Abstract:AIM: To conduct a systematic review and Meta-analysis to determine the differential effects of combined lutein and zeaxanthin supplementation on myopia prevention in teenagers. It also investigates the effects of supplements dosage, intervention duration, and geographical variation on intervention results. METHODS: A systematic search and screening of randomized controlled trials (RCTs) completed between 2014 and 2023 was undertaken using the PubMed, EMBASE, Cochrane Library, and Web of Science databases, in accordance with the PRISMA recommendations. The Cochrane risk of bias method was used to assess the quality of the studies. A Meta-analysis was performed using Stata 17.0 to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Subgroup analyses were performed to look at the effects of different doses, intervention periods, and geographic areas. Additionally, publication bias was assessed using Egger’s test. RESULTS: Ten studies including 1035 participants with myopia were analyzed. Supplementation with lutein and zeaxanthin resulted in a significant reduction in axial length elongation among adolescents in the intervention group (SMD=-0.40, P=0.001), an increase in macular pigment optical density (SMD=0.50, P=0.010), and an enhancement in visual sensitivity (SMD=0.53, P=0.008). Subgroup analyses revealed that participants receiving high doses and those undergoing intervention for more than 12mo exhibited significantly improved outcomes compared to those in the low-dose and short-term groups (high-dose vs low-dose: SMD=-0.41 vs -0.22, P=0.003; >12mo vs 6-12mo: SMD=-0.43 vs -0.23, P=0.004, respectively). Furthermore, Egger’s test indicated no significant publication bias (P=0.094). CONCLUSION: Combined lutein and zeaxanthin supplementation has a significant effect on myopia prevention in adolescents, with more pronounced benefits observed in high-dose and long-term interventions. The findings provide scientific evidence for its use as an adjunctive approach in myopia control.