Strabismus is a common condition that affects up to 5% children and can be associated with abnormal visual development, double vision, loss of depth perception and impaired binocularity [1]. It can also cause cosmetic concerns, negatively impact psychosocial wellbeing and reduce quality of life [2].
Botulinum toxin-A (BTXA) is a neurotoxin that temporarily paralyses muscles by blocking the release of acetylcholine at the neuromuscular junction, preventing muscle contraction. Botulinum toxin-A to extraocular muscles (EOM) realigns the eyes by temporarily paralysing the overactive muscles, enabling unopposed action of the ipsilateral synergist. This achieves a partial or complete correction of the strabismus.
The medical applications of BTXA were explored in the mid-20th century. Dr Alan Scott’s experiments in the 1970s successfully demonstrated its efficacy for strabismus. The Food & Drug Administration (FDA) approved BTXA for adult strabismus in 1989 [3].
Although unlicensed for childhood strabismus, National Institute for Clinical Excellence (NICE) guidelines mention BTXA as a management option [4]. Ipsen’s Dysport® (Abobotulinum toxin-A) is approved by the US FDA for treating paediatric spasticity in cerebral palsy [5]. At Moorfields Eye Hospital (MEH), Dysport® is used to correct ocular misalignment in children (Figure 1).
Figure 1: Child undergoing bi-medial rectus BTXA for small angle AACE.
Indications for BTXA in paediatric strabismus
The use of BTXA in strabismus in the paediatric population is categorised into therapeutic, diagnostic, and adjunctive with surgery. Botulinum toxin-A is commonly used in infantile esotropia (IET), acute acquired onset strabismus, small angle squints, congenital cranial dis-innervation syndromes, strabismus with inconclusive aetiology or inconsistent orthoptic measurements [6,7,8]. Diagnostic applications include assessing the risk of postoperative diplopia and potential for binocular single vision (BSV).
Therapeutic use
Infantile esotropia
Infantile esotropia occurs with an onset before the age of six months. Botulinum toxin-A treatment in IET is used by clinicians for multiple reasons: (1) to restore binocular alignment; (2) to achieve binocular function; and (3) to reduce the need for large angle surgery.
Restoration of alignment in IET is achievable with BTXA to a comparable level to surgery but most of the literature suggest that its role is most effective in younger patients and smaller esotropia [9-13]. The greatest alignment results were found for patients with angles of esotropia of less than 30–50 prism dioptres [12,13]. Despite the toxin needing repeating in some circumstances, there was evidence that there was a retained effect on the muscles in some cases [11,12]. Early treatment with BTXA is more successful in younger children due to the malleability of the visual system and minimal medial rectus muscle contracture [9,11,12].
While some studies suggest early BTXA injections can restore sensory fusion and stereopsis, recent research shows weak evidence, with outcomes comparable to surgery [10,11,14]. Clinicians should focus on achieving ocular alignment, considering restored binocularity as an added benefit.
Acute acquired comitant esotropia
Acute acquired comitant esotropia (AACE) is a sudden onset of esotropia with diplopia after infancy, comprising 0.3% of strabismus cases [15,16]. Causes include loss of fusion from monocular occlusion or vision loss, physical or psychological stress, or dissociation linked to moderate myopia or excessive near work [17].
Botulinum toxin-A realigns the visual axis and restores binocular function, with outcomes comparable to surgery [18,19]. A 1999 study showed 93% of AACE patients (mean age 5.4 years) improved significantly after a single BTXA injection, with 79% regaining stereopsis and maintaining alignment over 22 months without further surgery [20].
Small angle deviations
Botulinum toxin-A is effective for managing small-angle deviations, such as residual or consecutive deviations post-surgery, decompensating heterophorias, and small primary deviations when surgery would carry high-risk of overcorrection.
A 2004 review at MEH found 20% of patients with esotropia (age range 11–74 years with ≤20 prism dioptres esotropia) achieved long-term benefit from a single BTXA injection [21]. Another study (mean age of patients 15.2 ±8.3 years) showed BTXA effectively treated postoperative esodeviation after exotropia surgery, with esodeviation ≤18 prism dioptres at one month predicting success [22].
