Botulinum neurotoxin in the management of essential infantile esotropia
Introduction: To address the unmet need of delay in surgical correction of infantile esotropia (IE), a randomized clinical trial was undertaken to assess the efficacy and cost benefit of botulinum neurotoxin injection therapy (BNT) compared to surgery, which is the standard of care in IE, in children attending a large tertiary ophthalmology service in South Africa. Methods: In the first part, children <6years diagnosed with IE were randomized to receive either BNT injections (maximum of 3) or surgery with medial rectus muscle recessions. Clinical success was defined as alignment within 10 prism dioptres (PD) of orthotropia. A bottom-up cost comparison for the two procedures was done. In the second part, an open label study, the efficacy, and predictors of response to BNT injections in children with large and very large angle IE were investigated. The outcome of subsequent surgery in failed cases was analyzed. Results: Of the101 children with a mean (SD) age of 26.9 (14.5) months and a baseline angle of esotropia (AoE) of 62 (12.8) PD, 54 and 47 were randomized to BNT and surgery arms respectively. At 6 months of follow up, a successful outcome was seen in 20 (37%) and 33 (70.25%) respectively. Surgery was significantly more successful than BNT (OR=4.01,95%CI 1.74-9.22). Receiver operator characteristic analysis showed children under 21 months and AoE of <50PD at baseline were most likely to benefit from BNT therapy. Cost analysis of children achieving a successful outcome was significantly lower with BNT. Mean cost for eventual success was comparable for the 2 arms (ZAR9158.08 and ZAR9124.27 for the BNT and Surgery arms respectively (p=0.26)). The open labelled study of 117 children showed a mean (SD) reduction of 34.5PD (18) or 55.2% from baseline AoE after a mean of 2.2 injections. Age at intervention and size of esotropia were significant predictors. In those children who did not achieve a successful outcome with BNT, subsequent surgery may require less muscle recessions than what would have otherwise been necessary to correct the original AoE. Ninety percent had a favourable outcome with one surgical procedure in the study. Conclusion: Children <21 months old with a baseline AoE <50PD are most likely to benefit from BNT. Benefits of treating this subgroup of children with IE are that it is less costly compared to surgery and has the potential to reduce the waiting list for surgery in a resource constrained setting. Long term studies are needed to assess the impact of BNT on higher functions like stereopsis.!
A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, 2022