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

Abstract 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.