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.