover rate of 8.2%/min. Stimulated flow rates are much greater - up to 50 or 100 times more; 40-50 |xl in <1 min has been reported with nasal stimulus by ammonia. Since the myoepithelial cells which surround the acini of the lacrimal gland contract in this process, it seems possible that some of the released tears are preformed and the actual secretory process may be somewhat slower than at first appears. It is not clear whether there is a 'maximum' rate of secretion; sustained rates are generally less than the 40-50 |xl/min already mentioned.Regulation of Tear Production
The innervation of the lacrimal gland is complex. The reflex arc is particularly important, involving fibres from the fifth cranial nerve in the cornea, conjunctiva or surrounding tissues. There is also innervation by both the parasympathetic and the sympathetic systems, inducing positive and negative control of secretion respectively. The parasympathetic route indicates some of the complexity: starting from the lacrimatory nucleus in the brainstem of the facial nerve (cranial nerve VII), parasympathetic fibres follow the greater superficial petrosal nerve to the pterygopalatine ganglion; the conventional view is that from there the secretory fibres of the lacrimal nerve follow the zygomatico-cotemporal nerve and join the lacrimal nerve of the ophthalmic division of cranial nerve V and enter the lacrimal gland. However, there is evidence that a number of rami orbitales pass from the pterygopalatine ganglion and some of these travel directly to the lacrimal gland.
The innervation of the accessory lacrimal tissue is even less well known, but it is assumed that it is controlled in the same way as the main lacrimal gland, as they are histologically very similar.

Composition of the Tears in the Conjunctival Sac and Origins of Secretions
Several different collection techniques have been used, but usually collection is from the lower meniscus, or sometimes from the conjunctival surface of the slightly everted lid, or among the folds in the lower fornix. Some workers have used absorbent sponges placed in the lower fornix, which is effective but has the disadvantage of picking up mucus as well as fluid tears. It is still not possible to collect from the actual film, e.g. by blotting the ocular surface, without some damage to epithelial cells and contamination by cellular contents. One should be clear whether the aim is to collect stimulated or unstimulated tears. Stimulation of flow may be by bright lights, a cold stream of air on the cornea, tickling inside the nose or tweaking nasal hair, or by exposure to specific lacrimatory substances such as onion vapour, ammonia or chloracetophenone. If unstimulated tears are needed (for example, for osmolarity measurement), with collection at the slit-lamp, one must avoid passing the light beam across the pupil. We can classify the various components of the secretion as intrinsic or accessory in origin.

Intrinsic Secretions
Intrinsic secretions are produced in the main lacrimal gland (and presumably also from accessory lacrimal tissue since there is no apparent histological difference between the two types of tissue).

Aqueous Component
The aqueous part of the tears forms the bulk of the lacrimal secretion; it is actively secreted, and linked to the secretion of proteins (see below, (Major Proteins)- Although there is some input via aquaporin-controlled water channels in the corneal or conjunctival epithelium, its main source is the lacrimal tissue, where it is produced by the acinar epithelium and collected by the ductules. There is some modification and reabsorption in the ductules before delivery via the main lacrimal ductules to the outer upper fornix. It is possible by everting the temporal portion of the upper temporal lid and by finger pressure prolapsing the lacrimal gland slightly into the fornix to see one or two of the orifices, and if fluorescein is added then clear rivers can be seen in the fluorescing tears indicating the position of their orifices. During sleep or prolonged eye closure, the output of both proteins and water from the lacrimal gland changes (see below, 'Major Proteins').

The rate of secretion of lacrimal fluid varies considerably between the quiet eye and active stimulation (see 'Volume Flow of Tears into and from the Eye'). The ageing lacrimal gland suffers progressive fibrosis and loss of functional acinar tissue so its output gradually falls, creating tear film conditions similar to the earlier stages of the aqueous-tear-deficient form of dry eye.

Salts
Electrolytes are actively secreted by acinar and ductal epithelium of the lacrimal gland, and can be seen from the relative proportions of various ions not to be a serum filtrate. The pH of tears usually lies within the range 7.2-7.6 but may be higher on prolonged eye-opening through loss of C02; the value in neonates is about 6.8. Tears exert a buffering action due to their content of bicarbonate ion, proteins and other components, although the turnover rate has also been shown to be part of the response to pH challenge.

The osmolarity of the tears is determined almost entirely by their electrolyte content, since the molarity of even the major proteins is low in comparison. For normal unstimulated tears the generally accepted value is 302 ± 6mosm • kg1.

Major Proteins
Human tears contain four major proteins (each 15-20% or more of total protein) - lysozyme, lactoferrin, lipocalin and secretory IgA. The protein of unknown function previously referred to as 'tear-specific prealbumin' is now known as tear lipocalin, a member of the lipocalin superfamily of small proteins with lipid-binding properties. There is some evidence for interactions between lipocalin and both lysozyme and lactoferrin. Lysozyme, lactoferrin and lipocalin are secreted by the acinar tissue of the lacrimal gland. The secretory form of IgA, in contrast, is produced by interstitial plasma cells embedded in the gland but external to the acini; the IgA dimer, consisting of two monomeric IgA molecules held together by a J or joining piece, are transported through the acini and the secretory component characteristic of completed slgA is added. Control of secretion of lacrimal gland proteins appears to be linked to that of water: when output of water falls, so also does production of the proteins, and the concentrations of lysozyme, lactoferrin and lipocalin appear fairly constant. During sleep, as mentioned above, fluid secretion declines, and after about 2 h may approach zero. Output of slgA, however, continues as the plasma cells producing this protein are not under the same control as the lacrimal gland, and the same amount of slgA in a greatly reduced volume of aqueous appears as a steep concentration rise. At the same time, polymorphonuclear leukocytes accumulate, with the result that the tear film under the closed lids becomes much reduced in volume, sludgy and turbid, and has been described as being in a state of subclinical inflammation.

IgG and serum albumin are frequently also reported in tears, but since their levels vary with severity of disease or irritation it is considered that these proteins are not normal constituents but indicate leakage from conjunctival blood vessels.
The accessory lacrimal glands, making up 10% of all lacrimal tissue, are distributed at a number of sites within the conjunctiva. They have historically been named as the glands of Wolfring, Krause, etc. but appear to be histologi-cally identical to the main lacrimal gland and to have similar innervation. All the major lacrimal proteins have been identified immunochemically in this tissue. Although the reflex response to irritation is less pronounced, the tissue can produce enough lacrimal fluid to maintain an adequate tear film in the quiet eye even in the absence of the main lacrimal gland.

Accessory Secretions
Several components are added to the aqueous tears within the conjunctival sac, and it is the combination of all these which produces the physiologically functional tear film and influences its formation and stability.

Lipids
A complex mixture of lipids is delivered from the meibomian glands opening on the lid margin at the mucocutaneous junction. These glands are large, tubuloacinar structures lying within the tarsal plate and related to the sebaceous glands of skin; although the surrounding tissue is richly innervated, no specific fast-acting nervous stimulation is known, and they appear to be free-running, secreting lipid continuously. As with sebaceous glands of skin, modification of systemic hormonal status may affect output, but the response is on a scale of months. Compression of the tarsal plate in blinking causes a small amount of oil to be squeezed out of each gland, but repeated heavy or forcible blinking can deplete the supply within the duct of the gland so that delivery is reduced until synthesis catches up with excretion. Conversely, during sleep there is no squeezing of the glands, so the elastic ducts fill up until some critical pressure is reached and excess leaks out onto the closed lid margins, where it either flows or is rubbed away, or forms flakes on the lashes.

In the lid-opening phase after a blink, a fresh air/water interface is rapidly generated, and oil (or at least the more surface-active components) spreads onto the tear film, probably forming a largely monomolecular film. It is thought that this initial spreading is followed by a second phase in which a fluid but less surface-active fraction spreads over the first to produce a multilayered oil film structure. Its thickness can be estimated from its interference colours (e.g. as seen with the Keeler Tearscope®); normal thickness is in the range 40-90 |xm. The surface tension gradient created within the film by this spreading may cause Marangoni flow, pulling aqueous tears from the upper and lower menisci and thickening the overall tear film.

The meibomian oil contains several phospholipids, principally phos-phatidylcholine and phosphatidylethanolamine, which with a small amount of free fatty acids and cholesterol make up the surface-active fraction. The non-polar fraction consists largely of wax esters (fatty acid + long-chain fatty alcohol) and cholesterol esters; branching in many of the acyl chains ensures that the melting range of the mixture is close to lid-margin temperatures. Together, they form a layer shown to retard the evaporation of water from the surface of the tear film. Recently a model has been proposed for the structure of the oil film.

Lipids of non-meibomian origin have also been found in the tears, although reports are still incomplete. A mixture of non-polar lipids, mainly triacylglycerides, a small amount of phosphohpid, and a substantial proportion of unidentified glycolipids has been described. Since no free lipids are found in tear fluid, it is presumed that these are bound to lipocalin, which is the only major protein with strong lipid-binding characteristics.

Mucins
Mucins are a complex class of glycoproteins with a very high carbohydrate content; their main characteristic is the bottle-brush structure of a polypeptide backbone with many tandem repeats of amino acid sequences and a high proportion of serine, threonine andproline, with a large number of ohgosaccharide side chains O-glycosidically linked to Ser or Thr. They are the products of the family of MUC genes, and are of two main types: secreted or 'soluble' mucins of which the most important in the eye is MUC5AC, a gel-forming mucin produced in conjunctival goblet cells, and epithelial mucins, where the polypeptide backbone has a membrane-spanning region anchoring it to the plasma membrane of epithelial cells of cornea or conjunctiva, such as MUC1. The epithelial mucins (principally MUC1, 4 and 16) form the glycocalyx visible in transmission electron micrographs of the ocular surfaces, and a major function appears to be the anchoring of a gelatinous layer of secreted mucin so that a lubricating layer is present on all the surfaces gliding over each other during blinks or ocular movements. Mucins typically contain more than 50% carbohydrate, and water makes up more than 90% of mucin gel.

Minor Components and Small Molecules
Tears contain a large number of small molecules and minor components which can protect the corneal surface or which are produced in response to specific conditions such as inflammation. Defensins are a family of small proteins (Mr about 8,000) with antimicrobial properties (see below, 'Antimicrobial Protection'). Several cytokines associated with inflammation (IL-la and IL-1 (3, IL-6 and IL-8) have been identified in normal tears. However it is not always clear whether these factors are derived from the lacrimal gland or secreted by the conjunctival epithelium, or by leakage from the surrounding blood vessels. Enzyme activity of various kinds can be detected in tears, although the amount of the appropriate protein may be very low. Thus, catalase, superoxide dismutase, and glutathione peroxidase have been reported, among others, and are presumed to have an antioxidant protective role.

