The most definitive results come from the Age-Related Eye Disease Study (AREDS), published in October of 2001, and its follow-up study (AREDS2), published in May of 2013. AREDS was a very large study sponsored by the National Eye Institute that enrolled over 3500 subjects and followed them for an average of 6.3 years. The researchers found that subjects who took the antioxidant supplement consisting of high doses of zinc, vitamin C, vitamin E, and beta-carotene were less likely to have progression of their disease relative to the placebo group (20% versus 28%). This protective effect was seen in patients with moderate AMD (extensive intermediate size drusen or any large drusen) or advanced AMD (choroidal neovascularization or geographic atrophy) in at least one eye. No protection was seen in subjects with the earlier stages of the disease, and there was no protection against cataract formation. They recommended that all persons older than 55 years old have a periodic dilated eye examination and that those individuals found to have moderate to advanced AMD begin to take daily antioxidant supplements similar to the combination they studied. 

AREDS2 was a follow-up study that enrolled over 4200 AMD subjects at 85 sites across the United States for five years that tried to incorporate newer knowledge of ocular nutrition gained since the time AREDS was initiated. It examined whether or not addition of lutein and zeaxanthin or omega-3 fatty acids from fish oil (EPA and DHA), nutrients specifically concentrated in the human macula, could improve upon the results of the original AREDS formula. It also examined modifications to the AREDS formula that might enhance patient safety. Specifically, there were concerns that the high dose of beta-carotene could promote lung cancer in current and former smokers and that the high dose of zinc could cause gastrointestinal or urinary tract problems. Although AREDS2 did not meet its ambitious primary goal to improve the original AREDS benefit by another 25% increment, it did provide some important new results and guidelines. First, there was an additional 10% reduction of advanced AMD risk in subjects assigned to lutein/zeaxanthin versus those who did not. Removal of the beta-carotene doubled this improvement, most likely because it inhibited absorption of lutein and zeaxanthin. Unfortunately, fish oil supplements had no beneficial effect on risk of vision loss from AMD. No supplement combinations prevented cataract formation.

What are the current recommendations for the use of antioxidant vitamins for patients with age-related macular degeneration (AMD)?

The AREDS2 study group continues to recommend antioxidant supplements for patients with moderate and advanced AMD. Although the original AREDS formula continued to work well, lung
cancer concerns related to the high dose of beta-carotene suggest that current and former smokers should use lutein and zeaxanthin instead. Non-smokers could take either formula, but for simplicity, we at the Moran Eye Center will recommend the lutein/zeaxanthin formula for them, too. 

Where can I find these antioxidant supplements?

Try your local drugstore, grocery store, or health food store. Many ocular vitamin preparations are available, but you will need to read the label carefully to be certain you are getting the recommended levels of the vitamins and minerals.
Are there any side-effects or contraindications?

There were no serious side effects reported, but smokers and former smokers should avoid taking high-dose beta-carotene supplements because of the increased risk of developing lung cancer. AREDS2 did not recommend any changes in the zinc level. Doses of vitamin E higher than the levels used in AREDS2 have been linked to cardiovascular problems.

What is the role of diet?

It would be nearly impossible to consume the AREDS2 level of antioxidant intake by diet alone, but other studies have found that people who frequently eat dark green leafy vegetables rich in lutein (spinach, kale, broccoli, etc.) or fruits and vegetables rich in zeaxanthin (corn, peaches, persimmons, mangoes, etc.) have a lower risk of advanced AMD. Recent studies have also found that people who frequently consume cold water fish such as salmon that are high in omega-3 fatty acids have a lower risk of AMD, so diet is still important for anyone concerned about developing AMD.

Are herbal supplements effective against AMD?

Herbal compounds (bilberry, ginkgo biloba, eyebright, etc.) have been widely promoted by the health food industry to people at risk for AMD. No high-quality scientific studies have been performed to support their claims of effectiveness, so we are unable to offer any recommendations for or against their use.


• 80 milligrams of zinc oxide (other forms such as zinc acetate may be acceptable and doses as low as 25 mg may be OK)
• 2 milligrams of cupric oxide (to counteract copper deficiency induced by the zinc)
• 500 milligrams of vitamin C
• 400 international units (IU) of vitamin E (do not take higher doses)
• 10 milligrams of lutein (higher doses may be acceptable)
• 2 milligrams of zeaxanthin (higher doses may be acceptable)

Paul S. Bernstein, MD, PhD
Vitreoretinal Diseases and Surgery, Macular and Retinal Degeneration Research
Medical School: Harvard Medical School, Boston, MA
Academic Appointments: Professor of Ophthalmology & Visual Sciences, University of Utah School of Medicine Salt Lake City, UT
Dr. Bernstein’s clinical interests include age-related macular degeneration with special emphasis on the role of nutrition and environment in its treatment and prevention, inherited retinal and macular dystrophies, and surgical treatment of Vitreoretinal disorders such as diabetic retinopathy and retinal detachments.
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