DREAM Extension study supports primary trial conclusion

Results from a 12-month extension of a randomized, placebo-controlled, double-masked trial are consistent with the primary trial that did not support a beneficial effect of omega-3 fatty acid supplementation on dry eye disease.

Reviewed by Penny A. Asbell, MD, MBA

Results of the 12-month Dry Eye Assessment and Management (DREAM) study showed that dietary supplementation with oral omega-3 fatty acids is no better than placebo in relieving signs and symptoms of dry eye disease (DED).

Results from the 12-month DREAM Extension study are consistent with the findings of the primary trial, according to Penny A. Asbell, MD, MBA, study chairperson for the DREAM research group, and Barrett G. Haik Endowed Chair, chairperson and professor of ophthalmology, University of Tennessee Health Science Center, Memphis, TN.

“Many ophthalmologists and optometrists have considered nutritional supplementation with omega-3 helpful for dry eye patients and often added them to other treatment modalities such as artificial tears and topical anti-inflammatory agents,” she said.

However, Dr. Asbell explained that the high-level evidence for the U.S. population, i.e., results from double-blind randomly selected trials with large sample size, had not been available before DREAM.

“The goal of DREAM was to look at your typical dry eye patient with moderate-to-severe dry eye symptoms despite treatment for dry eye and then add on omega-3 to see if it would help both symptoms and signs,” she said.

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The study also could prove to be a challenge for both researchers and participants. Dr. Asbell also explained that the study was rigorous, and the main results did not show improvement when compared to placebo.

“The DREAM Extension study, adding a second year of treatment, was developed to explore long-term efficacy and safety of omega-3 use for dry eye and to see if any gains over one year of omega-3 treatment continued or were lost when omega-3 was discontinued,” she noted.

“This withdrawal trial is a unique approach in dry eye disease to better understand long-term treatment and its implications; most industry trials are relatively short weeks or-months, even though in clinical practice we may recommend a treatment for months or even years.”

DREAM and the DREAM Extension study are supported by the National Eye Institute. DREAM enrolled patients who had moderate to severe DED. The patients were to continue any existing DED treatments.

A total of 535 patients were randomly selected 2:1 to double-masked treatment with 3,000 mg omega-3 fatty acids (2,000 mg of eicosapentaenoic acid and 1,000 mg docosahexaenoic acid fish oil concentrate in triglyceride form) or placebo (refined olive oil 5 gm) for one year. The total daily dose of each study treatment was contained in five soft gelatin capsules, and the omega-3 fatty acid and placebo capsules were identical in size, color, and aroma.

The primary endpoint in DREAM analyzed average change from baseline at six and 12 months in Ocular Surface Disease Index (OSDI) score, and the results showed a significant improvement in both the omega-3 fatty acid and placebo arms with no significant differences between the two study groups.

At baseline, mean OSDI was approximately 45 and it decreased by an average of about 13 points in both groups. Compliance with the study treatment protocol, changes in DED signs (conjunctival staining, corneal staining, tear break-up time, Schirmer’s test score), use of other DED treatments, health-related quality of life, and adverse events were all analyzed as secondary outcomes. According to the data, there were no statistically significant differences between study groups in any of those measures.

Long-term supplementation

DREAM Extension, or the withdrawal trial, was part of the original protocol to determine whether continued use of omega-3 for two years increased efficacy and/or if withdrawal (i.e., stopping omega-3) led to a resurgence of dry eye symptoms and/or signs.

“We were not able to enroll as many patients as we needed for the Extension Trial, given the time needed to complete enrollment of the primary DREAM study, but we hoped the data we collected from the Extension trial would shed some light on the effects of long-term use of omega-3 for dry eye disease,” Dr. Asbell explained.

Patients were eligible for the DREAM Extension study if they were assigned to the omega-3 fatty acid group in the primary trial and completed the 12-month study visit.

A total of 43 patients participated in the DREAM Extension study, which was also double-masked. Patients were randomly selected 1:1 to continue omega-3 fatty acids treatment or were switched to placebo (olive oil 5 gm).

Patients similar

Patients in the extension trial were similar to those who had been enrolled initially in DREAM, and the two treatment groups in DREAM Extension were also similar to each other in their baseline characteristics at the start of the extension phase study.

Changes in DED symptoms assessed with the OSDI were analyzed by researchers as the primary outcome measure. At the end of the DREAM Extension study, the OSDI was increased slightly in both groups, but the changes were not statistically significant, and there was no statistically significant difference between study groups.

In secondary outcome analyses, the researchers found that there were no statistically significant differences within or between study groups in changes in signs of DED over time, including conjunctival staining, corneal staining, tear break-up time, or Schirmer test score. Adverse event rates were also similar among patients who were taking omega-3 fatty acids and those receiving the placebo.

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Disclosures:

Penny A. Asbell, MD, MBA
E: pasbell@uthsc.edu
This article is based on a poster presented at the 2019 annual meeting of the Association for Research in Vision and Ophthalmology. The DREAM study was published in 2018 [Dry Eye Assessment and Management Study Research Group. N Engl J Med. 2018;378(18):1681-1690].

Dr. Asbell receives research grants and had been a consultant to companies that market treatments for dry eye disease. She has not received any funding from companies related to omega-3.