To explore the efficacy of omega-3 fatty acids (FAs) on patients suffering from dry eye disease (DED), a complex inflammatory condition, we reviewed data from PubMed, Embase, ClinicalTrials.gov, Web of Science, and Cochrane CENTRAL in the past 10 years (2013 to 2023). These sources provided randomized clinical trials (RCTs) that examined the efficacy of omega-3 FAs on DED patients with accessible pre- and post-intervention data, excluding trials with overlapping participants, without omega-3 supplementation, or those lacking placebo control or quantitative assessments. Two independent reviewers extracted data related to dry eye symptom scores, tear break-up time (TBUT), Schirmer's tests, osmolarity, and corneal fluorescein staining (CFS), and the results were analyzed by Comprehensive Meta-Analysis software version 4. We incorporated 19 related RCTs assessed by the Cochrane Risk of Bias tool, encompassing 4246 DED patients with various etiologies. Patients given omega-3 treatment demonstrated more significant improvements in dry eye symptoms (Hedges' g = -1.047; p < 0.001), TBUT [standardized mean difference (SMD) = -0.939; p < 0.001], scores from the Schirmer test (SMD = -0.372; p < 0.001), CFS (SMD = -0.299; p = 0.037), and osmolarity (SMD = -0.721; p < 0.001) compared to those on a placebo regimen. In the meta-regression analysis of DED symptoms, the daily dose of omega-3 (coefficient = -0.0005, p = 0.002), duration of omega-3 intake (coefficient = -0.1399, p = 0.021), and percentage of eicosapentaenoic acid (EPA) (coefficient = -0.0154, p < 0.001) exhibited a significant positive correlation with a reduction in dry eye symptom scores. Apart from CFS, similar trends were noted in TBUT, Schirmer tests, and osmolarity scores. Based on the evidence, omega-3 FAs effectively reduce DED symptoms, especially in high doses, for a long duration, and with increased EPA levels. However, given the heterogeneity in study results and diverse patient characteristics, caution is needed in generalizing these findings. In conclusion, omega-3 FA supplementation is still recommended for DED management in clinical settings.
Keywords: dry eye disease; eicosapentaenoic acid percentage; fatty acid; meta-analysis; omega-3; systematic review.