The search for a way to prevent AMD continues

About ten years ago, researchers involved in the landmark Age-Related Eye Disease Study (AREDS) demonstrated that high doses of selected antioxidants and zinc slowed the progression of age-related macular degeneration (AMD) by a factor of 25 percent and reduced the risk of related vision loss by a factor of 19 percent. However, there was a slight catch: Only people with intermediate or unilateral advanced disease benefited from taking the high-dose cocktail, which consisted of vitamins C and E, beta-carotene, and zinc.

Still, the discovery represented a major step forward. And today, use of the supplement cocktail is standard care for nonsmokers at high risk for disease progression (typically, smokers are advised not to take the supplement because of concerns that high doses of betacarotene may increase their risk of lung cancer and death).

But now, a decade later, intriguing questions remain: Could a different combination of vitamins and minerals further reduce the risk of AMD progression? Are there other nutrients or medications that can slow disease progression in people with less severe forms of the condition or, better yet, prevent it from developing in the first place?

Preventing AMD

Preventing AMD from developing remains the holy grail for researchers. Although nothing has been proven to prevent AMD, researchers have identified several nutrients and medications that show promise—and some that don't.

Omega-3 fatty acids. Much interest centers around a type of polyunsaturated fat known as omega-3 fatty acids, which is found in abundance in fatty fish, such as salmon. Omega-3 fatty acids help fight inflammation and angiogenesis (the formation of new blood vessels), two factors that, when they occur in the eye, are associated with the development of AMD.

Findings from the Blue Mountains Eye Study in Australia, published in 2009 in the Archives of Ophthalmology, suggested that people who regularly ate one serving of baked or broiled fish each week were significantly less likely to develop early AMD than those who consumed lower amounts.

A 2008 meta-analysis of nine studies involving nearly 90,000 people, reported in the Archives of Ophthalmology, also found an association between high dietary intake of omega-3 fatty acids and a reduced risk of AMD. People who ate fish at least twice a week reduced their risk of early AMD by about 25 percent. But randomized, controlled trials are still needed to conclude that routine consumption of fish or omega-3 fatty acids prevents AMD.

B vitamins. Studies indicate a direct association between the risk of AMD and blood levels of homocysteine, an amino acid that is associated with cardiovascular disease. Research has shown that homocysteine levels can be lowered with sufficient intakes of B vitamins, specifically folic acid, vitamin B6, and vitamin B12.

Recently, an analysis of data from a randomized, controlled trial of more than 5,000 women who had or were at risk for cardiovascular disease but who did not have AMD at study onset found that daily consumption of a supplement containing those B vitamins significantly lowered the risk of developing AMD, compared with a placebo. The results were published in 2009 in the Archives of Internal Medicine and need to be confirmed in future research.

Statins. Like omega-3 fatty acids, these cholesterol-lowering drugs have anti-inflammatory and antiangiogenic properties that could protect against the development of AMD. However, a 2007 study of statins and their possible effect on AMD, published in the American Journal of Ophthalmology, confirmed earlier research showing that they had no appreciable effect on its development.

Aspirin. The anti-inflammatory properties of aspirin have made it a target for researchers seeking to halt the development of AMD. Though a handful of earlier studies described some benefit from using this drug, a large, randomized, placebo-controlled trial of nearly 40,000 women found that low-dose aspirin offered such a small protective effect against AMD that it was too weak to be meaningful. That may not be the last word, however. The researchers, who reported their findings in 2009 in Ophthalmology, say that the possibility of a modest protective effect warrants further study.

Herbal supplements. In addition to the preventive strategies noted above, herbal supplements like ginkgo biloba and bilberry have been used by some people for their purported AMD-fighting properties. No studies, however, have identified any direct benefit of using these supplements with respect to AMD.

Halting AMD Progression

Researchers are also working to identify additional nutrients and medications that can slow AMD progression in people who already have the disease.

Lutein and zeaxanthin. These two carotenoids—antioxidants that give yellow and leafy dark green vegetables their color—are of great interest to AMD researchers. Lutein and zeaxanthin are also found in the macula. Research has shown that people who consume greater amounts of lutein and zeaxanthin are less likely to develop AMD, prompting researchers to question whether increasing consumption of these carotenoids will slow the progression of AMD. A number of studies suggest that it will. And AREDS researchers hope that their latest investigation, AREDS-2, will provide a definitive answer about the value of lutein, zeaxanthin and omega-3s in preventing AMD progression.

In this study, which has been under way since 2006, participants were randomly selected to receive a supplement containing lutein and zeaxanthin, a supplement containing omega-3 fatty acids, a supplement containing all three nutrients, or a placebo pill.

Omega-3 fatty acids. Until the results of AREDS-2 are available, additional analyses of data from the original AREDS investigation provide some insight into the role of omega-3 fatty acids. One of these studies, published in the American Journal of Clinical Nutrition in 2009, found that people at moderate to high risk for disease progression who consumed the most omega-3 fatty acids over 12 years were 30 percent less likely to develop advanced AMD than those who reported consuming the least.

Statins. Less promising are data on statins. A large randomized study known as the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT), which was designed to evaluate the role of laser treatment in the prevention of progression to advanced AMD, looked at statin use among its participants as a secondary analysis. They found no evidence that statins offered a protective effect. In this 2009 Ophthalmology study of 744 people who were at risk for advanced AMD, statin users were no less likely than nonusers to develop advanced disease.

The Bottom Line

Currently, no nutrient or medication has been proven to prevent the development of AMD, and only the antioxidant combination found in the AREDS supplement has been proven to slow disease progression—albeit modestly and just in those with intermediate or unilateral advanced AMD.

So what should you do if you have mild AMD or want to prevent it altogether? It's too early to advise taking supplements containing omega-3s, lutein, zeaxanthin, and/or B vitamins to prevent AMD, but it's always a healthy move to consume the recommended dietary allowance (RDA) of each of these nutrients. Leafy dark green vegetables like kale, spinach, and collard greens contain lutein and zeaxanthin. Coldwater fatty fish, such as salmon, herring, mackerel, lake trout, and sardines, are good sources of omega-3 fatty acids.

Consider watching your consumption of omega-6 fatty acids, found in snack foods, salad dressing, mayonnaise, and margarine. In the Carotenoids in Age-Related Eye Disease Study (CAREDS), reported in 2009 in the journal Ophthalmology, a high consumption of this type of fat was associated with an elevated risk of AMD progressing to an intermediate stage. Associations such as this do not directly imply that omega-6 fatty acids cause AMD; however, it is reasonable to evaluate your consumption of these nutrients and keep them in check with the RDA (for omega-6 fatty acids, that's no more than 11 g per day for women 50 and older and no more than 14 g per day for men 50 and older).

As for vitamins B6 and B12 and folic acid, whole and fortified grain products, leafy greens, legumes, and liver are all good sources.

Last, follow your doctor's advice about taking aspirin or a statin for heart disease, but keep in mind that at least for now, there's little to suggest that you’re helping your eyes as well.

Publication Review By: Susan B. Bressler, M.D., Harry A. Quigley, M.D., Oliver D. Schein, M.D., M.P.H.

Published: 25 Feb 2011

Last Modified: 27 Jan 2015