Due to a lack of robust evidence, the evidence as to the benefits and harms of using botulinum toxin compared with surgery for strabismus is uncertain.
What did we want to find out?
We wanted to find out if botulinum toxin was better than surgery to treat strabismus. We also wanted to find out if botulinum toxin was associated with any unwanted effects.
What is strabismus?
Strabismus occurs when the eyes are not aligned. Usually one eye turns inwards or outwards. Less frequently, one eye turns upwards or downwards. It is commonly known as a 'squint'.
Strabismus can lead to blurred vision or double vision. In children, it can affect the long term development of vision in the affected eye. There are many causes of strabismus. In most cases, there are problems with the muscles or nerves around the eye.
Doctors can use botulinum toxin to stop individual muscles around the eye working for a while. This may help the eyes become more aligned and may lead to less blurred or double vision. One problem with using botulinum toxin is that it can result in a droopy eyelid (ptosis).
What did we do?
We searched for studies that investigated botulinum toxin injection compared with other treatment such as surgery in people with strabismus. We compared and summarized the results of relevant studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found four studies with 242 adults and children with strabismus. The biggest study was in 110 children and the smallest study was in 30 people. The studies were conducted in Canada, South Africa, and Spain. Two studies lasted for six months and the longest study lasted 36 months.
The review showed the following.
• Strabismus surgery may have better chance of recovering correct alignment of the eyes compared with botulinum toxin treatment in people requiring primary treatment or retreatment for strabismus.
• People treated with botulinum toxin may need to re-treat with surgery more frequently than people treated with surgery.
• Using botulinum toxin may not make any difference in the achievement of binocularity (the ability to focus on an object with both eyes and see a single image); and
• Ptosis (the upper eyelid drooping over the eye) occurred commonly in people receiving botulinum toxin in these studies. The number of people affected ranged from 2 to 4 in 10 people. Everyone recovered when treatment was stopped.
What are the limitations of the evidence?
We have little or no confidence in the evidence because there are not enough studies to be certain about the results of our outcomes, studies are small, and they are not designed and conducted well.
How up to date is this review?
The Cochrane researchers searched for studies that had been published up to 6 July 2022.
It remains unclear whether botulinum toxin may be an alternative to strabismus surgery as an independent treatment modality among certain types of strabismus because we found only low and very low-certainty evidence in this review update.
Low-certainty evidence suggests that strabismus surgery may be preferable to botulinum toxin injection to improve or correct strabismus when types of strabismus and different age groups are combined. We found low-certainty evidence suggesting botulinum toxin may have little to no effect on achievement of binocular single vision compared with surgery in children with acquired or infantile esotropia. We did not find sufficient evidence to draw any meaningful conclusions with respect to need for additional surgery, quality of life, and serious adverse events.
We identified three ongoing trials comparing botulinum toxin with conventional surgeries in the varying types of strabismus, whose results will provide relevant evidence for our stated objectives. Future trials should be rigorously designed, and investigators should analyze outcome data appropriately and report adequate information to provide evidence of high certainty. Quality of life and cost-effectiveness should be examined in addition to clinical and safety outcomes.
The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison with other treatment options for strabismus.
The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin.
We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers on 6 July 2022, together with reference checking to identify additional studies. We did not use any date or language restrictions in the electronic searches for trials.
We planned to include randomized controlled trials (RCTs) comparing botulinum toxin with strabismus surgery, botulinum toxin alternatives (i.e. bupivacaine) and conservative therapy such as orthoptic exercises, prisms, or lens therapy for people of any age with strabismus. All relevant RCTs identified in this update compared botulinum toxin with strabismus surgery.
We used standard methods expected by Cochrane and assessed the certainty of the body of evidence using GRADE.
We included four RCTs with 242 participants that enrolled adults with esotropia or exotropia, children with acquired esotropia, and children with infantile esotropia. The follow-up period ranged from six to 36 months. Two studies were conducted in Spain, and one each in Canada and South Africa. We judged the included studies to have a mixture of low, unclear and high risk of bias. We did not consider any of the included studies to be at low risk of bias for all domains.
All four studies reported the proportion of participants who improved or corrected strabismus, defined as ≤ 10 prism diopters (PD) at six months (two studies) or ≤ 8 PD at one year (two studies). Low-certainty evidence suggested that participants treated with the surgery may be more likely to improve or correct strabismus compared with those who treated with botulinum toxin (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.53 to 0.99; I² = 50%; 4 studies, 242 participants; low-certainty evidence).
One study, which enrolled 110 children with infantile esotropia, suggested that surgery may reduce the incidence of additional surgical intervention required, but the evidence was very uncertain (RR 3.05, 95% CI 1.34 to 6.91; 1 study, 101 participants; very low-certainty evidence).
Two studies conducted in Spain compared botulinum toxin with surgery in children who required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that botulinum toxin may have little to no effect on achieving sensory fusion (RR 0.88, 95% CI 0.63 to 1.23; I² = 0%; 2 studies, 102 participants) and stereopsis (RR 0.86, 95% CI 0.59 to 1.25; I² = 0%; 2 studies, 102 participants) compared with surgery.
Three studies reported non-serious adverse events. Partial transient ptosis (range 16.7% to 37.0%) and transient vertical deviation (range 5.6% to 18.5%) were observed among participants treated with botulinum toxin in three studies. In one study, 44.7% participants in the surgery group experienced discomfort. No studies reported serious adverse events or postintervention quality of life.