Abstract
BACKGROUND: Diabetic Retinopathy is a significant microvascular complication of diabetes mellitus characterized by progressive damage to the retinal vasculature. Current management strategies focus on modifying risk factors and treating established disease. Omega-3 polyunsaturated fatty acids (PUFAs) demonstrate anti-inflammatory, antioxidative, and vasculoprotective properties. OBJECTIVES: To evaluate the protective effects of omega-3 fatty acids on DR incidence, progression, and microvascular health across diverse diabetic populations. METHODS: A comprehensive literature search was conducted via PubMed, EBSCO Open Research, ScienceDirect, Wiley Online Library, and Google Scholar. A reviewer screened the potential articles against prespecified eligibility criteria. The risk of bias in the eligible studies was then evaluated using the Newcastle Ottawa Scale (NOS), a Risk of Bias visualization tool developed by the Cochrane Collaboration (ROB 2.0). Data were then systematically extracted and analyzed. RESULTS: Fourteen studies involving 139,879 participants were analyzed. Omega-3 fatty acid intake of ≥500 mg/day significantly reduced the risk of sight-threatening diabetic retinopathy (DR) by 48% (HR = 0.52; 95% CI: 0.31-0.88; p = 0.001). Subgroup meta-analysis showed a stronger associated protective effect in type 2 diabetes (T2D) compared to type 1 (T1D), with a pooled hazard ratio of 0.71 (log HR = -0.339; SE = 0.0667; p < 0.000001). The antioxidant benefits were linked by a pooled mean difference of -1.399 in oxidative stress markers (MDA/TBARS) (95% CI: -1.432 to -1.366; Z = 83.29; p < 0.00001), with no significant heterogeneity (I² = 0%). Further stratification showed robust effects in both RCTs (HR = 0.743; p = 0.002) and non-RCTs (HR = 0.514; p = 0.005). These findings support omega-3s-especially in T2D-as a non-pharmacologic intervention for DR prevention, likely through anti-inflammatory and vasoprotective mechanisms. CONCLUSION: Omega-3 fatty acid intake is associated with dose-dependent protection against diabetic retinopathy, with the greatest benefits from whole food sources, optimal omega-6/omega-3 ratios, and in well-controlled T2D patients.