Botulinum toxin type A in treating early-stage patients with small-angle acute acquired comitant esotropia

Abstract

AIM

To investigate botulinum toxin A (BTXA) efficacy on small-angle (≤25^Δ) acute acquired concomitant esotropia (AACE) in early-stage patients.

METHODS

The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study. A total of 72 small-angle AACE patients received BTXA extraocular muscle injection. Patients were grouped by onset-to-treatment time (Group A: ≤6mo, Group B: >6mo). Deviation of esotropia, eye alignment and stereopsis were analyzed at the period of pre/post-injection (1wk, 1, 3, and 6mo). Orthophoria rate at 6mo (horizontal deviation <10^Δ and binocular single vision) were considered as outcome index.

RESULTS

There were no significant baseline differences (P>0.05) between two groups except onset-to-treatment time (2mo vs 11mo, P<0.001). Higher orthophoria rates were in Group A at last follow-up (94.74% vs 73.53%, P=0.013). Post-BTXA deviations of two groups at 1mo showed no difference (P>0.05); while in 3 and 6mo Group A was significantly smaller than group B (all P<0.001). No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A. In Group B, deviation at 3mo (near: 2^Δ vs 0, P<0.001; distance: 4^Δ vs 0, P<0.001) and 6mo (near: 6^Δ vs 0, P<0.001; distance: 6^Δ vs 0, P<0.001) was significant increased compared to deviation at 1wk after treatment. Group A showed better stereopsis recovery in last follow-up compared to Group B (80″ vs 200″, P=0.002). Both groups obtained improved stereopsis after treatment (Group A: 80″ vs 300″, P<0.001; Group B: 200″ vs 300″, P=0.037).

CONCLUSION

BTXA is effective for AACE with small deviation (≤25^Δ) in early stage. Delayed treatment (>6mo) may reduce BTXA efficacy. Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

INTRODUCTION

Acute acquired comitant esotropia (AACE), a relatively uncommon form of esotropia, was initially identified by Burian and Miller in 1958^[1]. AACE is characterized by a sudden onset of horizontal diplopia and no significant impairment of eye movements. Mohney^[2] reported its prevalence of around 0.3% in childhood strabismus. In recent years, a notable rise in reported cases^[3], possibly attributed to the increased use of electronic screens^[4]–^[6]. AACE is classified into three types based on etiology and clinical features, with type III (Bielschowsky type) being the most prevalent in contemporary cases^[7]. This type commonly affects adolescents and adults and is frequently associated with varying degrees of myopia^[8]. The escalating incidence of AACE underscores the importance of research about early intervention. It will be crucial for treatment strategies and stereopsis protection for this intriguing ophthalmic condition.

Contemporary AACE treatments encompass prisms, surgical interventions, and extraocular muscle injections utilizing botulinum toxin A (BTXA). BTXA, with its FDA approval dating back to 1989, had a well-established clinical history in strabismus management. Its versatility extends to treating various ocular conditions, including congenital esotropia, paralytic strabismus, cyclic esotropia, and thyroid-associated ophthalmopathy^[9]. In 1999, Dawson et al^[10] pioneered the exploration of BTXA for AACE treatment in children. The outcomes of these early experiments indicated the efficacy of timely BTXA administration in achieving alignment and potential benefits for binocular visual function. Wan et al^[11] revealed that the success rate of BTXA was comparable to surgical interventions while proving to be a more cost-effective alternative.

While BTXA is known for its minimally invasive approach and repeatability, its efficacy in AACE may face challenges like recurrence or subsequent surgery^[12]–^[14]. The early instability of deviations in AACE often deters surgical interventions. However, the cases with severe diplopia and rapid stereopsis damage require prompt treatment, leading to a crucial consideration of the appropriate degree range and timing of BTXA injection for AACE in the early stage. The current consensus on BTXA for AACE is imperfect, with limited studies analyzing early intervention effects in patients with small-angle AACE. Our previous study has found that patients with less deviations and shorter time of onset to injection have better outcomes^[15]. However, our prior studies primarily focused on individuals with a disease duration of a year or more, and there was a lack of dedicated analysis concerning patients with small-angle AACE. In the current clinical landscape, there is a notable surge in the number of cases involving small-angle AACE, underscoring a compelling demand for targeted interventions.

