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Beyond pharmaceuticals: Slowing the progression of AMD via nutrition

Optometry Times JournalFebruary digital edition 2024
Volume 16
Issue 02

AREDS2 supplementation and close monitoring of gut microbiota may help patients at risk for vision loss.

Assortment of fruits, vegetables on table Image Credit: AdobeStock/AlexanderRaths

Image Credit: AdobeStock/AlexanderRaths

Macular degeneration is now considered to be the leading cause of irreversible blindness and visual impairment in the world. The study titled “The prevalence of age-related macular degeneration in the United States in 2019” found that almost 20 million Americans were living with some form of age-related macular degeneration (AMD).1 Approximately 1 in 10 Americans 50 years and older has an early form of AMD and approximately 1 out of every 100 Americans 50 years and older has the vision-threatening late form of AMD. As eye care professionals, we have a unique opportunity to influence patients with preventive “tools” for the prevention of devastating vision loss.

Education must be an integral part of patient care as we aim to reduce the prevalence of AMD. This article espouses that treatment for AMD lies somewhere between the science that is producing pharmaceutical agents and personalized nutrition in the form of tailoring general nutrition advice to a patient’s needs and preferences while taking into consideration lifestyle, genetics, and microbiome. The global human nutrition market (including nutritional food, beverages, and dietary supplements) was valued in 2019 with estimates in the range of US $350 billion and is projected to reach an upward growth rate of about 7% in the next 10 years.2 Patients are interested, listening, and ready to take control of their health. Eye care practitioners should pay attention to this shift not only as a business opportunity but also as a chance to promote holistic health and wellness.

Just look back to 2001 to see how eye care shifted with the original National Eye Institute AREDS (Age-Related Eye Diseases Study), which brought nutrition front and center with the way we treat macular degeneration. The results were guided by the power of nutrition as an antioxidant showing a reduction in the risk of progression from intermediate to advanced AMD by about 25%.3 Many more studies have been performed since AREDS that link carotenoids (pigments that give yellow, orange, and red fruits and vegetables their color) to the prevention of retinal disease.4,5 The incidence of age-related eye diseases is expected to rise with the aging of the population. Because oxidation and inflammation are implicated in the etiology of AMD, we can apply evidence that dietary antioxidants and anti-inflammatories may benefit and decrease the risk of age-related eye disease.6

Personalized medicine is an emerging practice within the medical community that uses an individual’s genetic profile to guide decisions about the diagnosis and treatment of disease. The widespread role of biomedical research continues to produce studies demonstrating the vital role that genomic information can play in clinical care. This genomic data is integrated with other multi-omic data (eg, proteomes, metabolomes, lipidomes, and/or microbiomes) in sophisticated ways to comprehensively analyze data.7 Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. SNPs influence the expression of genes responsible for metabolism of nutrients. Performing genetic testing can reveal gene expression, which can aid in designing a personalized nutrition prevention plan. Although genes are not diagnostic, nutritional genomics can be a valuable tool in developing personalized diets, including those for preventive eye care.

Studies show that up to 20% of macular degeneration has a genetic component. Tests can be performed easily in office through blood work or a cheek swab, and results can offer valuable information around the creation of a personalized plan for these patients. This plan may address risk categories in order to lower body mass index, cease smoking, or modify lifestyle habits. Supplementation options with the recommended lutein, zeaxanthin, and meso-zeaxanthin (making up the macular pigment) can be tailored based on the current nutritional status, stage of AMD, and risk factors. Studies show that concentrations of these carotenoids within the macular pigment layer of the retina can improve visual function for those with early AMD.8 Diagnostic testing exists via flicker photometry and autofluorescence imaging to assess the macular pigment optical density,9 which has also been linked as a biomarker for cognitive issues, including trouble with memory, focus, and decision-making.10 Keep the plan simple but consider specific food allergies and medication interactions when prescribing supplements. Strategies involving personalized nutrition for these conditions are soon to be established as research continues to expand in this field of study.

