The human fovea is highly specialized for excellent visual acuity and contrast sensitivity. To provide this capability the cones in the center of the fovea are smaller in diameter than parafoveal cones. To compensate for the decreases in cross sectional area relative to cones further from the center, the foveal cones have longer outer segments, and therefore a higher optical density of their cone photopigments. The cones also act as antennae: the inner segments collect light preferentially from the pupil and guide the light along the outer segments. These waveguide properties of the cones also vary across the fovea, with the cones in the foveal center accepting light from a wider region of the pupil than cones just a few hundred microns away. This increased collection of light from the pupil both increases their sensitivity and also allows them to use a wider region of the pupil, and thereby have higher optical resolution. Thus, the fovea represents a balance of factors which are tightly coupled to provide excellent vision. As the eye ages this balance may change. The curvature of the fovea changes (the foveal pit widens) and irregularities in the symmetric distribution of the cone photopigment appear. In addition, the high optical density of the foveal cones decreases, becoming more similar to cones a few degrees away from the center of the fovea. This change in optical density may occur due to either a decrease in the outer segment length, decreases in the amount of photopigment, or changes in the waveguide properties of the cones. With early ARM the optical density of both the foveal and parafoveal cones decrease even more. Modern optical technology now allows us to directly measure the optical factors controlling the capture of light by the foveal cones. We will use state of the art instrumentation and analysis techniques to study the fovea in normals and patients with early age-related macular degeneration (ARM). We will use adaptive optics imaging with an SLO to directly image the cones and related structures. We will use photoreceptor alignment reflectometry and retinal densitometry to measure the optical properties of the cones. We will relate changes to the cones in aging and early ARM to RPE health, determined by measuring near infrared light scattering and lipofuscin fluorescence. We will test whether changes in RPE health are related to changes in the optical efficiency of the overlying cones. These studies will provide a unique quantitative framework for evaluating the fovea of the human eye as an imaging system, and provide information on how the functional capacities of the fovea change with both age and early ARM. Such measurements will be critical for both understanding the development of ARM, and to better explain visual complications that occur prior to the permanent loss of vision.
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