Special Thanks

Article Written & Contributed by Kevin Cornwell, OD

When it comes to patient education and ocular disease management, optometrists are often asked the inevitable question “Is there anything else I can do”? Patients continually seek additional treatment options, in hopes of increasing their odds of preserving their sight.

Throughout the literature, there exists a multitude of evidenced-based strategies for nutraceutical supplementation to optimize ocular health. Oftentimes 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.

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 the 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.  There are countless studies, albeit controversial, touting the benefits on omega-3 supplementation in dry eye disease. However, have we overlooked the literature pertaining to omega-3 supplementation applicable to other types of ocular diseases?

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 for plant-based sources as compared to animal-based options.

DIABETIC RETINOPATHY

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, 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 complimenting standard diabetic retinopathy treatments.

AGE-RELATED MACULAR DEGENERATION

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 retinal pigment epithelium (RPE), along with an imbalance in retinal lipid composition have been linked to photoreceptor degradation in age-related macular degeneration (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 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, patients may want to consider these findings even in 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 less therapeutic.21

GLAUCOMA

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.

Tips and considerations

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, OD’s 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.

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/, https://www.wellnessfx.com/omegas and https://directlabs.com/ - Cardio IQ Omega 3s.

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

Omega-3 supplementation can be an excellent adjunct therapy in the management of diabetic retinopathy, glaucoma, or macular degeneration. It can also be incorporated into an otherwise healthy diet, for patients looking to reduce their risk of developing future sight-threatening diseases.

Special Thanks

Article Written & Contributed by Kevin Cornwell, OD

References

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