With the discussion of nutrition comes a focus on the microbiota as its expanding connections to immunity and ultimately retina health are uncovered. Scientific evidence has linked this imbalance in the gut biome to conditions such as Alzheimer disease, Parkinson disease, and multiple sclerosis. As literature reveals, communication exists between the gut microbiome and the eye, therefore, understanding its role will be helpful to personalize a nutrition plan for patients.11 The gut-eye axis represents the ability of gut bacteria to affect eye function.

Although the gut microbiota is expected to fluctuate and change throughout a lifetime, certain disruptions have detrimental impacts on health. The most dramatic changes in microbiota occur during infancy and old age when immunity is weakest, demonstrating a connection among the microbiota, the immune system, and aging.12 The decreased bacterial diversity and increase in bacterial population found in older adults can trigger a low-level inflammatory response.13 With chronic inflammation seen in AMD, the blood-retina barrier becomes vulnerable, resulting in the development of retinal lesions. Therefore, dysbiosis, or leaky gut-vessel barrier of the gut microbiome, has the propensity toward broad systemic inflammation, indicating the potential role of the gut microbiota in retinal disease progression.14

The AREDS study revealed that evidence of the role of bacteria in retinal disease is demonstrated by dietary supplementation, which has been proven an effective treatment to slow AMD disease progression.15 Metabolites or signals initiated by specific bacteria can be linked to cytokine production, T-cell regulation, and other alterations, leading to a further understanding and additional research into retinal disease pathways. As we know today, the microbiome can be impacted by diet, age, or changing environments. The conversation around nutrition continues to favor whole and minimally processed foods. Numerous studies have shown a Mediterranean diet offering the potential protective effects on the incidence and progression of AMD.16 The focus cannot be left to specific nutrients alone, but to the overall effect and interactions holistically on eye health.

Pharmaceuticals used to treat acute or chronic disease need to be factored as a contributor to drug-induced nutrient deficiency.17 Certain classes of drugs could be depleting vital nutrients necessary for visual health and function. While medications can have a positive and negative impact on patients’ lives, it is important to consider the risk and benefits when looking at the patient holistically. We can leverage nutrition and lifestyle interventions along with pharmacotherapy to minimize the risk of adverse effects and poor efficacy. Following are a few of the more common drugs we encounter with the potential nutrient deficiency that may need to be supplemented from long-term use:

  • HMG-CoA reductase inhibitors (statins): fat-soluble ω-3s, CoQ10
  • β-blockers: melatonin, CoQ10
  • Diuretics: B1, B6, B12, magnesium, potassium, selenium, zinc
  • Oral contraceptives: B6, B12, dysbiosis, tyrosine, vitamin C, zinc, magnesium, folic acid

What can we do as practitioners in the eye health space to reduce progression and prevention of AMD?

  1. Review a thorough history including dietary habits, medications, and supplement intake.
  2. Stress the importance of dietary lipids to increase the bioavailability of carotenoids.18
  3. Consider a referral when there is suspicion of gut dysbiosis. Recommend a focused nutrition plan around fiber and produce. The Mediterranean diet is a good starting point.19
  4. Stress the importance of daily UV protection.
  5. Recommend testing for genetic risk testing or macular pigment density in order to personalize a plan for prevention and further progression of AMD.
  6. Consider comanagement of cases if chronic disease and medication may be factoring into progression or risk.

As practitioners, it is our role to provide the tools while engaging patients to be part of a solution. If we can impact 1 small change in the short time we have with patients, we will be on the path toward influencing healthier habits. Follow-up is crucial in these cases in which vision loss is at risk. Although there is still no cure for AMD, good nutrition at all stages of life plays an important role in maintaining healthy eyes. As we embark on this shift toward lifestyle medicine, the science shows promising new evidence-based avenues aiming to reduce the statistics of debilitating vision loss from macular degeneration and retinal diseases.

