Consultant ophthalmic surgeon Miss Joanne Hancox details the use of botulinum toxin in the treatment of eye squints

There is widespread awareness of the use of botulinum toxin as an antiageing treatment, but it is a lesser-known fact that it can also be an excellent treatment for misalignment of the eyes, known as strabismus. Adults with strabismus (commonly referred to as squint) suffer clinically significant levels of depression and anxiety; higher than those with other chronic illnesses such as diabetes and rheumatoid arthritis. Patients undergoing corrective restoration of eye alignment report significantly better quality of life on both functional and psychosocial scores after treatment.^1-6

In some cases, surgery is not possible or patient preference is towards a less-invasive treatment. In the majority of cases, botulinum toxin to the extraocular muscles provides an alternative treatment.^7-10

This article aims to highlight how effective treatment with botulinum toxin A (BoNT-A) can be in adult strabismus and increase awareness of its benefit for this condition, which can have debilitating functional and emotional consequences. It is important to note here that this treatment is highly specialised and should only be performed by strabismus surgeon specialists. I do believe that it is important, however, that aesthetic practitioners are aware of the condition as patients may present or discuss it amongst their aesthetic concerns in clinic. Knowing when to appropriately refer patients on for treatment of strabismus is imperative.

Presentation of strabismus

Strabismus is a condition where the two eyes are not correctly aligned and one eye is deviated. Approximately 4% of the adult population are affected by strabismus and it is a common misconception that nothing can be done for this condition in adulthood.¹¹

The eyes can be misaligned horizontally with an esotropia, where the eye turns in, and exotropia, where the eye turns out. They can also be vertically misaligned with one eye sitting higher (hypertropia) or lower (hypotropia) than the other. Rarely, the eyes experience rotational misalignment (torsional strabismus).¹¹ The severity of the squint can vary on eye movement and in different directions of gaze.

Strabismus may be present from birth or arise at any time in life. Some adults will have had squints as children that were not corrected, and others may have had surgery, but the squint has recurred in later life. Some adults may even have no childhood history of a squint, but the control over eye movement has become more difficult over time and the squint becomes evident (decompensated phorias).¹¹

Frequently, no actual cause is identified, although there are a number of different medical and neurological conditions that can give rise to squints in adulthood. These include orbital, cranial nerve palsies or muscular conditions. Direct ocular trauma and head injury can also cause squints.¹¹

Psychosocial and economic impact of strabismus

If the squint is uncorrected, the effects on visual function can include double vision, visual confusion, loss of stereopsis (3D vision) and the inability to use the two eyes together.¹¹ This can result in loss of independence, inability to drive, increased risk of falls and decline in workplace performance. Psychosocial difficulties that may also be encountered include low self-esteem, anxiety and depression, reduced quality of life, poor employment opportunities and discrimination.¹¹

Studies have shown strabismus to have a debilitating effect on a person’s quality of life, mood, independence and livelihood. It has also been shown that employers are likely to discriminate against those with a squint compared to straight-eyed individuals. Studies in children have shown that as early as six years old, children show a significant preference for straight-eyed individuals in preference to those with a squint.¹¹

Treatment of strabismus

The most frequent intervention in the long-term management of strabismus remains to be surgery. It is recognised, however, that in some patients, surgery may be technically difficult or impossible. Some patients prefer to undergo a less invasive procedure with little disruption to daily life. In these cases, botulinum toxin provides a safe and suitable alternative to surgery.¹¹

The first use of botulinum toxin in the treatment of strabismus was in the mid 1970s by US-based ophthalmologist Mr Alan Scott, who was the first to pioneer work in the use of BoNT-A for strabismus. He published his initial work on the benefit in monkeys with induced strabismus in 1973 and the first success in human strabismus in 1979. Scott also led the way in its subsequent use in the aesthetic industry as it was noted that patients being treated for hemifacial and blepharospasm reported improvement in their wrinkles and migraines. The widespread use of BoNT-A in the aesthetic industry today, owes it legacy to the pioneering work of Scott in ophthalmology. Ophthalmologist Mr John Lee visited Scott in 1982 and introduced it in to the UK by setting up the first BoNT-A clinic for strabismus in 1984, at Moorfields Eye Hospital in London.¹²