A number of systemic drugs can be detected in the tears. The actual source (conjunctival vessel leakage, transport through corneal epithelium, or lacrimal gland secretion) is not always obvious. If corneal, this could imply a specific membrane-associated transport mechanism, or an ability to pass the tight intercellular junctions, and this latter is thought to be related to the lipid solubility of the drug. Thus, phenobarbital, carbamazepine and methotrexate, which all have reasonable lipid solubility, have been detected in tears at levels comparable to those in serum, whereas ampicillin is less lipid-soluble and is found only at a very low level compared to serum. Acetaminophen is excreted in the tears at comparable levels to serum. It is known that systemic cytosine arabi-noside can cause keratitits, and this is thought to follow secretion into the tears. Rifampicin and its metabolites appear in tears, which may be coloured red-orange and cause staining of contact lenses.

Functions of the Film

Nutritional Aspects
Because of the requirement for transparency, the cornea has no blood supply. Delivery of gases and nutrients by diffusion from blood vessels at the limbus would be too slow, so these are supplied directly from the tear film; the film acts as a coupling medium for oxygen from the air (as is clear from the comparative performance of contact lenses with differing Dk values). A similar function takes place on the endothelial side of the cornea from the aqueous humour of the anterior chamber. In the open eye the tears, being in contact with air, are assumed to be saturated with oxygen (i.e. 155mmHg); however, when the eye is closed, oxygen must be supplied by diffusion from the blood in the conjunctival vasculature (55mmHg), so the metabolic status of the corneal epithelium changes markedly between the two states. It should be noted that in the closed eye the coupling medium to the cornea must actually be the film of tear fluid filling the space under the lids. The thickness of this is not exactly known, and it is also assumed that there is a relatively thick mucous layer filling most of this space, caused by the apposition of the mucous layers covering both cornea and tarsal conjunctiva.

The tears transport oxygen to the corneal epithelium, and remove metabolic carbon dioxide. Comparatively few other nutrients are found in significant quantities. It is suggested that glucose is supplied to the cornea entirely from the posterior or endothelial side, and that the corneal and conjunctival epithelia are impermeable. Tear glucose levels are low, and little changed in diabetics; reports of higher levels may be due to local tissue damage and assay of released glucose. Lactate and pyruvate are also found, indicative of the metabolic activity of corneal tissue. The growth factors EGF and TGF-a have also been detected.

Protective Roles

These can briefly be classified in two distinct areas:

Physical Protection
Many threatening or noxious attacks on the eye are averted by the rapid blink reaction, or by aversion (head turning or brow lowering); some lighter invading materials such as airborne dust, hairs or bacteria may be reflected from the surface of the tear film, especially hydrophilic particles which have been observed to bounce off the oil film. The mucous gel coating of ocular surfaces traps, absorbs and immobilises many particles and microbes, and removes them from the eye as part of the mucous thread which is swept down into the lower fornix and eventually extruded onto the skin of the inner canthus. The lubricating action of the mucous layer also prevents shearing damage to the surface epithelium at the high speeds (as high as 20 cm/s) achieved during the blink.

Lipocalin is the principal lipid-binding protein in tears, and a role for this protein has been suggested in scavenging excess lipid from the ocular surface or the surface of the mucous layer to avoid the development of non-wettable patches that would lead to tear film break-up. As yet this has not been supported by analytical studies.

Antimicrobial Protection
Several of the components of tears have antimicrobial functions. Lysozyme is well known for its muramidase activity in the outer cell wall of Gram-positive bacteria, while both lactoferrin and lipocalin have iron-sequestering properties which inhibit siderophilic bacteria. Secretory IgA exerts immunological protection after priming of the plasma cells against specific microorganisms and viruses; priming can be via mucosa-associated lymphoid tissue in the conjunctiva or elsewhere. Recently a group of small protective peptides known as defensins have been identified in the tears by immunochemical means. Several members of the a and (3 families of defensins were identified in normal tears, lacrimal gland, and inflamed conjunctiva. These have a broad spectrum of antimicrobial activity (bacteria, fungi and viruses) and are claimed to accelerate epithelial healing.

All these factors need to be considered in relation to ocular surgery, especially physical aspects such as the placement of inflow ductules and puncta/ canaliculi for drainage, avoidance of distortion of surface or conformation of lids on globe, and the removal or remodelling of conjunctiva.

Structure and Stability of the Precorneal Film
Many structural models of the preocular tear film have been proposed over the last 50 years. These are mainly based on the three-layered structure of Wolff, which has a layer of gelatinous mucus in contact with the epithelial surface (since modified largely on the basis of electron-microscopical evidence to include the surface glycocalyx), the bulk of the thickness made up of an aqueous solution of the proteins and other water-soluble molecules, and a surface layer of meibomian oil. More recently, a model has been proposed for the rat involving only two layers, in which the bulk of the film was aqueous/mucous plus an oil layer, with no differentiation into separately identifiable aqueous and mucous layers. A somewhat similar model is suggested for the mouse. It is not clear whether either of these models should also be expected for the human, and space does not allow an extensive review of the aspects of all the available models. Despite much work on the human tear film and in many species of animal, we have not yet arrived at one consistent model which can satisfactorily explain all aspects of formation, stability and function of the film.

In view of the nutritive and protective properties of the tear film, it is clearly desirable for it to cover the exposed surface of the eye throughout the eye-open period between blinks. Evaporation can be measured, but we should remember that most evaporative loss will be from the film, while the bulk of the available fluid is in the menisci or under the lids, and it is from these compartments that samples are collected for analysis.

Hence local changes in osmolarity may be greater than usually thought, and corresponding effects on film stability may be masked.

The main test of tear film stability is the break-up time (BUT), i.e. the time taken after the last complete blink for signs of rupture and dewetting of the film to be detected. Tests differ in whether they are invasive (instillation of fluores-cein to show break-up as black spots, FBUT) or non-invasive (detection of distortions of the reflected image of a grid from the cornea, NIBUT), and the value taken to indicate the borderline between normal and unstable or dry eye may vary according to method: between 5 and 180 s (ca. 5-20 s for FBUT, or ca. 10-30 s for NIBUT). However, other factors such as number of repeat measurements, time of day or racial characteristics of the subject can also influence the outcome. Perhaps the most reliable use of BUT is in assessing the effectiveness of clinical treatment. FBUT is widely considered to have poor repeatability, although this may depend on the quantity of fluorescein introduced, since this can itself affect tear film stability. NIBUT also shows considerable variation when the same subject is measured on successive days, and also for repeated measurements on the same day, although this may be due to increased tearing in response to holding the eye open for long periods. Nevertheless, BUT is a valuable guide to tear film stability. It is considered satisfactory to take the mean of three successive measurements (in the case of FBUT, adding as little fluorescein as possible).

Tests on Tears
There are many tests which can be used to assess tear film composition or function. These may be classified as subjective, where some element of judgement is required on the part of the observer, such as in grading the extent or severity of a sign, on some predetermined scale such as 0-4, as -/+ or + to + + + ; or objective, involving use of methods or equipment capable of giving a more precise value. A further division is between those tests which can be carried out under clinical conditions (although the results may be interpreted elsewhere), and those where samples are examined in the laboratory or the patients themselves are examined outside the clinic.

Clinical Tests
Apart from the basic tear break-up test, these include estimating tear volume from the Schirmer paper strip test. The recommended Schirmer strip is of Whatman No. 41 filter paper 5 mm wide and 35 mm long, with the terminal 5 mm bent to hook over the lid margin. The test can be applied in various forms, which measure different aspects, but the nomenclature is confusing. The test can be with or without anaesthetic. Schirmer's original test (Schirmer I) is without anaesthetic and does not include stimulation, other than that due to the inserted paper. The 5-min wetting length is taken to represent the basal unstimulated flow. A wetted length of 15 mm or more is taken to indicate normal production. A variant of this is the Jones test which also measures the basal rate, but uses anaesthetic and is carried out in subdued lighting conditions to minimise reflex tearing. The normal response is a wetted length of 10mm or greater. If the basal rate is normal but the reflex response to stimulation is thought to be defective, Schirmer II can be applied, which uses anaesthetic but includes stimulation of reflex tearing by nasal irritation with ammonia vapour, onion vapour or a cotton applicator. A reading of 5 mm or less in 5 min is indicative of aqueous-deficient dry eye. There are numerous variants of the original Schirmer tests; despite many reservations about its meaning, it is still generally accepted that it gives useful information. The cotton-thread test is a variation of the Schirmer test, using a loosely-twisted thread which is less irritating to the eye (and less likely to provoke reflex secretion); the steady-state output of the lacrimal gland is being assessed, whereas without anaesthetic (and hence with the irritation of insertion of the paper) the reflex response of the lacrimal gland is probed. The disadvantage of the thread method is that because it does not provoke tearing, it measures only the fluid already available in the conjunctival sac.

The normality of tear volume is also estimated from meniscus height or meniscometry where meniscus curvature is calculated from reflection of a striped target.

The measurement of evaporation itself is possible under clinical conditions, but no commercial instrument exists. One instrument, which calculates evaporation rate from the rate of rise of humidity inside an eyecup, is currently used in assessment of dry eye patients in the clinic.

The use of the Fluorotron Master to measure turnover time or clearance rate of tears from the eye has been mentioned above in Volume Flow of Tears Into and From the Eye.

The thickness of the lipid layer is assessed from the interference colours seen on reflection of light using an instrument such as the Keeler Tearscope. Meibometry, in which the lid margin is blotted with a tape and the change in transmission of the tape due to the oil picked up is measured, can give information about the availability of oil, and if the lid margin is first cleaned of oil, about delivery from the glands. This is in fact the only currently available objective measure of meibomian gland output.

Laboratory Tests
These are generally more time-consuming or involve the use of more complex equipment than clinical tests. Samples of tears or other secretions must be taken, paying attention to the collection site or conditions. Thus the protein composition may be analysed by high-performance liquid chromatography, although this will show only the major proteins and not minor components, which may have to be detected by assaying collected column effluent fractions for enzyme activity or other functions. Alternatively, polyacrylamide gel electrophoresis can give detailed information about the protein composition of tears.