Cyclic esotropia
A single BTXA injection can disrupt the cycle and restore binocular function in cyclic esotropia. A 2019 study showed long-term success in two children, maintaining binocular function without recurrence for eight years [7]. Another case demonstrated restored binocularity with no recurrence one-year post treatment [23].
Intermittent exotropia
Studies indicate that BTXA is a viable alternative to surgery for correcting intermittent exotropia (IXT), proving at least as effective in restoring ocular alignment [24-26]. One study noted better motor fusion results with surgery [25] while another found BTXA particularly effective in children aged 2–4.5 years, regardless of the initial strabismic angle [24].
Duane’s syndrome
Botulinum toxin-A can reduce abnormal head posture and expand the field of binocular single vision. In a study of 88 patients with Duane’s syndrome (age range 5–68 years), 14% used long-term maintenance toxin, while 46.5% eventually required surgery [27]. Two smaller studies on patients under three years of age showed similar results with BTXA proving useful for improving abnormal head posture but strabismus required re-operation in half of the cases [28,29].
Diagnostic use
Botulinum toxin-A has valuable diagnostic applications, particularly in surgical planning [29]. It can:
a) Assess the true risk of diplopia in older children reporting double vision on the postoperative diplopia test (PODT) before definitive strabismus surgery.
b) Determine the risk of postoperative diplopia in cases of constant manifest strabismus where PODT results are inconclusive.
c) Temporarily correct strabismus to evaluate the potential for regaining binocular function, with assessments conducted 1–2 weeks post treatment.
BTXA augmentation of strabismus surgery
Botulinum toxin-A can be used in combination with strabismus surgery to achieve a greater corrective effect in large-angle strabismus [30,31]. This can be useful when correcting large-angle deviations such as large angle IET and exotropia or in cases of strabismus due to cranial nerve palsy [32].
Dysport® for paediatric strabismus
At MEH, Dysport® is the BTXA brand used for paediatric strabismus, delivered in a standard 2.5-unit dose (0.1ml saline). It’s administered via a 25-gauge needle, guided by electromyography (EMG) or forceps gripping the muscle through the conjunctiva. The needle remains in the muscle for one minute to prevent leakage. Injections are typically bilateral to avoid additional GA. Effects peak within seven days and last 1–6 months.
Advantages of BTXA in paediatric strabismus
Anecdotal evidence and meta-analyses suggest that BTXA injections for strabismus management are safe [1,13,33].
It’s a quick procedure; on average, it was found that strabismus surgery took six to seven times longer than BTXA allowing for shorter exposure to anaesthetic. This not only benefits the patient but also allows more patients to gain access to treatment [12]. Botulinum toxin-A is also associated with lower healthcare costs than surgery [32].
The BTXA injection is less invasive than surgery and produces no scarring which helps to preserve the ocular surface. This leaves scope for future surgical planning. The treatment is more comfortable for patients with a quicker recovery and minimal aftercare. This consideration is especially important for families with young children.
Side-effects of BTXA are mostly reversible and injections can be safely repeated within a short time frame if required. It’s important to note that this would require a repeat general anaesthetic and for this reason, repeat injections for children are generally not performed [34].
Botulinum toxin-A can augment surgery by reducing the need for multiple extraocular muscle procedures, shortening theatre time, and potentially lowering the likelihood of additional interventions. While it may not fully resolve misalignment, it often decreases the angle sufficiently to benefit long-term management [32].
Notably, exact angle measurements are less critical for BTXA use, making it ideal for children, where compliance with orthoptic assessments can be challenging.
Limitations and side-effects of BTXA in paediatric strabismus
Botulinum toxin-A is not licensed for use in paediatric strabismus and is often used off-label for the paediatric population [35]. Clinicians often wait until infants are slightly older before administration. Various BTXA brands exist with differing dosing units, complicating study comparisons. At MEH, Dysport® is the preferred BTXA brand (see above).
