Orthokeratology, 0.04% Atropine, and 0.01% Atropine for Myopia Control

Importance: Investigating the antimyopia efficacy and safety of orthokeratology and varying atropine doses in specific age groups could optimize personalized treatment choices. Objective: 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. Design, Setting, and Participants: 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. Interventions: Atropine, 0.01% or 0.04%, administered daily, or overnight orthokeratology for 2 years. Main Outcomes and Measures: The primary outcome was 2-year axial length (AL) growth. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT05357326.