EyeNet Magazine

Nutrition Emerges for AMD Prevention
By Miriam Karmel, Contributing Writer

There is mounting evidence that a heart-healthy diet and lifestyle is good not only for the old ticker but also for the eyes. Most recently, a series of reports based on the Progression of Age-Related Macular Degeneration Study have lent further credence to the hypothesis that cardiovascular disease (CVD) and AMD share a number of common, modifiable risk factors.

Growing Conviction
Johanna M. Seddon, MD, ScM, a macular degeneration specialist and principal investigator for the reports, says that her conviction regarding the shared risk factors is stronger now than it was five years ago when the longitudinal study enrolled 366 patients with AMD.

“Most surprising to me is how consistently we are finding the same risk factors,” said Dr. Seddon, director of epidemiology and a surgeon at the Massachusetts Eye and Ear Infirmary. “There was some doubt by some investigators whether there really was a connection between cardiovascular risk factors and AMD. More and more, we’re showing that there is a connection and the risk factors for cardiovascular disease and AMD are very similar.” Those risk factors include smoking, dietary fat, obesity, hypertension, lack of exercise and antioxidant intake—and, in some studies, high cholesterol levels.

The etiology of AMD remains unknown, but since at least the early 1970s, researchers have theorized that the same underlying vascular process or factors that influence CVD might also influence the development of AMD. Put differently, AMD may be to the eyes what atherosclerosis is to organs in the cardiovascular and cerebrovascular systems. Researchers like Dr. Seddon hope that finding the common mechanisms of the two diseases could lead to better understanding of the pathophysiology of AMD, and ultimately, better treatment and prevention measures.

While it has long been established that AMD and CVD share cigarette smoking as a risk factor, the research regarding other factors has been less conclusive. A review of the literature done from 1995 to 1998 by Dr. Seddon and Kristin K. Snow, MS, an epidemiologist at Harvard’s School of Public Health, referenced more than 150 articles on the subject.1 The literature is filled with inconsistent findings regarding the relationship between the two diseases. But Dr. Seddon said that her recent findings are consistent with those studies that have sufficient cases and large numbers of advanced cases. Her studies support the effect of dietary fat, obesity and C-reactive protein on the development and/or progression of AMD.

A Look at the Evidence
Dietary intake. Atherosclerosis, the underlying cause of most ischemic events, is associated with intake of specific types of fat. Some AMD researchers theorize that in a similar fashion, fats could affect ocular blood vessels or increase oxidative damage in the macula.

Dr. Seddon’s group found that higher intake of specific types of fats, rather than total fat intake, is associated with a higher risk for AMD. Two studies, one measuring fat intake on the relative risk for AMD, the other measuring progression, appeared in Archives of Ophthalmology.2,3 They found that a higher intake of vegetable, saturated, mono- and  polyunsaturated fats and trans-fatty acids was associated with a higher risk for AMD and progression of the disease. Also associated with higher risk is linoleic acid, an omega-6 fatty acid, often found in highly processed store-bought snack foods.

On the other hand, diets high in omega-3 fatty acids, found in certain types of fish, provided a protective effect, but only if intake of linoleic acid was low and fish intake was sufficiently high—two or more servings per week. Nuts were also protective.

This summer, a report on the benefits of fruit appeared in Archives of Ophthalmology.4 According to Dr. Seddon and her collaborators, fruit consumption was inversely associated with the risk of neovascular AMD. Participants who ate three or more servings per day of fruit had a 36 percent lower risk of AMD, compared with those who ate less than 1.5 servings per day.

Other associations linked to CVD did not pan out. For example, while polyunsaturated fat has been associated with an inverse risk for CVD in some studies, it has proved to be a risk factor for AMD. Also, alcohol does not have a protective effect with regard to AMD.
Obesity. An association between overall and abdominal obesity and progression of AMD was reported last year.5 The study found a statistically significant trend for increased risk for progression among those individuals who had a higher body mass index, larger waist circumference and higher waist-hip ratio. At the same time, physical activity tended to decrease the risk. It is theorized that obesity might increase the risk of AMD by increasing oxidative stress, promoting angiogenesis and contributing to low-grade inflammation.

C-reactive protein. Elevated C-reactive protein (CRP) values were found to be significantly related to AMD, according to a report earlier this year.6 CRP, a marker of systemic inflammation, is an independent indicator of risk for CVD and peripheral arterial disease. This finding may implicate the role of inflammation in the pathogenesis of AMD. It suggests that AMD may be another chronic, age-related inflammatory disease that is manifested in the eye, and supports some basic research findings on the pathophysiology of AMD.

It would be premature to make any clinical recommendations regarding CRP, said Dr. Seddon, who is planning further studies to confirm and determine the consistency of its association with AMD. But the other findings are compelling enough for clinicians to embrace and pass on to their patients, she said. “People overlook prevention. It deserves more attention.”

1 Ophthalmic Epidemiol 1999;6(2):125–143. 
2 Seddon, J. M. et al. Arch Ophthalmol 2001; 119(8):191–199.
3 Seddon, J. M. et al. Arch Ophthalmol 2003; 121(12):1728–1737.
4 Cho, E. et al. Arch Ophthalmol 2004;122(6): 883–892.
5 Seddon, J. M. et al. Arch Ophthalmol 2003; 121(6):785–792.
6 Seddon, J. M. et al. JAMA 2004; 281(6): 704–710.

Talking to Patients

A decade ago ophthalmologists had little advice for patients who were worried about AMD. Now, armed with a growing body of evidence, Dr. Seddon gives the following advice to her patients: “I tell them to think about all the risk factors you know for cardiovascular disease. It’s similar for AMD,” she said. “Don’t smoke. Eat a good healthy diet with a lot of fruits and vegetables. Watch your dietary fat intake. Eat one or two servings of fish a week. Make sure you control your cholesterol and blood pressure levels. I also mention controlling weight and getting physical exercise.”

For patients who already have intermediate AMD, or advanced disease in one eye, Dr. Seddon advises taking the supplement formulated for the Age-Related Eye Disease Study (AREDS). That supplement, containing vitamins C and E, beta-carotene and zinc, reduced the rate of progression of AMD by 25 percent over five years.

“It is the ophthalmologist’s responsibility to discuss this with his or her patients,” Dr. Seddon said. “[We] are another health care provider who can give patients this important message to prevent visual loss, as well as to prevent heart attacks and strokes.”

Other ophthalmologists are cautious about drawing parallels between the two conditions. “It’s not a slam-dunk relationship between cardiovascular disease and AMD,” commented Ronald Klein, MD, MPH, professor of ophthalmology and visual sciences at the University of Wisconsin, Madison. He noted that many studies, including AREDS, have not found coronary heart disease, stroke and high serum cholesterol to be related to AMD, suggesting that other nonatherosclerotic genetic and environmental factors may play a more important role in the pathogenesis of the disease.

“We have not yet solved the AMD puzzle, and there are genetic and other unknown factors, but the relationship between AMD and these modifiable factors should not be ignored,” said Dr. Seddon.

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