1. Apr 17,2019

AAO: Omega-3 Supplements for Dry Eye? Back to the Drawing Board

DREAM trial shows it improved dry eye symptoms, but so did an olive oil-based placebo

A lot of attention has been given to the potential health value of omega-3 fatty acid supplementation, including in ophthalmology to treat dry eye disease. “Unfortunately, we have not been able to demonstrate that omega-3 is helpful for dry eye disease,” said Penny A. Asbell, MD, the Barrett G. Haik Endowed Chair for Ophthalmology and Director of the Hamilton Eye Institute at the University of Tennessee. Dr. Asbell was part of the research team that conducted the Dry Eye Assessment and Management (DREAM) trial.

The good news is that omega-3 supplementation improved dry eye symptoms in individuals who received it during the year-long double-blind placebo-controlled study that involved more than 500 participants. However, patients who received an olive oil-based placebo improved just as much. Given the fact that most patients with dry eye tend to improve over time whether treated or not, Dr. Asbell’s team concluded that omega-3 provides no benefit. “Improvement over time cannot itself be interpreted as treatment efficacy in dry eye patients,” she noted.

The DREAM trial was funded by the National Eye Institute and the Office of Dietary Supplements at the National Institutes of Health. “This study was a little bit different than an FDA trial, which is very controlled,” explained Dr. Asbell. “I wanted real-world patients--the kind of people that you and I see who have dry eyes, have tried a lot of different things and they're still not happy. They may be using artificial tears, anti-inflammatory drops, or other treatments but are still symptomatic. They still have signs as measured by the slit lamp examination.”

Participants—all of whom exhibited similar baseline characteristics--were randomized 2-to-1 to receive either five omega-3 or five olive oil supplement soft gel caplets/day. The treatment group received a total of 3 grams of omega-3 (2 grams of EPA and 1 gram of DHA fish oil) daily, whereas the placebo contingent received a total of 5 grams of olive oil (the equivalent of 1 teaspoon)/day. The caplets were identical in size, color, and aroma. They were successfully field tested prior to the clinical trial. Fish essence and lemon was used to mask any difference between caplets.  Investigators evaluated signs and symptoms of dry eye disease via the Ocular Surface Disease Index (OSDI). They also assessed conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer’s test.

Results

OSDI score decreased >10 points in both groups. Additionally, conjunctival staining, corneal staining, and TBUT revealed slight improvement in the omega-3 group, but the difference was not statistically significant. No change was seen using Schirmer’s test throughout the year-long assessment.

How does Dr. Asbell explain the OSDI score improvement? “If you look at almost every clinical trial for dry eye disease, almost everybody improves. It may be a placebo response or regression to the mean. People do get better and we're not sure why to be honest.”

Dr. Asbell said she and her team have received many emails and other commentary wondering why they did not conclude that both omega-3 and olive oil supplementation improve dry eye disease. “Placebo is an active treatment,” we were told. However, participants took the equivalent of only 1 teaspoon of olive oil a day, which, she noted, is a small fraction of the amount suggested by advocates of the Mediterranean diet.

“We also looked at blood levels for all patients and we didn't see any change in oleic acid in either group,” she said, reinforcing the fact that the olive oil itself likely did not improve dry eye symptoms. “This was [the case] despite a high rate of compliance throughout the study.”

Dr. Asbell cited other work that essentially came to the same conclusions as the DREAM trial, including one published in 2017 [Holland E, Luchs J, Karpecki N, et al. Lifitegrast for the treatment of dry eye disease: Results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3). Ophthalmology. 2017 Jan;124(1):53-60. doi: 10.1016/j.ophtha.2016.09.025] and another in 2013  [Bhargave R, Kumar P, Kumar M, Mehra N, Mishra A. A randomized controlled trial of omega-3 fatty acids in dry eye syndrome. Int J Ophthalmol. 2013 Dec 18;6(6):811-6. doi: 10.3980/j.issn.2222-3959]. In these studies, researchers saw improvement in signs and symptoms in both groups, but there was no significant difference between treatment and placebo, she said.

Dr. Asbell added that some have evaluated omega-6, but she advised caution when interpreting these results. “In some of these trials, patients taking omega-6 got better, but there was no significant difference between [treatment and placebo groups]. Read more than just the bottom line [in these studies] in order to clearly understand the results.”

Some have suggested a trial comparing omega-3, olive oil, and no treatment. Dr. Asbell sees potential flaws in that. She is a strong advocate of masked, double-blind trials. For that reason, she said perhaps there could be another oil-based product to serve as placebo, but expressed concern about what exactly that would be.

“We are going to have to continue to look for other ways to address the signs and symptoms and dry eye disease. The good news is that there are a lot of new approaches being looked at There are plenty of options besides using omega-3.”

Asbell P. Omega-3 for dry eye: DREAM on! Talk presented at: AAO 2018 annual meeting; October, 26-30, 2018; Chicago.