The purpose of this proposal is to evaluate macular pigment (MP) levels as a modifiable risk marker for the development of age-related macular degeneration (AMD), and more generalized loss of neural retina and vision function with age. Some previous evidence suggests that MP, comprised of the dietary carotenoids lutein, zeaxanthin and meso-zeaxanthin, declines with age, and that preserving MP might help reduce risk for developing eye diseases and/or vision loss which become more common as we age. This has not been previously evaluated in large longitudinal studies. MP optical density (MPOD) can be simply and non-invasively measured. Therefore, MPOD assessment might be useful in screening to identify individuals, in middle-age, who are at higher risk for age-related vision los. Devices to assess MPOD are already adapted for clinical use, but evidence addressing longitudinal relationships of MPOD to AMD and vision loss is needed to make recommendations about their appropriate use. If MPOD predicts AMD and/or age- or disease-related vision loss, then early assessment would permit the targeting of individuals for testing a variety of preventive measures to lower risk, including those which would increase macular pigment. Evidence to address the gap in longitudinal data can be obtained at low cost by conducting a prospective follow-up study in the Carotenoids in Age-Related Eye Disease Study (CAREDS) cohort. MPOD, fundus photographs to assess AMD, and visual acuity measures were previously obtained in 1,791 women in 2001-2004. Annual follow-up of this cohort, in the Women's Health Initiative, assures low loss to follow up, documents mortality and new chronic diseases (including common age-related eye diseases), and provides extensive nutritional, genetic, lifestyle, and health data. Follow-up visits thirteen years later will be conducted to provide a second set of fundus photographs to document the relationships of MPOD to AMD incidence and/or progression. Second, MPOD at baseline will also be studied in relation to measures of structural and functional aging at follow-up. Structural measures include new measures of the thickness of the retina, across several layers and regions, using spectral domain optical coherence tomography (SD-OCT). Functional measures include the loss of visual acuity between baseline and follow-up, and additional secondary measures obtained at follow-up. Third, measures of MPOD levels at follow-up will be obtained to permit the first direct longitudinal estimate of MPOD declines with age, and to provide an opportunity to explore whether average age-related declines are lower in women with higher initial MPOD, and in women with higher intakes of lutein and zeaxanthin, between baseline and follow-up. The proposed research will constitute the largest and longest extant investigation of relationships of macular pigment to aging, age-related vision loss, and AMD, thereby advancing knowledge needed to understand the role of carotenoids in preserving vision with age and informing clinical guidelines.

Public Health Relevance

This research will provide the first evidence from long-term studies to determine whether having a low density of lutein and zeaxanthin in the retina of the eye, predicts aging of the retina, the development and progression of age-related macular degeneration, and the loss of vision. Simple techniques exist to measure lutein and zeaxanthin density in the macula of the eye, safely and at low cost. Therefore, this research may provide the opportunity to identify individuals at risk for age-related eye disease in middle-age, and the opportunity to lower risk for eventual vision loss by increasing the intake of lutein and zeaxanthin in foods and supplements and adopting other strategies to lower risk, thereby preserving vision as they age.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY025292-04
Application #
9513558
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Bhargava, Sangeeta
Project Start
2015-06-01
Project End
2020-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Mares, Julie (2016) Lutein and Zeaxanthin Isomers in Eye Health and Disease. Annu Rev Nutr 36:571-602