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.