A Meta-Analysis Assessing Change in Pupillary Diameter, Accommodative Amplitude, and Efficacy of Atropine for Myopia Control

Purpose: To determine the effect of atropine on pupillary diameter, accommodative amplitude as well as myopia progression. Methods: Medical databases and Cochrane Library were systematically searched for studies from 1980 until June 2020. The primary and secondary outcomes were: a) change in pupillary diameter (PD) and accommodative amplitude (AA) and b) annualized mean change in spherical equivalent and axial length with various concentrations of atropine compared to control. Results: Thirteen trials (6 RCTs, 7 observational studies) that studied 9 atropine concentrations (0.01-1.0%) were included. The relation between atropine and change in PD and AA was nonlinear; at < 0.10% atropine, the slope of the curve was steep but the change in PD (+0.7 mm; 95% CI: +0.1 to +1.4) and AA (-1.6D; 95% CI: -3.9 to +0.7) was smaller whereas at >= 0.10% atropine, the slope plateaued but change in PD (+3.2 mm, 95% CI: +2.8 to +3.5) and AA (-10.7D; 95% CI: -12.2 to -9.2) was high. Reduction in myopia progression with atropine at <0.10% and >= 0.10% as compared to controls was 0.37D (95% CI: 0.16 to 0.58) versus 0.75D (95% CI: 0.17 to 1.33) for spherical equivalent and -0.10 mm (95% CI: -0.24 to 0.05) versus -0.23 mm (95% CI: -0.34 to -0.13) for axial length. Conclusions: A nonlinear dose-response relationship exists between atropine and PD and AA. Further work is warranted to determine the concentration that provides maximal efficacy with tolerable side effects.