AS105 - Carotenoids in age-related eye disease study (CAREDS)

Investigator Names and Contact Information

Julie Mares (jmarespe@wisc.edu)

Introduction/Intent

Age-related eye diseases of the lens and retina are common in older Americans.^1-3 For example, approximately 55%-85% of Americans between the ages of 75 and 85 years have been estimated to either have cataracts or have undergone cataract surgery ^3,4 and 3% to 7% have late stages of macular degeneration.^1,2 In the next 50 years, when the number of people over the age of 75 years is expected to triple,⁵ these conditions will be even more common. These age-related conditions currently impose a large burden in health care costs⁶ and this burden will increase as the population ages.⁷ There is some evidence to suggest that certain plant pigments (the xanthophyll carotenoids, lutein and its structural isomer zeaxanthin) that are present in the foods we eat may protect against age-related macular degeneration (ARMD) and cataract.

Carotenoids have been hypothesized to protect against other age-related chronic conditions such as cardiovascular disease and cancers.^8,9 There is evidence that the absorption of carotenoids by the gastrointestinal tract and the uptake into tissues is variable across individuals,¹⁰ but there is little knowledge about the specific factors that influence uptake.¹¹ Tissue concentrations of carotenoids cannot be assessed non-invasively, except in the eye where levels of macular carotenoids can be determined by a novel technique using pyschophysical flicker photometry^12-14 .

Despite popular interest in the possibility that the xanthophyll carotenoid lutein, and its structural isomer zeaxanthin, may protect against the onset or progression of age-related macular degeneration, data to support this relationship is insufficient. Data are also accumulating to support a possible protective affect of diet xanthophylls on nuclear cataract. Observational studies that reflect long term relationships of intake of these xanthophyll carotenoids to their accumulation in the retina and the occurrence of these conditions in human populations are needed.

Specific Aims

This investigation augments information being collected in the National Institutes of Health sponsored Women's Health Initiative - Observational Study (WHI-OS) to identify specific dietary protective factors for the most common, costly and debilitating age-related eye conditions: age-related macular degeneration (ARMD) and nuclear cataract. This ancillary study is designed to investigate the relationships of xanthophyll carotenoid pigments in the diet and blood to those in the macula and to the prevalence of early age-related maculopathy (ARM) and nuclear cataract. The investigators hypothesize that women who have consistently low, compared with high, long-term dietary intakes of xanthophylls will have lower macular pigment density, higher prevalence of specific early macular abnormalities associated with ARM, and higher prevalence of nuclear cataract, even after adjusting for other lifestyle and diet attributes that may be correlated both with high xanthophylls diets and these eye diseases.

A second purpose of this study is to determine the physiologic and lifestyle attributes that influence the relationship between the intake of xanthophyll carotenoids and their presence in blood and in the ocular macula. This information may also provide insights regarding the determinants of tissue concentrations of carotenoids and can be applied towards a greater understanding of the relationships between carotenoids and the chronic diseases of aging.

1. Determine whether women in the WHI-OS selected from three sites who have sustained dietary levels of lutein and zeaxanthin in the lowest, compared to highest, quintile have:

   a. lower macular pigment density of xanthophylls,

   b. higher prevalence of ARM and specific macular lesions which increase the risk for developing late ARMD:

   • large, soft, indistinct drusen and
   • pigmentary abnormalities, and

   c. more severe nuclear sclerosis of the lens;

and to determine whether these relationships are maintained after adjusting for other lifestyle, medical and diet attributes that may be correlated with high xanthophyll diets and these eye conditions.

2. Identify dietary, lifestyle, health history and physiologic determinants of macular pigment density in women.

Results/Findings

For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.

References

1. Klein R, Rowland ML, Harris MI. Racial/ethnic differences in age-related maculopathy. Third National Health and Nutrition Examination Survey. Ophthalmology 1995;102:371-381.
2. Klein R, Klein BEK, Linton KLP. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 1992;99:933-943.
3. Klein BEK, Klein R, Linton KLP. Prevalence of age-related lens opacities in a population. The Beaver Dam Eye Study. Ophthalmology 1992;99:546-552.
4. Sperduto RD, Hiller, R. The prevalence of nuclear, cortical, and posterior subcapsular lens opacities in a general population sample. Ophthalmology 1984;91:815-818.
5. Treas J. Older Americans in the 1990s and Beyond. Population Bulletin, Population Reference Bureau, Inc. Washington, D.C., May 1995;vol 50, no. 2.
6. Steinberg EP, Javitt JC, Sharkey PD, Zuckerman A, Legro MW, Anderson GF, Bass EB, O'Day D. The content and cost of cataract surgery. Arch Ophthalmol 1993;111:1041‑1049.
7. Schneider EL. Guralnik JM. The aging of America. Impact on health care costs. JAMA 1990;263(17):2335‑40.
8. Ziegler RG. Carotenoids, cancer and clinical trials. Annal New York Acad Sci 1993;691:110-119.