Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia

Letters to the Editor COMPARISON OF BOTULINUM TOXIN WITH SURGERY AS PRIMARY TREATMENT FOR INFANTILE ESOTROPIA To the Editor: Campomanes and colleagues1 are to be congratulated for collecting such a large series of patients to compare the results of surgery versus botulinum toxin as primary treatment for infantile esotropia. It should also be pointed out, however, that, although alignment is possible with chemodenervation of the medial rectus muscles by botulinum toxin, Biglan and colleagues2 felt that a better rate of correction could be achieved by surgery within 1 week rather than the several weeks of fluctuating alignment following botulinum toxin injections. This fluctuation may be disruptive in the critical period for the development of binocular function (the first 6-24 months of age). Indeed, when I independently studied 2 groups of patients, surgically aligned cases versus botulinum toxin–aligned cases, with both groups achieving alignment for a minimum of 6 months within the sensitive period, more patients achieved sensory evidence for binocularity with fusion and gross stereopsis in the surgically aligned group when compared to the botulinum toxin– aligned group (c2 5 8.05, p \ 0.005).3,4 It appears reasonable to suggest that any comparison of the 2 methods of alignment would probably be more meaningful if it included the results of subsequent sensory testing as well as the motor tests that were used as criteria of success. Malcolm Ing, MD John A. Burns School of Medicine University of Hawaii, Honolulu, Hawaii

outcomes in deviations\30D. The authors point out that “in the United States, surgical treatment of infantile esotropia remains the standard of care.” This study should be inspiration for further comparative studies from other institutions to determine the most effective use of botulinum toxin in treating infantile esotropia. We continue to use botulinum toxin as our primary treatment for infantile esotropia. The motor outcome dissimilarity in this study compared with ours (as noted in Table 1) may have several explanations: preinjection alternate patching, mean deviation size, and close attention to refractive error (hyperopic) changes during follow-up periods, among others. We look forward to further comparisons that were not included in this study, such as detailed outcomes of sensory data, DVD, A and V patterns, postinjection refractive error changes, and latent nystagmus. The article represents a significant contribution toward a simpler, safer, and efficient method of treating infantile esotropia; the authors should be commended for their efforts. Keith W. McNeer, MD Mary G. Tucker, MD Virginia Commonwealth University, Richmond, Virginia Reference 1. de alba Campomanes AG, Binenbaum G, Eguiarte G. Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia. J AAPOS 2010;14:111-6. doi:10.1016/j.jaapos.2010.09.003 J AAPOS 2010;14:558. Copyright Ó 2010 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00

References 1. Campomanes A, Binenbaum G, Eguiarte G. Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia. J AAPOS 2010;14:111-6. 2. Biglan AW, Burnstein A, Rogers GL, Saunders RA. Management of strabismus with botulinum A toxin. Ophthalmology 1989;96: 935-43. 3. Ing MR. Botulinum alignment for congenital esotropia. Trans Am Ophthalmol Soc 1992;90:361-7. discussion 367-371. 4. Ing MR. Outcome of surgical alignment before 6 months of age for congenital esotropia. Ophthalmology 1995;102:2041-5. doi:10.1016/j.jaapos.2010.07.001 J AAPOS 2010;14:558. Copyright Ó 2010 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00

To the Editor: de alba Campomanes and colleagues1 deserve congratulations for their important, prospective study, in which they used a significant sample size to compare botulinum toxin to surgery as a primary treatment for infantile esotropia.1 Their data appear to support the use of botulinum toxin as an alternative to surgery with equivalent

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To the Editor: In the conclusions to their study, “Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia,” de Alba Campomanes and colleagues1 point out that chemodenervation is as effective as surgery in aligning deviations \30 D in stable, nonaccomodative infantile esotropia. They therefore suggest that careful selection of this subgroup of patients should have good outcomes with either therapeutic modality. We would like to pose a question regarding a different aspect of the study results. In the subgroup of 74 patients in whom one or more botulinum toxin injections was followed by an operation for horizontal alignment, was the amount of surgery performed smaller than would have been the case if no botulinum toxin had been given? In other words, did the injection achieve reduction of the angle to an extent that altered the indication for surgery, and if so, in how many of the patients? Any stable reduction in size of deviation after the administration of botulinum toxin would be an advantage because it would result in (1) a more accurate measurement on

