Efficacy, Systemic Safety, and Laboratory Outcomes of Low-Dose Atropine for the Prevention of Myopia Progression in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Primary Studies

Abstract

Introduction: Myopia is the most prevalent refractive disorder of childhood, projected to approach 50% of the population by 2050. Low-dose atropine (0.01–0.05%) is the most investigated pharmacological intervention to slow myopia progression. Methods: A systematic review and meta-analysis was conducted per PRISMA 2020, including RCTs, cohort, case-control, and cross-sectional studies. Risk of bias assessed with RoB 2 and NOS. DerSimonian-Laird random-effects models were used; heterogeneity quantified by I²; certainty by GRADE. Results: Twenty-eight reports from 22 independent populations comprising ≥5,251 children were included. Atropine reduced spherical equivalent refraction (SER) progression at 12 months (MD 0.232 D; 95% CI 0.160–0.304; p<0.001; I²=0%) and axial elongation (AL) (MD −0.106 mm; 95% CI −0.141 to −0.071; p<0.001; I²=36.1%). Effects persisted at 24–36 months: SER MD 0.200 D (p=0.019; I²=72.1%) and AL MD −0.101 mm (p=0.005; I²=61.9%). Fast progression proportion decreased (RR 0.710; p=0.003). Concentration-response gradient: 0.220 D, 0.350 D, and 0.540 D for 0.01%, 0.025%, and 0.05%. Laboratory outcomes: photopic mydriasis 0.431 mm and mesopic 0.268 mm (p<0.001). Systemic safety was favourable: photophobia not increased at 0.01% (RR 1.151; p=0.693). No serious adverse events occurred. Long-term heterogeneity originated from one US trial; its removal yielded SER MD 0.276 D (I²=0%) and AL MD −0.134 mm (I²=0%). Conclusion: Low-dose atropine 0.01–0.05% slows myopia progression with favourable systemic safety. Concentrations of 0.025–0.05% provide greater efficacy without prohibitive adverse effects. Atropine should be considered first-line therapy for progressive childhood myopia.