When it comes to patient education and ocular disease management, ODs are often asked the inevitable question “Is there anything else I can do?” In addition to Amsler grids, AREDS supplements, or prescriptions for Latanoprost, some patients seek additional treatment options, in hopes of increasing their odds of preserving their sight. Throughout the literature, there exists a multitude of evidence-based strategies for prescribing nutraceutical supplementation for our patients. Often times these can be complementary to standard-of-care treatments for glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. When done properly, these can promote healing and prevent disease progression among this patient population.

In the U.S. alone, the dietary supplement industry grosses approximately $30 billion per year, offering over 90,000 products.1 Doctors and patients can become easily confused without an in-depth understanding of published literature, clinical indications, and dosing.

When it comes to optimizing our patients’ ocular and systemic health, some of the most important nutritional supplements are arguably omega-3 fatty acids. These consist of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and alpha-linolenic acid (ALA). EPA and DHA primarily play an anti-inflammatory role within the body while countering the pro-inflammatory (but biologically necessary) effects of omega-6 fatty acids – arachidonic acid and linoleic acid. Optometrists have seen the countless studies, albeit controversial, touting the benefits on omega-3 supplementation in dry eye disease. However, have ODs overlooked the literature pertaining to omega-3 supplementation applicable to other types of ocular disease?

As we’ll explore more in this article, the science has repeatedly shown an association between systemic EPA/DHA deficiency and the pathogenesis of glaucoma, macular degeneration, type 2 diabetes, and diabetic retinopathy.

Over half of lipid content within the retinal photoreceptors is made up of DHA. DHA plays several key roles in the retina, including optimizing mitochondrial activity and inhibition of angiogenesis, inflammation, apoptosis, and mitigating oxidative stress.3 DHA is the primary structural fatty acid in our brain, facilitating learning, memory, and neurogenesis. EPA and DHA, when present in optimal levels, have also been shown to reduce the risk of a multitude of today’s chronic disease, including cardiovascular disease, cancer, dementia and various autoimmune disease.2

Studies have also shown an age-dependent decrease in EPA/DHA concentration in the neuronal tissues of the central nervous system. These deficiencies are thought to play a major role in the pathophysiology of neurodegenerative disease.4,5

A daily intake of omega-3’s between 1100mg to 1600mg for healthy adults is recommended by the NIH,31 while up to 3000mg/day of EPA/DHA can be taken safely according to the FDA.27

Dietary consumption of fish increases our plasma concentration of EPA/DHA more effectively than fish oil supplementation alone.35 Vegan/vegetarian patients can opt to take flax seed, chia seed, or hemp seed as an adequate source of EPA and DHA, however, conversion to EPA/DHA is significantly lower when compared to animal-based sources.


Retinal ischemia, poor ocular blood flow, & subsequent production of intraocular VEGF are all thought to play a significant role in the pathophysiology of diabetic retinopathy.

According to several studies, recommending EPA/DHA supplementation for our patients with obesity, metabolic syndrome, prediabetes, or diabetes can help improve metabolism and blood sugar levels. Evidence shows that regular EPA and DHA consumption can improve beta cell function in the pancreas and increases insulin sensitivity.22 In Finland, a 2014 study showed that regular consumption of 500-1000mg/day of EPA/DHA lowered the risk of developing type 2 diabetes by over 30% over 19 years.22

When it comes to regulating capillary permeability and inflammation within the retina EPA/DHA play a large role.6 Recent literature has also shown that dietary EPA/DHA can lower the risk of developing diabetic retinopathy by as much as 50%,32 while also improving treatment outcomes for patients with diabetic macular edema.33 While this is still a relatively new area of research, omega-3 supplementation could have a significant impact in mitigating the ocular manifestations of metabolic disease, while also serving as complementary therapy for patients undergoing treatment for diabetic retinopathy.


Dysfunctional retinal lipid composition and metabolism are thought to cause macular drusen. Patients undergoing prolonged anti-VEGF therapy have an increased risk of developing geographic atrophy and other adverse events.

Abnormal accumulation of lipid and lipoprotein debris within the RPE, along with an imbalance in retinal lipid composition have been linked to photoreceptor degradation in AMD.6 Since the turn of the century, we’ve seen significant advancements in the treatment options for exudative AMD, the leading cause of blindness among older individuals in the U.S.7 Despite standard-of-care treatment, up to 10% of these patients will continue to lose 3 or more lines of acuity over the course of their lifetime.7 Each year, the U.S. healthcare system spends roughly $10 billion dollars to treat exudative AMD.7,8 While these treatments can be successful and life-changing for many patients, they do place some individuals at an increased risk for geographic atrophy, thromboembolic events, stroke, neuronal toxicity, and even death. These adverse events are directly correlated with frequency and duration of anti-VEGF therapy.9-14 As primary eye care providers, ODs can consider recommending any complementary treatment strategies for these patients. Incorporating EPA/DHA supplementation in the right patient may reduce the risk of these poor visual and systemic outcomes.

