The benefits of omega-3 long-chain polyunsaturated fatty acids for the human body are well documented. These include foetal development, cardiovascular health, and cognitive function1, but in addition to these, certain omega-3 molecules have been associated specifically with ocular health, including dry eye syndrome and age-related macular degeneration.
Omega-3 Fatty Acids
The human body is not able to efficiently produce omega-3 fatty acids, meaning they must be obtained in sufficient amounts from the diet, whether from plant sources or fish. Medical research has prioritised three specific omega-3 molecules: alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA can be metabolised into the more useful EPA and DHA by the liver but at a very limited rate of up to 15%2 with some reported rates as low as 0.013% for DHA and 0.3% for EPA1.
Omega-3s, particularly DHA, is an important component of the phospholipids of cell membranes, and are found in especially high levels in the retina, as well as the brain1,2. EPA and DHA also play an important role in anti-inflammatory activity throughout the body as they compete against the pro-inflammatory omega-6 molecule arachidonic acid (ARA) for incorporation into cell membranes3. The anti-inflammatory role of omega-3 fatty acids becomes significant in certain ocular diseases with underlying chronic inflammation, such as dry eye and age-related macular degeneration (AMD).
Omega-3 in the Western Diet
Unfortunately, the Western diet is comprised of a high amount of omega-6 and a relatively low amount of omega-3, contributing to the high rates of cardiovascular disease and other illnesses with underlying inflammatory pathogeneses. As implied above, DHA and EPA must be obtained from dietary sources. ALA may be converted into DHA and EPA but this is an inefficient process.
Food sources of ALA include flaxseed oil and whole seeds, chia seeds, canola oil, and English walnuts. DHA and EPA are found in higher amounts in cold water fish such as salmon, tuna, herring, mackerel, and sardines, and in smaller quantities in less fatty fish such as trout, bass, and cod2. It is interesting to note that the DHA and EPA contained in fish is not produced by the fish themselves but rather by microalgae that the fish consume, thereby accumulating these fatty acid molecules within their tissues2. Fish that are farmed and fed ingredients not containing these marine microalgae are often found to contain lower levels of omega-3.
Manufactured omega-3 supplements are also a practical way of inserting DHA and EPA into the diet but care is advised to note the formulation and concentration of DHA and EPA to ensure these are at sufficient levels to provide any health benefit.
Dry Eye Disease
Dry eye disease is an increasingly prevalent condition in today’s world, contributed in part by changes to lifestyle such as the increased use of digital devices such as smartphones and computer screens. Because there is no single, definitive diagnostic tool or metric to diagnose dry eye, prevalence rates often vary, depending on the criteria used for diagnosis. The Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) reported a global prevalence of dry eye disease in the range of 5 to 50% with increasing prevalence found in older ages and females4.
The revised global definition of dry eye by the TFOS DEWS II committee is as follows:
“Dry eye is a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play aetiological roles5.”
One commonly accepted model of the tear film structure describes the tear film being comprised of three layers – a superficial lipid layer (produced by the meibomian glands of the eyelids), a thicker aqueous layer (produced by the lacrimal glands and accessory glands of the eyelid), and a thin mucin layer adjacent to the corneal surface (produced by goblet cells of the conjunctiva).
Dry eye disease may be categorised into two broad underlying aetiologies – aqueous deficiency dry eye and evaporative dry eye, both of which may be broken down into further sub-categories.
The signs and symptoms of dry eye disease vary in presentation and severity from patient to patient but the interview and clinical exam will often find:
Reduced tear break-up time (TBUT)
Reduced measurements on tests of aqueous production, such as Schimer’s testing
Staining of the ocular surface with diagnostic dyes such as sodium fluorescein and lissamine green
Increased signs of ocular surface inflammation, such as conjunctival hyperaemia and elevated tear osmolarity
Reports of feelings of dryness, grittiness, itching, or foreign body sensation in the eyes
Variable vision, particularly with blinking
The Role of Omega-3 in Dry Eye Disease
Research continues in the area of investigating the benefits of omega-3 supplementation as an adjunct treatment for dry eye disease, particularly cases with underlying meibomian gland dysfunction. To date, there is no global consensus on the optimal dosage or duration of treatment for dry eye with omega-3. While multiple studies have found beneficial effects of omega-3 supplements in reducing the prevalence and severity of the signs and symptoms of dry eye disease, numerous studies have also concluded there is no evidence to justify the claim that omega-3 supplementation is a useful adjunct treatment.
A meta-analysis of seven independent randomised controlled studies reported that oral omega-3 supplementation was found to provide significant improvements to the TBUT (relating to the quality of lipid secretions from the meibomian glands) and Schirmer testing (relating to production of the aqueous layer of the tear film). However, this systematic review failed to find any significant improvement to ocular surface disease index (OSDI) scores6, a dry eye questionnaire developed by Allergan Inc to “provide rapid assessment of the range of ocular surface symptoms7”. The conclusion from this paper was that omega-3 fatty acids are able to improve TBUT and Schirmer scores but did not improve the symptoms and ocular comfort of these dry eye patients6. Other studies were able to demonstrate improvements to symptoms with either OSDI scoring or other methods of subjective symptom scoring, as well as a significant decreased level of ocular inflammation8,9. More recently in 2018, The Dry Eye Assessment and Management Study Research Group did not find any significant differences in either symptoms or clinical signs (conjunctival staining, TBUT, and Schirmer testing) between participants taking a total daily dose of 3000mg of EPA and DHA supplementation and those taking a placebo capsule of olive oil10.
