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A new study shows that omega-3 supplements offer the same benefits as the study's placebo, olive oil. Researchers and other experts discuss trial results and what's next for ODs treating dry eye.
Optometrists have long recommended omega-3 fatty acid supplements to their patients with dry eye disease. Results from a recent study show that while omega-3s offer benefits, they did not offer significantly better outcomes than an olive oil placebo.
The Dry Eye Assessment and Management (DREAM) study1 was funded by the National Eye Institute, part of the National Institute of Health, and randomized more than 500 patients, following them for more than one year. This well-controlled trial calls into question current thinking that leads ODs to recommend omega-3 supplements to their dry eye patients.
“Every day ODs sit in the trenches, wondering how to deal with new treatments that bombard us,” says Optometry Times Editorial Advisory Board member Milton M. Hom, OD, FAAO. “For years, industry and experts have touted omega-3s for dry eye disease. But now, we have a well-designed, highly powered study showing the exact opposite results.”
Dr. Hom served as a principal investigator for the DREAM study; his comments are his own and do not represent the DREAM study.
Study subjects at 27 clinical centers were randomized to the active supplementation group or placebo group; the primary study analysis looked at 349 and 186 patients, respectively.
Eligibility criteria were age 18 years or older, presence of ocular symptoms for at least 6 months, use of or desire to use artificial tears an average of twice per day, and an Ocular Surface Disease Index (OSDI) score of 25 to 80.
Eligible patients also needed two out of four signs of dry eye in at least one eye: conjunctival lissamine green staining score of 1 or more, corneal fluorescein staining score of 4 or more, tear break-up time (TBUT) ≤7 seconds, and Schirmer with anesthesia result of 1 to 7 mm in 5 minutes.
Study subjects took five soft-gelatin capsules per day. Capsules in the active group contained omega-3s with 400 mg EPA and 200 mg DHA; capsules in the placebo group contained 100 mg refined olive oil (68 percent oleic acid, 13 percent palmitic acid, 11 percent linoleic acid). Both capsules also contained 3 mg vitamin E.
Patients in the study were permitted to continue their current dry eye regimens.
Says Penny Asbell, MD, FACS, MBA, study chair for the trial: “One of the good things about DREAM is that there is a lot of consistency. Every symptom group improved, so there was no difference between them. There were slight improvements in three or four of the signs groups, but there was no significant difference among those groups.”
Dr. Asbell is professor of ophthalmology, director of cornea and refractive services, and director of the department of ophthalmology cornea fellowship program at Icahn School of Medicine at Mount Sinai in New York City.
Another strength of the study is that it’s a real-world study, says Dr. Asbell.
“We took patients who were symptomatic despite whatever treatments they might be doing, and they were allowed to continue those treatments,” she says. “It was typical of the kinds of patients I see and other clinicians see in the office every day. We didn’t say you couldn’t do this or you couldn’t do that.”
Olive oil’s positive effects surprised DREAM researchers and others in the industry.
“I think we were not expecting olive oil to have such a robust effect, because patients improved enough in that group that the differences were not statistically significant,” says Optometry Times Editorial Advisory Board member Scott G. Hauswirth, OD, FAAO, who served as a clinician at a Minnesota study site. “We did learn from this study that the healthy fats/constituents of olive oil (oleic acid, linoleic acid, palmitic acid) also seem to have benefits in dry eye, and a healthy diet can and should be considered as a baseline to help those suffering from dry eye.”
Zac Denning, product science specialist at ScienceBased Health, points out that other omega fatty acids studied in dry eye, such as gamma-linolenic acid (GLA), were not included in the study.
“Olive oil turned out to be a surprise performer,” he says. “Because both oils improved dry eye signs and symptoms over the course of the trial, DREAM ended up essentially comparing two treatments, which it wasn’t designed to assess. Olive oil was clearly not a suitable placebo, and the lack of clear difference vs. the active treatment has caused confusion.”
According to Dr. Asbell, olive oil is used as a placebo in omega-3 trials for other diseases, such as cardiovascular disease and rheumatoid arthritis.
“As best we could determine, olive oil is not considered a significant effect on dry eye disease,” she says.
Subjects in the active study group received about 1 teaspoon of olive oil per day, which is less than the amount associated with the Mediterranean diet.
DREAM investigators took blood samples from subjects at baseline, 6 months, and 12 months. In examining red blood cells, researchers found that omega-3 components EPA and DHA increased significantly, according to Dr. Asbell; EPA increased about five times over baseline and the placebo group.
“When you look at the components of olive oil, such as oleic acid, which is about 68 percent of olive oil, both groups started the same with about the average amount found in the U.S. population,” Dr. Asbell says. “Neither group changed over the one year. I would think that if the olive oil components impacted systemically, we ought to see a change in those fatty acids in the red blood cells over the year.”
More data from the DREAM study will be forthcoming, says Dr. Asbell, including secondary endpoints not discussed in the main results. Additional exploratory endpoints include point-of-care testing such as MMP-9, tear osmolarity, and ocular surface imaging of non-invasive TBUT.
In the meantime, ODs must decide for themselves to continue recommending omega-3 supplements to their dry eye patients.
“This study completely changes everything,” says Dr. Hom. “Prescribing omega-3s was automatic for me, now I hesitate.”
Eating a Mediterranean diet may help, says Optometry Times Editorial Advisory Board member Stuart Richer, OD, PhD, FAAO.
“There was improvement in patient symptoms, as well as conjunctival and corneal staining and TBUT from baseline, meaning omega-3s and other healthy fats such as olive oil are helpful in treating dry eye,” Dr. Hauswirth says. “It underscores the value of implementing a healthy diet in patients with dry eye.”
Dr. Asbell suggests that clinicians look to other treatments for dry eye and ocular surface disease, such as new products coming to market soon. Another area to explore is meibomian gland dysfunction and its impact on the ocular surface.
“One of the clinical takeaways I would suggest is the money spent on omega-3s might be better spent on other dry eye treatments,” she says. “We need to look for things that are useful, but we need to look for those that have evidence to show that they’re useful and worth doing.”
Dr. Hom says that the change in clinical thinking about dry eye has yet to come.
“Until now, the preponderance of studies2 has shown omega-3s to be efficacious for dry eye,” he says. “This study stands alone on an island. History will decide the DREAM study’s place in our understanding and treatment of dry eye: alone on an island or significant turning point.”
1. The Dry Eye Assessment and Management Study Research Group. n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease. N Engl J Med. 2018 Apr 13. doi: 10.1056/NEJMoa1709691. [Epub ahead of print]
2. Hom MM, Asbell P, Barry B. Omegas and Dry Eye: More Knowledge, More Questions. Optom Vis Sci. 2015 Sep;92(9):948-56.