In 2014, a study was published looking at the effect of 1000mg/day of EPA/DHA supplementation on intraocular concentration of VEGF in patients undergoing treatment for wet AMD.7 The results showed over a 50% additional reduction in vitreal concentration of VEGF when compared to controls. This suggests that fish oil could be considered an adjunct treatment option for our patients being treated for exudative AMD. Cold-water fatty fish consumption at 2 to 3 servings per week has also been shown to reduce the risk in developing exudative AMD by up 50%.15-19 Therefore, ODs may want to suggest these findings to patients even with the earlier stages of AMD.

Since we are limited in our ability to naturally biosynthesize omega-3 fatty acids, dietary intake is essential, primarily through consumption of wild-caught cold-water fatty fish. Also commonly found in fish oil supplements, EPA and DHA are available in various formulations, including ethyl ester (EE) and triglyceride (TG) forms. The EE form of EPA/DHA was used in the AREDS 2 study,20 and may explain the unremarkable outcome on dry AMD progression as some studies have shown the EE form to be less bioavailable and therefore therapeutic.21


Poor ocular perfusion and ischemia to the optic nerve are also thought to have an impact on POAG pathogenesis and progression.

Studies have also shown a correlation between EPA/DHA deficiency, excess omega-6 intake, and the severity of primary open angle glaucoma.34 In animal models, EPA/DHA supplementation has been shown to lower intraocular pressure,23 while in human studies to improve visual field outcomes.24

The fatty acid composition on the red blood cell is thought to play an important role in autoregulation and vasodilation of eye’s microcirculation.24-26 EPA and DHA both help to improve ocular perfusion in this way, and can be considered an adjunct therapy for our glaucoma patients as well.

What type of omega-3 supplement is best to recommend? While there are several plant-based sources of omega-3’s primarily consisting of ALA (ie: hemp, flaxseed, or chia seeds), these are poorly converted to EPA and DHA by the body (roughly 10%). The most effective form of EPA/DHA to ingest is from cold water fatty fish, such as sardines, anchovies, salmon or krill (and their associated supplements). Doctors and patients can use references like https://labdoor.com/ for more information on nutritional supplement testing and ranking by safety, quality, and value. Due to an increased risk of bleeding, ODs should exercise caution to patients on blood thinners (ie Aspirin, Plavix, Coumadin) and advise speaking with PCP prior to starting any consistent EPA/DHA supplementation.

Some doctors may think it’s naïve, or even insane to view nutritional supplementation as a potential game-changer when treating their patients. As healthcare providers, it’s always beneficial to our patients to have more tools and information in the clinical toolbox. Having the knowledge to educate our patients on current evidence-based therapy is increasingly important as we strive to provide optimal patient care, while also reducing the burden on the healthcare system.

Our ancestors were thought to have had an average omega-6/3 ratio ranging from 1:1 to 4:1. Today, in the western world, the average ratio exceeds 15:1 and is thought to play a large role in the dramatic increase in chronic disease we now face.2 Various direct-to-consumer lab services offer at-home testing for determining the omega-6/3 ratio, these include https://omegaquant.com/ ($79.95), https://www.wellnessfx.com/omegas ($99) and https://directlabs.com/ – Cardio IQ Omega 3s ($138). A reduction in omega-6 fatty acid consumption is also important to implement as well. These include industrial seed oils,28,29, excessive nuts/grains, processed foods, and farm-raised fish30

When it comes to our motivated patients, recommending omega-3 supplementation can be an excellent adjunct therapy in the management of diabetic retinopathy, glaucoma, or macular degeneration.


