From DREAM to reality

A 1-year, multicenter, doublemasked, randomized, placebo-controlled clinical trial supported by the National Eye Institute found that oral omega-3 fatty acid supplementation (3,000 mg/day) was not effective treatment for moderate-to-severe dry eye disease.

Dietary supplementation with oral omega-3 fatty acids is no better than placebo in relieving signs and symptoms of dry eye disease (DED), according to results of the DRy Eye Assessment and Management (DREAM) study.

Supported by the National Eye Institute, the double-masked, randomized DREAM study assigned 535 patients 2:1 to daily treatment with 3,000 mg omega-3 fatty acids or placebo for 1 year. Eligible patients had moderate-to-severe DED and were to continue existing DED treatments. They were enrolled at 27 ophthalmology and optometry practices across the United States.

Average change from baseline at 6 and 12 months in Ocular Surface Disease Index (OSDI) score was analyzed as the primary endpoint and was significantly improved in the omega-3 fatty acid and placebo arms, but the difference between groups was not statistically significant. There were also no statistically significant differences between treatment groups in secondary outcome measures analyzing compliance with the study treatment protocol, changes in DED signs, use of other DED treatments, health-related quality of life, and adverse events.

“In 2017, authors of the TFOS DEWS II Management and Therapy Report concluded that the role of essential fatty acids for treating DED is not completely understood,” said Penny Asbell, MD, MBA, Study Chair for the DREAM research group and professor of ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY.

“They noted that although a sizeable number of clinical trials have been conducted, most were of short duration, they showed contrasting findings, and there were few high-quality randomized controlled clinical trials to inform practice,” Dr. Asbell said.

The DREAM study was designed to address the limitations of previous research, and it had many strengths, she noted.

“The DREAM study was free of pharmaceutical bias and evaluated the more bioavailable form of omega-3 fatty acids using a higher dose than in any previous DED randomized trial and for a full year to reduce potentially confounding from seasonal effects,” Dr. Asbell said.

In addition, the DREAM study had a welldefined population representing real-world patients who had signs and symptoms of DED despite existing treatment, the participants were compliant with treatment, and the study had a high patient retention rate, Dr. Asbell said.

“The bottom line from the DREAM study is that omega-3 supplementation is not an effective treatment for the typical patient with moderate-to-severe dry eye disease,” she said.

Eligibility criteria

Patients were eligible for DREAM if they had DED symptoms for at least 6 months, an OSDI score of 25 to 80 at a screening visit, and an OSDI score of 21 to 80 at the baseline eligibility confirmation visit.

In addition, they had to:

• use or desire artificial tears at least twice daily in the previous 2 weeks;
• have at least two of the following four signs of DED in the same eye at the screening and eligibility confirmation visits: > conjunctival staining score ≥1, corneal fluorescein staining score ≥1, tear break-up time (TBUT) ≤7, Schirmers test with anesthesia ≥1 and ≤7 mm in 5 minutes;
• be willing to continue treatments for DED, that cause ocular dryness, and affecting inflammation (corticosteroids, other immunosuppressive agents); and
• be compliant with placebo during the 2-week run-in.

Contact lens wearers and patients with a history of LASIK, recent ocular surgery, or use of <1200 mg omega-3 fatty acids were excluded.

The omega-3 fatty acid supplement contained 2,000 mg of eicosapentaenoic acid (EPA) and 1,000 mg docosahexaenoic acid (DHA) fish oil concentrate in (re-esterified) triglyceride form.

The placebo was refined olive oil 5 gm. The total daily dose of each study treatment was contained in five soft gelatin capsules, and the placebo was manufactured to be identical to the omega-3 fatty acid supplement in size, color, and aroma.

Results

The two treatment groups were well-matched at baseline. DREAM participants had a mean age of approximately 58 years, 81% were female, and about three-fourths were white.

At baseline, mean OSDI score was approximately 45, and mean scores for DED signs were 3 for conjunctival staining, 3.9 for corneal fluorescein staining, 3.1 for TBUT, and ≥9.3 for the Schirmer test.

“Most people qualified for the study based on their ocular surface staining or TBUT scores,” Dr. Asbell said.

At baseline, 79% of participants were using artificial tears, 38% were using topical cyclosporine, and approximately 20% were using warm lid soaks.

By 3 months, OSDI scores had decreased by an average of about 12 points in both groups. The changes from baseline were statistically and clinically significant, and stable at months 6, 9, and 12.

“In the primary endpoint analysis, there was a treatment difference of 1.4 points favoring the omega-3 group, but it was not statistically significant,” Dr. Asbell said. “Overall, more than 50% of patients in each group had an OSDI score improvement of at least 10 points, which is considered clinically significant.”

In both treatment groups, mean Schirmer test results were unchanged throughout follow-up, while there were minimal improvements in the other three DED signs, but they were similar in magnitude in the two treatment groups.

In addition, the review of changes in existing DED treatment showed an overall decrease from baseline at 12 months in both groups, but with no significant difference between groups.

There were also no statistically significant differences between treatment groups in analyses of OSDI subscale scores, Brief Ocular Index-2 total and subscale scores, and SF-36 total and component scores.

Prespecified subgroup analyses conducted to identify whether omega-3 fatty acid supplementation might be particularly beneficial in patients with certain characteristics found no signals when patients were divided into two groups by baseline OSDI score, severity of DED signs, omega-3 serum levels, and percentage of HLA-DR+ epithelial cells.

The safety review showed serious adverse events occurred in 6% of patients treated with the omega-3 fatty acid supplement and in 8.1% of placebo-treated controls. Non-serious adverse events occurred at a rate of just over 60% in each group.

Disclosures:

Penny Asbell, MD
E: penny.asbell@nyc.rr.com
This article was adapted from Dr. Asbell’s presentation at the 2018 meeting of the American Society of Cataract and Refractive Surgery. The DREAM study has been published [Dry Eye Assessment and Management Study Research Group. N Engl J Med. 2018;378:1681-1690. 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 fatty acid supplementation.