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The DREAM is over

This National Eye Institute-supported clinical trial shows that oral omega-3 is no better than placebo in relieving signs and symptoms of dry eye disease

Howard Larkin

Posted: Friday, July 6, 2018


Penny Asbell MD

Do you think omega-3 helps dry eye patients? In an instant poll at the American Society of Cataract and Refractive Surgery Cornea Day 2018, 90% of ophthalmologists in the audience answered that it is beneficial for at least some patients.

However, the 10% who said omega-3 is not beneficial for dry eye were correct, according to a major new study. The Dry Eye Assessment and Management (DREAM) study found no significant difference in outcomes at six and 12 months between 349 patients treated daily with 3,000mg fish oil supplement and 186 receiving an olive oil placebo in addition to ongoing treatments for moderate-to-severe dry eye disease (DED).

“This National Eye Institute-supported clinical trial shows that oral omega-3 is no better than placebo in relieving signs and symptoms of dry eye disease,” DREAM Study Chair Penny Asbell MD announced at the ASCRS meeting in Washington, DC, USA. The results were simultaneously published in the New England Journal of Medicine. (DOI: 10.1056/NEJMoa1709691).

REAL WORLD TEST
The 12-month prospective randomised trial included patients at 27 centres who had DED symptoms for at least six months prior to study enrolment. Using patients already in treatment for DED replicated the conditions under which patients typically are treated, which should make the results more representative of actual clinical practice, Dr Asbell noted.

The patients in the study also used or desired artificial tears at least twice daily, and many were using other treatments, including cyclosporine drops, warm eyelid soaks and lid scrubs. Participants also had at least two signs of DED such as conjunctival or corneal staining, and abnormal tear film break-up time (TBUT) or Schirmer’s test, did not use more than 1,200mg daily omega-3 supplements, and had no history of LASIK, recent ocular surgery or current contact lens use.

The primary endpoint was reduction in symptoms measured by the Ocular Surface Disease Index (OSDI) instrument, with secondary endpoints changes in signs as measured by staining, TBUT and Schirmer’s.

At 12 months, mean OSDI scores in the treatment group fell -13.9 points compared with -12.5 points in the placebo group. With missing data imputed, the difference was -1.9 points, which is not statistically or clinically significant. The results were consistent across all pre-specified subgroups, including patients with moderate or severe disease and those with higher 
or lower omega-3 blood levels, Dr 
Asbell reported.

Objectively, there was no difference in changes in conjunctival staining or Schirmer’s scores between the two groups, and no significant difference in corneal staining or TBUT, she added. Adverse events were also similar between the two groups.

Patients receiving the active supplement, which included 2.0g EPA and 1.0g DHA, showed increased omega-3 blood levels, suggesting a compliance rate of more than 80% over the 12 months.

CONCLUSIVE EVIDENCE
The DREAM study was undertaken to provide solid evidence on the efficacy of omega-3 supplements, which have been widely prescribed for DED despite limited evidence, Dr Asbell said. She noted that a 2013 American Academy of Ophthalmology Preferred Practice Pattern statement found no evidence favouring efficacy (www.aao.org/ppp), while a 2017 report from the Tear Film and Ocular Surface Society Dry Eye Workshop (DEWS II) cited mixed results among short-term studies and a lack of high-quality randomised trials (Jones L et al. Ocul Surf 2017;15:575-628).

So why do so many ophthalmologists apparently believe omega-3 supplements help patients with DED? There may be several reasons, Dr Asbell told EuroTimes.

Human nature is one reason. “In clinical medicine and in general humans like to determine cause and effect: If I had a glass of warm milk before bed and I slept well ‘warm milk’ must work. What appears to work for one person, we think works for everyone,” Dr Asbell said.

Many are committed to “natural treatment”, and omega-3 seems like it should work; it is difficult to “give up” that point of view.

She noted that both groups in the trial reported improvements in dry eye symptoms of more than 10 points, which is considered clinically significant. This suggests that listening and responding to patient concerns may be a useful adjunct to dry eye treatment.

Since reporting the results on April 13, Dr Asbell has received many comments. Some questioned the use of olive oil as a placebo, suggesting that it, too, may be helpful with dry eye. However, the amount of olive oil used was insignificant (one teaspoon per day) compared with a Mediterranean diet, she said. Blood levels of olive oil compounds also were similar between the two groups at baseline and at 12 months, she added.

Dr Asbell believes the trial methodology was robust and the results must be respected.

“The results are pretty definitive. No matter how you look at the data, omega-3 supplements are not an effective treatment for moderate to severe dry eye disease.”