The DREAM team says n-3 no better than placebo for dry eye. What should we do?
By Dr. Elise Kramer, O.D.
I know I will take heat from some of my colleagues for publishing this commentary. All I have to say is: “Don’t shoot the messenger.” This new study should make for some interesting discussion and debate in our community of dry eye specialists.
I’ve always been a true believer in practicing evidence-based medicine. My inherent scepticism may come from my father, who is the principal investigator of several large, multicentre epidemiologic studies and randomized trials. Or maybe it’s just in my genes. Whatever the explanation, I try to base my diagnostic and therapeutic practice on the best published research evidence.
Dry eye disease (DED) is a hot topic. Most recently-graduated optometrists learned that omega-3 fatty acid supplementation should be part of the basic, or at least initial, treatment of DED. In fact, sales of fish- and other animal-derived supplements are $1-billion annually in the United States, according to the Nutrition Business Journal. Many formulations are sold over the counter, while some require a prescription from a licensed physician or can only be purchased from a health care center. Despite insufficient evidence from randomized trials establishing the efficacy of omega-3s, clinicians and their patients use the supplements for a wide range of conditions with inflammatory components, DED being one of them.
This past May, the DREAM (Dry Eye Assessment and Management) Research Group published a multi-center, randomized, double-blind “real-world” clinical trial assessing the efficacy and safety of oral omega-3 supplementation for the treatment of dry eye disease (DED). This well-conducted trial provides the most reliable and generalizable evidence thus far on omega-3 supplementation for DED, with 27 centers enrolling 535 participants with a history of at least six months of moderate to severe dry eye. Among them, 349 participants were randomly assigned to receive 3 grams (five capsules) daily of fish-derived omega-3 fatty acids. Each daily dose contained 2000 mg of eicosapentaenoic acid (EPA) and 1000 mg docosahexaenoic acid (DHA). This is the highest dose ever tested for treating DED. The other 186 people were randomly assigned to a placebo containing 5 grams (also five capsules) of olive oil daily. The capsules were visually indistinguishable, and both sets of capsules provided 3 mg per day of vitamin E, an anti-oxidant. The trial was double-blind, meaning that both the study participants and their clinical care givers were blind to (unaware of) the treatment assigned.
Also of importance and unlike most industry-sponsored trials, participants were free to continue taking their previous DED medications, such as prescription eye drops and artificial tears. This is realistic, since omega-3s are generally used as adjunctive therapy, i.e., for symptomatic DED patients who requested additional treatment. Adherence to the assigned treatment group was excellent in both groups, based both on capsule counts and measurement of red blood cell EPA and DHA levels.
The Ocular Surface Disease Index (OSDI), a 100-point scale for measuring dry eye symptoms, was used to measure change from baseline in trial participants. After 12 months, mean symptom scores in both treatment groups had improved considerably, but no statistically significant difference between the two groups was observed in the magnitude of symptom improvement (13.9 points in the omega-3 group and 12.5 points in the placebo group). Similar, no statistically significant difference was observed in change in clinical signs of DED, based on clinicians’ standardized tests of the amount and quality of tear film and the integrity of the ocular surface. Interestingly, half of the participants taking placebo reported substantial symptom improvement during the 12-month study. In summary, the results of the DREAM trial do not support the use of omega-3 supplements in patients with moderate to severe DED.
The judicious use of current best evidence should always be combined with clinical expertise in making decisions about the care of individual patients. I’m putting my prescription of omega-3 on hold for moderate to severe dry eye patients. What about you?
Thank you to Dr. Elise Kramer, O.D. for contributing to Global Insight.
Dr. Elise Kramer OD, FAAO, FSLS
Optometrist and Contact Lens Specialist
Residency Coordinator, Scleral Lens Education Society (SLS)
Former resident at the Miami VAMC and Bascom Palmer Eye Institute 2012-13
University of Montreal School of Optometry graduate ’12