Atropine, red-light therapy, and lenslet spectacles for premyopia: a systematic review and meta-analysis.

PURPOSE: Earlier onset of childhood myopia is associated with greater subsequent progression and a higher risk of high myopia and related ocular complications. This systematic review and meta-analysis evaluated whether low-concentration atropine, repeated low-level red-light therapy (RLRL), and study-specific lenslet-array spectacle designs reduce refractive change and axial elongation in non-myopic children classified as premyopic. METHODS: This review was registered in PROSPERO (CRD420251252431) and conducted according to PRISMA 2020. PubMed, Web of Science, and Scopus were searched from inception to 17 July 2026. Eligible studies were randomized controlled trials with follow-up ranging from 3 to 24 months that included children meeting study-specific criteria for premyopia and reported cycloplegic spherical equivalent (SE) and/or axial length (AL). Risk of bias was assessed using the Cochrane tool, and certainty of evidence was evaluated using GRADE. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated using RevMan 11.4.2. RESULTS: Eight randomized controlled trials were included, seven conducted in China and one in India. At 12 months, 0.01% atropine was associated with a smaller myopic shift in SE (4 studies; 574 participants; MD, + 0.32 D; 95% CI, 0.12 to 0.52; I² = 72%; low-certainty evidence). RLRL also favored a smaller myopic shift (2 studies; 307 participants; MD, + 0.38 D; 95% CI, - 0.05 to 0.81; I² = 0%; very-low-certainty evidence). One study-specific positive Lenslet-Array-Integrated spectacle design involving 173 participants reported an MD of + 0.45 D (95% CI, 0.38 to 0.52). For AL, atropine showed a trend toward reduced axial elongation (MD, - 0.13 mm; 95% CI, - 0.26 to - 0.00; I² = 74%; very-low-certainty evidence), whereas RLRL showed an MD of - 0.16 mm (95% CI, - 0.30 to - 0.01; I² = 0%; very-low-certainty evidence). The lenslet-array study reported an MD of - 0.31 mm (95% CI, - 0.42 to - 0.20). Technical reporting and adverse-event assessment were incomplete, particularly for optical and red-light interventions. CONCLUSION: Available randomized evidence suggests that some interventions may reduce early refractive change in children classified as premyopic, while effects on axial elongation remain less certain. Atropine had the largest evidence base, but certainty was low for SE and very low for AL. RLRL and the study-specific lenslet-array spectacle design showed potential benefits; however, limited replication, incomplete technical characterization, restricted geographic representation, and insufficient long-term safety evidence limit confidence and generalizability.