  1. Manson, J E, and S S Bassuk. “Vitamin and Mineral Supplements: What Clinicians Need to Know.” JAMA, U.S. National Library of Medicine, 6 Mar. 2018, www.ncbi.nlm.nih.gov/pubmed/29404568
  2. Simopoulos, A P. “The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases.” Experimental Biology and Medicine (Maywood, N.J.)., U.S. National Library of Medicine, June 2008, www.ncbi.nlm.nih.gov/pubmed/18408140
  3. Souied, Eric H., et al. “Oral Docosahexaenoic Acid in the Prevention of Exudative Age-Related Macular Degeneration: The Nutritional AMD Treatment 2 Study.” Ophthalmology, Elsevier, 8 Feb. 2013, www.sciencedirect.com/science/article/pii/S0161642013000079?via%3Dihub
  4. Denis, I., Potier, B., Heberden, C., & Vancassel, S. (2015). Omega-3 polyunsaturated fatty acids and brain aging. Current Opinion in Clinical Nutrition and Metabolic Care, 18(2), 139-146. doi:10.1097/mco.0000000000000141
  5. Song, C., Shieh, C., Wu, Y., Kalueff, A., Gaikwad, S., & Su, K. (2016). The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer’s disease: Acting separately or synergistically? Progress in Lipid Research, 62, 41-54. doi:10.1016/j.plipres.2015.12.003
  6. SanGiovanni, JP, and EY Chew. “The Role of Omega-3 Long-Chain Polyunsaturated Fatty Acids in Health and Disease of the Retina.” Progress in Retinal and Eye Research., U.S. National Library of Medicine, Jan. 2005, www.ncbi.nlm.nih.gov/pubmed/15555528
  7. REZENDE, F. A., LAPALME, E., QIAN, C. X., SMITH, L. E., SANGIOVANNI, J. P., & SAPIEHA, P. (2014). Omega-3 Supplementation Combined With Anti–Vascular Endothelial Growth Factor Lowers Vitreal Levels of Vascular Endothelial Growth Factor in Wet Age-Related Macular Degeneration. American Journal of Ophthalmology, 158(5), 1071–1078. http://doi.org/10.1016/j.ajo.2014.07.036
  8. Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, Klein R, Tielsch JM, Vijan S, Saaddine J. The Economic Burden of Major Adult Visual Disorders in the United States. Arch Ophthalmol. 2006;124(12):1754–1760. doi:10.1001/archopht.124.12.1754
  9. Danis, R. P., Lavine, J. A., & Domalpally, A. (2015). Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects. Clinical Ophthalmology (Auckland, N.Z.), 9, 2159–2174. http://doi.org/10.2147/OPTH.S92359
  10. Stewart, M. W. (2012). The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology. Mayo Clinic Proceedings, 87(1), 77–88. http://doi.org/10.1016/j.mayocp.2011.10.001
  11. Robinson, GS, et al. “Nonvascular Role for VEGF: VEGFR-1, 2 Activity Is Critical for Neural Retinal Development.” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology., U.S. National Library of Medicine, May 2001, www.ncbi.nlm.nih.gov/pubmed/11344092
  12. Grunwald, J. E., Daniel, E., Huang, J., Ying, G., Maguire, M. G., Toth, C. A., … Martin, D. F. (2014). Risk of Geographic Atrophy in the Comparison of Age-related Macular Degeneration Treatments Trials. Ophthalmology, 121(1), 150–161. http://doi.org/10.1016/j.ophtha.2013.08.015
  13. Avery RL, Gordon GM. Systemic Safety of Prolonged Monthly Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular EdemaA Systematic Review and Meta-analysis. JAMA Ophthalmol. 2016;134(1):21–29. doi:10.1001/jamaophthalmol.2015.4070
  14. Thulliez M, Angoulvant D, Pisella P, Bejan-Angoulvant T. Overview of Systematic Reviews and Meta-analyses on Systemic Adverse Events Associated With Intravitreal Anti–Vascular Endothelial Growth Factor Medication Use. JAMA Ophthalmol. Published online March 22, 2018. doi:10.1001/jamaophthalmol.2018.0002
  15. Querques, Giuseppe, and Eric H. Souied. “The Role of Omega-3 and Micronutrients in Age-Related Macular Degeneration.” Survey of Ophthalmology, Elsevier, 27 Jan. 2014, www.sciencedirect.com/science/article/pii/S003962571400023X?via%3Dihub
  16. Tan, J S, et al. “Dietary Fatty Acids and the 10-Year Incidence of Age-Related Macular Degeneration: the Blue Mountains Eye Study.” Archives of Ophthalmology (Chicago, Ill. : 1960)., U.S. National Library of Medicine, May 2009, www.ncbi.nlm.nih.gov/pubmed/19433717
  17. Cho, E, et al. “Prospective Study of Dietary Fat and the Risk of Age-Related Macular Degeneration.” The American Journal of Clinical Nutrition., U.S. National Library of Medicine, Feb. 2001, www.ncbi.nlm.nih.gov/pubmed/11157315