Through comparing orthophoria rates and follow-up deviations in AACE cases with varying durations from onset to BTXA, the study aims to highlight the benefits of early BTXA application (≤6mo from onset) in patients with small-angle AACE (≤25^Δ). This research offers insights into optimizing BTXA use in managing AACE.

SUBJECTS AND METHODS

Ethical Approval

The study was approved by the Ethics Committee of Renmin Hospital of Wuhan University (WDRY2020-K211) and was conducted according to the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study.

Study Design and Setting

The study was a retrospective cohort study. Information of 72 AACE patients who met the study criteria was selected from medical record system (March 2019-June 2023). Patients were divided into two groups according to the time from onset to treatment: Group A: ≤6mo; Group B: >6mo. The deviations of esotropia, stereopsis and orthophoria rate at final follow-up were observed. To investigate the benefit of timely BTXA treatment after onset in patients with small-angle AACE. All patient information is captured from the health information system. The study used the STROBE cohort reporting guidelines^[16].

Subjects

The database has been successfully used in previous study about AACE. Because it is objective by using alternate prism cover testing (APCT), patients from 3 different strabismus doctors were selected to avoid bias. Patients with missing information or missing follow-up visits are not included. Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Inclusion and Exclusion Criteria

Inclusion criteria: 1) sudden onset of strabismus with a known onset date; 2) accompanied by mainly ipsilateral horizontal diplopia; 3) intermittent or constant; 4) equal strabismus angle in all directions, indicative of concomitant strabismus; 5) deviations ≤25^Δ; 6) patients who only received 1 injection were selected for analysis.

Exclusion criteria: 1) strabismus due to craniocerebral diseases; 2) motor neuron or muscular system diseases; 3) paralytic, restrictive, vertical, A/V, or unexplained strabismus; 4) history of strabismus surgery and amblyopia; 5) pregnant or lactating women; 6) allergy to BTXA components; 7) deviation alleviation >10^Δ after cycloplegia; 8) patients with ptosis or the level of strabismus/diplopia existing changes during a day were excluded.

Routine and Ophthalmological Examination

Basic information was collected (general health, genetic history, family history, past history), excluding patients with neurological disorders and past history of eye disease. All patients received chest radiographs, electrocardiograms upon admission and ophthalmic examination.

Essential data of ophthalmology encompassed the onset date of strabismus, duration from symptom manifestation to hospital admission, daily near-work duration, characteristics and duration of strabismus and diplopia, and relevant medical/allergy history. Standard ophthalmological assessment incorporated evaluations of both uncorrected visual acuity and best-corrected visual acuity, cycloplegic refraction, intraocular pressure, slit lamp examination, and fundus photography. Strabismus assessments comprised alternate prism cover testing at near and distance, examination of ocular movements (nine-directions photograph), and stereopsis evaluations using the Titmus Book Examination. The alternate prism cover testing was performed at least twice after admission, in the morning and afternoon. Comprehensive CT/MRI scans were universally conducted to exclude neurological disorders. The anatomical position and morphology of the extraocular muscles were observed to exclude strabismus due to thyroid-associated eye disease or heavy eye syndrome and other extraocular muscle degeneration disease. Scheduled follow-ups at 1wk, 1, 3, and 6mo post BTXA extraocular muscle injection encompassed evaluations of strabismus, eye alignment, movements, and stereopsis. The 6-month follow-up duration ensured the thorough dissipation of immediate botulinum toxin effects.

Treatment of Botulinum Toxin A

Prior to treatment, patients underwent a comprehensive evaluation by anesthesiologists. Four younger patients (<12y) chose inhalation anesthesia after exclusion of contraindications. The remaining patients were 16 years of age or older and all met the indications for local anesthesia. For adult patients, the subconjunctival infiltration anesthesia was performed by intra conjunctival injection of 2% lidocaine of the operated eye, and 0.01% epinephrine hydrochloride was dropped into the conjunctival sac to constrict the blood vessels. Powdered lyophilized crystals of botulinum toxin (BOTOX, Allergan) were diluted with 2 mL of saline. The corresponding dose of BTXA was withdrawn with a 1 mL syringe (0.02 mL/U). An incision was made in the nasal conjunctiva, and the rectus medialis muscle was hooked. BTXA was injected into the muscle belly 5-6 mm after the muscle stopping point, and no oozing after injection indicated success. Dosage: <20^Δ with 1.0-2.5 U; 20^Δ-40^Δ with 2.5-4.0 U.

