Laird Harrison

May 10, 2017

LOS ANGELES — People with dry eyes may improve their symptoms by taking re-esterified omega-3 fatty acid supplements, researchers say.

Although omega-3 supplements are already a standard treatment for dry eyes in the United States, there are few prospective trials testing these supplements in dry eye disease, especially the re-esterified form.

"In the last few years, nutritional supplements have gained quite a bit of attention in the ocular surface, but there hasn't been a lot of scientific evidence documenting the benefits," Alice T. Epitropoulos, MD, from Ohio State University in Columbus, told Medscape Medical News.

She presented her findings here at the American Society of Cataract and Refractive Surgery (ASCRS) 2017 Annual Congress and, with colleagues, published them in the Cornea.

When the meibomian glands do not produce adequate lipids, tear film evaporates more quickly and tear film osmolarity increases, triggering a chain of events that includes inflammation and ocular surface damage.

Ingestion of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) raises the levels of fatty acids in the meibomian gland secretions. Because they stay in a liquid form at body temperature, they prevent the blockage of meibomian gland ducts, increasing the quality of the glands' secretions and reducing tear film evaporation.

In addition, omega-3 fatty acids break down into molecules that suppress the inflammatory pathways involved in meibomian gland–related ocular surface disease.

Omega-3 fatty acids occur naturally in fish oil. A retrospective study of 32,470 women showed that those who ate five to six servings of tuna per week were 66% less likely to be diagnosed with dry eye disease than those who ate two or fewer servings, Dr Epitropoulos and colleagues note.

However, most people do not get enough omega 3 fatty acids from eating fish, so fish oil supplements are widely used.

A previous small randomized controlled trial showed significantly better scores in tear breakup time (TBUT), ocular surface disease index (OSDI), meibum expressibility, and meibum quality in people taking fish oil supplements, according to Dr Epitropoulos.

However, most commercial fish oil supplement producers add alcohol to remove mercury and other toxins from the oil. The alcohol converts the triglycerides in fish oil to an ethyl ester compound that is not found in nature and is difficult to absorb. A handful of fish oil supplements are re-esterified to remove the alcohol; previous research has shown this is more easily absorbed.

Therefore, Dr Epitropoulos and colleagues wondered whether a re-esterified omega-3 supplement might provide even greater benefits in patients with dry eye disease.

To find out, they recruited 105 adults with dry eye disease and meibomian gland dysfunction stage 1 or 2 and a tear osmolarity of at least 312 mOsm/L in at least one eye. They excluded patients who were using topical cyclosporine or corticosteroids or taking nonsteroidal anti-inflammatory drugs, glaucoma medications, or oral omega-3 fatty acid supplements.

They randomly assigned 54 of the patients to take 1680 mg EPA and 560 mg DHA re-esterified omega-3 fatty acid (PRN Dry Eye Omega Benefits softgels; PRN Physician Recommended Nutraceuticals) daily.

The other 51 subjects took 3136 mg safflower oil daily. There were no significant differences between the groups in age, sex, ethnicity or baseline tear osmolarity, TBUT, OSDI, oxford corneal staining grade, meibomian gland dysfunction stage, or Schirmer score. However the omega-3 group had a lower baseline omega-3 index, a measure of plasma omega 3.

Both groups showed improvements in most of these measures at 6 weeks. Safflower oil contains linoleic acid, an omega-6 fatty acid, which may also have benefits for meibomian gland dysfunction.

However, at week 12, the improvements in OSDI, tear osmolarity, TBUT, and omega-3 index levels were all greater in the omega-3 group, by a statistically significant margin.

Table. Outcome Change from Baseline to Week 12

  Re-esterified Fish Oil (Omega-3 Fatty Acid), n = 54 Safflower Oil (Omega-6 Fatty Acid) Control, n = 51 P Value
Tear film osmolarity (mOsm/L) −19.4 −8.3 0.004
TBUT (seconds) 3.5 1.2 0.002
OSDI (0 - 100) −17.0 −5.0 0.002
Omega-3 index, % 3.0 0.2 <0.001
Oxford corneal staining grade (1 - 5, lower is better) −0.7 −0.6 0.712

In addition, at week 12, the number of subjects testing positive for matrix metalloproteinase-9 (a proteolytic enzyme produced by stressed epithelial cells on the ocular surface) dropped by 67.9% in the omega-3 group compared with 35.0% in the control group.

The decrease in corneal staining did not reach statistical significance in either group. This measure is a late-stage sign, and patients in this study may have been too early in their condition to show it, the researchers reasoned. Similarly, the study did not register significant improvement in meibomian gland function, perhaps because the follow-up was not long enough.

Tear volume as measured by the Schirmer test also did not show significant improvement in these patients, and the authors speculated that this measurement may simply be too variable to be useful.

Overall, Dr Epitropoulos concluded that the study provides strong evidence to support supplementation with re-esterified omega-3 fatty acids. "I think using re-esterified omega-3 products should be included as a primary therapy for dry eye disease," she said. She recommended 2 g/day taken either as a capsule or a liquid.

In the panel discussion that followed her presentation, Martin Dirisamer, MD, from Linz, Austria, asked Dr Epitropoulos whether she thought patients could get a similar benefit by modifying their diets.

Dr Epitropoulos responded that it was unlikely they could reach a sufficient plasma level of omega-3 fatty acids through diet alone.

Dr Dirisamer also asked whether there were any adverse effects from the supplements. "There have been some reports of [gastrointestinal] upset, so I usually recommend taking the omega 3 with food, and that helps tremendously," Dr Epitropoulos said.

Session moderator Jodi Luchs, MD, from Hofstra Northwell School of Medicine in East Garden City, New York, told Medscape Medical News that the findings add significantly to what is known about omega-3 fatty acids in the treatment of dry eye disease.

"Those of us who treat dry eye have a good sense that they are efficacious, but there have not been a large group of prospective trials," he said. "There are some other studies going on that will give us a greater data set."

He noted that no study has yet compared the re-esterified form to the ethyl ester form as a treatment for dry eye.

Dr. Epitropoulos received compensation from PRN Physician Recommended Nutraceuticals for participating in the study, and so did some of her coauthors, one of whom was an employee of the company. Dr Dirisamer and Dr Luchs have disclosed no relevant financial relationships.

American Society of Cataract and Refractive Surgery (ASCRS) 2017 Annual Congress. Presented May 8, 2017.

Cornea. 2016;35:1185-1191. Abstract

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