Low-Dose Atropine and Other Interventions for Pediatric Myopia: A Systematic Review and Bayesian Network Meta-analysis of Efficacy and Post-treatment Outcomes

INTRODUCTION: Although the comparative efficacy of interventions for pediatric myopia control has been explored, the trade-off between on-treatment efficacy and post-treatment rebound remains unclear. We evaluated the comparative efficacy and durability of effect of low-dose atropine (LDA, <0.1%) vs other interventions for pediatric myopia using Bayesian network meta-analysis (NMA). METHODS: Randomized controlled trials (RCTs) investigating the efficacy and safety of interventions for pediatric myopia were identified through a systematic review. Outcomes included change from baseline in spherical equivalent refraction (SER) and axial length (AL) after 1 or 2 years of treatment, and 12 months after treatment cessation. Evidence was synthesized in a hierarchical Bayesian NMA with a dose-response ordering constraint model to improve precision and interpretability for decision-making. Heterogeneity was explored in network meta-regressions (NMR). RESULTS: The systematic review identified 117 RCTs evaluating 24 active interventions. Twenty-two RCTs and one study arm were excluded from quantitative synthesis because of missing outcomes or violation of the transitivity assumption. LDA concentrations ≥0.01% significantly slowed myopia progression compared with an inactive control over 2 years in a dose-dependent manner and showed numerically larger, though statistically non-significant, effects compared with optical interventions. Moderate‑to‑high dose atropine and repeated low‑intensity red‑light, alone or combined with orthokeratology, showed greater short‑term efficacy; however, 12 months post‑cessation, these interventions were associated with clinically meaningful rebound exceeding progression in untreated controls. In contrast, LDA was not associated with clinically meaningful rebound. Combining 0.01% atropine with orthokeratology improved efficacy relative to LDA monotherapy over 2 years, but post-treatment rebound data were unavailable. NMRs indicated baseline SER, baseline progression, geography, and race as effect modifiers, albeit with borderline significance. CONCLUSIONS: These findings describe the comparative efficacy and rebound profiles of treatments for pediatric myopia. Within the current evidence base, atropine concentrations of 0.01% to 0.05% showed sustained on-treatment benefit with minimal post-treatment rebound.