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 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). After a switch to placebo from atropine 0.01%, 0.025%, or placebo, LS mean (standard error) SE change from month 24 to 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. Least squares 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.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.