Most paediatric treatments occur under general anaesthetic (GA). Electromyography can guide injections, though GA variability affects EMG reliability and BTXA precision. Repeat injections may have reduced efficacy, potentially requiring surgery for alignment [12].
The effects of BTXA are transient so whilst this is beneficial for its side-effect profile, it does mean that the effect on the ocular alignment is often temporary. As previously discussed, this means that the injections do need to be repeated to maintain effect. Side-effects are usually transient, resolving within 2–3 weeks [34]. However, children are at higher risk of ptosis under GA due to toxin leakage into the levator palpebrae superioris. Over-correction, whilst potentially undesirable by patients and families, is considered a positive outcome, associated with prolonged treatment effects [13,36].
Conclusion
Botulinum toxin-A effectively reduces strabismus angles in paediatric patients, providing a safe, quick, less invasive and repeatable alternative to surgery. While used for various ocular deviations, it’s most common in IET, AACE and small-angle strabismus. Literature indicates BTXA outperforms surgery in cases with potential for normal or near-normal BSV (e.g. AACE), small-angle strabismus and in patients at high risk of postoperative double vision [14]. Ultimately, treatment decisions depend on surgeon discretion, parental preference and the child’s wellbeing. However, standardised international trials are needed to compare brands and doses for clearer treatment pathways. Ultimately, treatment decisions depend on surgeon discretion, parental preference, and the child’s wellbeing
Table 1: Adverse events associated with botulinum toxin injections in strabismus.
References
1. Robaei D, Rose KA, Kifley A, et al. Factors associated with childhood strabismus. Ophthalmology 2006;113(7):1146–53.
2. Schuster AK, Elfein HM, Pokora R, et al. Health-related quality of life and mental health in children and adolescents with strabismus – results of the representative population-based survey KiGGS. Health Qual Life Outcomes 2019;17(1):81.
3. Scott AB, Honeychurch D, Brin MF. Early development history of Botox (onabotulinumtoxinA). Medicine (Baltimore) 2023;102(S1):e32371.
4. https://cks.nice.org.uk/topics/squint-in
-children/management/management/
5. Syed YY. AbobotulinumtoxinA: A Review in Pediatric Lower Limb Spasticity. Paediatr Drugs 2017;19(4):367–73.
6. Rowe FJ, Noonan CP. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev 2017;3(3):cd006499.
7. Unsal AIA, Özkan S, Ziylan S. Role of Botulinum Toxin Type A in Cyclic Esotropia: A Long-Term Follow-up. J Pediatr Ophthalmol Strabismus 2019;56(6):360–4.
8. Gupta S, Gan J, Jain S. Efficacy of Botulinum Toxin in the Treatment of Convergence Spasm. Strabismus 2018;26(3):122–5.
9. McNeer KW, Tucker MG, Spencer RF. Management of essential infantile esotropia with botulinum toxin A: review and recommendations. J Pediatr Ophthalmol Strabismus 2000;37(2):63–7; Quiz 101–2.
10. Campos EC, Schiavi C. Bellusci C. Critical age of botulinum toxin treatment in essential infantile esotropia. J Pediatr Ophthalmol Strabismus 2000;37(6):328–32; Quiz 354–5.
11. Gursoy H, Basmak H, Sahin A, et al. Long-term follow-up of bilateral botulinum toxin injections versus bilateral recessions of the medial rectus muscles for treatment of infantile esotropia. J AAPOS 2012;16(3):269–73.
12. Mayet I, Ally N, Alli HD, et al. Botulinum neurotoxin injections in essential infantile esotropia-a comparative study with surgery in large-angle deviations Eye (Lond) 2021;35(11):3071–6.
13. de Alba Campomanes AG, Binenbaum G, Eguiarte GC. Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia. J AAPOS 2010;14(2):111–6.
14. Bort-Martí AR, Rowe FJ, Sifre LR, et al. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev 2023;3(3):CD006499.
15. Clark AC, Nelson LB, Simon JW, et al. Acute acquired comitant esotropia. Br J Ophthalmol 1989;73(8):636–8.
16. Buch H, Vinding T. Acute acquired comitant esotropia of childhood: a classification based on 48 children. Acta Ophthalmol 2015;93(6):568–74.
