Orthokeratology, 0.04% Atropine, and 0.01% Atropine for Myopia Control: A Randomized Clinical Trial.

Abstract

Investigating the antimyopia efficacy and safety of orthokeratology and varying atropine doses in specific age groups could optimize personalized treatment choices. To evaluate the efficacy and safety of orthokeratology, 0.04% atropine, and 0.01% atropine in controlling myopia among older children and adolescents over a 2-year treatment period. This 3-arm, parallel-design, multicenter randomized clinical trial was conducted from June 2021 to August 2023 at the Shanghai Eye Disease Prevention and Treatment Center and the Shanghai Ninth People's Hospital. A total of 209 children aged 8 to 15 years with refractive errors between -1.0 diopter (D) and -4.0 D were enrolled in this study. Primary data analysis was conducted from December 2024 to January 2025, with additional analysis conducted from April 2025 to May 2025. Atropine, 0.01% or 0.04%, administered daily, or overnight orthokeratology for 2 years. The primary outcome was 2-year axial length (AL) growth. Among 209 children enrolled in this study, mean (SD) age was 10.5 (1.79) years, and 104 participants (49.8%) were female. Mean (SD) spherical equivalent (SE) was -2.55 (0.85) D, and mean (SD) AL was 24.7 (0.79) mm. Of 209 enrolled children, 48 of 69 in the 0.01% atropine group (69.6%), 48 of 68 in the 0.04% atropine group (70.6%), and 53 of 72 in the orthokeratology group (73.6%) completed the 2-year follow-up. Children receiving 0.04% atropine had a significantly reduced AL increase than those receiving 0.01% atropine (difference, 0.18 mm; 95% CI, 0.11-0.26; P < .001). Nonsignificant but clinically meaningful difference was found between the 0.01% atropine group and the orthokeratology group (difference, 0.08 mm; 95% CI, 0.003-0.15; P = .04). Regression analyses revealed that older age was associated with less AL growth for all groups, while a more myopic SE at baseline predicted slower axial elongation for the orthokeratology group. The 0.04% atropine group had a higher risk of photophobia than the 0.01% atropine group (11 of 48 patients [22.9%] vs 1 of 48 patients [2.1%], respectively; difference, 20.8%; 95% CI, 8.3%-33.4%; P = .002). In the orthokeratology group, 19 of 72 participants (26.4%) showed slight corneal fluorescein staining. In this randomized clinical trial of participants aged 8 to 15 years, 0.04% atropine was more effective than 0.01% atropine or orthokeratology to control myopia, despite a higher incidence of photophobia. These findings support 0.04% atropine as a superior treatment compared with orthokeratology or 0.01% atropine for older children and adolescents with myopia similar to those enrolled in this trial, although longer-term follow-up is warranted. ClinicalTrials.gov Identifier: NCT05357326.