Efficacy Evaluation

Efficacy was assessed based on Rowe's criteria for BTXA treatment of strabismus, defining cure as horizontal strabismus ≤10^Δ at the last follow-up, with the absence of diplopia and the achievement of binocular monovision^[17].

Statistical Analysis

Statistics analyses were performed using SPSS 22.0. Non-normally distributed data were expressed using the median (range). Wilcoxon test was used for nonparametric tests for between and within-group comparisons. Repeated measures data were compared using the Friedman test. The Chi-square test was used for the comparison of rates. Statistical significance was defined as P<0.05.

RESULTS

Characteristics of the Subjects

A total of 198 AACE patients in the system were screened and 72 eligible patients were finally included (42 males and 30 females). The study cohort flow diagram is shown in Figure 1. The median age was 28y (range: 10-55), and the median daily near-work time was 9h (range: 4.5-12.0). The median spherical equivalent was -4.25 D of right eye (range: -13.75 to +1.75) and -3.75 D of left eye (range: -14.00 to +1.00). There were no statistically significant differences in gender ratio, age, spherical equivalent, or near-work time between Groups A and B (P>0.05). Group A exhibited a significantly shorter median time from onset to treatment than Group B (2mo vs 11mo, P<0.001; Table 1).

Figure 1. Cohort flow diagram of the study.

AACE: Acute acquired concomitant esotropia; BTXA: Botulinum toxin A; PD: Prism diopter.

Table 1. Characteristics before BTXA.

Characters	Group A	Group B	U/χ²	P
Patients	38	34	-	-
Sex ratio (male/female)	25/13	17/17	1.841	0.175a
Age of onset (y)	27 (16-55)	29 (10-55)	1.040	0.298b
Spherical equivalent (D), right	-4.00	-4.38	0.621	0.534b
Spherical equivalent (D), left	-3.88	-3.75	1.476	0.140b
Near-work time (h/d)	8.5 (4.5-12)	9 (5.5-12)	1.504	0.292b
Time from onset to BTXA (mo)	2 (0.5-6)	11 (7-24)	7.346	<0.001b

BTXA: Botulinum toxin A. ^aChi-square test; ^bWilcoxon test.

Median (range)

Orthophoria Rates at Final Follow-up

There were no differences in injection doses (P=0.834) and types (37/2 vs 29/5, P=0.155) between Groups A and B (Table 2). The 36 patients in Group A [94.74%, 95% confidence interval (CI): 87.3%-100%] and 25 patients in Group B (73.53%, 95%CI: 57.9%-89.2%) were orthophoria after 6mo (χ²=6.235, P=0.013).

Table 2. Comparison of injection doses, types, and orthophoria rates between groups.

Parameters	Group A	Group B	U/χ²	P
Orthophoria at 6mo (%)	36/38 (94.74)	25/34 (73.53)	6.235	0.013a
Injection dose (U), median (range)	2 (1-3)	2 (1-3)	0.210	0.834b
Injection type (unilateral/bilateral)	37/2	29/5	2.021	0.155a

^aChi-square test; ^bWilcoxon test.

Deviations Difference after Botulinum Toxin A Treatment

There were no significant difference in median deviations between Groups A and B before, 1wk, and 1mo after treatment; while in 3 and 6mo after treatment Group A was significantly smaller than group B (all P<0.001).

In Group A, the deviation significant decreased after BTXA treatment (near: Friedman test=92.415, P<0.001; distance: Friedman test=93.862, P<0.001). Pairwise comparisons revealed significant deviations differences between pre-BTXA and 1wk (both near and distance: 18^Δ vs 0, P<0.001), 1mo (both near and distance: 18^Δ vs 0, P<0.001), 3mo (near: 18^Δ vs 2^Δ, P<0.001; distance: 18^Δ vs 0, P<0.001), and 6mo (near: 18^Δ vs 1.5^Δ, P<0.001; distance: 18^Δ vs 2^Δ, P<0.001) after treatment, respectively. However, no statistically significant differences were observed among all post-BTXA deviations of near and distance (P>0.05).