17. Lekskul A, Chotkajornkiat N, Wuthisiri W, Tangtammaruk P. Acute Acquired Comitant Esotropia: Etiology, Clinical Course, and Management. Clin Ophthalmol 2021;15:1567–72.
18. Song D, Qian J, Chen Z. Efficacy of botulinum toxin injecton versus bilateral medial rectus recession for comitant esotropia: a meta-analysis. Graefes Arch Clin Exp Ophthalmol 2023;261(5):1247–56.
19. Wan MJ,Mantagos IS, Shah AS, et al. Comparison of Botulinum Toxin with Surgery for the Treatment of Acute-Onset Comitant Esotropia in Children. Am J Ophthalmol 2017;176:33–9.
20. Dawson EL, Marshman WE, Adams GG. The role of botulinum toxin A in acute-onset esotropia. Ophthalmology 1999;106(9):1727–30.
21. Dawson EL, Lee JP. Does Botulinum toxin have a role in the treatment of small-angle esotropia? Strabismus 2004;12(4):257–60.
22. Yang HK, Kim DH, Hwang J-M. Botulinum toxin injection without electromyographic guidance in consecutive esotropia. PLoS One 2020;15(11):e0241588.
23. Jones A, Jain S. Botulinum toxin: a novel treatment for pediatric cyclic esotropia. J AAPOS 2014;18(6):614–5.
24. Spencer RF, Tucker MG, Choi RY, McNeer KW. Botulinum toxin management of childhood intermittent Exotropia. Ophthalmology 1997;104(11):1762–7.
25. Su H, Fu J, Wu X, et al. Comparison of Botulinum toxin type A with surgery for the treatment of intermittent exotropia in children. BMC Ophthalmol 2022;22(1):53.
26. Li Y, Wu X. Observation of botulinum toxin a management in childhood with intermittent exotropia. Chin J Ophthalmol 2008;44(11):967–71.
27. Dawson EL, Maino A, Lee JP. Diagnostic use of botulinum toxin in patients with Duane syndrome. Strabismus 2010;18(1):21–3.
28. Maya JF, de Liaño RG, Catalán MR, Rayward O. Botulinum toxin treatment in patients up to 3 years of age who have esotropic Duane retraction syndrome. Strabismus 2013;21(1):4–7.
29. Sener EC, Yilmaz PT, Fatihoglu ÖU. Botulinum toxin-A injection in esotropic Duane syndrome patients up to 2 years of age. J AAPOS 2019;23(1):25.e1–25.e4.
30. Çiçek FD, Erdur SSK, Karaaslan N. Botulinum Toxin A Augmentation of Strabismus Surgery for Large-Angle Strabismus: A Retrospective Case Series and Literature Review. J Pediatr Ophthalmol Strabismus 2025;62(1):5–11.
31. Özkan SB. Golden Indications and an Overview on the Use of Botulinum Toxin in Strabismus. Turk J Ophthalmol 2023;53(6):377–85.
32. Wan MJ, Gilbert A, Kazlas M, et al. The Effect of Botulinum Toxin Augmentation on Strabismus Surgery for Large-Angle Infantile Esotropia. Am J Ophthalmol 2018;189:160–5.
33. Solebo AL, Austin A-M, Theodorou M, et al. Botulinum toxin chemodenervation for childhood strabismus in England: National and local patterns of practice. PLoS One 2018;13(6):e0199074.
34. Issaho DC, Carvalho FRS, Tabuse MKU, et al. The use of botulinum toxin to treat infantile esotropia: a systematic review with meta-analysis. Invest Ophthalmol Vis Sci 2017;58(12):5468–76.
35. https://www.nice.org.uk/about/nice-communities/
nice-and-the-public/making-decisions-about-your-care/
information-for-the-public-on-medicines
36. Rowe F, Noonan C. Complications of botulinum toxin A and their adverse effects. Strabismus 2009;17(4):139–42.
[All links last accessed March 2025]
Declaration of competing interests: None declared.
