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Research to Prevent Blindness

Diet and Ocular Disease

[Note: this is an older, but still potentially useful, article from the RPB archives.]

Julie A. Mares-Perlman, Ph.D.
University of Wisconsin-Madison Medical School
Madison, Wisconsin

SUMMARY

Studies in the Beaver Dam Eye Study Cohort add to the epidemiologic data that suggest that the foods we eat and supplements we take are related to the development of cataract and macular degeneration. two common age-related eye diseases. There are two contributions that are unique to the studies in the Beaver Dam. Wisconsin population. First, these studies provide data suggesting that diet may be related to early stages of the development of age-related changes in the eye which are thought to precede advanced stages of cataract and macular degeneration. Many studies to date have focused on later stages of these conditions. A second contribution is the finding that a broader range of dietary components than previously investigated in prior epidemiologic studies may be related to the occurrence of these conditions. Overall, results of studies in this and other populations suggest that dietary recommendations to minimize risk for other chronic diseases may also lower the risk for age-related eye disease. Further prospective studies and clinical trials are needed to determine specific nutrients involved and their impact on the development of different types and stages of cataract and macular degeneration.

BACKGROUND

Cataract and age-related macular degeneration, degenerative conditions of the lens and retina, become more common as we age. They are among the most important causes of visual loss and eye-related health care expenditures. Cataract is the leading cause of blindness worldwide. In the United States, surgical removal of lenses with cataracts accounts for a significant proportion of the Medicare budget. Macular degeneration is the major cause of blindness in older Americans because the treatment currently available for this condition is only effective in a fraction of people and cannot reverse the disease. As the number of people surviving into the 7th through 9th decades of life increases over the next 50 years, the impact of these conditions on both quality of life and health care costs will increase.

Because of the costs and limitations of treating cataract and macular degeneration, preventing or delaying.the development of these conditions may be the only way to limit their impact. Epidemiologic research in the past decade has been aimed at identifying modifiable lifestyle factors that may prevent them. Animals or humans with diets deficient in one of several nutrients develop pathologic changes in the lens and retina that are associated with cataract and macular degeneration, suggesting that dietary components may influence these conditions. However, gross nutrient deficiencies are not common in the United States. Epidemiologic studies are needed before we can understand the importance of smaller changes in diet in the larger population.

CATARACT

There are many dietary components that may play a role in the development of cataract. One group of components are those which neutralize damaging molecules called free radicals. The high exposure of the lens of the eye to light encourages the development of such molecules. Some nutrients, such as vitamins C and E and carotenoids such as beta-carotene, can directly neutralize these molecules. Other nutrients such as riboflavin, selenium, and zinc play a role in enzyme systems that rid the body of these potentially damaging molecules. Another group of dietary components that have the potential to influence cataract development are certain types of sugar and other nutrients involved in the utilization of these sugars. The accumulation of some sugars in the blood leads to the formation of sugar alcohols in the lens which cause swelling and rupturing of lens cells. However, this is probably a factor in only those people who are unable to regulate the level of various sugars in the blood.

AGE-RELATED MACULAR DEGENERATION

As with cataract, antioxidant nutrients, which neutralize free radicals, may play a role in the development of age-related macular degeneration. Like the lens, the retina is exposed to high levels of light which favors the formation of free radicals. The retina also contains large amounts of polyunsaturated fats which are susceptible to damage by these free radicals.

Another group of nutritional factors that may influence the development of this condition are those that promote the development of lipid deposits in arteries (atherosclerosis). Atherosclerosis, a risk factor for heart disease and stroke. has been suspected of being involved in the development of macular degeneration for several decades. Recently. more evidence for this idea has accumulated. In a study of Dutch elderly,' Dr. Johannes R. Vingerling and coworkers from the Erasmus University Medical School in Rotterdam, The Netherlands, found that people who had atherosclerotic plaques in their carotid arteries were more likely to have age-related macular degeneration. Several, but not all, epidemiologic studies have also observed higher rates of age-related macular degeneration among people who have habits or medical conditions thought to increase risk for atherosclerosis such as smoking, high blood pressure, and high levels of cholesterol in the blood. These findings have renewed interest in the hypothesis that dietary factors that promote atherosclerosis may encourage this age-related decline in the central area of the retina. Thus, diets high in antioxidant nutrients and low in fats which are thought to lower the risk for atherosclerosis may also lower the risk for age-related macular degeneration.

