Mediterranean Diet on Development and Progression of Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Observational Studies

Introduction: Age-related macular degeneration (AMD) is a leading cause of vision impairment. A Mediterranean diet (MD) has been suggested to provide protective effects against AMD development and progression due to its antioxidant and anti-inflammatory properties. However, inconsistencies in findings across observational studies have been reported. This systematic review and meta-analysis aim to synthesize the existing evidence on the relationship between adherence to the MD and AMD development or progression. Methods: A systematic search was conducted using MEDLINE (via PubMed), Web of Science, and SCOPUS, following PRISMA guidelines. Observational studies assessing MD adherence in relation to AMD risk or progression were included. Meta-analyses were performed separately for each study design using odds ratios (ORs) for cross-sectional and case-control studies and hazard ratios (HRs) for prospective cohort studies. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated via funnel plots. Results: Eight studies were included: two cross-sectional, three case-control, and three prospective cohort studies. The meta-analysis of cross-sectional studies (pooled OR = 0.96; 95% CI: 0.83-1.11; p = 0.6243; I2 = 0%) found no significant association between MD adherence and AMD. However, the weight distribution was highly imbalanced, limiting interpretability. Meta-analyses of case-control and prospective cohort studies demonstrated a significant protective effect of MD adherence: case-control studies showed a 34% reduction in the odds of AMD progression (OR = 0.66; 95% CI: 0.54-0.81; p < 0.0001; I2 = 41.5%), while prospective cohort studies indicated a 23% reduced risk of AMD progression (HR = 0.77; 95% CI: 0.67-0.88; p < 0.0001; I2 = 0%). Conclusions: This systematic review and meta-analysis suggest an inverse association between adherence to the MD and AMD progression, particularly in case-control and prospective cohort studies. Despite the small number of included studies, these findings highlight the potential role of diet in AMD management. Future research should focus on larger, well-controlled prospective studies with standardized dietary assessments. Key Points: 1. Higher adherence to the MD is associated with a reduced risk of AMD progression, with meta-analyses of case-control and prospective cohort studies showing 34% lower odds (OR = 0.66) and 23% reduced risk (HR = 0.77) of disease progression, respectively. 2. No significant association was found in cross-sectional studies (OR = 0.96; 95% CI: 0.83-1.11), likely due to methodological limitations and the challenge of establishing a temporal relationship between diet and AMD progression. 3. Despite the limited number of studies, findings suggest a potential role of diet in AMD management. Future research should prioritize larger, well-controlled prospective studies with standardized dietary assessments.