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Purpose Utilize high resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD). Methods Forty asymptomatic subjects were recruited (9 males, 31 females; 51–69 years, mean=61.4 years). Comprehensive eye exam, fundus photography and high-resolution retinal imaging using SD-OCT and adaptive optics (AO) were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. AO scanning light ophthalmoscope (AOSLO) images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject. Results RR was not significantly predictive of fundus grade (p=0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade ≥ 1 had a 12% decrease in density (p<0.0001) and a 5% increase in spacing (p=0.0014). No association between genetic RR and either cone density (p=0.435) or spacing (p=0.538) was found. Three distinct AOSLO phenotypical variations of photoreceptor appearance were noted in patients with grade 1–3 fundi. These included variable reflectivity of photoreceptors, decreased waveguiding, and altered photoreceptor mosaic overlying drusen. Conclusions Our data demonstrate the potential of multimodal assessment in the understanding of early anatomical changes associated with AMD. AOSLO imaging reveals a decrease in photoreceptor density and increased spacing in patients with grade 1–3 fundi, as well as a spectrum of photoreceptor changes, ranging from variability in reflectivity to decreased density. Future longitudinal studies are needed in genetically characterized subjects to assess the significance of these findings with respect to the development and progression of AMD.

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