AS471 - Macular pigment in aging and age-related eye disease
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Investigator Names and Contact Information
Julie Mares [jmarespe@wisc.edu]
Introduction/Intent
The purpose of this proposal is to determine whether the density of the dietary carotenoids in the macula, which comprise "macular pigment", is a modifiable risk factor for vision loss with aging and the development of age-related macular degeneration (AMD). It addresses the National Eye Institute High Priority Research Area PA-13-332, "Intersection of Aging and Biological Mechanisms of Eye Disease" by advancing evidence about the role that macular pigment (MP) may play in aging and common, costly age-related diseases in the retina. If MP optical density (MPOD) predicts vision loss and/or AMD, then simple and non-invasive tests might be useful in early screening at low- cost in middle age to identify individuals who are at high risk for their future development. Such screening might be useful in identifying participants for testing preventive measures, and ultimately to target individuals for interventions to enhance MP and lower risk. Devices to assess MPOD are already adapted for clinical use, but evidence needed to make clinical recommendations about their use is insufficient.
There exists a unique opportunity to conduct the proposed prospective study at low added cost, in the Carotenoids in Age-Related Eye Disease Study (CAREDS) cohort, in which MPOD, fundus photographs to assess AMD, and visual acuity were previously obtained in 2001-2004. Annual follow-up of this cohort and assessment of health outcomes in the Women's Health Initiative, over 19 years since they were 50 to 79 years of age, assures low loss to follow up and provides extensive nutritional, genetic, lifestyle, and health data. This cohort has also been followed for annual mortality updates and to assess physician diagnosis of common age-related eye diseases.
We plan to invite the anticipated 1,304 surviving women to participate in 13-year follow-up visits to obtain fundus photographs to assess AMD incidence and progression and to obtain second measures of visual acuity to calculate vision loss. We will investigate the relationships of age to morphological measures of retinal health, assessed by spectral domain optical coherence tomography (SD-OCT) and relationships of MPOD to age-adjusted OCT outcomes. We will also investigate the relationships of age to functional measures of ocular health, as indicated by contrast sensitivity and responses to a low luminance questionnaire, which reflect broader processes of vision function than visual acuity measures. Finally, we will obtain second measures of MPOD to explore MPOD stability or age-related changes and determinants of changes. The proposed research will constitute the largest long-term longitudinal investigations of relationships of MPOD to AMD, age-related vision loss, and ocular health.
Specific Aims
We plan to conduct the first large prospective study to determine whether macular pigment optical density (MPOD) predicts the incidence and progression of age-related macular degeneration (AMD) and loss of vision over 13 years in women 55 to 84 years of age at baseline, adjusting for the competing risk of mortality. We will further determine the relationships of MPOD to age-adjusted morphological features of the retina assessed by the thickness of retinal regions and drusen area determined by spectral domain optical coherence tomography (SD- OCT) imaging. We will also determine the cross-sectional and longitudinal relationships of MPOD to age-adjusted measures of vision functions which are important to daily independent functioning: scores on dark adaptometry and contrast sensitivity tests and on a low luminance questionnaire.
These goals can be achieved at low added cost by recruiting 1,304 surviving members of the Carotenoids in Age-Related Eye Disease Study (CAREDS) to return for follow-up visits. Data from the proposed study will provide the first estimates of the long-term stability, or change, in MPOD that occurs with aging and disease. MPOD might decline with age as some1,2 but not other3 studies suggest. We will also be able to determine whether any changes over time are related to levels of macular carotenoids in diet or supplements or to other genotypes or phenotypes which previous studies suggest may preserve MP.4,5
Despite current commercialization of devices to measure macular pigment, there is not adequate evidence of clinical utility. If MPOD is found to be predictive of the development of AMD or vision loss, it could be useful in mid-life screening during routine eye examinations to identify people who are at risk for developing AMD or vision loss in later life. Screening using MPOD testing could identify "at risk" persons to target for efficient study samples in clinical trials of a variety of preventative measures. Early risk identification could provide patient motivation to lower risk by adopting healthy lifestyles, including increasing the intake of macular carotenoids, decades before vision-threatening pathology is clinically evident.
We have the following specific aims:
1. To determine whether MPOD at baseline is inversely related to lower risk for the incidence and progression of AMD and decline in visual acuity over 13 years.
2. To determine whether MPOD at baseline and follow-up are related to subclinical morphological indicators of retinal health, as assessed by SD OCT, and functional indicators of ocular health, as assessed by dark adaptometry and scores on a contrast sensitivity test and a low luminance questionnaire.
3. To investigate the relationship of macular pigment levels at baseline (2001-2004) to:
A) The prevalence of glaucomatous optic nerve features at baseline and follow-up (2016-2017).
B) Glaucoma incidence, with confirmed clinical diagnoses based on visual field loss at follow-up in CAREDS participants.
Exploratory Aim: To determine the predictors of maintaining or achieving an above average MPOD from baseline to follow-up.
