Atropine Ophthalmic Solution to Reduce Myopia Progression in Pediatric Subjects: The Randomized, Double-Blind Multicenter Phase II APPLE Study

Purpose:The purpose of this study was to assess the dose-response effects of low-dose atropine on myopia progression and safety in pediatric subjects with mild-to-moderate myopia. Methods:This phase II, randomized, double-masked, placebo-controlled study compared the efficacy and safety of atropine 0.0025%, 0.005%, and 0.01% with placebo in 99 children, aged 6-11 years, with mild-to-moderate myopia. Subjects received 1 drop in each eye at bedtime. The primary efficacy endpoint was change in spherical equivalent (SE), while secondary endpoints included changes in axial length (AL) and near logMAR (logarithm of the minimum angle of resolution) visual acuity and adverse effects. Results:The mean & PLUSMN;SD changes in SE from baseline to 12 months in the placebo and atropine 0.0025%, 0.005%, and 0.01% groups were -0.55 & PLUSMN;0.471, -0.55 & PLUSMN;0.337, -0.33 & PLUSMN;0.473, and -0.39 & PLUSMN;0.519 D, respectively. The least squares mean differences (atropine-placebo) in the atropine 0.0025%, 0.005%, and 0.01% groups were 0.11 D (P=0.246), 0.23 D (P=0.009), and 0.25 D (P=0.006), respectively. Compared with placebo, the mean change in AL was significantly greater for atropine 0.005% (-0.09 mm, P=0.012) and 0.01% (-0.10 mm, P=0.003). There were no significant changes in near visual acuity in any of the treatment groups. The most common ocular adverse events were pruritus and blurred vision, each occurring in 4 (5.5%) atropine-treated children. Changes in mean pupil size and amplitude of accommodation were minimal. Conclusions:Atropine doses of 0.005% and 0.01% effectively reduced myopia progression in children but no effect was noted with 0.0025%. All doses of atropine were safe and well tolerated.