Tear osmolarity is a good indicator of high rates of evaporative loss, and can be measured on collected tear samples. The Clifton nanolitre osmometer (depression of freezing-point principle) is still considered the gold standard method despite its many practical difficulties; the Wescor vapour pressure osmometer is simpler and could be used in the clinic, but may have a considerable reading error with tear samples < 1 |xl, which one must use to avoid reflex lacrimation and dilution of the tear film during collection [59]. A simple, rapid and very sensitive commercial instrument is promised, but was not available at the time of writing.Tests of Quality
Whereas one can, by detection of deviations from normal composition, conclude that the tears are of less than the required quality to maintain stability and function, it is much harder to devise tests to establish whether the performance of a sample of whole tears is of the required quality. Perhaps the only such test is tear ferning. A small sample of fluid tears (about 2 |xl) is placed as a droplet on a clean microscope slide and allowed to dry, then examined under the microscope . Viewed at X50 to XI00, feathery patterns of salt crystals are seen, and the degree of complexity of these correlates well with other measures of tear quality or performance. Although often called the 'mucus ferning' test, it is in fact less dependent on mucus content than on the balance of electrolytes, but much more exploratory work needs to be done before it can be considered altogether reliable.
Compositional tests as indicated in 'Laboratory Tests' can be applied to show that some assumed best or 'normal' assembly of components is present. But this is complicated in that it changes to some extent with age or other physiological states (e.g. the menstrual cycle). Vital staining can also give information about the completeness of the film. Thus, in the same way that fluorescein is used to indicate breaks in the epithelial surface, staining with rose bengal is considered to depend on breaks in the mucous layer covering the ocular surface, revealing the unprotected and presumably unlubricated epithelial surface beneath.

Physical properties such as viscosity or surface tension can be measured if adequate volumes of tears are available, and can indicate the normality of the tears.

Conclusions
The normal tear film is metabolically functional, protective, and nutritive. Problems arise if its stability is compromised by anatomical factors such as the improper meeting of lids or the closeness of their fit to the globe, blockage of the drainage routes, surface roughness or epithelial damage. Inflammation involves the secretion into the conjunctival sac of many additional components, of both tissue and serum origin, and these can materially alter the physiological functioning of the tears. These factors must all be taken into consideration in planning surgical procedures.

Contact lenses applying removing and cosmetics

2010-01-26T11:25:00.000-08:00

contact lenses applying removing and cosmetics

Periodic cleaning is the important part of care of contact lenses, however, unfortunately far not always observed. The tendency to formation of adjournment on lenses causes of their cleaning. Irregular cleaning accelerates formation of adjournment and leads to a number of negative consequences. For the best understanding of functions of cleaners it is necessary to understand the mechanism of formation of adjournment at first. Adjournment on lenses are defined as a cover, a surface or the matrix formation which is not washed off by a plaintive film at blinking.

The factors influencing formation of adjournment.

It is important to mean, that such factors set. Four of these factors the following:

Change depending on the patient;
Material of which the lens is made;
Mode of care of lenses;
Environment.

Changes depending on the patient.

Such changes are rather considerable. The form and degree of adjournment at each patient the different. Some patients seldom clean lenses and, nevertheless, do not observe increase in adjournment. Others apply a cleaner some times in a week and are compelled to change often lenses owing to formation of adjournment. At the third adjournment during very short time are formed.

Adjournment

Any cover, surface or the matrix formation which is not washed off by a plaintive film at blinking. Distinctions in formation of adjournment cannot be always carried into the account of leaving of the patient for the lenses, these distinctions can speak also features of individual chemistry of a body of the patient. Just as some people have predisposition to formation of a tooth stone or hardening of the arteries, some people have predisposition to formation of adjournment on contact lenses.

Material for manufacturing of lenses.

Formation of adjournment also depends on a material of which lenses are made. Adjournment are usually formed on RGP and firm lenses while albuminous adjournment are more likely formed on soft lenses. Soft ionic lenses with the high maintenance of water absorb much more fibers, than not ionic soft lenses with the low maintenance of water.

Leaving mode.

The leaving mode can influence formation of adjournment also. The patient not capable regularly to clean a lens more likely receives accruing adjournment. Besides, the system of thermal disinfection leads to acceleration of formation of albuminous adjournment on soft contact lenses.

Environment.

Environment factors: air pollution and flower pollen can influence also type and degree of formation of adjournment on lenses. The dehydrated medium leads to formation of adjournment at some patients. Additional factors include: cosmetics application, for hands and some preparations for an oral cavity.

Clinical value of the adjournment formed on contact lenses.

Researchers have come to conclusion, that in six months of carrying of soft contact lenses of 50 % of clinical symptoms depend on formation of adjournment. Adjournment on the contact lenses used by patients, speak action of one or several above-stated factors.

Dryness of an eye often name insufficient quantity of tear for maintenance of a comfortable condition of an eye. More the general definition of dryness of an eye says, that this disease is caused or insufficient volume of a plaintive film, or infringement of quality or stability of a plaintive film. If the plaintive film well functions, it provides comfortable carrying of contact lenses. Infringements of a plaintive film, in turn, are connected with inflammatory reactions, changes in integrity of a surface of an eye and difficulties for comfortable and safe carrying of lenses.

Evolution of our representations about dryness of an eye

One of attempts to classify clinical displays of dryness of an eye has been made Holly and Lemp which have allocated five categories of a syndrome of a dry eye. The first category - deficiency when is broken wettability of a surface of an eye. The second stability of a plaintive film is broken because of insufficiency or a layer. The third category - deficiency of a liquid when in a plaintive film the volume of a liquid phase is lowered. The fourth category - anomaly of a century or infringement of function of blinking when distribution of a plaintive film on an eye surface suffers. Last, fifth category - anomaly of a surface of an eye when the changed surface breaks stability of tear. Though classification of a syndrome of a dry eye was intuitively useful at the characteristic of various clinical types of dryness of an eye, the instructions on importance of a plaintive film as surface-active layer which the physical, physical and chemical phenomena or some conditions of a surface of an eye can be broken nearby became its greatest achievement. As the understanding of pathological conditions of dryness of an eye has improved, definition of disease of a dry eye became more detailed. The recognition of a role of plaintive secretion and its dependence on integrity of a surface of an eye has changed this definition. The recognition also an integrated role of an inflammation both plaintive bodies, and eye surfaces has placed new accents in definition of dryness of an eye. The best practical definition of dryness of an eye sounds today so: Dryness of an eye is a dysfunction of interaction of a surface of an eye and plaintive glands which leads to inflammatory secretion of necessary components of a plaintive film with the subsequent damage of a surface of an eye, and also to occurrence of symptoms of irritation of eyes and discomfort.

Syndrome of a dry eye

The dry eye caused by deficiency of a water phase in tear. As our understanding of clinical signs of dryness of an eye has improved, has improved as well understanding of anomalies of a plaintive film, plaintive glands and an eye surface. Completion of volume of tear was a therapy basis for many years. With that end in view applied various types of liquids, including more difficult combinations of polymers, such as greasing substances. The recognition of that fact, that a plaintive film it is not simple water, and the structure consisting of three components: a liquid and elements, has led to an estimation of function of tear not only as to a washing and protecting liquid, but also as auxiliary and supporting film for an eye surface. The tear chemical compound was defined taking into account structure of electrolits and other dissolved substances developed by plaintive glands or getting to tear owing to leak from vessels. Low level of the proteins typical for a plaintive liquid was found out in patients with dryness of an eye in tear. Research of interrelation of dryness of an eye with a system condition allows to judge predisposition and the starting mechanism of development of the inflammation conducting to a dry eye. It has helped to explain the big disease of dryness of an eye at men and women in advanced age and at women in a postmenstrual pause. Moreover, data speak about especially at their use in the form of local therapy, can render anti-inflammatory effect and improve symptoms of a dry eye. Clinical tests of androgen-containing preparations now proceed.

The dry eye caused raised tear of tear Raised evaporation which involves instability of a plaintive film and dryness of an eye, is observed at disease of glands, carrying of contact lenses and at infringements of mobility of a century. The raised evaporation of tear is often aggravated with deficiency of a liquid at dryness of an eye as these illnesses often arise simultaneously.

Dryness of an eye and contact lenses

Successful carrying of contact lenses depends on integrity and stability of a plaintive film. Finally, the plaintive film is responsible for greasing and hydration of contact lenses. Hydration of a lens and a tear exchange under a lens provide transport of necessary quantity of oxygen to a surface of an eye and removal from an eye surface. Contact lenses increase evaporation of tear and can accelerate occurrence of dryness of an eye. Long carrying of contact lenses can reduce sensitivity of a cornea and break normal balance between reflex secretion of tear and an eye surface. Thus, the less contact lens changes normal sensitivity of a cornea and tear physiology, the better shipping of a lens. One of the most widespread reasons of intolerance of contact lenses and refusal of their carrying is dryness of an eye and the instability of a plaintive film caused by a pathology of glands. The control over a condition of eyelids and improvement of stability of tear can eliminate available problems and to improve shipping of contact lenses. Carrying of contact lenses will be successful at patients with a normal plaintive film and function of eyelids. The most transferable and safe contact lenses will be lenses which is better are compatible to a plaintive film and least break stability of a normal plaintive film.

Interrelation of a contact lens and quantity/quality of a plaintive film which it is washed, is a contact lens solving for safe carrying. The understanding of a clinical picture and changes at dryness of an eye can help to avoid or prevent intolerance of contact lenses and to improve results of carrying of contact lenses. Both it is important to doctor, and patient to reveal possible risk factors of development of dryness of an eye and to compensate as far as possible infringements of stability of a plaintive film.

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Presbyopia Treatment Surgery Symptoms Signs Causes

2010-01-26T11:23:00.001-08:00

Presbyopia Treatment Surgery Symptoms Signs Causes

The presbyopia also known as illness of short hands, is the term describing an eye in which the natural crystalline lens does not accommodate. Accommodation is an ability of an eye to change the focal length. In its basis ability of a crystalline lens to change the optical force by change of the geometry - thickness in the central part, curvature of forward and back surfaces, position in an eye lays. Approximately at 40-year-old age the crystalline lens becomes less flexible, loses the ability to change the form and position, and accommodation is gradually lost. It is normal process which tests everyone.

The majority of people with normal sight in a youth is closer by 40 years starts to pay attention to difficulties at reading of the texts, printed small a font. The font seems low-contrast, blurring. Eyes quickly get tired. First text removal on more distance from eyes helps the majority of people. But as a result it appears, that without points or contact lenses not to manage any more. This process can proceed up to 65 - 70 years that will be shown in necessity to wear more and more strong plus glasses or lenses. At some people, with the latent far-sightedness, sight afar after 40 years too worsens. Laser or surgical correction Here can already be necessary. However, people with short-sightedness of weak and average degree do not notice influence presbyopia as well see close.

