The use of omega-3 fatty acid (FA) supplements as a foundational treatment for dry eye disease (DED) has seen some controversies in the last few years; so where do we stand in 2022?

We know that the AAO’s preferred practice patterns and all the major algorithms, including DEWS I and Tear Film & Ocular Surface Society-DEWS II, CEDARS/ASPENS and ASCRS, recommend the addition of oral omega fatty acid intake as a first-line treatment even for mild DED. Yet I find that many clinicians jump to prescription topical treatments and/or procedures before starting omega-3 fatty acid supplements as a baseline therapy. Why is this?

CONFLICTING FINDINGS

It could be uncertainty created by conflicting studies for eye-care providers and patients alike. The DREAM trial led to a great deal of confusion due to the conclusions that were headlined. Indeed, both the control arm with olive oil and the study arm with omega-3 FA demonstrated improvement. However, statistical significance was not achieved between the two arms.¹

On the other hand, a 2016 study led by Alice Epitropoulos, MD, and in which I participated, the “Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes,” reinforced the use of omega-3s as a foundational treatment for DED. Our results demonstrated that oral consumption of re-esterified omega-3 fatty acids is associated with statistically significant improvement in tear osmolarity, omega-3 index levels, tear breakup time, MMP-9 and ocular surface disease index symptom scores.²

In 2019, the debate created by the DREAM trial was further clarified with the publication of a study led by Giuseppe Giannaccare, MD, PhD, a meta-analysis that included 17 randomized studies with 3,363 patients and even included the DREAM trial as well as the Epitropoulos study.³ It validated the use of omega-3 FA supplements and concluded, “Omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with DED.”

More recently, the OMEMI and REDUCE-IT trials resulted in some alarming headlines about a possible link between omega-3 FA supplements and atrial fibrillation (AFib) in high-risk cardiovascular patients.

It is somewhat interesting that an increased AFib association was seen in these studies while most studies display a beneficiary relationship between omega-3 index levels and cardiovascular disease.^4-7 A less bioavailable, synthetic ethyl ester form omega-3 FA supplement (not the triglyceride form found in our diet and in some supplements) was used in these studies. Further research is needed to ascertain whether the omega-3 formulation may have played a role in the AFib association.

STANDARDIZATION NEEDED

In addition to conflicting study outcomes, another reason omega supplements may not be prescribed as initial line of therapy is the lack of understanding about the various forms and doses of omega-3 FA supplements.

In Epitropoulos et al’s randomized placebo controlled multi-center study, a little over 2000 mg of an EPA/DHA re-esterified formula was utilized for these results.² In my opinion, this has become the gold standard protocol for omega-3 fatty acid supplementation. It is incumbent upon physicians to recommend a product by name and to become familiar with its formulation.

Left up to a patient to determine not only the brand but also the daily milligram amount can lead to further confusion. For example, a patient who was referred to me for symptomatic dry eye swore to me that she was taking her omega-3 supplements on a regular basis. Upon further questioning on the brand and the dosage, it turned out that she was eating two chewable gummies a day with a low, non-therapeutic dose of omega-3s. With proper education, she switched to one teaspoon of the liquid PRN omega supplement (Omega-3 supplements tailored to treat DED, above) due to her difficulty swallowing capsules.

PLAY THE LONG GAME

Another reason some physicians jump to prescription options instead of recommending omega-3 FA supplements is to rapidly optimize the ocular surface in preparation for surgery. In my opinion, both a rapid-acting option as well as the omega-3 FA can be concurrently prescribed: one to address the immediate need and the other, for long-term maintenance therapy.

MY EXPERIENCE

I have utilized omega-3 FA supplementation as an initial therapy for my dry eye patients for years. I have been pleased to find that many mild dry eye patients are well controlled on these supplements when combined with a good quality artificial tear and a moist heat mask. For more moderate to severe cases, additional prescription or interventional approaches need to be layered on top of the foundational therapy.

Following the peer-reviewed treatment algorithms with re-esterified omega-3 FA supplements containing 2000 mg or more as first-line therapy is consistent with the science of 2022. OM

REFERENCES

1. Asbell PA, Maguire MG, Peskin E, et al. Dry Eye Assessment and Management Study (DREAM): Study Design and Baseline Characteristics. Contemp Clin Trials. 2018 Aug;71:70-79.
2. Epitropoulos AT, Donnenfeld ED, Shah ZA. Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes. Cornea. 2016 Sep;35:1185-1191.
3. Giannaccare G et al. Efficacy of omega-3 fatty acid supplementation for treatment of dry eye disease. Cornea. 2019
4. Kalstad AA, Myhre PL, Laake K, et al. The Omega-3 fatty acids in elderly with myocardial infarction (OMEMI) trial. Circulation. Epub ahead of print, Nov. 15, 2020. https://tinyurl.com/mr4bs4er . Accessed Mar. 22, 2022.
5. Bhatt DL, Miller M, Brinton EA, et al. Reduction of cardiovascular events with icosapent ethyl — intervention trial (REDUCE-IT). Circulation. 2020;141:367–375.
6. Harris WS, Tintle NL, Etherton MR, Vasan RS. Erythrocyte long-chain omega-3 fatty acid levels are inversely associated with mortality and with incident cardiovascular disease: The Framingham Heart Study. J Clin Lipidol. 2018 May-Jun;12:718-727.e6. Epub 2018
7. Von Schacky C, Harris WS. Cardiovascular benefits of omega-3 fatty acids. Cardiovasc Res. 2007 Jan 15;73:310-315.

Cynthia Matossian, MD, is the founder of Matossian Eye Associates, an affiliate of Prism Vision Group, with multiple offices in Pennsylvania and New Jersey. She specializes in refractive cataract surgery and dry eye disease.

Disclosure: Dr. Matossian is a consultant to Physician Recommended Nutriceuticals and ScienceBased Health.