Systematic Review and Meta-Analysis of RCTs on Efficacy of Conventional vs. Emerging Treatments for Amblyopia

Amblyopia affects 1-4% of the population and remains a leading cause of unilateral visual impairment, with adherence and residual deficits limiting outcomes of standard therapies. This systematic review and meta-analysis compared the effectiveness of conventional and emerging amblyopia treatments in children, adolescents, and adults with anisometropic, strabismic, or mixed amblyopia. Following PRISMA guidelines and PROSPERO registration (CRD420251123552), PubMed, Web of Science, and Scopus were searched up to 5 August 2025 for randomized controlled trials. Sixty-six trials (sample sizes 7-404) were included, with thirty-six contributing to the meta-analysis. Primary outcomes were best-corrected visual acuity (logMAR) and stereopsis. Risk of bias was assessed using the Cochrane tool, and certainty of evidence was assessed using GRADE. Atropine penalization and occlusion demonstrated equivalent effects on visual acuity (mean difference 0.04 logMAR; 95% CI -0.04 to 0.12; moderate-certainty evidence). Digital, dichoptic, binocular, and virtual reality therapies showed a statistically significant but small improvement over patching (mean difference 0.02 logMAR; 95% CI 0.00-0.04; low-certainty evidence). Pharmacological adjuvants combined with patching yielded slightly larger gains (mean difference 0.08 logMAR; 95% CI 0.03-0.13; low-to-moderate certainty). No consistent benefit was observed for stereopsis outcomes. Overall, the certainty of evidence ranged from low to moderate, and most pooled effects were below commonly accepted thresholds for clinically meaningful visual acuity improvement (≈0.1 logMAR, one line). Atropine and occlusion remain equivalent first-line treatments, while adjunctive and multimodal approaches may offer limited additional benefit in selected patients when adherence, tolerability, and engagement are prioritized.