Patients with dry eye may not significantly benefit from supplementation with fish-derived omega-3 fatty acids, according to findings from a year-long randomized, controlled trial.

The results, reported earlier this month in The New England Journal of Medicine, are the most reliable and generalizable evidence thus far on omega-3 supplementation for dry eye disease, and goes against what previous trials have shown. These new observations were surprising to many eye care providers that routinely prescribe omega-3s for this condition.

“This study is sure to stir up a lot of controversy,” commented Julie Schallhorn, MD, an assistant professor of clinical ophthalmology at the University of California, San Francisco.

Both Dr. Schallhorn and Sumitra S. Khandelwal, MD, an associate professor of ophthalmology at Baylor College of Medicine, point out that though the DREAM (Dry Eye Assessment and Management) study was rigorous and well executed, the results should be taken in context.

“It looked at one type of omega-3 formulation. Its placebo was olive oil, which could have its own anti-inflammatory properties,” explained Dr. Khandelwal. “In addition, it was a real-world study, which has pros and cons, one of which being that additional treatment was not controlled. All that being said, it is the first study of its kind and opens the door to discussion of management of dry eye.”

Conducted at 27 centers across the United States, the NEI-funded DREAM trial was a double-masked study that enrolled 535 individuals with moderate to severe dry eye disease. The treatment arm consisted of 349 patients who took 3,000 mg of omega-3 (2000-mg eicosapentaenoic acid and 1000-mg docosahexaenoic acid) daily—the highest dose ever tested for treating dry eye disease. The 186 individuals who were randomly assigned the control arm took 5,000 mg of olive oil. Unlike in most industry-sponsored trials, all participants were free to continue taking their previous dry eye medications.

After 1 year, both the active supplement and placebo groups reported significantly improved Ocular Surface Disease Index (OSDI) scores from baseline (13.9 vs 12.5 points, respectively). However, the 1.4-point difference did not reach statistical significance (P=0.21). Other ocular surface parameters—including conjunctival staining, corneal staining, tear break-up time, and Schirmer’s test scores—were also comparable between groups.

“I think this study really highlights how much we don’t understand about the complex interplay between patient-reported symptoms and clinical dry eye disease,” concluded Dr. Schallhorn. “Moving forward, it may make sense to start investigating psychometric factors in future dry eye trials to try to help us better understand the treatment of dry eye disease.”