Signs symptoms

It is difficult to make out details at work close

The small text looks low-contrast

For reading brighter and direct illumination is required

To read the text, it is necessary to take away it on the big distance

Weariness and pressure of eyes at reading

The presbyopia is found out at sight and refraction check.

Treatment

Treatment presbyopia is simple, but the hobby completely depends on age of the patient, style of a life, a trade. If sight afar good, also there are problems only with sight close, most easier to choose glasses. In other situation (with correction bifocals will be necessary for a distance) or two pairs points - one for a distance. Other variant is a so-called sight: one eye is adjusted on sight afar, another - on sight close. It can be spent contact lenses or surgery.

The presbyopia (age far-sightedness) is a pathology of a refraction of an eye connected with the years. Approximately by 40 years of a life the person has sclerous changes in a crystalline lens that leads to consolidation of its kernel so, ability of an eye to accommodation is broken. Therefore to the person points for reading are required. This process progresses with the years, that plus of dioptries for reading leads to increase, and approximately by 60-70 years the crystalline lens absolutely loses ability to change the radius of curvature and people should dress points about plus lenses and separate points for "distance" (for example, for reading of a dioptry and for a distance - for people not suffering neither short-sightedness, nor a far-sightedness). It is inevitable age process which to stop it is impossible. Age changes differently pass for people with different pathologies of a refraction.

The presbyopia with a congenital far-sightedness is shown more often in sight decrease, both for reading, and for a distance, practically simultaneously. Thus, presbyopia aggravates a congenital (axial) far-sightedness.

Presbyopia at people with short-sightedness, especially with small, are in the most favourable if it is possible so to say, position. This minus compensates loss of accommodation and removes the moment of putting on of points. Patients with short-sightedness, most likely, will not require at all similar points. People with such degree of short-sightedness wear glasses for a distance and remove points for work close.

The presbyopia, or as her often name, senile sight traps the person, as a rule, on the middle of its course of life, is elderly about forty years. There is inconvenient a reading, especially in the evening. Sight afar usually remains normal. As a rule, presbyopia at comes earlier, rather than miopia. Many people perceive sight worsening with the years as natural result of ageing. "I am already old, they and consequently sight quite often brings me speak." It is considered, that with the years crystalline lens fabrics are condensed also it ostensibly does not allow a muscle to change curvature of a crystalline lens to focus an eye on nearby object. Followers have visually proved, that widespread opinion on inevitable deterioration of sight with the years, wrongly. It was neatly expressed in P.Bregg's this occasion: " The age does not weaken eyes. The age is a measure, instead of force. The age is the best pretext which they can find to justify the wrong vital habits which were the reason of deterioration of sight. ".

Presbyopia considered as one of forms. In the theory he, as is known, did not consider a crystalline lens as the accommodation factor, therefore its hardening should not affect with the years accommodation in any way. The reason of deterioration of sight at presbyopia sees in the mental pressure caused by effort to make out nearby objects. Some other opinion adheres one of followers. He considers, that the unique reason of approach presbyopia is a wrong food. "Up to today, he writes, it was supposed, that with achievement by the person of middle age of an eye naturally change the form (being slightly compressed), doing thus inconvenient vision of NEARBY objects and causing presbyopia.

It is considered as causing inconvenience, but a necessary payment which we should bring for so long existence in this world! This problem dares a glasses wearing with convex lenses. Very much few of millions suffering senile sight (or their medical advisers) realise, that for this change in visual possibilities their WRONG HABITS of a FOOD within 45-50 years of their life answer; but it, undoubtedly, illness, and sight of many suffering from presbyopia can be restored simple introduction of a reasonable diet and performance of several simple exercises on eyes. To underline vital communication between food and sight, it is enough to inform, that there are data on set of authentic cases of the bad sight cured by simple STARVATION. The clarification which has improved at starvation leads the collected stocks of products of ability to live which hammered in muscles and the blood vessels surrounding eyes. As result, muscles relax, and sight improves ".

To the book "System Bregg for sight improvement" pays attention to importance of receipt of enough of vitamins in an organism of people of an average and advanced age. She writes: "Senile sight is in most cases directly connected with a vitamin C lack, and there where there is a lack of one vitamin, deficiency of other important vitamins" is always observed. Last phrase of the author should be understood so: by special researches it has been established, that efficiency duty of vitamins can increase or decrease depending on presence of certain substances, for example, other vitamins. So, it has been defined, that efficiency of some vitamins of group In and vitamin C at their combinative reception. In more details you can familiarise with questions of the correct organisation of a diet in section.
System Bejtsa recommends at presbyopia:

1. Daily to read a small font at good and at dim illumination. Reading can be spent as without points (if it is possible), and to them. The Same measure is considered an effective prophylactic against presbyopia if it to spend daily, since 35 years.

2. To use correctly organised diet. It is recommended to reduce a share of sweet and fat dishes in a diet and to increase a share bitter by taste and fresh vegetables.

3. As considers presbyopia as one of forms (far-sightedness), you should follow all volume that is written in the previous section for the exercise, intended for them.

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Does laser eye surgery disqualify you from being a military pilot?

2010-01-25T10:37:00.000-08:00

Answer

--------------------You can answer in comments--------------------

Does laser eye surgery disqualify you from being a military pilot?

On the statistican, every third person a sign with a problem of bad sight. Short-sightedness and a far-sightedness - these concepts are old as the world. And throughout all history people search for ways of laser eye surgery military pilot struggle against them.

What harms to our eyes?

Overstrain of eyes - long and intensive visual loadings at a short distance, bad illumination of a workplace, wrong planting at reading and the write letter, excessive hobby for the TV and the computer. Add in this list stressful situations, smoking … the Factors influencing decrease of sight it is valid much.

But it is not necessary to forget, that the main enemy of our eyes are wrong methods of correction of sight.

If for laser eye surgery work are at a short distance used incorrectly picked up (too strong or weak) points or contact lenses is provokes an overstrain of a muscle of an eye and promotes short-sightedness increase.

Do not adjoin directly to eyes so, do not provoke occurrence of eye diseases.
By means of points it is possible to change the image.
Points do not demand constant, careful leaving.
Points are a most simple and widespread way of correction of sight.
To people with bad sight confidently to feel itself, they need to be carried constantly (or «on itself», or with itself).
Incorrectly chosen glasses often become the reasons of frustration of nervous system, headaches and unconscious laser eye surgery military pilot conditions.
Sight in points not absolutely natural: the form and the size of subjects can be deformed.
Handles of points limit lateral sight.
Points can be lost during the most improper moment or even to break.
Points can spoil appearance.
Points reflect light. Especially it is unpleasant during dark time of days when because of this effect there can be a time blinding.
Mist over at temperature change.
Do not approach at whom the difference between sight of eyes makes more than 2,0 D.
Contact lenses
Pluses Minuses
Sight in contact lenses more natural, than in points. The size and the form of subjects are not deformed.
Contact lenses move together with eyes, therefore there are no image distortions as it happens at a glasses wearing.
Carrying of the contact lenses intended for correction of sight, does not influence in any way appearance.
Do not limit lateral sight.
Approach also to those people at whom the difference between sight of eyes makes more than 2,0 D.
Adjoin directly to an eye cornea, therefore can provoke development of its diseases.
Carrying of contact lenses demands regular checks of sight from the ophthalmologist.
Do not laser eye surgery replace points completely. In addition to lenses at least one points necessarily will be necessary to you.
Contact lenses are necessary for putting on and removing every day, carefully to disinfect. Lenses of long carrying cannot be recommended the majority of people.
At carrying of contact lenses the "mote" which has got to an eye, will hurt and will demand to repeat procedure of snimanija-clothing of lenses. Or you should take advantage of points.
Silicone as a part of lenses can become the laser eye surgery military pilot allergy reason
On official data of one of the companies-manufacturers of contact lenses, long carrying of lenses becomes the reason of complications and deterioration of sight at 56 % of the patients constantly using this way of correction of sight
Contact lenses cannot use during cold and some other diseases.
Contact lenses need to be changed periodically
Sooner or later there is a refusal of carrying of contact lenses as quality of correction of sight decreases
Sight correction by a technique lasik

The result of correction has all those pluses which are at ideally good sight.
Relieves of all minuses connected with extras for improvement of sight (points, contact lenses).
Laser correction is the most effective and safe way of correction of the sight, recognised as leading ophthalmologists of all world.
Correction of sight by means of laser correction is possible on both eyes simultaneously.
Laser correction provides demanded result at the minimum risk of occurrence of by-effects;
Has a wide spectrum of application - in the absence of contra-indications eliminates short-sightedness (to - 15,0 D), a far-sightedness (to + 5,0 D),

Long-term supervision over patients have shown - laser correction does not cause sight deterioration.
Has age restrictions. As at children's and teenage age bodies of sight at the person are yet definitively generated, and sight can vary, eksimer-laser correction spend after 18 years.
Laser correction does not protect from an age far-sightedness. Therefore at its carrying out after 40-45 years, necessity for points for work at a short distance (at reading, sewing) remains.
Has certain contra-indications to application (various diseases of eyes and the general diseases, specific features of a structure of an eye, etc.)

5 main advantages of laser correction of sight on a method lasik:

1.

It is not necessary to endow time. Laser correction passes absolutely without serious consequences, under local anaesthesia (eye drops). Influence lasts 20-60 seconds. Correction is spent is out-patient, you will be free"this very day.
2.

It is not necessary to wait after correction «in a pitch darkness» while sight will be restored. The world at once «will start to come back» to you. With each minute more and more accurate and bright. Usually in some hours the person already sees much better, than laser eye surgery before correction.
3.

It is not necessary to suffer a pain. Laser correction on a method lasik and the regenerative period after it pass without serious consequences. Some time is possible sensation of the alien body, the laser eye surgery military pilot branch raised tears. And to suffer a pain to you it is not necessary.
4.

It is not necessary to limit itself. No restrictions - neither on physical, nor on visual loadings - after laser correction are present. On the contrary, you will feel yourselves freely, as never! Not without reason laser correction recommend to people who test the raised loadings: to parachutists, pilots.
5.

It is not necessary to spend a fantastic sum. Actually cost of laser correction quite justifies itself - for years of carrying of contact lenses you will spend not smaller money. You do laser correction once and for all. And if to consider, that its result does not change in due course, your expenses will quite pay off.

