EyeWorld India September 2018 Issue

50 EWAP CORNEA September 2018 by Rich Daly EyeWorld Contributing Writer Study shows little effect from omega-3 fatty acids Recent research finds that placebo had equivalent efficacy as a mainstay dry eye treatment C linicians have long recommended the use of supplements of n-3 fatty acids (omega-3 fatty acids) to relieve dry eye symptoms. Recent research has cast doubt on that treatment. A multicenter, double-blind clinical trial with randomly as- signed moderate to severe dry eye patients provided 329 patients with a daily oral dose of 3,000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids, and 170 patients received an olive oil placebo for 12 months. The study, known as the Dry Eye Assessment and Management (DREAM) trial, found no signifi- cantly different mean change in the score on the Ocular Surface Disease Index between the active supplement group and the placebo group (−13.9 points and −12.5 points). 1 The results were consistent across pre-specified subgroups. Additionally, the study found no significant differences between active and placebo groups in mean changes from baseline in the con- junctival staining score, corneal staining score, tear break-up time, and the Schirmer’s test. “It definitively showed [an omega-3 fatty acid supplement] was not more beneficial than placebo in the year-long study,” said Penny Asbell, MD, professor of ophthal- mology, Icahn School of Medicine at Mount Sinai, New York. “Given those results, I don’t see recom- mending omega-3 to patients who are symptomatic and have mod- erate to severe dry eye disease. It doesn’t seem to be any better than placebo.” Anat Galor, MD, associate professor of ophthalmology, Bas- com Palmer Eye Institute, Universi- ty of Miami, described the research as “well executed” although there are different interpretations of the results. “But the fact stands that the ac- tive omega-3s did not do any better than the olive oil,” Dr. Galor said. Fatty acid supplements’ role as the first treatment offered by most clinicians treating dry eye due to its track record and peer- reviewed findings of its safety and efficacy make the study’s finding “borderline shocking,” said John Sheppard, MD, clinical director, Thomas R. Lee Center for Ocular Pharmacology, Eastern Virginia Medical School, Norfolk, Virginia. “The results were surprising for just about everyone in the dry eye field,” Dr. Sheppard said. Concerns raised Among those raising questions about the study was Cynthia Ma- tossian, MD, in private practice in New Jersey and Pennsylvania. Dr. Matossian said the study failed to provide the scientific struc- ture required to define conclusive outcomes because patients were permitted to use a wide variety of treatments for their dry eye includ- ing topical cyclosporine and could change adjunctive therapies at will. “As a result, I think there were too many variables allowed to derive a strong conclusion,” Dr. Matossian said. Dr. Galor understands that there are criticisms regarding the use of other medications during the trial. However, this design was chosen in order to study the use of omega-3s in a “real world setting.” While some view this as a weakness, it can also be consid- ered a strength of the study. Other strengths included the large num- ber of patients enrolled and lack of commercial interests as the study was funded by the National Eye Institute at the National Institutes of Health. Dr. Asbell said the patients were chosen to reflect the typical dry eye patient who comes into ophthalmologists’ offices. “They have already tried tears, maybe some other things, and they are still unhappy,” Dr. Asbell said. “It’s the kind of person who comes into the office and says, ‘What else can you do for me? I’m still symp- tomatic; my dry eye still bothers me.’” Dr. Sheppard acknowledged the subset analysis performed by the study authors but wanted a deeper analysis of previous dietary intake in each group and their dry eye severity. He also raised questions about the olive oil placebo and the need for “a true placebo control.” “In our trial we used an inert solid, and it was difficult to get that preparation,” Dr. Sheppard said about his previous dry eye supple- ment research. 2 “With the refined low phenolic content olive oil five pills a day control group I have some reserva- tions that there might have been a positive therapeutic effect,” Dr. Sheppard said. Refined olive oil contains palmitoleic 3 and oleic 4 acids, both of which possess anti- inflammatory properties. Dr. Asbell noted that her study shared the common characteristic