Efficacy and Safety of Low-Concentration Atropine in Slowing Myopia Progression in Children in Japan: The Randomized, Double-Blind Phase II/III ORANGE Study.

Purpose: To evaluate the efficacy and safety of low-concentration atropine ophthalmic solution for slowing disease progression in children with myopia and assessing rebound phenomenon after treatment cessation. Design: A randomized, double-masked, placebo-controlled, phase II/III clinical trial in Japan. Subjects: Children (n = 299) aged 5-15 years with cycloplegic objective spherical equivalent (SE) -1.0 to -6.0 diopters (D) in both eyes. Methods: Subjects were randomized to atropine 0.01%, 0.025%, or placebo (1 drop once daily before bedtime in both eyes) for 24 months before receiving atropine 0.01%, 0.025%, or placebo for a further 12 months. Main Outcome Measures: The primary endpoint was mean SE change from baseline at month 24; axial length (AL) change was a secondary endpoint. Safety evaluations included ocular adverse drug reactions (ADRs). Results: Mean SE change from baseline at month 24 with atropine 0.01%, 0.025%, and placebo was -1.31 (standard deviation [SD]) 0.71), -1.02 (SD 0.86), and -1.65 (SD 0.90) D, respectively; least squares (LS) mean (standard error) differences versus placebo were 0.34 (0.08) D and 0.65 (0.08) D (both Conclusions: Atropine 0.01% and 0.025% slowed myopia progression in children. There was a small, not clinically meaningful, rebound in myopia progression after the cessation of atropine treatment. Both concentrations were well tolerated. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.