Efficacy and Safety of Low-Concentration Atropine in Slowing Myopia Progression in Children in Japan: The Randomized, Double-Blind Phase II/III ORANGE Study
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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 following treatment cessation. Design Randomized, double-masked, placebo-controlled, phase 2/3 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 (standard deviation [SD]) SE change from baseline at month 24 with atropine 0.01%, 0.025%, and placebo was –1.31 (0.71), –1.02 (0.86), and –1.65 (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 P < 0.0001). Mean (SD) AL change from baseline at month 24 with atropine 0.01%, 0.025%, and placebo was 0.64 (0.31), 0.51 (0.36), and 0.74 (0.36) mm, respectively; corresponding LS mean (standard error) treatment differences versus placebo were –0.11 (0.03) mm ( P < 0.05) and –0.23 (0.03) mm ( P < 0.0001). Following a switch to placebo from atropine 0.01%, 0.025%, or placebo, LS mean (standard error) SE change from month 24 at month 36 was –0.61 (0.07), –0.75 (0.07), and –0.40 (0.07) D, respectively, which suggested a small, concentration-dependent myopia progression "rebound" effect, which was not considered to be clinically meaningful. LS mean (standard error) AL change from month 24 to month 36 was 0.30 (0.03), 0.32 (0.03), and 0.21 (0.03) mm, respectively. The most common ocular ADR over 24 months was photophobia, mostly mild, occurring in 1.0–10.9% of children receiving atropine 0.01%, 0.025%, or placebo. 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.
Source: Ophthalmology Science
Authors: Kyoko Ohno-Matsui, Tae Igarashi-Yokoi, Yukie Migita, Yutaka Yamakawa
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funder: Santen
OpenAlex ID: W4415017382