  18. Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Dietary ω-3 Fatty Acid and Fish Intake in the Primary Prevention of Age-Related Macular Degeneration A Systematic Review and Meta-analysis. Arch Ophthalmol. 2008;126(6):826–833. doi:10.1001/archopht.126.6.826
  19. Augood, C, et al. “Oily Fish Consumption, Dietary Docosahexaenoic Acid, and Eicosapentaenoic Acid Intakes, and Associations with Neovascular Age-Related Macular Degeneration.” The American Journal of Clinical Nutrition., U.S. National Library of Medicine, Aug. 2008, www.ncbi.nlm.nih.gov/pubmed/18689376
  20. Fish Oil: EE vs. TG Omega-3s – Which Is Better? www.sciencebasedhealth.com/Fish-Oil-EE-vs-TG-omega-3s-which-is-better-W119.aspx
  21. Dyerberg J, et al. Bioavailability of n-3 fatty acids. In n-3 Fatty Acids: Prevention and Treatment in Vascular Disease, SD Kristensen, EB Schmidt, R DeCaterina and S Endres, eds. Bi and Gi Publishers, Verona—Springer Verlag, London pp. 217-26, 1995, https://pdfs.sematicscholar.org/250c/765a1459ca58d998d292f9b3e7d7bb07eb89.pdf
  22. Virtanen, J. K., Mursu, J., Voutilainen, S., Uusitupa, M., & Tuomainen, T. (2013). Serum Omega-3 Polyunsaturated Fatty Acids and Risk of Incident Type 2 Diabetes in Men: The Kuopio Ischemic Heart Disease Risk Factor Study. Diabetes Care Dia Care, 37(1), 189-196. doi:10.2337/dc13-1504
  23. Nguyen, C. T., B. V. Bui, and A. J. Sinclair. “Dietary Omega 3 Fatty Acids Decrease Intraocular Pressure with Age by Increasing Aqueous Outflow.” Investigative Ophthalmology and Vision Science (2007): n. pag.
  24. Cellini, M., N. Caramazza, P. Mangiafico, G. L. Possati, and R. Caramazza. “Fatty Acid Use in Glaucomatous Optic Neuropathy Treatment.” Acta Ophthalmologica Scandinavica 76.S227 (1998): 41-42.
  25. Acar, Niyazi, Olivier Berdeaux, Pierre Juaneda, Stéphane Grégoire, Stéphanie Cabaret, Corinne Joffre, Catherine P. Creuzot-Garcher, Lionel Bretillon, and Alain M. Bron. “Red Blood Cell Plasmalogens and Docosahexaenoic Acid Are Independently Reduced in Primary Open-angle Glaucoma.” Experimental Eye Research 89.6 (2009): 840-53.
  26. Ren, Hongmei, Nwabueze Magulike, Kebreab Ghebremeskel, and Et Al. “Primary Open-angle Glaucoma Patients Have Reduced Levels of Blood Docosahexaenoic and Eicosapentaenoic Acids.” National Center for Biotechnology Information. U.S. National Library of Medicine, 4 Nov. 2005.
  27. CFR – Code of Federal Regulations Title 21.” Substances Affirmed as Generally Recognized as Safe, Accessdata.fda.gov, www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=184&showFR=1
  28. Ramsden, Christopher E, et al. “The Sydney Diet Heart Study: a Randomised Controlled Trial of Linoleic Acid for Secondary Prevention of Coronary Heart Disease and Death.” Federation of American Societies for Experimental Biology, 1 Apr. 2013, www.fasebj.org/doi/abs/10.1096/fasebj.27.1_supplement.127.4
  29. Pearce, Morton Lee, and Seymour Dayton. “INCIDENCE OF CANCER IN MEN ON A DIET HIGH IN POLYUNSATURATED FAT.” The Lancet, 6 Mar. 1971, www.thelancet.com/journals/lancet/article/PIIS0140673671910865/abstract
  30. Sprague, M., Dick, J. R., & Tocher, D. R. (2016). Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006–2015. Scientific Reports, 6, 21892. http://doi.org/10.1038/srep21892
  31. Office of Dietary Supplements – Omega-3 Fatty Acids.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/#h2
  32. Chew EY. Dietary Intake of Omega-3 Fatty Acids From Fish and Risk of Diabetic Retinopathy. JAMA. 2017;317(21):2226–2227. doi:10.1001/jama.2017.1926
  33. Lafuente, María, et al. “COMBINED INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA: Two-Year Randomized Single-Blind Controlled Trial Results: RETINA.” The Journal of Retina and Vitreous Diseases, July 2017, journals.lww.com/retinajournal/fulltext/2017/07000/COMBINED_INTRAVITREAL_RANIBIZUMAB_AND_ORAL.10.aspx
  34. Yu M, Chen B, Gong B, Shuai P, Wu Z-Z, Lin W. Association of n3 and n6 polyunsaturated fatty acids in red blood cell membrane and plasma with severity of normal tension glaucoma. International Journal of Ophthalmology. 2015;8(3):476-483. doi:10.3980/j.issn.2222-3959.2015.03.08
  35. Visioli, F, et al. “Dietary Intake of Fish vs. Formulations Leads to Higher Plasma Concentrations of n-3 Fatty Acids.” Lipids., U.S. National Library of Medicine, Apr. 2003, www.ncbi.nlm.nih.gov/pubmed/12848287