In experimental animal study, -despite having controversy on optimum age of surgical alignment- earlier surgical alignment provides a better developed neurophysiologic matrix for binocular result7–11. A clinical investigational study was done by Ing, in furtherance of the experimental studies. Ing did report that despite a good motor alignment, patients who were aligned after 24 months of age demonstrated a significantly lower evidence of binocularity2. And he suggests that alignment should be accomplished by 2 years of age in infantile esotropic patients2. The preference of most strabismus specialists is of surgery for achieving the alignment before 2 years of age because botulinum toxin effect is not predictable12. Even if, botulinum toxin is preferred; there is no consensus on implemented dose and implementation way12. An interesting result of a meta-analysis done by Issaho DC is on dose response. They observed an inverse association between the dose of botulinum toxin. For every 1 IU increased in the mean dose, there was a reduction of 0.1% in the success rate12. Besides, some authors used the transconjunctival technique with EMG assistance in the procedures13–16 while others opted for no EMG assistance17–20. Nevertheless, the reported success rates of botulinum toxin injection were 68–76%, as high as the surgical success rate20–23. Although there is a scarcity on comparative studies between botulinum toxin injection versus muscle surgery, results are in botulinum toxin injection's favour20. These facts are confirmed in a prospective study24: They did report that botulinum toxin injection is as effective as surgery before the age of 24 months. This fact was pointed out by Von Noorden: A precise examination may be impossible for a child under age of 12 months. So, the age of initial adequate alignment can not be determined exactly for patients who undergo surgery. And alignment may be achieved late after initial surgery25. This is also true for patients who receive botulinum toxin. Because an adequate dose adjustment for each and every one have not been achieved to date in literature. As a result, exotropia developed in all of the patients of this study. On the other end of this argument, Campos did report that exotropia after the first injection was a good predictor of success because consecutive exotropia confirms that the implemented dose is enough26. So we can say a 5 IU of botulinum toxin is enough for children younger 10 months old. This amount of dose was confirmed in another way in a comparative study: Botulinum toxin in initial was given 4 IU -just 1 IU less than the used dose of this study- in this study and they did report that consecutive exotropia did not develop in any patient of the botulinum group20. Development of consecutive exotropia after botulinum toxin injection also confirms that the injection is done to right place and it can be used as a sign instead of EMG guidance if it is not available.
Transient ptosis and IOHF developed in all the patients of this study. This rate is the worst ever reported13. Mild transient ptosis may be attributed to overdose but in some way it seems inevitable. Because, even with a less dose it can develop20. But, IOHF development in all the patients can not be attributed to botulinum dose or the nature of infantile esotropia. Despite that, DVD and nistagmus did not develop in any patient. When all these consequences such as presence of IOHF and absence of DVD and nistagmus are taken into account in this select case series, a monocular esotropia with a 1.0 visual acuity in dominant eye or a vertical strabismus with a 1.0/1.0 visual acuity are features of acquired esotropia rather than of infantile esotropia. Infantile esotropia accompanies DVD by 50%-90%, IOHF by 70%, latent nystagmus by 40%, and optokinetic asymmetry27. These are the most consequences of infantile esotropia even in surgically aligned patients. Because infantile esotropia occurs in a more sensitive period in term of visual maturation. Amblypia or absence of stereopsis can be more profound than acquired esotropia28. So, if the child can be kept in align by botulinum toxin and if rectus muscles are not to be disturbed by invasive corrections, because rectus muscles are in maturation phase in infancy, DVD or latent nistagmus can be prevented as shown in this series. Even more, patients can achieve a 1.0/1.0 visual acuity if they receive adequate vision therapy as exampled in case 1. Because the main success of botulinum toxin injection is underlied by mechanisms other than the direct mechanism of its action. The change in alignment after injected botulinum toxin brings the eyes to an acceptable anatomic range. Then binocular visual system establishes and gets to function. While the direct effects of botulinum toxin slowly dissipates, the binocular system starts to receive feedbacks from disparities in the motor alignment. Thus, rebooting the binocular visual system sustains motor fusion and maintains alignment29. This mechanism makes botulinum toxin injection more advantageous than surgical alignment. But, as Campos did report, infants around the age of 6.5 months respond this mechanism the best26. Because contracture in the medial rectus muscles increase over time24. And it can be said that botulinum toxin injection can reboot binocularity, prevent infants from rectus muscles’ motor imbalance during visual maturation period, and carry the infant to a less sensitive period in term of visual maturation. And it can be asserted that if the infants had been compliant in their follow-ups and receive adequate vision therapy they would have a better chance in developing orthophoria. By this effort infantile esotropia can be changed into a more manageble form. The highlight of this study is that infantile esotropia management should be divided in two periods: Beginning, infant's strabismus should be aligned by botulinum toxin until an age when precise examination can be done and until sensory and motor visual system maturate. Later, it should be managed as an acquired esotropia. However, the results of a single and small case series provides limited evidence to support or refute this suggestion as an effective management option for infantile esotropia. Future retrospective or prospective studies with a larger number of participants and with fewer methodological limitations and biases are necessary.
This study has a number of limitations: This series is the work of one surgeon. So the treatment decisions and follow-up appointments were determined by the one surgeon. Most likely, some patients who have kept ocular alignment had needed less vision therapy while the patiens who ended up with monocular esotropia had needed more vision therapy. As a consequence, some patients, in some way, missed out of adequate vision therapy. As such, the effect of vision therapy in treatment strategy was not standardized. Therefore, this needs to be further studied in larger series, done by more than one surgeon, of patients that had standardized vision therapy and regular follow-ups.
Also, this study focused on just motor response and did not test for fusion. So a comment on the fusions of the patients who became orthophoric cannot be done. On the other hand, the study's children were younger than 10 months when they received botulinum toxin and they received a uniform single dose such as 5 IU in each muscle. Also they had a follow-up in their 6th-8th year. So, this study was able to report a very late situation of very select children with infantile esotropia. From this aspect, this study is of unique in the literature.