Patient demographics

The study included 228 patients diagnosed with AACE who received their first BTXA injection at the CS Eye Clinic from the same surgeon. The patient demographic characteristics are presented in Table 1.

Table 1. Demographic and clinical characteristics of included patients

The patients’ ages ranged from 12 to 75 years, with a mean age of 30.9 ± 11.9 years. The minimum age of 12 years was selected because, in Japan, public health insurance covers BTXA treatment for strabismus only for patients aged ≥12 years. The study population comprised 93 (41%) men and 135 (59%) women. The duration from symptom onset to the initiation of BTXA treatment varied significantly, with a median time to treatment of 36.5 months (range: 0.2–486.7 months). The mean angle of esotropia at a distance was 28.9 ± 14.2 PD. Most (97%) patients exhibited stable esotropia at a distance, while a small proportion (3%) had esophoria at a distance. Near stereopsis was absent and present in 76 (33%) and 152 (67%) patients, respectively. The mean observation period was 9.1 ± 8.2 months.

Injection details

Overall, 318 BTXA injections were administered, with an average of 1.4 ± 0.8 injections per patient. The mean dosage per injection was 2.7 ± 0.9 units.

Treatment outcomes

The treatment outcomes of the 165 patients observed for more than 6 months after the initial injection are shown in Figure 1. Successful results were achieved in 85 cases (52%). Ten (6%) cases demonstrated improvement, and three (2%) showed no change.

Fig. 1

Treatment outcomes. Success was achieved in 85 (52%) patients, improvement in 10 (6%), and no change in 3 (2%). Repeated injections were required in 40 (24%) patients. Surgery was performed in 27 (16%) patients who did not opt for additional botulinum toxin type A (BTXA) injections due to recurrence, insufficient effect, or adverse events

A subset of 40 (24%) patients required repeated injections because of esotropia recurrence. Surgery was performed in 27 (16%) patients who did not opt for additional BTXA injections owing to recurrence, inadequate response, or adverse events.

Changes in the distance angle of deviation

The changes in the distance angle of deviation over time are shown in Figure 2. Before the treatment, the mean angle of deviation was 28.6 ± 12.0 PD. One month after treatment, this angle significantly reduced to 2.3 ± 12.9 PD (P < 0.0001). At the final observation, the mean angle of deviation slightly increased to 10.2 ± 11.4 PD, indicating some degree of regression but still showing a marked improvement from the pre-treatment measurements (P<0.0001).

Fig. 2

Longitudinal changes in the distance angle of deviation. The mean pre-treatment angle of deviation was 28.6 ± 12.0 prism diopter (PD). One month after treatment, it significantly decreased to 2.3 ± 12.9 PD (P < 0.0001). At the final observation, the angle of deviation slightly increased to 10.2 ± 11.4 PD, showing significant improvement compared to the pre-treatment angle (P<0.0001)

Proportion of distance esophoria

Changes in the proportion of distance esophoria are shown in Figure 3. Before treatment, 222 (97%) patients had distance esotropia, while six (3%) patients had distance esophoria. One month after treatment, the number of patients with distance esotropia had decreased to 66 (30%), whereas that of those with distance esophoria had increased to 153 (70%) (P<0.0001). At the final observation, 57 (35%) patients had distance esotropia, and 107 (65%) patients had distance esophoria, showing a significant increase in the proportion of distance esophoria compared with pre-treatment (P<0.0001).

Fig. 3

Proportion of distant esophoria. Before treatment, six (3%) patients had distant esophoria. One month after treatment, the number of patients with distant esophoria increased to 153 (70%) (P<0.0001). At the final observation, 107 (65%) patients had distant esophoria, showing a significant increase in the proportion of distant esophoria compared to pre-treatment (P < 0.0001).

Proportion of near stereopsis less than 100 arcsec

The proportion of patients with good near stereopsis <100 arcsec also showed notable changes (Fig. 4). Before treatment, 84 (37%), 68 (30%), and 76 (33%) patients had near stereopsis <100 arcsec, near stereopsis ≥100 arcsec, and no stereopsis, respectively. One month after treatment, 137 (62%), 62 (28%), and 21 (10%) patients achieved near stereopsis <100 arcsec, near stereopsis ≥100 arcsec, and no stereopsis, respectively. At the final observation, 124 (75%), 27 (16%), and 14 (9%) patients had near stereopsis <100 arcsec, near stereopsis ≥100 arcsec, and no stereopsis, respectively, indicating a significant improvement in near stereopsis over time. The proportion of patients with good near stereopsis significantly increased over time (1 month, P=0.0005; final observation, P<0.0001).

Fig. 4

Proportion of near stereopsis <100 arcsec. Before treatment, 84 (37%) patients had near stereopsis <100 arcsec. One month after the treatment, 137 (62%) patients achieved near stereopsis <100 arcsec. At the final observation, 124 (75%) patients had near stereopsis <100 arcsec, demonstrating a significant increase in the proportion of patients with good near stereopsis over time (at 1 month, P=0.0005; at the final observation, P<0.0001).

Adverse events

Adverse events were observed in 224 patients, as summarized in Table 2. The most common adverse event was blepharoptosis, which occurred in 53 (24%) patients, followed by hypertropia in 35 (16%). Overcorrection and ocular motility dysfunction, which were considered excessive pharmacologic effects rather than true adverse events, were observed in 49 (22%) and 33 (15%) patients, respectively. All of these events were transient and resolved spontaneously within approximately 1 month. In some cases, multiple events occurred in the same patient.

Relationship between dosage and adverse events

The relationship between the dosage of BTXA and the occurrence of adverse events was examined. The group that experienced adverse events, including blepharoptosis or hypertropia (n=78), received a higher average dose of BTXA than the group without these adverse events (n=146). The average dose in the adverse event group was 3.01 ± 0.99 units, while the group without adverse events received 2.60 ± 0.87 units; this difference was statistically significant (P =0.001).

Factors contributing to success

The analysis suggests that the duration from onset to treatment (P=0.018) and post-treatment overcorrection (P=0.0073) independently influenced the likelihood of success. Specifically, a shorter duration from onset to treatment and post-treatment overcorrection were associated with higher success rates. The results are summarized in Table 3.

Table 3. Factors Contributing to Success (Multivariable Logistic Regression Analysis)