PURPOSE:To determine, if there are identifiable retinal structural changes associated with genetic risk for age-related macular degeneration (AMD). MATERIALS AND METHODS:Seventy-three subjects (range 51.5 to 68.9 years) participated in this prospective study. Subjects were recruited based on the presence of a family history of AMD in one or both parents. All participants underwent a complete ophthalmic exam and imagery for staging of disease severity and genetic testing to assess genetic risk for AMD development. Optical coherence tomography (OCT) imaging was performed on all participants. Semi-automated retinal layer segmentation was performed to assess retinal structural changes. RESULTS:Of 73 subjects, 47 subjects had normal appearing retina with no evidence of drusen or other changes consistent with AMD, 16 subjects were classified as early AMD, and 13 were designated as intermediate AMD. Retinal volume measures of total retina, outer retina, outer nuclear layer and the retinal pigment epithelium, were not related to AMD classification, genetic risk scores, or age. The thickness of the outer retina showed statistically significant thickening in the foveal region in only the intermediate AMD group and a statistically significant thickening of the RPE in early and intermediate AMD groups in the central retina. CONCLUSION:No consistent changes were observed in retinal structure at multiple locations that are associated with pre-clinical AMD, based on AMD genetic risk or with aging within the age range of our cohort.