Twice-daily administration improves the effectiveness of 0.01% atropine for controlling myopia in slowing axial elongation and refractive progression.

Purpose: It remains unclear whether increasing the frequency of administration of 0.01% atropine improves its effectiveness in slowing axial elongation or refractive progression. This study compared twice-daily 0.01% atropine administration and traditional once-nightly administration.

Methods: A hybrid design was adopted incorporating both retrospective and prospective elements, with participants observed for 1 year. The control group (received saline eye drops) and once-daily 0.01% atropine group (Atropine-1 group) were derived from two previous trials, while the twice-daily 0.01% atropine group (Atropine-2 group) was enrolled prospectively. A total of 163 participants were included in the intention-to-treat set, with 51, 70 and 42 participants in the control, Atropine-1 and Atropine-2 groups, respectively. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in cycloplegic spherical equivalent refraction (SER).

Results: Compared with the control group (0.48 ± 0.22 mm), both Atropine-1 (0.26 ± 0.17 mm) and Atropine-2 (0.15 ± 0.18 mm) groups showed significantly reduced AL elongation (p < 0.001). Notably, Atropine-2 significantly improved slowing of AL elongation compared with Atropine-1 (p = 0.008). The result of the secondary outcome (adjusted SER change) was consistent. Atropine-2 was significantly more effective in slowing SER progression (-0.15 ± 0.37 D) than Atropine-1 (-0.41 ± 0.50 D) (p = 0.02). Based on a multivariable model, age was identified as the key covariate to perform subgroup analyses. In the younger subgroup (8-10 years), AL elongation was significantly reduced in the Atropine-2 group (0.16 ± 0.17 mm) compared with the Atropine-1 group (0.36 ± 0.22 mm; p = 0.002). In the older subgroup (10-12 years), there was no significant difference in progression. Consistent results were observed in the sensitivity analyses based on the per-protocol set.

Conclusion: Twice-daily administration of 0.01% atropine was more effective than once daily in slowing AL elongation and SER progression in children 8 to 10 years of age. Further investigation with extended follow-up is warranted to substantiate this finding.