GOED says results of null trial on omega-3s’ effects on dry eye have been overstated

A recent NIH-funded study has clouded the issue of whether omega-3s can ameliorate the symptoms of dry eye disease.

The study, published on Friday in the New England Journal of Medicine, looked at the effect of a high dose of EPA and DHA as an adjunct therapy in addressing this condition. The multi center study was called the Dry Eye Assessment and Management (DREAM) trial and was coordinated through the University of Pennsylvania.

Dry eye disease, also known as keratoconjunctivitis sicca, is a chronic inflammatory condition that is relatively common in older people. According to the researchers, this condition affects about 14% of the population and causes ocular discomfort, fatigue, and visual disturbances that interfere with reading, computer use and driving.

Large trial group

The researchers recruited 537 patients, who were randomly assigned at a 2:1 ratio of treatment to placebo groups. The treatment group received 3 grams of omega-3s per day, in five capsules, each containing 400 mg of EPA and 200 mg of DHA, for a total daily dose of 2000 mg of EPA and 1000 mg of DHA. The placebo group downed five capsules of refined olive oil. Both placebos and omega-3 capsules (which were made by contract manufacturer Access Business Group) contained trace amounts of vitamin E.

The primary outcome the patients were assessed for was the mean change from baseline measured via a tool called the Ocular Surface Disease Index (ODSI). The researchers also looked at blood levels of omega-3s and several other measures, including the conjunctival staining score, corneal staining score, tear break-up time, and the result on Schirmer’s test, which involves placing test paper into contact with the eye to measure how much moisture soaks into the strips.

The researchers found that the test subjects’ ODSI scores improved slightly more than the placebo group, but not in a statistically significant manner. Their blood levels of omega-3s did rise, which was primarily measured to confirm adherence to the supplementation regime.

Attempt to model ‘real world’ conditions

The trial was structured as a ‘real world’ assessment of the effects of omega-3s on this condition. Subjects, who were recruited at private and academic optometry and ophthalmology practices throughout the United States, were allowed to continue their current therapies for managing their conditions. The researchers reasoned that few patients would seek to manage their conditions with omega-3s supplementation alone.

After all the data was crunched, the researchers noted that as in other dry eye trials, a large placebo effect was observed. But they could find no effect for the supplementation. “We found no evidence of a beneficial effect of n−3 fatty acid supplements as compared with placebo supplements among patients with dry eye disease,” they wrote.

The researchers did note that assessing the totality of research into the effects of omega-3s supplementation on dry eye disease suffers from a lack of comparable studies. The DREAM trial used the highest omega-3s dose tested thus far, they said. Other trials used different doses and fewer participants, and were done in places such as India with different dietary patterns that could skew the results.

GOED: Import of complicated trial is overstated

The Global Organization of EPA and DHA Omega-3s (GOED) said in a statement that despite the researchers’ goal to test a “real world” scenario, the trial structure could be seen as adding in multiple confounding factors.

“Given that many of the trial participants were already using other treatments upon recruitment and continued to use them throughout the study, this was not a study of omega-3 alone (monotherapy). Treatments included: artificial tears (79.4% omega-3 group, 79.0% placebo group), cyclosporine drops (38.4% omega-3 group, 38.2% placebo group), warm lid soaks (22.9% omega-3 group, 18.3% placebo group), lid scrubs or baby shampoo (16.0% omega-3 group, 14.5% placebo group), and other (48.7% omega-3 group, 53.2% placebo group),” the organization wrote.

The organization also took issue with wording of the accompanying press release, which, along with the study abstract, could likely be the only contact mainstream news outlets will have with the research. The press release was titled “Omega-3s from fish oil supplements no better than placebo for dry eye.” That is an overstatement of the results, GOED maintained.

“While it may be true that ‘omega-3s are generally used as an add-on therapy,’ it doesn’t excuse misleading the public by making a definitive statement about the lack of omega-3s benefits for dry eye. The reality is that additional research is needed to determine the effectiveness of omega-3s as monotherapy for dry eye disease,” GOED stated.

Source: New England Journal of Medicine

n−3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease”

April 13, 2018 DOI: 10.1056/NEJMoa1709691

Authors: Asbell PA, Maguire MG, Pistilli M, et al.