Alternative ways of treatment of sight:

1.
Bioadditives do not pass clinical tests, and are not medical products. Vitamin substances containing in them can have positive an effect on a condition of eyes, but do not influence in any way improvement of visual functions.
2.
Courses of restoration of sight on author's methods. Include daily multilevel complexes of exercises, trays for eyes, massage, meditation, diets. The regularity and intensity of passage of a course promotes a voltage reduction in a visual muscle. The effect of courses is in many respects caused by the general condition of an organism, and also patience and a constancy of the person. It is faster not courses, and a way of life.
3.
Punch glasses. Like the above described exercises, such points weaken pressure of eyes at intensive visual loadings. However it is known, that is frequent at using such points change of a habitual field of vision, deterioration of conditions of binocular sight is marked. Neither short-sightedness, nor a far-sightedness do not eliminate such points. Besides, in modern realities to avoid fakes at purchase of such points difficult enough.
4.
Carrots, bilberry and others «natural sources» vitamins useful to eyes.
The bilberry helps to keep visual acuity, promotes removal of weariness from eyes after work at artificial light, with the computer, TV viewing. The bilberry contains the antioxidants, helping to restore many functions of an organism and powerfully to counteract ageing. However constantly to use in food the necessary quantity of a bilberry it is problematic enough, and extracts and preparations on the basis of a bilberry never can replace a laser eye surgery military pilot unique complex of the useful substances containing in fresh berries.
There is an opinion, that sight can be improved the carrots use. Carrots contain provitamin A and carotin which participate in processes of restoration of function of eyes. At a lack of this vitamin the person badly sees in twilight. Vitamin A has no other relation to eyes. It is possible to eat carrots ton, but visual acuity from it will not improve at all.

How to the person to make a correct choice?

The method of correction of sight should be appointed only the qualified doctor-ophthalmologist on the basis of data of complex diagnostic inspection of all functions of an eye. It will laser eye surgery help to avoid errors and the errors, which price - loss of qualitative sight.

To whom to entrust restoration of the sight?

At first signs of deterioration of sight it is necessary to address urgently to the ophthalmologist. Absence of correction or correction by incorrectly picked up points or lenses can lead to fast deterioration of sight and development of progressing short-sightedness. And such serious eye diseases as the glaucoma, a cataract or a layer of a retina without timely intervention of the doctor have irreversible character and lead to blindness. Trust the sight to professionals!

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Is laser eye surgery is good for whose having sight problem? Or is there any exercise to reduce the sight?

2010-01-25T08:38:00.000-08:00

Question

Answer

Is laser eye surgery is good for whose having sight problem? Or is there any exercise to reduce the sight?

Sudden loss of sight by one of eyes (full or partial when in sight there is a dark stain) which is not accompanied by a pain. Comes as a result of blood circulation infringement in an eye retina. It is characteristic for people with the general infringements of blood circulation.

To cause first aid, it is possible to press laser eye surgery some times through an eyelid approximately, it promotes expansion of vessels.

Occurrence before "veil" eyes, sensation, that all of you see as though through a sheet of water, at eye movement "flashes" or "lightnings" are observed. These symptoms are characteristic for a retina. Can arise after strong pressure.

What to do? Ask to cause somebody first aid. Transportation in lying position is necessary for you. Both eyes need to be closed a bandage.

Sight fall for no apparent reason only close at preservation of usual sight afar. Can arise at application of the medicines containing atropine and its analogues, or as a result of infection development (a botulism, a diphtheria)

What to do? To stop visual work. Urgently to address to the doctor.

That you did not have sudden problems with sight, it is necessary to pass once a year diagnostics. We pay your attention, that full enough picture of a condition of visual system can be received only at survey on the modern equipment. It allows not only to ascertain, but also to predict occurrence of eye illnesses. The doctor will tell about what problems can trap you, and will define, what medicines in the presence of laser eye surgery diseases to you are necessary for having near at hand for the urgent help.

Trauma or burn reception is always an extreme situation which does not leave time for reflexions that it is necessary to undertake, or on information search. Therefore we advise to you to remember, as needs to be conducted in similar cases. After all if it is a question of damage of eyes, roads happen literally seconds.

Chemical burns as some substances can already be absorbed in an eye within 15 seconds are most dangerous in this sense. Burns are caused by alkalis (a water solution of ammonia) and acids (acetic acid, nitric).

If acid or alkali have got to an eye, it is necessary to begin immediately its washing under flowing water (over a fountain, under the crane, from a teapot or from a cup, etc.). Thus eyelids should be as much as possible opened. General time of washing should make 30 minutes.

If you had a first-aid set it is better to wash out an eye specially prepared solution. For neutralisation of acids it is 2 % a soda solution, for neutralisation of alkalis of 2 % a solution of boric acid (or 1 % a solution of acetic acid). Such solutions turn out at soda cultivation (a powder of boric acid) or 100 ml (third of glass) 9 % of vinegar on 1 litre of warm boiled water and move under pressure by means of a laser eye surgery pear or a syringe without a exercise to reduce needle. If eyelids cannot be opened widely, to put on a syringe a thin tube and to get it under eyelids from an external corner of an eye.

After washing it is necessary to address to the doctor or in traumatologic point.

At thermal burns, that is the burns caused by a hot liquid or a flame, weight of a condition depends on their temperature.

In case of a burn it is necessary to give to the victim anaesthetising, to put to eyes a cold damp compress and urgently to send in an eye hospital or traumatologic point in lying position.

Even easy (in our opinion) eye contusions can lead to serious changes, up to sight loss. Therefore we do not advise to you to make to the diagnosis independently. Do not think, that if in some days the bruise has started to resolve and the eye is not ill, normally moves and sees, how usually, at you everything is all right. Consequences (in the form of damage of a retina or formation of development of such disease as a glaucoma) can prove in some weeks or even years.

In case of a trauma it is necessary to apply a bandage both eyes, if necessary to give anaesthetising and urgently to send the victim in an eye hospital. From that, how much quickly to you it managed to be made, can depend directly what sight to you will manage to be kept.

To each of us the mote got to an eye. Usually removal of a similar alien body does not cause difficulties. But if it is not washed away by tear and it does not manage to be got by laser eye surgery means of a wadded stick, and the eye continues to be ill, there is a raised photosensitivity, it is necessary to address to the expert.

It is especially important, if before to you something has got to an eye, you without necessary protection were engaged in metal working (processing or similar works). In that case the smallest shaving can get and in an eye. Many do not consider "mote" dangerous as in some cases eyeball wounds are not accompanied by a bleeding and visual infringements. And it can cost much to you, and as in direct, and figuratively.

In case of hit in an eye of an alien body it is necessary to apply a bandage both eyes and urgently to send the victim in an eye hospital in lying position. If necessary to give to it anaesthetising.

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How bad do your eyes have to be to not be able to get laser eye surgery?

2010-01-25T07:06:00.000-08:00

Answer 1

Answer 2

How bad do your eyes have to be to not be able to get laser eye surgery

Distribution of personal computers, plasma panels of TVs and monitors force ophthalmologists to reflect on preventive maintenance and removal of a computer visual not be able to get laser eye surgery syndrome (Computer Vision Syndrome) which is often combined with a syndrome of "a dry eye».

The sight of the person generated during long evolution, in the XX-th century has appeared is a little adapted for work with the computer image. The screen picture bad eyes have differs from natural that it self-shone, instead of reflected. Visual loading essentially increases because of necessity of constant moving of a look from the monitor screen on the keyboard and the paper text. Frequently the workplace is correct and rational to organise impossibility (patches of light on the screen of the monitor from external sources, wrong distance from eyes to the screen, the unsuccessful choice of colours, excessively big brightness of the screen) aggravate a situation.

The greatest general exhaustion is caused by work in a dialogue mode. Special loading on sight is represented by the computer drawing - performance and a correcting of working drawings by means of the not be able to get laser eye surgery personal computer.

The problem consists in the following: many of us spend till 8 o'clock a day in front of the computer, on work, houses or in game club. Even you now read this material, looking at the monitor.

In risk group «computer syndrome» - active users of personal computers at the age from 18 till 40 years. Complaints of the people spending the most part of bad eyes have working hours behind the screen of the monitor, it is possible to divide on two groups:

- The optical

Visual acuity decrease;

The slowed down refocusing from near subjects on distant and back (accommodation infringement);

Doubling of subjects;

Fast exhaustion at reading.

- The physical

Burning in eyes;

Feeling of "sand" under centuries;

Pains in the field of eye-sockets and a bad eyes have forehead;

Pains at movement of eyes;

Reddening of eyeballs.

Research of visual functions at people, within several years of personal computers working behind screens, has revealed decrease in volume of accommodation in comparison with age norm and the big frequency of short-sightedness in comparison with people of the same age, not connected with the computer. At the persons showing the above described complaints, all these changes have been not be able to get laser eye surgery expressed more sharply. Research of influence of the work with the display on sight has shown, that for a labour shift there is a reduction of volume of accommodation, and at some users develops time (so-called false) short-sightedness.

In a modern life without the computer not to manage any more. But how from «inevitable harm» to transform it into really useful assistant?

Do not neglect visiting of the ophthalmologist, and be not engaged in self-treatment.

Use special drops for the eyes, replacing tear

Limit an operating time behind the computer no more than 4 hours per day

Do obligatory pauses in an operating time at a short distance every 20-30 minutes

The correct organisation of a workplace and rational operating mode has great value.

Especially important observance corrected for children and teenagers when refraction formation has not developed yet and excessive loading can lead to short-sightedness development. Children are recommended to spend time at the personal computer only with the informative purpose

Get special points with progressive lenses in which the zone of clear vision corresponds to look moving at work on various distances. Application of such points for intensive users of the personal computer has given decrease in visual exhaustion and improvement of indicators of accommodation in comparison with usual points at 85 % of workers.

At observance of the listed recommendations the quantity of the errors made by the operator, especially in second half of day decreases, irritability and headaches leave, the emotional condition improves. In points with the computer filter comfortably in a premise shined with artificial light sources, (especially luminescent lamps) since points improve spectral structure of light getting to eyes. In them it is comfortable in the street, in cloudy weather - it is visible more accurately and more contrastly, and in a sunny not be able to get laser eye surgery day they do not pass very active short-wave part of a spectrum in eyes. Thus, points with the computer filter can be recommended for constant carrying. And it is very important, for more than 50 % of programmers - people in points.

ALL RECOMMENDATIONS SET FORTH ABOVE SHOULD BE DISCUSSED WITH THE OPHTHALMOLOGIST!

Dryness of eyes rather widespread problem among users the computer. Consider, that the reasons of a wide circulation of dryness of eyes among users of the computer a little:

More rare blinking of the user at work on the computer (frequency of blinking makes about third of usual frequency);

Widely opened eyes at image examining on the monitor, it leads to increase in speed of evaporation of tear from an eye surface.