  1. Rein DB, Wittenborn JS, Burke-Conte Z, et al. Prevalence of age-related macular degeneration in the US in 2019. JAMA Ophthalmol. 2022;140(12):1202-1208. doi:10.1001/jamaophthalmol.2022.4401
  2. Lordan R. Dietary supplements and nutraceuticals market growth during the coronavirus pandemic - implications for consumers and regulatory oversight. PharmaNutrition. 2021;18:100282. doi:10.1016/j.phanu.2021.100282
  3. AREDS/AREDS2 clinical trials. National Eye Institute. Updated November 19, 2020. Accessed January 15, 2024. https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies-aredsareds2/about-areds-and-areds2
  4. Ho L, van Leeuwen R, Witteman JC, et al. Reducing the genetic risk of age-related macular degeneration with dietary antioxidants, zinc, and ω-3 fatty acids: the Rotterdam study. Arch Ophthalmol. 2011;129(6):758-766. doi:10.1001/archophthalmol.2011.141
  5. AREDS2 Research Group, Chew EY, Clemons T, et al. The Age-Related Eye Disease Study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology. 2012;119(11):2282-2289. doi:10.1016/j.ophtha.2012.05.027
  6. Rasmussen HM, Johnson EJ. Nutrients for the aging eye. Clin Interv Aging. 2013;8:741-748. doi:10.2147/CIA.S45399
  7. Green ED, Gunter C, Biesecker LG, et al. Strategic vision for improving human health at the forefront of genomics. Nature. 2020;586(7831):683-692. doi:10.1038/s41586-020-2817-4
  8. Akuffo KO, Nolan JM, Peto T, et al. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration. Br J Ophthalmol. 2017;101(2):190-197. doi:10.1136/bjophthalmol-2016-308418
  9. Wooten BR, Hammond BR Jr, Land RI, Snodderly DM. A practical method for measuring macular pigment optical density. Invest Ophthalmol Vis Sci. 1999;40(11):2481-2489.
  10. Kelly D, Coen RF, Akuffo KO, et al. Cognitive function and its relationship with macular pigment optical density and serum concentrations of its constituent carotenoids. J Alzheimers Dis. 2015;48(1):261-277. doi:10.3233/JAD-150199
  11. Zhang Y, Wang T, Wan Z, et al. Alterations of the intestinal microbiota in age-related macular degeneration. Front Microbiol. 2023;14:1069325. doi:10.3389/fmicb.2023.1069325
  12. Nagpal R, Mainali R, Ahmadi S, et al. Gut microbiome and aging: physiological and mechanistic insights. Nutr Healthy Aging. 2018;4(4):267-285. doi:10.3233/NHA-170030
  13. Chen M, Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. J Leukoc Biol. 2015;98(5):713-725. doi:10.1189/jlb.3RI0615-239R
  14. Rinninella E, Mele MC, Merendino N, et al. The role of diet, micronutrients and the gut microbiota in age-related macular degeneration: new perspectives from the gut⁻retina axis. Nutrients. 2018;10(11):1677. doi:10.3390/nu10111677
  15. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417-1436. doi:10.1001/archopht.119.10.1417
  16. Wu Y, Xie Y, Yuan Y, et al. The Mediterranean diet and age-related eye diseases: a systematic review. Nutrients. 2023;15(9):2043. doi:10.3390/nu15092043
  17. LaValle JB. Hidden disruptions in metabolic syndrome: drug-induced nutrient depletion as a pathway to accelerated pathophysiology of metabolic syndrome. Altern Ther Health Med. 2006;12(2):26-33.
  18. Kiokias S, Proestos C, Varzakas T. A review of the structure, biosynthesis, absorption of carotenoids-analysis and properties of their common natural extracts. Curr Res Nutr Food Sci. 2016;4(Special Issue Carotenoids March 2016). doi:http://dx.doi.org/10.12944/CRNFSJ.4.Special-Issue1.03
  19. Merle BMJ, Colijn JM, Cougnard-Grégoire A, et al. Mediterranean diet and incidence of advanced age-related macular degeneration: the EYE-RISK consortium. Ophthalmology. 2019;126(3):381-390. doi:10.1016/j.ophtha.2018.08.006
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