In Group B, the deviation significant also decreased after BTXA treatment (near: Friedman test=100.336, P<0.001; distance: Friedman test=115.612, P<0.001). Pairwise comparisons revealed significant deviations differences between pre-BTXA and 1wk (near: 18^Δ vs 0, P<0.001; distance: 16^Δ vs 0, P<0.001), 1mo (near: 18^Δ vs 0, P<0.001; distance: 16^Δ vs 2^Δ, P<0.001), 3mo (near: 18^Δ vs 2^Δ, P<0.001; 16^Δ vs 4^Δ, P=0.004), and 6mo (near: 18^Δ vs 6^Δ, P<0.001; distance: 16^Δ vs 6^Δ, P<0.001) after treatment, respectively. Deviation post-BTXA at 3mo (near: 2^Δ vs 0, P<0.001; distance: 4^Δ vs 0, P<0.001) and 6mo (near: 6^Δ vs 0, P<0.001; distance: 6^Δ vs 0, P<0.001) was significant increased compared to deviation at 1wk after treatment (Figure 2, Tables 3 and 4).

Figure 2. Changes of deviations before and after BTXA treatment.

A: Changes of near deviations (33 cm) before and after treatment in two groups; B: Comparisons of near deviations (33 cm) within groups after BTXA treatment; C: Changes of distance deviations (6 m) before and after treatment in two groups; D: Comparisons of distance deviations (6 m) within groups after BTXA treatment. PD: Prism diopter; BTXA: Botulinum toxin A. ^aP<0.001.

Table 3. Comparison of near deviations (33 cm) at pre- and post-BTXA.

Group	Pre-BTXA	Post-BTXA				Friedman test	P
		1wk	1mo	3mo	6mo
A	18 (12, 25)	0 (-4, 2)a	0 (-2, 2)a	2 (-4, 4)a	1.5 (-6, 12)a	92.415	<0.001
B	18 (12, 25)	0 (-4, 4)a	0 (-4, 2)a	2 (-2, 20)a,b,c	6 (-2, 25)a,b,c	100.336	<0.001
Wilcoxon test	0.739	1.076	0.507	4.093	3.983	-	-
P	0.460	0.282	0.612	<0.001	<0.001	-	-

^aP<0.05 compared with pre-BTXA; ^bP<0.05 compared with 1wk post-BTXA; ^cP<0.05 compared with 1mo post-BTXA. PD: Prism diopter; BTXA: Botulinum toxin A.

median (range), PD

Table 4. Comparison of distance deviations (6 m) at pre- and post-BTXA.

Group	Pre-BTXA	Post-BTXA				Friedman test	P
		1wk	1mo	3mo	6mo
A	18 (14, 25)	0 (-8, 3)a	0 (-8, 4)a	0 (-4, 3)a	2 (-4, 15)a	93.862	<0.001
B	16 (12, 25)	0 (-4, 6)a	2 (-2, 4)a	4 (0, 25)a,b,c	6 (-2, 25)a,b,c	115.612	<0.001
Wilcoxon test	1.525	1.501	1.519	6.182	5.075	-	-
P	0.127	0.133	0.129	<0.001	<0.001	-	-

^aP<0.05 compared with pre-BTXA; ^bP<0.05 compared with 1wk post-BTXA; ^cP<0.05 compared with 1mo post-BTXA. PD: Prism diopter; BTXA: Botulinum toxin A.

median (range), PD

Comparison of Stereopsis Between Two Groups

There was no difference of stereopsis between two groups before treatment (P=0.459). Both groups demonstrated improved stereopsis after treatment (Table 5). However, Group A showed a better stereopsis recovery at the final follow-up, compared with Group B (P=0.002).

Table 5. Comparison of stereopsis in both groups.

Stereopsis	Group A	Group B	U a	P
Pre-BTXA	300″ (50″-800″)	300″ (40″-Nil)	0.740	0.459
Post-BTXA 6mo	80″ (40″-400″)	200″ (40″-Nil)	3.086	0.002
U a	5.312	2.087	-	-
P	<0.001	0.037	-	-

^aWilcoxon test. Nil: More than 800″; BTXA: Botulinum toxin A.

median (range)

Complications

There were not statistical difference between the complications in two groups of 1wk after treatment (73.7% vs 70.6%, P=0.768; Table 6). Symptoms resolved 1mo post-BTXA in patients with ptosis (n=5) and 3mo post-BTXA in vertical strabismus cases (n=3, <10^Δ). The most prevalent complication after injection was exotropia (n=10), yet symptoms resolved for the majority of patients in the final follow-up, with small exotropia (<10^Δ) persisting in 4 patients without symptoms. One patient experienced limited eye movement after injection, but symptoms completely resolved within 3mo.