For syndrome reduction «a dry eye» at work on the computer it is necessary to provide correct working conditions, first of all:

Correctly to establish the monitor screen (the centre see on 10-20 below eyes of the user)

To choose correctly distance (not less than 50 see) to the monitor

Besides, users of the computer should be reminded of necessity more often to blink at first signs of dryness of eyes

It is necessary as from time to time to close eyes and to make some get laser eye surgery circular (rotary) movements

It is useful to arrange 2 - 3 minute breaks at work on the computer, focusing a sight at a long distance.

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Laser eye surgery correction reviews

2010-01-25T06:12:00.000-08:00

Laser eye surgery correction reviews

About riches of world around, about sounds and paints, smells and temperature, size and about many other things we learn thanks to bodies laser eye surgery correction. By means of sense organs the human body receives the various information on a condition of the external and internal environment in the form of sensations.

The Laser eye surgery reviews sensation is the elementary mental process consisting in reflexion of separate properties of subjects and the phenomena of a material world, and also inwardnesses of an organism at direct influence on corresponding receptors.

Sense organs receive, select, accumulate the information and transfer it in a brain every second receiving both laser eye surgery correction processing this huge and inexhaustible stream. As a result there is an adequate reflexion of world around and a condition of the organism. In the given work the question of "Development of sensations" will be investigated.

1. Features of development of hearing and sight at newborns

Within centuries on the majority of questions the answer was categorical: the newborn does not see and does not hear. It was the well-known theory «the child - a digestive path» which asserted, that the child at least within several weeks reacts only to stomach requirements; basically it is necessary to feed and change clothes of it only.

It - as pure wax on which the adult can engrave all as a white sheet of paper on which it is possible to write, everything. Besides, spoke: «Being born, the child so is attacked, that is in full confusion». In a word, the omnipotent adult appeared before absolutely unarmed and on what not reacting newborn.

But, maybe, these theories were put forward basically by men (doctors and scientists) whereas the opposite opinion laser eye surgery correction proceeding from women, had few chances to be heard.

Presently there was a full revolution in sights at the newborn: he hears, sees, possesses feeling of sense of smell and perceives! It is the new theory accepted many. It is possible to continue the long list of the perceptions, attributed to the child since the birth.

Opening do not become in one day (unless in exclusively rare cases). In any area of opening are a fruit of the long researches undertaken by numerous researchers simultaneously in many countries.

In the last 20 or even 30 years all over the world are marked research boom; researches are directed on finding-out of possibilities of the newborn. That you could imagine amount of works, I will tell: on last world congress devoted to chest children which has been called for the purpose of summarising of modern knowledge of the child (till a birth, during it and after a birth), there were 1500 experts of 20 nationalities from the different countries; 500 messages have been made.

So, the newborn is more developed and susceptible, than it was considered earlier, and in many areas since sensual perception.

Sight. The child sees since the birth, but its sight in 20 times is worse, than at adults; it still indistinct, indistinct. The child sees only outlines of subjects (mobile and motionless), being on distance only 25-30 sm from his eyes. But it is enough of it, that the newborn reacted to various illumination: if light too bright, he tests inconvenience, blinks or closes eyes.

The Laser eye surgery reviews kid distinguishes brilliant and red subjects; it can look after movement of a brilliant red sphere. It has been noticed, that from first days of the newborn the oval form, a moving subject with red and laser eye surgery correction brilliant stains involve. It at all the rebus, simply such oval corresponds to a human face. The child can watch movements of such "person" and if thus to it talk, he blinks.

But though the child also pays attention to the form similar to a human face, it does not mean, that he learns someone from the people surrounding it. On it more many time is required to it.

If to generalise data of researches (when and how the child starts to distinguish mother or the person who is looking after it, and also other people) it is possible to draw a conclusion, that the child learns mother on a smell at the age of 10 days, on a voice - through 5 eyes - at the age of 3-5 (data vary depending on research methods). It is unconditional, difficult to differentiate various sensations and perceptions (visual, acoustical or olfactory); has reached that one of researchers, to reveal visual perception, has placed mother behind a mirror without an amalgam.

But we will return to our newborn. It has been noticed, that it difficult drawings, than simple more interest. In the first days if it to show two sheets of paper - one grey, and another - in a black-and-white cage, he will look at the second sheet. It have defined, observing of the child through an aperture in the screen - it is visible, that in its cornea the checkered leaf is reflected. Means, he looks at it.

Sight of the newborn is developed insufficiently as till a birth it did not have a possibility it to take advantage (the truth, some scientists consider, that already in a womb of mother the child reacts to bright light;). But sight of the child will quickly develop. The kid tries to look even at night; in darkness it opens and closes eyes, looks around (such supervision has been spent by means of infra-red beams).

Children considerably differ from each other in that, as to visual activity; the impression is made, that one children waste time on others.

Rates of development of the child in all areas are various throughout all period of the childhood.

Some words in summary. Quite laser eye surgery correction often it seems, that eyes of the newborn mow, as its eye muscles are insufficiently developed to co-ordinate movements of eyes (but in most cases it really only seems).

Hearing. At the child it is developed more than sight, and it is normal, as the newborn heard during the pre-natal life (anyway, in the last 2) much. Hence, there is nothing surprising that the baby does not shudder when claps a door or strong noise is distributed; as his ear is already trained, he can distinguish close and far noise. Even when the kid sleeps with the compressed cams and near to it are whispered, he starts to turn and blink. If silent conversation proceeds, the child starts to potter and wake up.

Certainly, Laser eye surgery reviews he learns human speech as already heard it till a birth; in this opinion all researchers, but in a question whom he hears better - the father or mother converge, opinions disperse. The majority of doctors considers, that, still being in a uterus the child hears a voice of the father as he perceives low sounds is easier is better, and being on light, newborn becomes more sensitive to higher sounds, a voice of mother.

At last, it has been noticed, that when round the child it is very noisy, it stops up ears literally and thus isolates itself from environment. One of researchers noticed, that the child with whom carried out the difficult test for it, has started to shout, then has suddenly become silent and has fallen asleep; when the test has been finished also equipment switched off, the newborn has immediately woken up and has again started to shout.

Taste. To the newborn 12 from a sort; if to drip to it on lips of sweet water it looks rather happy and if - a lemon juice it will make a grimace. The child since a birth distinguishes sweet, salty, sour, bitter. Its sugar calms, the bitterness and acid raise.

For a long time it is known, that children very much early have flavouring sensations. Wet nurses always knew, that some products, such as caraway seeds, fennel, a green anise, laser eye surgery correction improve taste of milk. The child with pleasure sucks such milk, and milk secretion thus amplifies. Other products are characteristic that impact to milk unpleasant relish: it-garlic, an asparagus, an onions, cabbage. The child with whom feed with industrial production milk, receives fresh food without any "surprises".

Sense of smell. The example which has become by the classical: if to the newborn two napkins allow to smell, one of which was in touch with a parent breast, and another - is not present, the child will turn to the first napkin. This experiment is done by the American researcher with the 10-day baby. But the record has been beaten by group of researchers which have made the same experiment with the 3-day newborn. And it is no wonder, after all thanks to sense of smell the child learns about affinity of a parent breast.

Touch. The newborn is very sensitive to that as with it address. Some gestures calm him, others - raise. Parents find out it very much early. However sensitivity of a skin and reaction to contact leave in depth of a pre-natal life of the child: in a tummy of mother he felt a liquid surrounding it, concerned uterus walls, during sorts he felt as all body strong periodic laser eye surgery correction reductions of a uterus thanks to which was born.

How it was Laser eye surgery reviews possible to establish with such accuracy level of sensitivity of the newborn? Sometimes in rather simple ways, in other cases - by means of difficult devices.

Direct supervision over direct reaction of the child concerns simple ways on the activator; it turns a head, reacts to deaf, far or easy noise, and sometimes on the contrary, ceases to react to all these sounds; he shouts or ceases to shout, blinks, moves feet, strains finitenesses shudders. Any almost inaudible gesture, any grimace or shout have for it value.

As at once it is difficult to see and note all, researchers have removed kilometres of films about babies in various situations - on hands of the father, mother, the pediatrist; before subjects of every possible forms and colours; at various illumination, etc. Then these films are looked through in the slowed down rate; stop the image return a film back and write down all reactions of the child, Thanks to such films any detail does not escape eyes of the observer.

Record of palpitation of the child has allowed to make set of supervision also; thanking it the conclusion has been drawn, that the newborn reacts to a female voice, than on the man's more. In the first case palpitation was slowed down, in the second - remains without changes.

More precisely to find out, the baby reacts to what sounds, make the following experiment: to it give to a dummy in which the tiny radio receiver registering a rhythm of movements is located. Then to the child allow to listen to various sounds; the rhythm of its movements changes, that allows to draw a conclusion on sensitivity of the kid to various laser eye surgery correction sounds.

Miniaturization of electronic devices has allowed to spend and more difficult researches. For example, by means of very small microphone entered under a cover after at sorts the bubble has burst, it was possible to learn, what sounds surround the child till a birth.

So, the newborn as whom considered deprived of any perception earlier, "closed" in relation to world around, has appeared ready to reaction to its numerous associates, biologically programmed for set of feelings.

So all the same has changed in the relation to the newborn as a result of these researches? The sight of the adult at the child, and also the relation to it has in essence changed, that, certainly, certain impact on the kid will make.

2. Development of sensations

As sensations result from influence defined on a corresponding receptor, classification of sensations starts with properties which cause them, and receptors which these influence. On character of reflexion and the location of receptors it is accepted to divide sensations into three groups:

Reflecting properties of subjects and the phenomena of an environment and having receptors on a body surface;

The having receptors located in internal bodies and fabrics of a body and reflecting a condition of internal bodies;

Which receptors are located in muscles and sheaves and giving the information on movement and position of our body. A subclass representing sensitivity to movement, and corresponding receptors.

It is possible to subdivide on two groups: contact and receptors. Contact receptors transfer irritation at laser eye surgery correction direct contact to objects influencing them. Them concern: flavouring receptors. Receptors react to the irritations proceeding from remote object. Them concern visual, acoustical and olfactory. I name only five receptors corresponding to kinds of sensations, but actually them much more.

The touch structure, along with tactile sensations (sensations of a touch), includes quite independent kind of sensations - temperature. Temperature sensations not only are a part of touch, but have also independent, more a general meaning for all process of thermoregulation and heat exchange between an organism and environment. Intermediate position between tactile and acoustical sensations is occupied with vibrating sensations. The big role in the general process of orientation of the person in environment is played by sensations of balance and acceleration. The difficult system mechanism of these sensations covers a vestibular mechanism, vestibular nerves and various departments of a bark, a subcortex and a cerebellum.

