Low-Concentration Atropine (0.01%, 0.025%, 0.05%) for Myopia Progression in Children: A Systematic Review and Meta-Analysis

Objective: Myopia has reached epidemic proportions globally, with approximately 50% of the world population projected to be affected by 2050. Low-concentration atropine eye drops (0.01%, 0.025%, 0.05%) have emerged as a primary intervention for myopia control. Several meta-analyses on this topic have been published; however, none have included the most recent trials nor separately analyzed premyopia prevention outcomes. This systematic review and meta-analysis evaluates the efficacy and safety of these concentrations for myopia progression control and premyopia prevention. Methods: We searched PubMed, Web of Science, Embase, and Cochrane CENTRAL from database inception through April 2026. Randomized controlled trials (RCTs) comparing 0.01%, 0.025%, or 0.05% atropine with placebo or no treatment in children were included. Studies were screened using PICOS criteria (Population, Intervention, Comparison, Outcomes, Study design). Meta-analysis was performed using DerSimonian–Laird random-effects models. Subgroup analyses were conducted by concentration, follow-up duration, and population (myopia progression vs. premyopia prevention). Results: Of 18 full-text articles assessed, 8 RCTs (n = 1756) met all PICOS criteria and were included in the quantitative synthesis. For myopia progression, 0.01% atropine demonstrated significant efficacy at 1 year (pooled MD = +0.291 D, 95% CI: 0.199 to 0.384; p < 0.0001; I2 = 29.1%) and at 2 years (pooled MD = +0.174 D, 95% CI: 0.056 to 0.291; p = 0.0038; I2 = 0%). The 0.05% concentration showed the largest effect (pooled MD = +0.520 D, 95% CI: 0.409 to 0.630; p < 0.0001; I2 = 0%). Clinically, a 0.25 D difference over 1–2 years may translate to approximately 0.50 D cumulative benefit over a typical 5-year treatment course, potentially reducing the risk of high myopia. For premyopia prevention, a narrative synthesis was performed due to extreme heterogeneity between studies (I2 = 99.2%). All concentrations showed an excellent safety profile with no serious adverse events. Conclusions: Low-concentration atropine is effective for myopia progression control at all three concentrations, with a concentration-dependent gradient (0.05% > 0.025% > 0.01%). The 0.01% concentration offers a reasonable balance of efficacy and tolerability. Further independent validation of the 0.05% concentration is warranted. The premyopia prevention indication requires additional well-designed RCTs.