Advancing the Standard of Care?

A leading specialist explains why it can make sense to recommend the AREDS2 formulation now.

By Michael J. Cooney, MD MBA

I am among a growing number of retina specialists who recommend high doses of oral macular xanthophylls (lutein and zeaxanthin), plus omega-3 long chain polyunsaturated fatty acids, for patients who are at risk for progression of age-related macular degeneration (AMD).

Although a number of my peers believe we should wait for the results of the AREDS2, a multicenter randomized trial that will report on the effects of these supplements in 2013, I believe we have enough evidence to justify their use now.

WHAT IS THE STANDARD OF CARE?

I would be the first to admit that the standard of care remains the AREDS daily formulation (vitamin C, 500 mg; vitamin E, 400 IU; beta-carotene, 15 mg; zinc, 80 mg; and cupric oxide [copper], 2mg). These supplements would be indicated for patients with extensive intermediate drusen or large drusen (category 3) and advanced AMD in one eye, including either geographic atrophy in the center or neovascular AMD (category 4).

Above are color (top) and red-free (bottom) photographs of the retina of a patient with high risk dry AMD. Many retina specialists believe enough evidence has accumulated to justify using AREDS2 supplements in such a case.

However, scientific evidence increasingly supports the use of lutein, zeaxanthin and omega-3 fatty acids in AMD. In my opinion, the positive findings of AREDS¹ have lowered the bar for any additional nutritional formulas we might consider.

Numerous observational studies, some even completed by AREDS researchers, point to a positive association between lutein and zeaxanthin and the risk of AMD.^2-6 We have also seen a positive association established between omega-3 fatty acids and reduced risk of AMD.^7-12

In light of this evidence, recommending these supplements seems to make sense. Research led by Johanna Seddon, MD, demonstrates that healthy diets have been specifically associated with reduced risk of AMD. Positive findings have been linked to intake of fish and nuts¹⁴ and avoidance of vegetable, monounsaturated and polyunsaturated fats as well as linoleic acid.¹⁴

Every decision we make involves calculating the risk-benefit ratio of any given intervention. I believe the current evidence and good safety profile of xanthophylls and omega-3 fatty acids support their use. In fact, I rarely recommend beta-carotene any longer because lutein, a xanthophyll that is naturally found in the macula, is a stronger antioxidant.

WHAT TO TELL PATIENTS

I encourage patients to lead healthy lifestyles, take vitamins, exercise and lower their body mass. I counsel them on smoking cessation, hypertension control and the consumption of green leafy vegetables, low-fat foods and more fish. I also recommend either AREDS1-type or AREDS2-type supplements, depending on examination findings. It's important to remember that a patient can seldom reach the desired AREDS level of these nutrients through diet alone.

Besides patients with intermediate AMD (category 3 or 4), I believe those with less significant macular changes and/or significant risk factors should be considered for supplements. For example, the daughter of a patient with advanced AMD may ask how she can avoid her mother's disease. Mindful that the heritability of AMD has been estimated to be up to 71%,¹⁵ I would recommend she undergo a dilated eye examination once a year after age 50. Assuming she has otherwise normal risk factors and a normal macula, I may also recommend lifestyle changes and the use of supplements at lower dosages.

WHEN AREDS2 FINDINGS ARE AVAILABLE

Like the rest of us, I'll be anxious to learn the results of AREDS2. The research may confirm and possibly fine-tune approaches many of us are already using. The final report, like all data in this expanding area, will be most welcome.

Emphasize Compliance Many patients don't fully comply with vitamin and nutritional therapy. For example, one study (Hochstetler et al) of 64 subjects showed that only 43% were taking AREDS vitamins in the recommended dosages. We need to frequently remind our patients of the importance of consistently taking their supplements. — Michael J. Cooney, MD, MBA

KEY POINTS TO REMEMBER ► Observational studies show a positive association between dietary lutein and zeaxanthin and the risk of AMD.2-6 ► Good nutrition and omega-3 supplementation help protect against AMD.13,14 ► The heritability of AMD has been estimated to be up to 71%.15 ► Reduced risk of AMD has been linked to intake of fish and nuts and avoidance of vegetable, monounsaturated, and polyunsaturated fats as well as linoleic acid.13,14

REFERENCES

1. Age-Related Eye Disease Study Research Group. A randomized, place-bocontrolled, 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.
2. Gale CR, Hall NF, Phillips DI, Martyn CN. Lutein and zeaxanthin status and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci. 2003;44(6):2461-2465.
3. SanGiovanni JP, Chew EY, Clemons TE, et al; for Age-Related Eye Disease Study Research Group. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225–1232.
4. Tan JS, Wang JJ, Flood V, Rochtchina E, Smith W, Mitchell P. Dietary antioxidants and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology. 2008;115(2):334-341.
5. SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005;24(1):87-138.
6. SanGiovanni JP, Chew EY, Clemons TE, et al. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20. Arch Ophthalmol. 2007;125(5):671-679.
7. SanGiovanni JP, Chew EY, Agrón E, et al. The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23. Arch Ophthalmol. 2008;126(9):1274-1279.
8. Sangiovanni JP, Agrón E, Meleth AD, et al. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr. 2009;90(6):1601-1607.
9. Chiu CJ, Klein R, Milton RC, Gensler G, Taylor A. Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements? Br J Ophthalmol. 2009;93(9):1241-1246.
10. Chua B, Flood V, Rochtchina E, et al. Dietary fatty acids and the 5-year incidence of age-related maculopathy. Arch Ophthalmol. 2006;124(7):981-986.
11. Augood C, Chakravarthy U, Young I, et al. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration. Am J Clin Nutr. 2008;88(2):398-406.
12. Christen WG, Schaumberg DA, Glynn RJ, Buring JE. Dietary {omega}-3 fatty acid and fish intake and incident age-related macular degeneration in women. Arch Ophthalmol. 2011;129(7):921-929.
13. Seddon JM, Rosner B, Sperduto RD, et al. Dietary fat and risk for advanced age-related macular degeneration. Arch Ophthalmol. 2001;119(8):1191-1199.
14. Seddon JM, Cote J, Rosner B. Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. Arch Ophthalmol. 2003;121(12):1728-1737.
15. Seddon JM, Cote J, Page WF, Aggen SH, Neale MC. The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences. Arch Ophthalmol. 2005;123(3):321-327.
16. Hochstetler BS, Scott IU, Kunselman AR, Thompson K, Zerfoss E. Adherence to recommendations of the age-related eye disease study in patients with age-related macular degeneration. Retina. 2010;30(8):1166-1170.

---

Dr. Cooney is a partner with Vitreous Retina Macula Consultants of New York, New York. He is also a consultant for Bausch + Lomb.