As I See It

摘要

JUST A FEW POINTSAlong with two prestigious experts in dry eyes, Alice Epitropoulos, MD, and Cynthia Matossian, MD, I submitted a letter to the editor of the NEJM with our concerns. I was surprised that the letter was not accepted for submission, so I thought I’d share why so many of us objected to its hyped-up conclusion. Also, I acknowledge that I have received consultation fees from a company that distributes an omega-3 product.Despite claims that research subjects were “well-defined,” closer examination revealed that numerous design flaws introduced significant etiological and methodological variability, which created an uncontrolled study environment where definitive conclusions could not be drawn:Subjects were not recruited for dry eye disease (DED) according to the Tear FilmandOcular Surface Society’s 2017 definition but according to the 2007 definition in place at the time of the study’s design. That 2007 definition states elevated osmolarity as a sequelae, not as an etiological cause of DED. So tear osmolarity wasn’t part of the screening process. TBUT was not required.Subjects had confounding disease states with similar dry eye symptoms. While that may reflect what ophthalmologists see in the real world in their DED patients, the various conditions — such as thyroid disease (18.6%), rheumatoid arthritis (10.9%) and Sjogren’s syndrome (9.5%) — have different etiologies. This would have resulted in varying patient responsiveness to the study’s omega-3 therapy.Subjects were allowed, in both the active and placebo arms of the study, to use a wide variety of other therapies, including artificial tears and gels, cyclosporine drops and corticosteroids, as well as warm lid soaks, scrubs or baby shampoo. Subjects could even use omega-3 supplements, up to 1,200 mg per day. Even more shocking: Participants could change treatments throughout the study, which 75% did.The “placebo” was 5 grams of olive oil compared to 3 grams of the omega-3 studied. Olive oil is known to have anti-inflammatory properties, hardly an inactive ingredient.1Even with all this, 61% of subjects in the omega-3 arm experienced improvement, a dramatically higher success rate than for many pharmaceutical products. The distorted spin on the study attempted to controvert the well-documented benefits of omega-3 for patients with true DED.2 A very well-controlled study published in Cornea in 2016 showed definitive improvement in tear osmolarity, MMP-9, OSDI, TBUT and omega-3 index in subjects taking a re-esterified omega-3 supplement, compared to a true placebo.