AOA 2023: Nutritional strategies in dry eye disease: The importance of omega-3s

Reviewed by Mark W. Roark, OD, FAAO

The integration of best-available evidence, clinical expertise, and patient preferences and values is the way clinicians should decide on a course of nutritional therapy for treating DED. (Adobe Stock / anaumenko)

Mark Roark, OD, FAAO, presented multiple lines of evidence for use of omega-3s to treat dry eye disease (DED) at the 2023 Optometry’s Meeting, hosted by the American Optometric Association, this year in Washington, DC.

“Nutritional intervention is a logical treatment strategy when considering disease etiology and can help maintain ongoing control of DED, while complementing the impact of other treatment procedures.” Roark said.

“Nutrition offers a safe approach with no to minimal side effects, is accessible, often more affordable than other treatments, and offers holistic benefits that can be quite significant.”

Nutritional intervention is level 1 therapy, according to the 2017 Tear Film and Ocular Surface Society's Dry Eye Workshop II,¹ and a 2019 Cochrane Systematic Review assessing 34 randomized clinical trials found that when omega-3s are added to standard treatments such as artificial tears and warm soaks, DED symptoms improve compared to using those treatments alone.²

This report also concluded that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were more effective than omega-6 fatty acids in controlling the symptoms of DED.2 Studies that delay nutritional intervention until DED becomes moderate or severe fall outside of the recommended protocol and should be evaluated carefully.

Roark described a 3-pronged approach for nutritional intervention, in addition to the recommendation of increasing dietary intake of oily fish.

In step 1, a product is selected, prescribed, dispensed, i.e., ≥2 grams of triglyceride EPA plus DHA/day (balanced ratio), and the clinical response monitored.

Step 2 involves omega-3 index red blood cell membrane testing after 3 to 4 months. The omega-3 dose is titrated to exceed an index of 8%. The clinical response is monitored and if signs or symptoms persist, the clinician moves to the next step.

In step 3, omega complete blood testing is performed, and gamma-linolenic acid (GLA) is added if di-homo-GLA (DGLA) is low. Clinical findings are monitored, and blood levels are rechecked since responses vary and often are affected by factors such as genetics. Patient values must be considered.

Roark described a number of studies supporting the use of omega-3 fatty acids in DED.

Preliminary research has shown improvement in meibomian gland secretions and levels of meibum DHA with reduced ocular signs and symptoms with properly dosed EPA plus DHA.³ Other studies show reduced inflammation as evidenced by improved tear film cytokine levels after 12 weeks with oral and topical omega-3s,⁴ and evidence for corneal neuroprotection.⁵ A well-designed study found reduced tear osmolarity, inflammatory markers, and symptoms associated with an increased omega-3 index in participants with DED, but without severe meibomian gland dysfunction.⁶

Those findings were in contrast to the controversial Dry Eye Evaluation and Management (DREAM) Study,⁷ a multicenter, 12-month trial that evaluated the role of omega-3 fatty acids in moderate-to-severe DED; no statistically significant benefit was seen with the use of omega-3 fatty acids compared with placebo in patients with this level of DED. However, Roark pointed out several concerns with this study, including the fact that more than 75% of patients in the active treatment and placebo groups had a change in their multifaceted treatment regimens during the study period.

Of note, a meta-2019 analysis⁸ provided evidence that omega-3 fatty acid supplementation significantly improved DED findings. Improvements were seen in symptoms, corneal fluorescein staining, tear break-up time, and Schirmer scores.

A discussion of the mechanism of action of polyunsaturated fatty acids showed that increasing dietary EPA and DHA dampens the inflammatory response and reduces the risk of chronic inflammation through formation of specialized pro-resolving mediators (SPMs).⁹ DHA is the primary source of these with some contribution from EPA, but no SPMs have been found for the omega-66 DGLA.

“It is essential for the inflammatory trigger to be turned off,” Roark emphasized.

He also noted the importance of achieving optimal levels of EPA plus DHA in body tissues, as determined by the omega-3 index previously mentioned. The target is greater than 8% to 12%, which is infrequently reached by most Americans. This index is a predictor of risk for fatal coronary heart disease events and other important health outcomes.¹⁰ Research indicates that those with an omega value of 8% have a 35% lower risk of a sudden fatal heart attack compared with individuals at 4%.¹¹

Roark concluded that the integration of best-available evidence, clinical expertise, and patient preferences and values is the way clinicians should decide on a course of nutritional therapy for treating DED.

Mark Roark, OD, FAAO, is in private practice in Fishers, IN.

Email: markroark.od@gmail.com

References

1. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15:276-283. doi: 10.1016/j.jtos.2017.05.008.

2. Downie LE, Ng SM, Lindsley KB, Akpek EK. Omega‐3 and omega‐6 polyunsaturated fatty acids for dry eye disease. Cochrane Database Syst Rev. 2019;12: CD011016.

3. Smith SG, Gross MB, Sandnes OE. Methods for improving the quality of the meibum composition of meibomian glands. Accessed June 19, 2023. https://patents.google.com/patent/US9381183B2/en

4. Downie LE, Gad A, Wong CY, et al. Modulating contact lens discomfort with anti-inflammatory approaches: A randomized controlled trial. Invest Ophthalmol Vis Sci. 2018;59:3755-66.

5. Chinnery HR, Golborne CN, Downie LE. Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study. Ophthalmic Physiol Optics. 2017;37: 473–81.

6. Epitropoulos AT, Donnenfeld EC, Shah ZA, et al. Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes. Cornea. 2016;35:1185-91.

7. Asbell PA, et al. Dry Eye Assessment and Management (DREAM©) Study: Study design and baseline characteristics. Contemp Clin Trials. 2018;71:70–9.

8. Giannaccare G, Pelligrini M, Sebastiani S, et al. Efficacy of omega-3 fatty acid supplementation for treatment of dry eye disease. Cornea. 2019;38:565–73.

9. Serhan CN, Levy BD. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest. 2018;128:2657-69.

10. Harris WS, von Schacky C. The Omega-2 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004;39:212-20.

11. Harris WS, Del Gobbo L, Tintle NL. The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies. Atherosclerosis. 2017;262:51-4.