Table 6. Complications 1wk after treatment.

Complications	Group A	Group B
Ptosis	3/38 (7.8)	3/34 (8.8)
Vertical strabismus	1/38 (2.6)	2/34 (5.9)
Transient exotropia	6/38 (15.8)	4/34 (11.8)
Movement limitation	0	1/34 (2.9)
Without complications	28/38 (73.7)	24/34 (70.6)

χ²=1.824, P=0.768.

n (%)

DISCUSSION

This retrospective cohort analysis delves into the influence of varying time intervals from onset to BTXA treatment on efficacy, focusing particularly on individuals with small deviations (≤25^Δ) in AACE. All participants underwent a 6-month follow-up after BTXA injection. Stratifying patients into two groups based on the duration of AACE (Group A: ≤6mo, Group B: >6mo), our objective was to elucidate the advantages of prompt treatment post-onset of AACE. The orthophoria rate at the 6-month follow-up served as the primary outcome measure. The 11 patients experienced relapse during the final follow-up, predominantly from Group B (9/11, 81.82%). Notably, patients receiving BTXA within 6mo of AACE onset demonstrated significantly higher success rates (Group A: 94.74% vs Group B: 73.53%) and better retention or recovery of stereopsis (from 300″ to 80″) at follow-up. Conversely, those receiving BTXA beyond 6mo post-onset exhibited comparatively limited improvement in stereopsis (from 300″ to 200″). These findings underscore the critical role of timely BTXA intervention in optimizing outcomes for AACE patients. In Group A, the shortest duration from onset to treatment was 2wk, resulting in sustained eye alignment for an extended period post-treatment. Conversely, Group B demonstrated a notable resurgence in deviation (near and distance) at 3mo post-treatment. Notably, among Group A patients, none experienced recurrence whose time from onset to treatment was less than three months.

AACE, once considered a rare form of strabismus, has seen a significant rise in prevalence^[18]. Despite its increasing occurrence, the etiology remains unknown, with potential factors including near work, accommodative convergence, fusion function, and physical and psychological stress^[4],^[19]–^[21]. According to Burian and Miller's classification^[1], AACE comprises type I (Swan type), type II (Franceschetti type), and type III (Bielschowsky type). Types I and II are often linked to monocular vision loss and traumatic experiences, while type III is prevalent in myopic older children or adults. While intracranial lesions^[22], systemic diseases^[23], and medications^[24]–^[25] can also cause acute-onset esotropia, diagnosing AACE requires comprehensive systemic examinations and imaging tests^[26]. Although Burian and Miller's classification is commonly used, some scholars need more support. In 2015, Buch and Vinding^[21] proposed a more detailed classification with seven subtypes. In 2003, Spierer^[8] reported 10 cases of adult AACE, primarily type III, with all patients being myopic (spherical equivalent: -4.7 D), suggesting a strong association between AACE and myopia. Similarly, Lee and Kim^[27] reported 16 predominantly type III patients with a mean spherical equivalent of -2.55 D, highlighting the increasing prevalence of type III AACE in clinical settings. Cai et al^[28] found that AACE patients were mostly myopic and that supine position and near-distance work without glasses were independent risk factors for AACE. This is similar to the findings in our result, where the patients also had an average near-distance work of up to 8-9h per day.

The use of BTXA in clinical treatment has a longstanding history. In 1980, Scott^[29] conducted experiments with BTXA injections in adults with esotropia, discovering a positive correlation between doses and corrective effects. In 1997, McNeer et al^[30] treated 76 infants with congenital esotropia using BXTA, achieving a 93% success rate in those treated before age 1, with two-thirds establishing stereopsis over a 3-year follow-up. Campos et al^[31] similarly reported an 88% success rate in a study of 60 infants with congenital esotropia over an average 5.2-year follow-up. This evidence suggests that BTXA can significantly benefit early-onset or acute esotropia affecting visual function. 1999, Dawson et al^[10] pioneered BTXA treatment for AACE in children, achieving an overall success rate of 79% after an average follow-up of 22mo.