From my observations, between 50-65 BoNT-A injections for strabismus are given in the two clinics that run at Moorfields on a weekly basis, likely more than anywhere else in the world. Much work has been done and published on the indications of BoNT-A in strabismus. Its effects are beneficial in a range of different squints. Those that have been shown to benefit include:

• Deviations as a consequence of previous childhood squint, consecutive or residual deviations¹³
• Deviations as a result of poor eyesight – sensory or secondary deviations¹⁴
• Intermittent deviations with poor ability to keep the eyes straight (reduced fusion)^15-17
• Cranial nerve palsies (third, fourth, sixth)^18-21
• Squints as a result of other ocular surgery^22,23
• Congenital squints, such as Duane syndrome²⁴
• Small angle squints²⁵
• Complex pathologies such as chronic progressive external ophthalmoplegia, thyroid eye disease and myasthenia gravis¹²

BoNT-A mechanism of action

The mechanism of action in treating squints with BoNT-A is the same that occurs when treating other muscles in the body, but the doses are much smaller. This ranges from 1-5 units depending on the centre. After the initial work done by Mr Lee at Moorfields the dose given is consistently 2.5 units in 0.1ml, compared to the typical single dose of 20 units that may be injected into a forehead. The BoNT-A causes a blockade at the neuromuscular junction of the chosen extraocular muscle that has been injected.¹²

It is not the intention to paralyse the muscle completely as this would affect the motility of the eye. The desired effect is a weakening of the injected muscle such that the eyes are able to take up normal alignment, with little or no effect on eye movement. The paralysis should not be excessive, such that the injected muscle is limited in its direction of action and the eye is unable to move normally.

No effect is seen for two days and then weakening of the affected muscle is observed. The maximum effect occurs two weeks following the injection of the toxin. After reaching a peak at two weeks following the injection, the effect gradually wears off over the following three to four months. Some patients, however, find much longer-term benefit.

The injection of BoNT-A into the extraocular muscles is an extremely skilled procedure and, as mentioned above, can only be performed by a trained strabismus surgeon specialist. This is due to the fact that the muscles are not visible when viewing the eyeball and an injection given too deeply could penetrate into the eye, through the sclera and result in permanent sight loss.¹²

For a safe, low-risk procedure, all injections are performed under electromyography (EMG) guidance. During the preparation for the procedure, anaesthetic drops are applied to the surface of the eye and electrodes are attached to the forehead above the eye that is to be injected.

The BoNT-A needles are pre-loaded and attached to a further electrode. When these electrodes are plugged into the EMG machine, they complete a circuit. Once it has been confirmed that the patient is comfortable and cannot feel any discomfort, they are first asked to look away, then back into the direction of the muscle that requires the injection. This movement gives a signal when the appropriate muscle is firing. This signal confirms the correct presence of the needle in the muscle and the BoNT-A is only injected when a suitably strong signal is detected. This minimises the risk of complications.

Patients are reviewed again two weeks following the procedure, where a top-up injection can be given if the effect was only partial. A further appointment is made for three to four months where the patient can discuss if they found the treatment useful and wish to proceed with a further injection. There is no limit to the number of injections that can be performed over time. Studies have shown that with long-term BoNT-A use, the average angle of the strabismus decreases significantly over time and the frequency of required injections decreases.^12,25 Patients who have had multiple injections over time have demonstrated much higher quality of life (QoL) scores than new adult patients with squints. Following the toxin injection, their QoL score compared favourably with straight-eyed controls.²⁵

Considerations

Potential complications that can occur are ptosis, leakage of the toxin to the levator muscle of the lid, or unwanted ocular deviations due to leakage to the other extraocular muscles. The potential for this is reduced by leaving the injection in situ for 30 seconds before removing the needle.¹² Occasionally, bleeding on the surface of the eye (subconjunctival haemorrhage) or bruising around the eye can occur, but the effects are temporary. The serious risk of the needle penetrating the eye (globe perforation) is extremely rare and occurs in about 1 in 10,000 cases.¹²

Conclusion

It’s important for aesthetic practitioners to be aware of the treatments available for strabismus as, in the majority of cases, there is no need for adults to remain untreated and suffer the functional and emotional consequences. Long-term injections with BoNT-A is a good treatment approach for maintaining ocular alignment. It is a convenient and straightforward procedure that takes only minutes to perform, with excellent benefits in improved ocular alignment. Treatment provides the potential to correct strabismus in cases where surgery would not be possible and where the patient finds it preferable to surgery.