Despite the results of the 2018 study, there currently remains no consensus or indisputable conclusion about the benefits or lack thereof for omega-3 supplementation in the treatment of dry eye.
Age-Related Macular Degeneration
AMD is considered a significant cause of blindness in the UK and is untreatable in as many as 90% of patients11. As the name suggests, the prevalence of AMD increases with age with one study finding advanced AMD at a prevalence of 2.2% in a Caucasian UK population between 65-69 years of age, increasing to over 21.2% in those over 90 years old12.
The macula of the eye is crucial for central vision. It contains the highest density of cone photoreceptors throughout the eye by a significant margin, allowing it to discern fine detail such as words and facial features. Because of this, the macula requires a significant amount of energy and subsequently produces a high level of metabolic waste. A layer of the retina directly involved with supporting the function of the photoreceptors of the macula (and the rest of the retina) is the retinal pigment epithelium (RPE); the pathophysiology of AMD has traditionally been associated with degenerative changes to this layer, due to the presence of inflammation and oxidative stress3.
Early AMD is typically asymptomatic and diagnosed with ophthalmoscopy by an eyecare practitioner. Extracellular deposits of metabolic waste material known as drusen accumulate within the retina in a form of the disease known as dry AMD. In intermediate and advanced stages of dry AMD, confluent areas of geographic RPE atrophy develop, which eventually lead to photoreceptor death and loss of vision at the macula. A later stage of AMD is known as wet, or neovascular AMD, characterised by the formation and haemorrhaging of neovascular blood vessels through the choroid layer of the retina11.
The presence of both geographic atrophy in dry AMD and neovascularisation in wet AMD, and subsequent scarring, can result in the severe and permanent loss of central vision.
Treatments are currently available for wet AMD only, in the form of regular injections of anti-vascular endothelial growth factor (anti-VEGF) medications into the vitreous humour of the eye; this may slow or cease the progression of the disease but typically substantial vision loss remains. There is currently no available treatment for dry, atrophic AMD.
The Role of Omega-3 in AMD
As mentioned earlier, DHA and EPA play important roles within the retina; DHA in particular is a major component of photoreceptor segment membranes3. DHA and EPA have also been found to be able to moderate inflammatory processes often implicated in the pathogenesis of certain retinal diseases, such as AMD, by suppressing VEGF signalling and pro-inflammatory cytokines in the retina3.
A large, multicentre study associated with the well-known AREDS (the Age-Related Eye Disease Study) found that participants with a higher level of omega-3 intake were approximately 30% less likely to develop advanced AMD after 12 years when compared to peers with a low reported omega-3 consumption13. However, the AREDS2 study was unable to demonstrate that supplementation of omega-3 fatty acids provided any further effect of reducing progression of AMD when added to the existing components of the AREDS1 formulation for AMD14. A subsequent review of the findings of the AREDS2 noted several issues with its methodology and protocol, concluding that the study was not adequately designed to fully investigate the beneficial effects of omega-3 fatty acids in AMD progression15.
Many epidemiological studies have been able to validate the benefits of omega-3 for AMD. A large prospective study published in 2001 followed over 70 000 participants over a 10 to 12-year period, concluding that increased DHA and EPA consumption may confer protective effects against AMD16. Specifically, it was noted that:
Total fat intake was associated with an increased risk of AMD
Animal and vegetable fat intake were both linked to modest increases in risk of AMD
Saturated, monounsaturated, and trans unsaturated fats were all linked to modest increases in AMD risk
DHA intake was associated with a modest decreased risk of AMD
Fish intake of more than four times a week was associated with a lower risk of AMD than fish consumption of three or less times a week
While research into the role of omega-3 supplementation in the treatment and prevention of certain ocular diseases continues, consideration of the existing evidence in support of omega-3 supplementation for dry eye disease and AMD3 leads to a logical conclusion in support of eyecare practitioners suggesting the inclusion of omega-3 supplements in the absence of any contraindications.