The current challenge in AACE lies in refining the consensus on early intervention^[32]–^[33]. A key question is whether BTXA is universally suitable for all types and degrees of AACE. Typically, AACE presents with moderate or small angles, though a few cases may exceed 50^Δ-60^Δ or more. More significant deviations often undergo surgical intervention, leaving a gap in BTXA efficacy analysis, particularly for small-angle AACE^[34]. Routinely, patients have the option of surgical correction and the stability of the procedure is relatively favorable^[35]–^[38]. However, the disadvantage is that it is quite invasive and there is also the potential for secondary surgery. Chen et al^[39] proposed categorizing AACE into smaller (<20^Δ) and larger (>20^Δ) groups, emphasizing the need for differentiated clinical features and treatments. While there is no strict prohibition against attempting BTXA treatment for large-angle AACE, established norms and indications suggest its relatively positive efficacy in small to moderate deviations of comitant strabismus (<40^Δ)^[40]. Previous analyses have not analyzed the efficacy of a range of deviations in isolation, and subjects have often included small deviations as well as large angles of AACE^[10]–^[11],^[13]–^[14],^[41]–^[42]. Consequently, this study focuses on the clinically prevalent range of AACE with small deviations (≤25^Δ).

Another critical aspect influencing the efficacy of BTXA in AACE may be the timing of intervention. Type III AACE exhibits considerable variability in onset age, myopia degree, and AC/A ratio^[43]. The duration from symptom onset to treatment varies widely across studies, ranging from weeks to years, necessitating a more detailed exploration in research. Dawson et al's^[10] study revealed that timely BTXA injections within 8wk of onset resulted in favorable outcomes, with 80% of children remaining orthoptic and gradually establishing stereopsis. Similarly, Wan et al^[11] reported an average onset-to-treatment duration of 3mo, while Xu et al^[42] observed a success rate of 82.8% at a 6-month follow-up, with onset-to-treatment ranging from 1 to 96wk. These findings collectively suggest that early BTXA application is practical in AACE treatment. Chen et al^[44] found a compensatory increase in the volume of the lateral rectus in patients with AACE by quantitative MRI analysis, which may have arisen in a long-term effort to overcome diplopia. This finding further may bolster the benefits of early treatment, as indicated by our conclusions.

Considering the metabolic pattern of BTXA, its peak impact on extraocular muscles typically occurs around one week post-injection^[45]. In alignment with this, our study observed a significant improvement in patients' eye alignment at the one-week follow-up, occasionally with mild overcorrection. The general mechanism of BTXA action continues for approximately 3mo, during which most corrected eye positions tend to maintain orthophoria after the drug's effects have dissipated^[29]–^[30],^[46]. This sustained effect is thought to be linked to factors such as muscle atrophy, enhanced fusion mechanisms, and relief of muscle tension^[46]. The time from onset to treatment might influence these factors, impacting the maintenance effect of BTXA. While most patients remained well-aligned at the final follow-up, those with delayed treatment (>6mo from onset) exhibited a tendency toward deviation rebound in between-group and within-group comparisons. In Group B, statistically significant recovery of esotropia was noted at 3 and 6mo post-injection, compared to the alignment observed 1wk after treatment.

Our study is not without limitations, notably the relatively short follow-up period for patients. Specifically, those in group B demonstrated a notable inclination towards recurrence during the late follow-up phase, potentially necessitating further interventions such as re-injection or surgery in the future. Extending the duration of follow-up could provide a more comprehensive understanding of the metabolic characteristics and durability of BTXA treatment. Additionally, the sample size of our cohort may be considered relatively small, warranting a larger number of cases for robust analysis in subsequent studies. Methodologically, while our study adopts a cohort design, it is inherently retrospective in nature. Thus, future research endeavors may benefit from prospective designs with adequately powered sample sizes to thoroughly elucidate the efficacy of BTXA for AACE.

In conclusion, BTXA is a viable and effective option for treating AACE. The sustained efficacy of BTXA in maintaining eye alignment shows a declining trend over time, potentially linked to the time from onset to BTXA treatment. Provided contraindications are excluded, individuals with small-angle AACE stand to benefit from early-stage BTXA treatment (≤6mo from onset).