Oral Nutritional Supplements for Dry Eye Disease. A Systematic Review with Pairwise and Exploratory Network Meta-Analysis of Randomized Controlled Trials

Oral supplements are widely used for dry eye disease (DED), but their effects and relative merits are uncertain. Five databases (to 18 June 2026) and two trial registers were searched for randomized trials of oral supplements against placebo or no supplement. Classes were pooled against control in sign-confirmed DED with random-effects models and Hartung-Knapp intervals. A network model was exploratory. Certainty was rated with GRADE. We included 57 trials (6,615 participants), 29 (2,272 participants) in the primary analyses. The Ocular Surface Disease Index differed by −4.4 points (95% CI −9.0 to 0.2) with marine omega-3 (6 trials) and by −5.2 points (−8.8 to −1.7) with omega-3 combinations (4 trials), both below the 7-point threshold for an important difference. Marine omega-3 increased tear break-up time by 1.32 seconds (0.05 to 2.60, prediction interval −1.3 to 4.0). Certainty was very low for 40 of 48 comparisons and low for 8. All comparisons between classes were indirect, across dissimilar trials and controls, with very low certainty. Twenty trials reported no safety data. Some classes had favorable average estimates against control, but effects were small, imprecise or inconsistent, and classes cannot be ranked. Current evidence does not support routine use. CRD420261432518, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261432518.