Swanson, D., Block, R., & Mousa, S. A. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Advances in nutrition (Bethesda, Md.)2012, 3(1), 1–7. doi:10.3945/an.111.000893 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262608/. Accessed 8/7/19]
National Institutes of Health, Office of Dietary Supplements. Omega-3 Fatty Acids. 2019. [https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/#en3. Accessed 8/7/19]
Wang H, Daggy B, P: The Role of Fish Oil in Inflammatory Eye Diseases. Biomed Hub 2017;2:1-12. doi: 10.1159/000455818 [https://www.karger.com/Article/FullText/455818#. Accessed 8/7/19]
Stapleton, F., Alves, M., Bunya, V.Y., Jalbert, I., et al. TFOS DEWS II Epidemiology Report. Ocul Surf 2017, 15 (3):334-365. https://doi.org/10.1016/j.jtos.2017.05.003. [https://www.sciencedirect.com/science/article/pii/S154201241730109X?via%3Dihub. Accessed 8/7/19]
Craig, J.P., Nichols, K.K., et al. TFOS DEWS II – Definition and Classification Report. Ocul Surf 2017, 15 (3): 276-283. https://doi.org/10.1016/j.jtos.2017.05.008 [https://www.sciencedirect.com/science/article/pii/S1542012417301192?via%3Dihub. Accessed 8/7/19]
Liu, A., & Ji, J. (2014). Omega-3 essential fatty acids therapy for dry eye syndrome: a meta-analysis of randomized controlled studies. Medical science monitor : international medical /journal of experimental and clinical research, 20, 1583–1589. doi:10.126/59/MSM.891364 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165511/. Accessed 8/7/19]
Ocular Surface Disease Index (OSDI). PROQOLID. [https://eprovide.mapi-trust.org/instruments/ocular-surface-disease-index. Accessed 8/7/19]
Oleñik, A., Jiménez-Alfaro, I., Alejandre-Alba, N., & Mahillo-Fernández, I. (2013). A randomized, double-masked study to evaluate the effect of omega-3 fatty acids supplementation in meibomian gland dysfunction. Clinical interventions in aging, 8, 1133–1138. doi:10.2147/CIA.S48955 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770496/. Accessed 8/7/19]
Bhargava, R., Kumar, P., Kumar, M., Mehra, N., & Mishra, A. (2013). A randomized controlled trial of omega-3 fatty acids in dry eye syndrome. International journal of ophthalmology, 6(6), 811–816. doi:10.3980/j.issn.2222-3959.2013.06.13 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874521/. Accessed 8/7/19]
Dry Eye Assessment and Management Study Research Group, Asbell, P. A., Maguire, M. G., Pistilli, M., Ying, G. S., Szczotka-Flynn, L. B., … Shtein, R. M. (2018). n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease. The New England journal of medicine, 378(18), 1681–1690. doi:10.1056/NEJMoa1709691 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952353/. Accessed 8/7/19]
Ambati, J., & Fowler, B. J. (2012). Mechanisms of age-related macular degeneration. Neuron, 75(1), 26–39. doi:10.1016/j.neuron.2012.06.018 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404137/. Accessed 8/7/19]
Wilde, C., Poostchi, A., Mehta, R. L., MacNab, H. K., Hillman, J. G., Vernon, S. A., & Amoaku, W. M. (2017). Prevalence of age-related macular degeneration in an elderly UK Caucasian population-The Bridlington Eye Assessment Project: a cross-sectional study. Eye (London, England), 31(7), 1042–1050. doi:10.1038/eye.2017.30 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519272/. Accessed 8/7/19]
SanGiovanni JP, Agrón E, Clemons TE, Chew EY. ω-3 Long-Chain Polyunsaturated Fatty Acid Intake Inversely Associated With 12-Year Progression to Advanced Age-Related Macular Degeneration. Arch Ophthalmol.2009;127(1):109–116. doi:10.1001/archophthalmol.2008.518 [https://jamanetwork.com/journals/jamaophthalmology/fullarticle/420997. Accessed 8/7/19]
The Age-Related Eye Disease Study 2 (AREDS2) Research Group*. Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. JAMA. 2013;309(19):2005–2015. doi:10.1001/jama.2013.4997 [https://jamanetwork.com/journals/jama/fullarticle/1684847. Accessed 8/7/19]
Souied E, H, Aslam T, Garcia-Layana A, Holz F, G, Leys A, Silva R, Delcourt C: Omega-3 Fatty Acids and Age-Related Macular Degeneration. Ophthalmic Res 2016;55:62-69. doi: 10.1159/000441359 [https://www.karger.com/Article/FullText/441359#. Accessed 8/7/19]
Eunyoung Cho, Shirley Hung, Walter C Willett, Donna Spiegelman, Eric B Rimm, Johanna M Seddon, Graham A Colditz, Susan E Hankinson, Prospective study of dietary fat and the risk of age-related macular degeneration, The American Journal of Clinical Nutrition, Volume 73, Issue 2, February 2001, Pages 209–218, https://doi.org/10.1093/ajcn/73.2.209. [https://academic.oup.com/ajcn/article/73/2/209/4737397. Accessed 8/7/19]
The author of this article takes full responsibility for the accuracy of this article and is not in any way affiliated or employed by Intelligent Formula – any views stated is entirely the author’s view.
About the Author:
Jane Chong, B.Optom
Jane graduated from the University of Melbourne in 2012 with a Bachelor of Optometry and therapeutic endorsement. She has worked as a clinical optometrist ever since, gaining valuable experience across ocular disease management, contact lenses prescribing, paediatric optometry, and general optometry.
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