EPIDEMIOLOGIC STUDIES

Epidemiologic studies can contribute insights about the degree to which these various nutritional factors are important predictors of the occurrence of cataract and macular degeneration in humans. The availability of results from many epidemiologic studies inform us about how certain we can be that specific relationships exist as well as the settings in which these relationships apply. Several studies suggest that dietary factors are related to cataract2-5 and macular degeneration." However, there are others that show no relationships," ° and the specific nutrients related to cataract and macular degeneration vary between studies. The inconsistencies between studies can help us learn about specific settings in which diet is more or less related to these conditions. More epidemiologic data are needed to understand these relationships. Studies conducted in the Beaver Dam population can contribute to the body of existing epidemiologic evidence about relationships of a broad range of foods and nutrients to these eve diseases and can provide insights about dietary components which may be related to the early stages of their development.

TECHNIQUES

Our research is conducted in a group of middle-aged and older-aged adults living in Beaver Dam. Wisconsin. Most of the adults over the age of 45 years (88%) have participated in the Beaver Dam Eye Study that was started in 1987 by Drs. Ronald and Barbara Klein. Professors of Ophthalmology. University of Wisconsin-Madison Medical School. These people are being followed over time. Data reported in this session were obtained from initial interviews and examinations which took place over a 2.5-year period between 1988 and 1990. In the initial examination, photographs of the lens and retina were obtained from most of the adults (83c%) along with blood samples and information about their medical history and lifestyle. The eye photographs were examined by trained graders, masked to the person's identity. using detailed standard protocols to describe the presence and severity of opacities (cloudiness) in the three different areas of the lens and abnormalities in the part of the retina which is involved with central vision (the macula).

In home interviews. a random sample of participants were also asked to give detailed information about foods and vitamin supplements consumed in two time periods: 19871990 (at the time of the eye exam) and 1978-80 (ten years prior to the exam). Information was collected from 2003 people who answered questions about how often and how much they consumed 100 types of foods and specific types of vitamin and mineral supplements.

STATISTICS

Cataract. Most people had early stages of opacities, which could progress to cataracts that interfere with vision. We found that people who reported taking multivitamin supplements ten years prior to the eye exam had a 40% lower chance for having more central opacities than people of their same age who did not take supplements.'° Supplement use was related to clearer lenses among middleaged people and among older people. These relationships remained after taking into account cigarette smoking and heavy drinking. which are also related to more severe cataract. This apparent protective influence of supplements might reflect the contribution of antioxidant nutrients, but it is too soon to know this with certainty. Most people took supplements containing these and other vitamins and minerals. Another explanation of these results which cannot be ruled out at this time is that people who take vitamin supplements also have other unmeasured behaviors which protect against cataracts.

People who had more severe central opacities also reported different dietary habits than those who had clearer lenses." Men who ate the highest amount of vegetables were less likely to have opacities. Both men and women who ate higher levels of high fiber breads and cereals (those containing whole grains) also had less severe opacities. Women who drank milk had clearer lenses. These findings could be due to the fact that many of these foods and multivitamins provide certain antioxidants. However, people who consumed higher levels of known antioxidants did not have clearer lenses than people with lower levels. The foods related to lower rates of early cataracts may contain other antioxidant substances or other protective substances which currently are not measured or included in supplements.

Age-related Macular Degeneration. We evaluated the links between nutrients in the diet and blood and the early changes in the macula that may lead to the development of advanced macular degeneration. People who had intakes of saturated fat and cholesterol in their past diets in the highest 20c7c of the population had 809i and 60% higher chances for having early macular degeneration than those with intakes in the lowest 20%." High intakes of butter, the food which contributed the majority of saturated fat in the diets of Beaver Dam adults, were related to a greater chance of having macular degeneration, whereas high intakes of margarine were related to a lower chance. The possibility that people who eat butter and other sources of saturated fat have different behaviors or genes which promote macular degeneration needs to be pursued in future research studies in this and other populations.

Higher levels of antioxidants in the serum or diets were not generally related to lower rates of early macular degeneration (except for a weak association with zinc in the diet).'' These findings do not necessarily rule out a protective role of antioxidant nutrients. People's diets may have changed recently making it difficult to detect such links. Furthermore, antioxidant nutrients might be more important in preventing later stages of the disease which existed in few people in this population.

SIGNIFICANCE AND HUMAN INTEREST

Results of studies in experimental animals and early epidemiologic studies have provided the basis for several compelling hypotheses about ways that specific dietary components may influence the development of common age-related changes in the lens and retina. Studies in the Beaver Dam population, in conjunction with studies in other populations. suggest that diets that are low in one or more nutrients are related to having several types of early and late degenerative changes in the eye. Determining the dietary components that are definitively involved requires many years and several types of scientific studies. Studies in animals have informed us about specific ways that dietary components can alter the development of cataract or macular degeneration. We need the results of clinical trials and large population studies in humans, many of which are currently underway. to gain additional information about the importance of specific dietary components in humans. Because we cannot, at this time, be certain about the specific dietary components that may be involved, it is premature to recommend taking vitamin supplements, which have limited combinations of nutrients, in order to prevent age-related declines in vision.

