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Johanna M. Seddon, MD; Umed A. Ajani, MBBS; Robert D. Sperduto, MD; Rita Hiller, MS; Norman Blair, MD; Thomas C. Burton, MD; Marilyn D. Farber, PhD; Evangelos S. Gragoudas, MD; Julia Haller, MD; Dayton T. Miller, PhD; Lawrence A. Yannuzzi, MD; Walter Willett, MD; the Eye Disease Case-Control Study Group

JAMA. 1994;272(18):1413-1420.

Abstract
Objective.
—To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults.

Design.
—The multicenter Eye Disease Case-Control Study.

Setting.
—Five ophthalmology centers in the United States.

Patients.
—A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex.

Main Outcome Measures.
—The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses.

Results.
—A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend=.02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend=.001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend<.001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods.

Conclusion.
—Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.

(JAMA. 1994;272:1413-1420)

Author Affiliations
From the Epidemiology Unit (Drs Seddon and Ajani) and the Retina Service (Drs Seddon and Gragoudas), the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, and the Channing Laboratory (Dr Willett), Harvard Medical School, Boston, Mass; the Department of Epidemiology (Drs Seddon and Willett) and the Department of Nutrition (Dr Willett), Harvard School of Public Health, Boston; the National Eye Institute, Bethesda, Md (Dr Sperduto and Ms Hiller); the Department of Ophthalmology, University of Illinois at Chicago (Drs Blair and Farber); the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee (Dr Burton); the Wilmer Eye Institute, Baltimore, Md (Dr Haller); the Division of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Miller); the Manhattan Eye, Ear, and Throat Hospital, New York, NY (Dr Yannuzzi); and the Brigham and Women's Hospital, Boston, Mass (Dr Willett).

Footnotes
A complete list of the participants in the Eye Disease Case-Control Study Group was published in the following article: The Eye Disease Case-Control Study Group. Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol. 1992;110:1701-1708.

Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla, May 5, 1993.

Reprint requests to the Epidemiology Unit, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (Dr Seddon).

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