Intermittent exotropia is the most common type of strabismus in East Asian children [15,16,17]. One of its greatest dangers is the progressive loss of binocular visual function, which may not be recovered without timely intervention. For decades, surgery has been considered the standard procedure for the treatment of intermittent exotropia in children. Several limitations have emerged in the implementation of the procedure, including postoperative scar adhesions, variable reliability and accuracy, and inconvenient general anesthesia. In addition, the high recurrence rate of IXT (22–59%) is a major problem [9, 10]. Therefore, a second or even multiple surgeries may be required, which increases the suffering of the child. Recently, the use of BTA in ophthalmic surgery has brought light to a new approach for the treatment of IXT and has been used as an initial, secondary and adjunctive treatment in several studies .BTA injection can control eye position and maintain some binocular visual function through chemical denervation, thus delaying the age of surgery and reducing the number of operations. Previously, most of the research were based on small sample sizes and single-group observational studies (usually around 30 subjects), such as Spencer , Wu , and Etezad  who reported stable success in 69, 76.67, and 86% of patients, respectively. However, the lack of comparison between BTA and surgery in case-control conditions leads to controversial conclusions.
In the present study, we enrolled 144 children with IXT with indications for surgery and divided them into a BTA injection group and a surgery group. The treatment success rate at the last follow-up at 6 months in the injection group, evaluated with eye position, was 52.8%, which was as effective as the surgery group (66.7%, P = 0.13), but lower than previous studies. A variety of reasons may be involved, including different evaluation metrics for surgical success, the preoperative angle of deviation in pediatric IXT patients, and the inclusion of repeat injections. Previous studies  showed no significant dependence of the efficacy of BTA injection on the dose of injection, and the dose in the above-mentioned study was 2.5 IU (the same as in the present study), so the dose of BTA was not considered to be a factor affecting the success rate.
Overall, there is a generally accepted criterion for success in intermittent exotropia surgery. As mentioned in the review, several articles used “within +4 PD esotropia to -10 exophoria” [12, 20, 21] However, previous BTA literature on childhood strabismus mostly used the success criterion of “+/− 10 PD”. In our study, success was set as a deviation between − 10 PD and + 10 PD , which is consistent with Scott’s original evaluation in the study of BTA for strabismus in children . It is also consistent with other studies reporting evaluation metrics regarding BTA injections for the treatment of concomitant strabismus in children, in which the deviation angle in the success criteria for strabismus treatment ranged from 8 PD to 12 PD, with 10 PD being the most [7, 8, 11, 13, 14]. In addition, previous studies have shown that large deviation degree can affect treatment outcome. Lennerstrand G stated that patients with deviation degree>40 PD had poor BTA treatment and required repeated injections . Spencer  and Etezad  reported that the mean preoperative deviation of patients was − 29.1 ± 1.7 PD and 30.9 ± 7.1 PD, respectively, with success rates of 69 and 86%. In contrast, in the present study, the preoperative deviation was − 35.9 ± 7.3 PD, which is greater than the above-mentioned data in the literature. In addition, 40.3% (29 subjects) had a deviation between 40 PD and 50 PD, which may affect the success rate. A third reason is that when assessing success rates, previous literature tends to include final follow-up results for repeat injections. The study by Spencer et al.  reported 12 patients who received repeat injections (seven patients received two BTA injections and five patients received three injections), nine of whom continued to show favorable eye alignment after more than 1 year of follow-up. We include in this article only the results of the initial single injection. The final follow-up of children with repeated injections has not been completed, and the final results are not known because many children did not complete the 6-month follow-up after the second injection, which may also be a factor in the lower orthostatic rate than previously reported.
Binocular vision is an important indicator of visual performance and one of the key mechanisms for eye position control in patients with IXT. Several articles have highlighted the relationship between satisfactory treatment outcome and recovery of binocular vision. McNeer et al. showed that early injection of BTA in binocular medial rectus for patients with congenital esotropia reconstructed motor and sensory fusion function with long-term effects comparable to surgical correction . Etezad et al. reported that 66.7% of patients with IXT achieved excellent fusion function at 6-month follow-up after BTA injection . In our study, 68.1% of patients in the injection group achieved good fusion control at the 6-month follow-up after treatment, which was lower than that of the surgery group. The reason for this may be due to the greater overcorrection (consecutive esotropia) early in the child after BTA injection, which may impair fusion. If consecutive esotropia persists, patients may experience severe loss of sensory function; diplopia, suppression, amblyopia, and loss of binocular vision may occur [24, 25]. In our study, overcorrection (consecutive esotropia) lasted for a maximum of 3 months, with most patients lasting 1 month. Short-term overcorrection did not cause other damage to the patients, but the establishment of fusion was worse than in surgical patients. For simultaneous vision and distance stereopsis 6 months after treatment, there were no statistical differences between the injection and the surgery groups. For stereoacuity measurements, both the injection and surgery groups showed a considerable preference for near stereopsis before and after treatment, which is consistent with the clinical features of IXT. At 6 months post-treatment, binocular visual function improved at all levels compared to baseline, except for near stereopsis.
Complications of BTA injections for strabismus have been reported to include ptosis, amblyopia, overcorrection, and vertical strabismus  In our study, diplopia, ptosis, and subconjunctival hemorrhage were observed in 72 subjects, 19 subjects and 1 subject, respectively. These complications gradually diminished from 1 month to 6 months during the follow-up period. The upper eyelid ptosis did not cover the pupil, and these symptoms disappeared within 1 to 3 months. Therefore, no children with occlusion amblyopia have been observed. Compared to the complications of surgery, the complications of BTA injections are milder, shorter in duration, and less painful for the child.
Pediatric general anesthesia poses significant considerations for parents and adds to the burden of the procedure. Compared to traditional extraocular muscle surgery, approximately half of the children in the BTA injection group could be performed with local anesthesia and a second injection could be performed. This also demonstrates that BTA injections are significantly more convenient than surgery, while reducing the demand on medical resources and improving the operability of repeat injections. Furthermore, in China, parents prefer local anesthesia for surgery. BTA not only facilitates local anesthesia injection, but also increases the possibility of local anesthesia surgery, as the binocular visual function can be preserved after BTA injection and the age of surgery can be postponed, which is more in line with the needs of Chinese parents.
This study has several limitations. First, and most importantly, the study was limited by short-term follow-up. Children with well-controlled fusion with intermittent exotropia and no amblyopia are usually examined every 6 to 12 months . The follow-up period for BTA injections reported in the literature ranges from 6 to 44 months [7, 8, 11, 13, 14], with a minimum of 6 months of follow-up according to Scott’s recommendations . Based on this, a 6-month follow-up was chosen as the final time point for observing the results in this study. However, the short follow-up period does represent a major limitation, and continuous follow-up is still needed to study the long-term efficacy of BTX injection in intermittent exotropia. In addition, the timing and dose of repeat injections and the relationship between baseline deviation and repeat injections are worth exploring. Tengtrisorn  used twice the initial dose of BTA injection as a second dose for the treatment of esotropia in children, achieving success in 72.7% of cases. And the sample size is still small, and the researchers will continue to expand the sample size for further studies.