Comparative efficacy and safety of different concentrations of atropine for myopia control in children.
Atropine is known to be an effective intervention to delay childhood myopia progression. Nonetheless, there is as yet no well-supported evidence ranking the clinical outcomes of various concentrations of atropine.
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov on Apr 14, 2021. We selected studies involving atropine treatment of at least 1-year duration for control of myopia in children. We performed a network meta-analysis (NMA) of placebo-controlled and head-to-head randomized controlled trials (RCTs) and compared 8 atropine concentrations (1, 0.5, 0.25, 0.1, 0.05, 0.025, 0.02, and 0.01%). We ranked the atropine concentrations for the corresponding outcomes by P-score (estimate of probability of being best treatment). Our primary outcomes were mean annual changes in refraction (diopters/year) and axial length ([AXL] millimeters/year). We also extracted data on the proportion of eyes showing myopia progression and safety outcomes (photopic/mesopic pupil diameter, accommodation amplitude, distance/near best-corrected visual acuity [BCVA]).
Thirty (30) pairwise comparisons from 16 RCTs (3,272 participants) were obtained. Our NMA ranked the 1, 0.5 and 0.05% atropine concentrations as the 3 most beneficial for myopia control based on P-scores, as assessed for both primary outcomes: 1% atropine (mean difference and 95% CI in refraction compared to control: 0.81 [0.58;1.04]; AXL: -0.35 [-0.46;-0.25]), 0.5% atropine (refraction: 0.70 [0.40;1.00]; AXL: -0.23 [-0.38;-0.07]), 0.05% atropine (refraction: 0.62 [0.17;1.07]; AXL: -0.25 [-0.44;-0.06]). In terms of myopia control as assessed by relative risk (RR) for overall myopia progression, 0.05% was ranked as the most beneficial atropine concentration (RR:0.39 [95% CI: 0.27;0.57]) followed by 1% (0.43 [0.33;0.56]). The ranking probability for adverse effects (photopic/mesopic pupil diameter and accommodation amplitude) tended to decline as the atropine concentration was increased, though this tendency was not evident for distance BCVA. No valid network was formed for near BCVA.
The ranking probability for efficacy was not proportional to dose (i.e., 0.05% atropine was comparable to that of high-dose [1 and 0.5%]), though those for pupil size and accommodation amplitude were dose-related.