A Randomized, Double-Masked, Placebo-Controlled Clinical Trial of Two Forms of Omega-3 Supplements for Treating Dry Eye Disease

Purpose: To assess the efficacy of 2 forms of oral long-chain omega-3 (omega-3) essential fatty acid (EFA) supplements, phospholipid (krill oil) and triacylglyceride (fish oil), for treating dry eye disease (DED). Design: Randomized, double-masked, placebo-controlled clinical trial. Participants: This study was conducted at a single site and involved 60 participants with mild to moderate DED who were randomized (1: 1: 1) to 1 of 3 groups: placebo (olive oil), krill oil, or fish oil supplements. Methods: Participants received 1 of the 3 interventions: placebo (olive oil 1500 mg/day), krill oil (945 mg/day eicosapentaenoic acid [EPA], + 510 mg/day docosahexaenoic acid [DHA]), or fish oil (1000 mg/day EPA + 500 mg/day DHA) for 90 days, with monthly study visits. Main Outcome Measures: Primary outcome measures were mean change in (1) tear osmolarity and (2) DED symptoms (Ocular Surface Disease Index [OSDI] score) between days 1 and 90. Secondary outcomes included mean change in key clinical signs (tear stability, tear production, ocular surface staining, bulbar and limbal redness, tear volume, anterior blepharitis, meibomian gland capping) and tear inflammatory cytokine levels. Results: In total, 54 participants completed the study. At day 90, tear osmolarity was reduced from baseline with both krill oil (mean +/- standard error of the mean: -18.6 +/- 4.5 mOsmol/l; n = 18; P < 0.001) and fish oil (-19.8 +/- 3.9 mOsmol/l; n = 19; P < 0.001) supplements, compared with placebo (-1.5 +/- 4.4 mOsmol/l; n = 17). OSDI score was significantly reduced at day 90 relative to baseline in the krill oil group only, compared with placebo (-18.6 +/- 2.4 vs. -10.5 +/- 3.3; P = 0.02). At day 90, there were also relative improvements in tear breakup time and ocular bulbar redness, compared with placebo, for both forms of omega-3 EFAs. Basal tear levels of the proinflammatory cytokine interleukin 17A were significantly reduced in the krill oil group, compared with placebo, at day 90 (-27.1 +/- 10.9 vs. 46.5 +/- 30.4 pg/ml; P = 0.02). Conclusions: A moderate daily dose of both forms of long-chain omega-3 EFAs, for 3 months, resulted in reduced tear osmolarity and increased tear stability in people with DED. Omega-3 EFAs in a predominantly phospholipid form (krill oil) may confer additional therapeutic benefit, with improvements in DED symptoms and lower basal tear levels of interleukin 17A, relative to placebo. (C) 2016 by the American Academy of Ophthalmology