Journal of AAPOS

Volume 14 Number 6 / December 2010 prism cover test, (2) a reduced amount of surgery on small eyes, and (3) a possible reduction in incidence of consecutive exotropia. Finally, one may assume that a chemodenervated muscle may respond differently to surgical repositioning. On this note, it would be interesting to know the rate of success of surgery in the 74 patients who had previously received botulinum toxin injection(s) and how it compares with the 65.8% success rate of surgery as first-line treatment in 120 patients, if these 2 groups are at all comparable. Asimina Mataftsi, MD, MRCOphth Ken K. Nischal, FRCOphth Clinical and Academic Department of Ophthalmology Great Ormond Street Hospital, London, United Kingdom Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece Developmental Biology Unit, Institute of Child Health University College London, London, United Kingdom Reference 1. de Alba Campomanes AG, Binenbaum B, Campomanes Eguiarte G. Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia. J AAPOS 2010;14:111-16. doi:10.1016/j.jaapos.2010.09.004 J AAPOS 2010;14:558-559. Copyright Ó 2010 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00

REPLY To the Editor: We agree with Dr. Ing that sensory outcomes are important and that the assessment of stereoacuity will be valuable in future comparative studies. We are concerned, however, that the evidence cited by Dr. Ing is slightly misleading and should not be used to draw any conclusion favoring surgery over botulinum toxin with regard to sensory outcome. Dr. Ing’s conclusions are drawn from combining the results of 2 separate small case series rather than a single comparative study. In a 1995 nonconsecutive series,1 Dr. Ing found that 10 of 16 patients who underwent surgical alignment before the age of 6 months for congenital esotropia had gross stereopsis, whereas only 1 patient achieved fine stereopsis. He reported that these patients represented “best-case” results, but the selection criteria for the study are unclear. In his letter, he compares these findings with a second nonconsecutive case series of 12 children treated with botulinum toxin.2 He found that 6 of 12 children had gross stereopsis based on his personal unmasked assessment. In contrast, according to the paper, the treating surgeons felt that 11 of 12 had evidence of binocularity. Further, we feel that the statistical test reported in Dr. Ing’s letter is not appropriate. He has compared the proportion of infants with stereopsis from 2 separate small case series of children treated at different centers with

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varying degrees of intervention (1, 2, or 3 muscles operated on or injected at a time), and with poorly defined selection criteria. Under these circumstances, such a statistic is not interpretable. Perhaps more appropriate statistics might be simple binomial confidence intervals around the point estimates for each series considered independently. For the botulinum toxin series, this would be 6 of 12 (50%, 95% CI, 21%-79%). The wide confidence interval demonstrates that even this small case series may be consistent with other larger, more rigorous studies, which have found that the stereoacuity results obtained with botulinum toxin are in fact encouraging3,4 and similar to those obtained by surgery.5 Dr. Mataftsi raises a very interesting question: among children who do not achieve motor alignment with a single set of botulinum injections, is the esotropic deviation reduced and therefore is the amount of surgery less in those patients that receive botulinum toxin but do not achieve a successful motor outcome? She nicely summarizes a number of advantages that could result from a stable reduction in the size of the deviation, in the event that surgical correction is subsequently pursued. We addressed this question in the following way: In our study, there were 78 children who received only 1 injection. Conservatively excluding 5 children who were exotropic after 1 injection, as these children would artificially magnify any estimate of the reduction in esotropic deviation, the remaining 73 children had a preinjection mean deviation of 40D and postinjection mean deviation of 29D (p \ 0.0001). The mean change was 11D (95% CI, 8.6%-14.2%), with a maximum reduction of 42D and a maximum worsening of the esotropic angle of 15D. These findings would suggest that botulinum toxin injection typically results in a decrease in the esotropic deviation and in the amount of surgery performed, which has been reported previously by us (de Alba Campomanes AG. Pan-American Academy of Ophthalmology, Cancun, Quintana-Roo, Mexico, May 2007. PAAO abstract PP1441), and others.6 With regard to Dr. Mataftsi’s second question, the success rate for surgery in the 74 children who had 1 or more injections prior to surgery was 51% (95% CI, 39%-63%); however, one should interpret this subgroup analysis with caution, particularly if comparing it with the success rate of children who only had surgery, as the decision to pursue surgery lay with the parents, and we cannot exclude the possibility that infants who failed 1 or more botulinum toxin injections possessed a confounding factor that made them less likely to achieve motor success. We also think that other potential advantages of botulinum toxin in these patients are the improvement in the accuracy of the examination and diagnosis, the potential for reduced amount of surgery, and the possible reduction in the incidence of consecutive exotropia, as Dr. Mataftsi suggests. In our study, the rate of consecutive exotropia was not different in the 2 groups (3%) but longer follow-up is required to evaluate this potential benefit. Finally, we thank Drs. McNeer and Tucker for their comments and their pioneering work, and we look forward