Diets low in animal fat are already recommended to reduce the chance of getting cardiovascular diseases such as heart disease and stroke. Findings in the Beaver Dam population are the first to indicate that such diets may be related to protection against developing early age-related macular degeneration as well. Currently, Americans are encouraged to eat diets which are high in fruits, vegetables, and grains and low in sugar and fat, and to moderate alcohol intake. These recommendations result in diets that are rich in many nutrients because they have a high ratio of vitamins and minerals to calories. Thus, higher levels of many nutrients are eaten for the same number of calories taken in each day. Results of several studies, suggesting that higher intakes of one or more vitamins and minerals are related to lower levels of age-related eye diseases, are consistent with these recommendations. Getting vitamins and minerals from foods, such as fruits, vegetables and grains rather than supplements, is safe and has the added benefit of providing other potentially protective compounds that these foods contain.

Results of studies in Beaver Dam suggest that making improvements in diet at or before middle-age may be important to health and quality of life in the later years. In this population, diet was related to several early degenerative changes in the lens and retina. Future studies in this and other populations will determine whether these early degenerative changes increase one's chance for getting advanced cataract and macular degeneration. If this is the case, improvements in diet in middle-age, when these early changes are occurring, may have long-term consequences.

REFERENCES

(1) Vingerling JR, Dielemans 1. Bots ML. Hofman A, Grobbee DE. de Jong PTVM: Age-related macular degeneration is associated with atherosclerosis. Am J Epidemiol 1995:142:404-409. (2) Leske MC. Chylack

LT, Wu S-Y: The lens opacities case-control study. Risk factors for cataract. Arch OphThalmol 1991:109:244251. (3) Mohan M. Sperduto RD, Angra SK, Milton RC, Mathur RL. Underwood BA. Jaffery N, Pandya CB, Chhabra VK, Vajpayee RB, Kalra VK, Sharma YR. India-US case-control study of age-related cataracts.

Arch Ophthalmol 1989:107:670-676. (4) Sperduto RD, Hu T-S, Milton RC. Zhao JL, Everett DF Cheng QF age-related conical, nuclear, and posterior subcapsular Blot W1, Bing L, Taylor PR, Li JY, et al. The Unman.. cataracts. Am J Epidemiol 1991:133:541-553. (9) Cataract Studies: Two nutrition intervention trials. Arch Sanders TAB, Haines AP, Wormald R, Wright LA. Ophthalmol 1993:111:1246-1253. (5) Vitale S, West S. Obeid 0. Essential fatty acids, plasma cholesterol, and Hallfrisch l, Alston C, Wang F Moorman C. Muller D, Singh V. Taylor HR. Plasma antioxidants and risk of cortical and nuclear cataract. Epidemiology 1993:4:195203. (6) Seddon JM. Ajani UA. Sperduto RD, Hiller R, Blair N, Burton TC. Farber MD, Gragoudas ES, Haller J, Miller DT, Yannuzzi LA. Willett W: Dietary carotenoids, vitamins A. C. and E, and advanced agerelated macular degeneration. JAMA 1994:272:14131420. (7) West S, Vitale S. Hallfrisch J. Munoz B, Muller D. Bressler S, Bressler NM. Are anuoxidants or supplements protective for age-related macular degeneration? Arch Ophthalmol 1994:112:222-227. (8) The Italian-American Cataract Study Group. Risk factors for fat-soluble vitamins in subjects with age-related maculopathy and matched control subjects. Am J Clin Nuir 1993:57:428-433. (10) Mares-Perlman JA. Klein BEK, Klein R. Ritter LL: Relation between lens opacities and vitamin and mineral supplement use. Ophthalmology
1994:101:315-325. (I1) Mares-Perlman JA. Brady WE. Klein BEK. Klein R, Haus GJ. Palta M. Ritter LL, Shofi SM. Diet and nuclear lens opacities. Am J Epidemiol 1995:141(4):322-334. (12) Mares-Perlman JA. Brady WE. Klein R. VandenLangenberg GM. Klein BEK. Palta M: Dietary fat and age-related maculopathy. Arch OphThalmol 1995:113:743-748. (13) Mares-Perlman JA, Brady WE, Klein R, Klein BEK. Bowen P. Stacewicz-Sapuntzakis M. Palta M: Serum antioxidants and age-related macular degeneration in a populationbased case-control study. Arch. Ophrhalmol: (In Press).

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