Abstract / Summary
Low-dose atropine eye drops slow childhood myopia progression, but randomized evidence in European children and for intermediate concentrations remains limited. This study evaluated 0.02% and 0.04% atropine for 12-month myopia control in Czech children. The MARS study was an investigator-initiated, phase IIIb, multicenter, randomized, double-masked, placebo-controlled trial. Children aged 6–11 years with documented accelerated prerandomization axial length (AL) elongation and cycloplegic spherical equivalent refraction (SER) from −0.50 to −4.75 D were randomized 2:1:1 to nightly 0.02% atropine, 0.04% atropine, or placebo. The primary endpoint was the between-group difference in AL change at Month 12 for 0.02% atropine versus placebo. Linear mixed-effects models accounted for inter-eye correlation. Repeated-measures and multiple-imputation sensitivity analyses assessed the effect of missing data. A total of 191 participants (351 eyes) were included in the primary analysis. Compared with placebo, adjusted mean between-group differences in AL change were −0.144 mm for 0.02% atropine (95% confidence interval [CI] −0.201 to −0.087; P < 0.0001) and −0.157 mm for 0.04% atropine (95% CI −0.222 to −0.092; P < 0.0001). Corresponding differences in SER progression were 0.352 D (95% CI 0.199 to 0.505; P < 0.0001) and 0.389 D (95% CI 0.214 to 0.564; P < 0.0001). No statistically significant difference was detected between 0.02 and 0.04% atropine for AL (0.013 mm; 95% CI −0.043 to 0.069; P = 0.8935) or SER (−0.037 D; 95% CI −0.189 to 0.115; P = 0.8802). Sensitivity analyses yielded consistent AL estimates. Nightly 0.02% and 0.04% atropine reduced axial elongation and myopia progression over 12 months compared with placebo. The trial was not designed or powered to establish equivalence between the active doses; within this sample, no statistically significant difference was detected between them. European Clinical Trials Database (EudraCT no. 2020–002046-16), Clinical Trials Information System (CTIS), EU Clinical Trial (EU CT) no. 2024–515888-54-00. Myopia (nearsightedness) often worsens as a child’s eye grows longer, increasing the risk of eye disease later in life. Atropine eye drops can slow this progression, but evidence in European children and for intermediate doses is limited. In the MARS trial, Czech children aged 6–11 years were randomly assigned to use 0.02% atropine, 0.04% atropine, or inactive placebo drops every night. Neither families nor investigators knew the assignment. After 12 months, both atropine groups had less eye growth and less worsening of myopia than the placebo group. Analyses that accounted for missing measurements gave similar results. The study did not detect a statistically significant difference between the two atropine doses, but it was not designed to prove that the doses are equivalent. Corneal measurements did not explain the treatment effect; the difference was driven by slower eye growth. Detailed pupil, accommodation, visual-comfort, and adverse-event outcomes are reported or planned separately. These findings support both 0.02% and 0.04% atropine as effective options for slowing myopia progression in the studied population, while longer follow-up is needed to assess durability, tolerability, and rebound after treatment stops.