Project Summary/Abstract In the past two decades, we have learned that variants in CFH, ARMS2/HTRA1 and other genetic loci are major risk factors for age-related macular degeneration (AMD) and that nutritional supplementation with AREDS2 antioxidant vitamins, minerals, and carotenoids could slow the progression of this blinding disorder. Despite recommendations by the American Academy Ophthalmology (AAO) against routine genetic testing for AMD risk, many members of the public express an interest in pursuing such testing, and direct-to-consumer laboratories already market them commercially. The AAO's expert panel did not assert that these tests do not accurately reflect eventual risk of visual loss from AMD, but rather that there is no proof that knowledge of AMD risk has any quantifiable impact on behavior that could mitigate the incidence of AMD in their senior years. A prospective study to show that knowledge of AMD risk could decrease incidence of AMD decades later would settle this controversy and would be consistent with research recommendations of the AAO expert panel, but it is not currently feasible due to the large number of subjects and prolonged time required. Instead, we propose a shorter, Phase 2 randomized clinical trial to study if quantifiable biomarkers of healthy behavior (skin and ocular carotenoid levels) improve in response to knowledge of AMD risk. We hypothesize that individuals who are informed of a high risk of eventual AMD will be more likely to make sustained changes in behavior associated with decreased incidence of AMD later in life such as smoking cessation, weight loss, decreased light exposure, and diets rich in carotenoids relative to subjects who have deferred testing or who are informed of low risk. These lifestyle changes will then result in improved levels of lutein, zeaxanthin, and other carotenoids measured in the skin at one year by resonance Raman spectroscopy (RRS) and reflectance spectroscopy (RS) and by autofluorescence imaging (AFI) and fluorescence lifetime imaging ophthalmoscopy (FLIO) in the eye. We will conduct a randomized, controlled clinical trial of immediate versus deferred disclosure of AMD risk in a 3:1 ratio in up to 80 normal individuals age 18 to 64. Systemic and ocular carotenoid status will be assessed objectively by skin RRS and RS and by ocular AFI and FLIO. We expect that subjects informed of high risk of AMD will be more likely to initiate and sustain positive lifestyle changes that will raise their skin and ocular carotenoid scores significantly at their one-year study visit. We will also determine correlations between AMD genetic risk with baseline ocular and systemic carotenoid status using current and newer methods of imaging.