From the Laser eye surgery reviews point of view of data of a modern science the accepted division of sensations on external and internal is not enough. It is possible to consider some kinds of sensations outwardly-internal. Them concern temperature and painful, flavouring and vibrating, myshechno-articulate and statiko-dynamic.

Sensations is a form of reflexion adequate. The adequate activator of visual sensation is the electromagnetic radiation characterised in lengths of waves in a range from 380 to 770, which are transformed in the visual analyzer to the nervous process generating visual sensation. Acoustical sensations - result of influence on receptors of sound waves with frequency of fluctuations from 16 to 20000 Hz. Tactile sensations are caused by action mechanical on a skin surface. Vibrating, getting special value for deaf persons, are caused by vibration of subjects. The specific have also other sensations (temperature, olfactory, flavouring). However various kinds of sensations are characterised not only specificity, but also the general for them by properties. Quality, intensity, duration and spatial localisation concern such properties.

The visual sensation possesses some inertia and disappears not right after how the caused ceases to operate. On inertia of sight, on preservation of visual impression in a current of some time the cinema principle is based.

The similar phenomenon occurs and in other laser eye surgery correction analyzers. For example, acoustical, temperature, painful and flavouring sensations also proceed some time after eye surgery action.

For sensations spatial localisation also is characteristic. The spatial analysis which is carried out by receptors, gives us data on localisation in space. Contact sensations (tactile, painful, flavouring) correspond that part which influences. Thus localisation of painful sensations happens poured and less exact, than tactile.

The various sense organs giving to us of data on a condition of an external world surrounding us, can display these phenomena with more or smaller accuracy. Sensitivity of a sense organ is defined minimum which in the given conditions appears capable to cause sensation. The minimum force causing hardly appreciable sensation, is called as the bottom absolute threshold of sensitivity.

Smaller force, so-called do not cause occurrence of sensations, and signals about them are not transferred in a brain bark. The bark during each separate moment from infinite quantity of impulses perceives only vitally actual, detaining all the others, including impulses from internal bodies. Such position is biologically expedient. It is impossible to imagine an organism life at which the bark of the big hemispheres equally would perceive all impulses and provided on them reactions. It would lead an organism of inevitable destruction.

The bottom threshold of sensations defines level of absolute sensitivity of the given analyzer. Between absolute sensitivity and threshold size there is an inverse relationship: the less size of a threshold, the above sensitivity of the given analyzer.

Our analyzers possess various sensitivity. The threshold of one olfactory cage of the person for corresponding laser eye surgery correction odorous substances does not exceed 8 molecules. To cause flavouring sensation, it is required, at least, in 25 000 times more molecules, than for creation of olfactory sensation.

Sensitivity visual and an acoustic analyzer is very high. The human eye as have shown S.I.Vavilov's experiences, is capable to see light at hit on a retina only 2 - 8 quanta of radiant energy. It means, that we would be capable to see in full darkness a burning candle on distance to 27 kilometres. At the same time that we have felt a touch, it is necessary in 100 - 10 000 000 times eye surgery more for energy, than at visual or acoustical sensations.

Absolute sensitivity of the analyzer is limited not only bottom, but also the top threshold of sensation. As the top absolute threshold of sensitivity is called the maximum force at which else there is adequate operating a sensation. The further increase in force operating on our receptors, causes in them only painful sensation (for example, very loud sound, blinding brightness).

The size of absolute thresholds, both bottom, and top, changes depending on various conditions: character of activity and to increase the person, a functional condition of a receptor, force and duration of irritation.

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lasic eye surgery

2009-06-16T05:24:00.000-07:00

You wish to make correction of sight or you only reflect on it?
There are some reasons to make sight correction:

1. YOU WILL SEE!!!!
Restoration of the highest quality of sight (clearness, brightness, contrast), excellent evening and night sight, absence of doublings from bright objects.
2. You will open for yourselves new possibilities of a life with high-grade sight: the most safe driving, playing sports, productive leisure, career.
3. There is no dependence on points and contact lenses.
4. You will get rid of the complexes connected with their carrying: be released from a superfluous burden, receive aesthetic effect, we will find a self-trust.
5. Preparations or procedures lasic eye surgery any more be not required to you that it is good to see. Operation pays off for some years.
The medical centre "Person of clinics" - clinic the Enlightenment - sight correction

Five reasons on which it is necessary to make lasic eye surgery

1. Unique installation for sight correction.
«ESIRIS» - last working out of the world leader of manufacture of the hi-tech medical equipment of firm Sshwind. It is laser installation of sixth, last generation, has absorbed all experience of modern laser surgery and is the sample of achievements of world ophthalmology. Thanks to unique technological features, it has variety of advantages in front of other lasers:
The medical centre the Person of clinics - clinic the Enlightenment - sight correction - High-speed system of tracking movements of an eye during correction, absolute accuracy of delivery of a laser beam to a cornea surface. At such frequency it is possible to consider, that the eye is absolutely motionless in relation to a laser beam.
- Influence of a beam of the laser by a principle of "a flying point» that gives more careful "polishing" of a cornea and sparing evaporation of a corneal fabric
- The most perfect device in the world for formation of a corneal rag. Owing to a special pendular design, at rag formation, protects the central part of a cornea from deformation, provides a constant thickness of a rag and its ideal smoothness, does impossible a full cut of a rag. In practice it means improvement of quality of correction and fast rehabilitation after operation. An enlightenment - unique clinic which is equipped lasic eye surgery.

3. The newest techniques of restoration of sight.
Super LASIK - the most progressive technology of modern eksimer-laser surgery. Advantage of this technique consists not only in visual acuity restoration, but also in its highest quality.

Advantages lasic eye surgery
- A guarantee of restoration of sight in day of operation.
- Possibility of restoration of visual acuity above 1 after operation.
- Absence of considerable restrictions on visual loadings after operation.
- In the evening after carrying out of laser correction it is possible to operate the car, to work on the computer, to watch TV, read.
- Exclusive accuracy of carrying out of correction.
- The individual approach, allowing to achieve an ideal surface of a cornea.
- Possibility of correction of errors of operative intervention on other lasers.
- The high sharpness and quality of sight is reached.

4. Availability of operation lasic eye surgery.
For today of operation on sight restoration on installation lasic eye surgery are spent only abroad. The clinic the Enlightenment gives unique possibility for the patients to be operated on the best equipment, at the most skilled doctors. Operation cost on sight restoration incomparably is less, than in Moscow and, especially, abroad.

5. Versatility of clinic.
Short-sightedness, far-sightedness, astigmatism, a cataract, a squint, various diseases of a retina - here it is far not the full list of diseases with which our experts will consult. At your service absolutely all directions of treatment of eye diseases: surgical, therapeutic both optical. Technical and the mental potential which our clinic possesses, allows to solve problems with sight lasic eye surgery at absolutely new qualitative level, with the maximum accuracy, safety and responsibility for an end result.
Sight is a completeness and integrity of the life. And new sight is a new life. Brighter, free and high-grade.

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Astigmatism treatment and correction

2009-06-16T04:54:00.000-07:00

Аstigmatism is a pathology of a refraction of an eye at which sphericity of a cornea is broken, i.e. in different meridians different refracting force and the subject image at passage of light beams through such cornea turns out not in the form of a point, and in the form of a straight line piece. The person thus sees subjects deformed, in which one lines accurate, others - washed away. Congenital astigmatism to 0,5 dioptries meets at the majority of people and concerns to functional which practically does not influence visual acuity. However, as practice shows, astigmatism already in 1 dioptries and more lowers sight and worsens visual comfort. Such version of a pathology comes to light approximately in 10 % a case among 25 % of children with all kinds amitropis. With astigmatism early correction of sight by means of cylindrical points is necessary for such patients. The main preventive maintenance consists in it, a squint and visual discomfort.

Аstigmatism - the reasons and occurrence terms.

The occurrence reasons astigmatism up to the end are not studied. In most cases astigmatism has congenital and inherited character, comes to light at children's age. However operations or eye traumas can be the reason astigmatism. The image of subjects at astigmatism indistinct, places washed away, straight lines look bent. Except defects of visual perception, astigmatism it is usually accompanied by fast fatigue of eyes, sight fall, headaches.

astigmatism treatment: If in a family there are patients astigmatism - the child should be necessarily examined the ophthalmologist. Аstigmatism comes to light only at full ophthalmologic inspection. The patient astigmatism feels only visual acuity decrease. For correct definition of degree astigmatism and, especially its axes, careful computer inspection is necessary. Even small errors in diagnostics can lead to full intolerance of points or lenses, and also to sight deterioration.

Illumination mode - visual loadings only at good illumination, with use of a ceiling light, a desk lamp 60-100 Vt not to use a fluorescent lamp

The mode visual and physical activities - is recommended to alternate visual pressure to active, mobile rest.

The gymnastics for eyes - in 20-30 minutes of employment is recommended to spend gymnastics for eyes

Conservative astigmatism treatment

Early diagnostics astigmatism - full ophthalmologic inspections, including computer research of axes of an eye.

Correct correction of sight - by means of points with special cylindrical lenses or special contact lenses picked up by the ophthalmologist.

Training of muscles - responsible for eye accommodation (laser stimulation, video computer correction of sight, the medical products, special courses of eye gymnastics) - under supervision of the ophthalmologist astigmatism treatment

Strengthening actions - swimming, massage of a zone of eyelids, a contrast shower etc. under the recommendation of the ophthalmologist.

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Мethod corrections astigmatism

Now there are three recognised ways of correction astigmatism treatment, namely:

Points - the most widespread method of correction astigmatism, especially at children's age. At astigmatism points with special cylindrical lenses - positive or negative - depending on a kind astigmatism are used. At all advantages, points deliver to the owner weight of inconveniences - are constantly spoilt, mist over, slip and fall, prevent to go in for sports and any other active physical activity. Points do not provide 100 % of correction of sight. Points essentially limit lateral sight, break three-dimensional effect and spatial perception that is especially important for drivers. At failure or falling the broken glass lenses can cause a serious trauma. Besides, incorrectly chosen glasses can serve as the reason of constant overfatigue of eyes and to progressing astigmatism. Nevertheless, points and for today remain the most simple, cheap and safe method of correction astigmatism.

