Two year randomised trial of twice versus once daily 0.01% atropine for childhood myopia control with real world extension

Abstract To assess the efficacy of 0.01% atropine eye drops in myopia control with different frequencies (nightly versus twice daily) over a two-year period. Children aged 6 to 13 years with a post-cycloplegic spherical equivalent refraction (SER) between − 0.75 and − 6.00 D were randomly assigned in a 1:1 ratio to receive 0.01% atropine either nightly (QD) or twice daily (BID) during Phase I (the first year). Participants were then given the option to continue into Phase II (the second year), a real-world extension phase without randomization. The primary endpoint was axial length (AL) change over two years; SER change was a key secondary endpoint. A two-year follow-up was completed for 20 and 28 participants in the QD and BID groups, respectively. Over two years, the adjusted increase in AL was 0.523 mm in the QD group and 0.372 mm in the BID group, with an adjusted between-group difference of − 0.132 mm (95% CI − 0.246 to − 0.019; P = 0.023). Adjusted SER progression was − 1.087 D in the QD group and − 0.447 D in the BID group, with an adjusted difference of 0.640 D (95% CI 0.351 to 0.930; P < 0.001). During Phase II, no significant between-group differences were found in AL or SER changes ( P = 0.916 and P = 0.247). Twice-daily 0.01% atropine was associated with slower myopia progression over two years, but no significant additional benefit was observed during the second year in this small real-world extension.