Re-esterified triglyceride ω-3 fatty acid supplementation did not improve symptoms of dry eye disease associated with meibomian gland dysfunction, a randomized trial from South Korea showed, adding to the growing body of evidence against the popular therapy.

The change in Ocular Surface Disease Index (OSDI) from baseline to 6 and 12 weeks was -20.5 and -22.7 in the ω-3 fatty acid group and -15.1 and -18.8 in the grape-seed oil control group (P=0.12 and P=0.28, respectively), reported Joon Young Hyon, MD, PhD, of Seoul National University College of Medicine in the Republic of Korea, and colleagues in JAMA Ophthalmology.

There were no changes in safety or adverse events with the dietary supplement in either group.

“I do not think they work,” said Penny A. Asbell, MD, MBA, of the University of Tennessee Health Science Center in Memphis, in an interview with MedPage Today. Asbell, who was not involved in the current study, led the landmark DREAM study, which found no benefit with fish-derived omega-3 fatty acids compared with an olive oil placebo in patients with moderate-to-severe dry eye disease.

Dry eye disease may be the most common reason that patients seek eye evaluations, although exact numbers are hard to track because it’s not always documented in medical records, Asbell explained. While some patients report pain and vision abnormalities, “they have different ways of describing something that doesn’t feel quite right about their eyes.”

Artificial tears are the old standby treatment, but they don’t always clear up the problem, Asbell noted. Several FDA-approved medications are available, including immunomodulators that reduce inflammation on the ocular surface, and many more are in development.

Researchers have studied omega-3 supplements in dry eye disease for years, Asbell said, adding that patients often like the idea of taking over-the-counter fish oil supplements because they consider them a natural product, but studies have repeatedly questioned their value.

Hyon and colleagues launched this study as a follow-up to Asbell’s 2018 trial. They noted that trials have shown mixed results with omega-3 fatty acids in dry eye disease, highlighting a 2016 trial that found benefits from re-esterified omega-3 fatty acids.

In an invited commentary, Ian J. Saldanha, MBBS, MPH, PhD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, noted that the study findings “are largely consistent with much of the existing evidence.”

However, he pointed out that the researchers linked some secondary outcomes, such as greater changes in upper and lower eyelid telangiectasia and eyelid wiper epitheliopathy grades, to omega-3 supplements, raising the prospect that higher doses could be beneficial.

“In sum, more work may need to be done before the field makes a firm conclusion and fully closes the chapter on omega-3 fatty acid supplements for patients with evaporative dry eye,” Saldanha wrote.

For her part, Asbell said the new study appears valid, but she questioned why the control was grape-seed oil, which the authors noted has antioxidant properties and may protect the eye from oxidative stress. She also wondered if the study participants may have been getting high amounts of omega-3 fatty acids from their diets, and noted that dry eye disease itself is difficult to measure.

If patients with dry eye disease want to try omega-3 supplements, Asbell said the risks are limited, other than bleeding linked to high doses, and there could be a beneficial placebo effect. She also pointed out that patients must take several large capsules a day to reach recommended doses.

For this double-masked, parallel-group study, the researchers recruited 132 patients with dry eye disease associated with meibomian gland dysfunction at seven institutions from September 2020 to January 2023. Mean age was 50.6 years, and 78% were women. Mean baseline OSDI scores for the ω-3 fatty acid and grape-seed oil groups were 43.5 and 44.1, respectively.

The patients were randomly assigned to four daily doses of 1,680 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid (via a product called De3 Omega Benefits that is made by the study sponsor) or four daily doses of 3,000 mg of grape-seed oil.

A total of 58 and 57 patients in the two groups completed 12 weeks of follow-up. There were no differences in compliance with dietary supplement intake between groups (95.8% and 95.4%, respectively).

Hyon and team reported no differences between the groups in eye drop use or mean visual acuity.

In regard to limitations, the researchers noted that the study period was short, the sample size was small, and no placebo was used.