Contact lenses - contact lenses are applied to correction astigmatism, small degree (to 3 dioptries). At astigmatism are used special - lenses which the ophthalmologist should pick up. All restrictions and inconveniences, as well as to other kinds of contact lenses are peculiar to Torichesky lenses.

Laser correction - for adult people (is more senior 18 years) at the stable form astigmatism modern ophthalmology offers the most progressive way of correction - laser correction astigmatism. The best technology of laser correction of sight today is laser - the operation, guaranteeing to the patient with astigmatism normal sight, without what or restrictions.

Eye cataracts

2009-06-16T04:26:00.000-07:00

The cataract is an age disease, therefore there is it, as a rule, after 60 years. But there are exceptions. Exceptions consist that the cataract reason can be various are certain diseases, a trauma or harm about which too it will be possible to talk. But average term of occurrence of a cataract - approximately 60 years and later.

And it is possible to prepare somehow for this process, to prevent it?

It is very difficult because if to speak about disease - eye cataracts, this display of extreme degree of ageing of an organism if we speak about a cataract age. Therefore to prevent it is possible, keeping a healthy way of life, certainly, and, knowing the heredity, it is even more to it to aspire. Well, and if to speak about the cataracts which reasons is the trauma or harm any, - it is natural, to protect itself from possible eye traumas, to use certain protective adaptations on harmful manufactures and so on. Well, it is absolutely bad, if the person is sick of any serious diseases as a diabetes or rheumatism, - careful treatment and preventive maintenance of these diseases here is necessary.

What most important recommendations about preventive maintenance eye cataracts?

It is a lot of them, and the majority of them concerns a category of the general recommendations about observance of norms and rules of a healthy way of life: not to smoke, not to abuse alcohol, to try not to have excess weight, regularly to be engaged in physical exercises, to try to protect itself from excessive emotional stresses. Though all these positions carry, apparently, too the general character and are directed on preventive maintenance not only one cataract, practice shows, that though their observance does not guarantee the person against cataract occurrence, but their obvious non-observance can promote cataract.

There are also important special recommendations about cataract preventive maintenance. Them concerns: protection of eyes against an ultraviolet and microwave radiations - as active stimulators of formation of free radicals; care at a drug intake, fabrics raising a photosensitivity eye. It is not necessary to abuse soda drinks and to drink many coffee. Special attention the control over level of sugar of blood and a choice - by means of the doctor, of course, - the optimal method of treatment even demands the most initial displays of a diabetes which is one of the main enemies of the visual device of the person. Various external influences can be the reasons of cataracts. Them concerns not only microwave influence, this and radiating influence, influence of other kinds of energy. I will dare to explain a little bit. The cataract is a cataract. You have correctly translated the Greek term, but many patients so translate it literally and consider a cataract as such grown turbid film. Actually the crystalline lens represents a convexo-convex lens which consists of strictly ordered fibres which provide its transparency. Throughout a life the crystalline lens continues to grow, fibres are formed again and again. And here defeat of a crystalline lens also leads to occurrence of such opaque fibres which cause eye cataracts. Therefore any influence on a crystalline lens, a growing crystalline lens, leads to its turbidity.

In our practice we meet radiating cataracts - a consequence of an ionising radiation which can arise at failures on nuclear objects or at persons who work with an ionising radiation. There can be a cataract - at influence of chemical any agents and so on.

Actually the word eye cataracts never should sound so terribly as it is perceived by people. In general, the word "cataract" sounds any sentence. Anything similar, very often such smallest of turbidity of congenital character in a crystalline lens which is similar to a button thick, they exist since the birth, and people live many years easy, not knowing, that they have these of turbidity and that they have a cataract congenital, and someone is casual once it about it will tell. So not always the word "cataract" sounds so terribly.

The main criterion quality of sight which the person has, it first, and degree of defeat of a crystalline lens as this cataract nevertheless should serve. After all any, even the smallest turbidity too name a cataract. Naturally, quality of sight is checked in unusual conditions, not only at fine illumination, but also at the raised and lowered illumination, not only at examining of subjects of 100 percent contrast, but also at the lowered contrast which we constantly meet in the life. That is it, as a rule, all those conditions which arise at the person at work any kind. And here if visual acuity suffers in these conditions, here it is necessary to worry.

If the person already has short-sightedness, a far-sightedness how it can distinguish what occurs because of a cataract, from the usual condition?

If the person till 60 years had a fine sight afar and suddenly there is any false short-sightedness, whence it undertook, not clearly, and the person starts to see better close, it not the most good sign because it is a sign of development of a nuclear cataract. And on the contrary, if the person had points +, it always was considered far-sighted, and suddenly at it plus starts to vary on a minus is besides a sign of development of a cataract. That is it is possible to tell about it in absentia.

The sign is, naturally, deterioration eye sight. Sight deterioration can arise and from other reasons, it can be short-sightedness growth, for example, but it, as a rule, concerns young men at the age of 20-25 years when growth such comes to an end. Any changes of visual acuity should guard, and the timely control, timely inspection at the ophthalmologist will show, whether there is at the patient a treatment of a cataract or not.

In medical encyclopaedias and manuals till the latest time about any methods of treatment eye cataracts, except surgical, it was not mentioned at all. Nevertheless, in medical practice variety of the means, having doubtless treatment-and-prophylactic an effect is widely enough used, especially at early stages of development of process of cataract. The drops containing substances, connecting molecules of sugars concern number of such means in a crystalline lens that interferes with its turbidity, in particular.

More 25 years ago one of few has been included in the American pharmacological directories, received such honour, homoeopathic remedies - so-called eye drops which are used since then for treatment of early stages of a cataract.

All listed preparations concern a category of the cores, but in practice is still auxiliary, concerning a category "useful" - to them drops, polyvitamins and many other things concern.

If the patient addresses to the ophthalmologist with initial signs of disease eye cataracts treatment always begins by means of conservative means with the obligatory account of the possible reasons of development of pathological process, in particular a diabetes, and in the absence of data about presence of other reasons which could cause sight fall. At far come changes in a crystalline lens the positive effect comes only as a result of well developed surgical treatment. In this connection the cataract is considered, though also the most widespread, but at the same time and the most cured form of a pathology of sight.

Complications, really, exist, at any kind of operations they can exist. And theoretically such complications, statistically it is a lot of. Certainly, matters situations of the concrete patient as there has passed eye operation. If operation has passed without complications can exist only insignificant which can be eliminated easily, for example: the raised hypostasis of fabrics which necessarily passes at additional treatment; the raised intraocular pressure, short-term, as reaction to those or other power properties of the equipment which is used at operation; or any hemorrhages connected with a condition of an organism of the given concrete patient; or, God forbid, any inflammation with participation of the infection, which reason too can be various. But thus each patient who goes on operation, should understand, that danger of such complications as at surgery any kind, always existed, exists and will exist, and it necessarily should agree to operation eye cataracts, it should be discussed with it.

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Cataracts treatment

2009-06-16T03:56:00.000-07:00

The review of modern methods cataracts treatment

Cataract
Unique way cataracts treatment - surgical intervention. The first mentions of surgical treatment of a cataract meet in a dated fifth century B.C. the Indian manuscript. The method described there - reclinacis - consists in simple removal of the grown turbid crystalline lens and as it is not strange, is used till now. The person after such operation on cataract removal really starts to see, but the eye deprived of a crystalline lens cannot normally carry out the functions any more. For more or less normal sight additional correction by means of powerful, from above 20D, points is required.

Modern methods cataracts treatment are based on replacement of the grown turbid crystalline lens with an artificial implant. Distinguish 2 basic of a method:

introcapsular extractions
Traditional extracapsular extractions

Thus most widespread method cataracts treatment in Europe, the USA and Japan is the method laser removal of a cataract.

Introcapsular extractions
At this method the muddy crystalline lens leaves completely together with all capsule. Global infringement of internal structure of an eye can cause weight of by-effects and complications, therefore such operation is applied only in case of a posttraumatic cataract when preservation capsul a bag is simply impossible.

At traditional extracapsular extractions in a cornea the wide cut through which the kernel of a crystalline lens and lenticular weights leaves becomes. The lenticular bag remains untouched. After removal of the grown turbid crystalline lens the lens is implanted into it. This operation allows to keep appreciably natural structure of an eye, but, because of an extensive zone of intervention and imposing of the big seams, demands the long rehabilitation period and can lead to development postoperative astigmatism. There is less dangerous method of treatment - laser removal of a cataract.

At this method the damaged crystalline lens before removal mechanically is split up inside capsular a bag for small parts. It allows to reduce width of a cut and appreciably to reduce negative by-effects of the previous method. By the most safe method for today all over the world it is recognised emulsifikasion.

Laser cataracts treatment is the technics conceived and developed in the sixtieth years Charles Kelman for the purpose of removal of a cataract through a small cut. Such operation does not provoke development postoperative astigmatism, provides fast anatomic and functional restoration; besides, considering, that laser removal of a cataract can be carried out at local anaesthesia, operation is carried out in out-patient conditions, that essentially reduces emotional, physical and economic expenses of the patient. Through a microcut (2,75 mm) the ultrasonic probe is entered into the crystalline lens chamber. Under the control of the computer program the weights of a kernel of a crystalline lens destroyed by ultrasound are sucked away, then through the same microcut the special injector in a crystalline lens capsule enters a flexible turned off lens with crystal memory. Procedure does not demand suture, reduces danger of entering of an infection to a minimum and is carried out is out-patient.

Unique lack laser cataracts treatment - the high cost price and, as consequence, a high total cost of operation on cataract removal by the given way. In aspiration to lower the cost price many clinics go on partial simplification of technology or use of cheap implants. According to leading experts in this area - - such method of economy is not justified absolutely not. Real advantages of operation are shown only under condition of full observance of all technological nuances - from the disposable complete set of linen, tools and account materials before use of the special cleared intraocular eye entered directly in the forward chamber, instead of by an injection for an eyeball. Besides it is necessary to use expensive modern with memory of type AcrySof of firm Alcon. Therefore laser cataracts treatment in our centre costs really expensively. We offer the patients constrained in money resources traditional operation extracapsular extractions as are absolutely convinced, that at use of the best modern lenses such as Cilco firms Alcon and full observance of technology traditional operation gives the best effect, than laser removal of a cataract.

From purely surgical point of view, for such transition the wide experience in carrying out of operations on extracapsular extractions is necessary. Laser removal of a cataract obliges the surgeon to use simultaneously hands, feet, sight and hearing. The surgeon should reach static and dynamic balance. Considering, that under the concept should be carried out always in tightly closed chamber in the closed system, it is possible to name it "three-dimensional" surgery. The surgeon should concern with attention movements in all three planes.

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