|
Numerous retinal pathologies affect cone photoreceptor photopigment density, making it a potentially attractive functional biomarker for detecting and tracking disease progression. Conventional methods to measure photopigment density include psychophysical color matching, microspectrophotometry, and retinal densitometry, but these are either subjective, measure the aggregate response/change of thousands of cones, or are performed ex vivo. Recently, we have developed a method to measure spectral sensitivities of individual human cone photoreceptors objectively, non-invasively, and in vivo with adaptive optics optical coherence tomography (AO-OCT). In preliminary results we have observed variability in the spectral sensitivities of individual cones of the same type (S, M or L) that we hypothesize attributes to inter-cone variations in photopigment density. If correct, this may be of significant clinical interest. Here, we test this hypothesis by (1) deriving an expression for the relative photopigment densities of individual cone photoreceptors based on a theoretical model of the cone absorption process and (2) using this expression to estimate photopigment density from our AO-OCT measurements of spectral sensitivity. Our mean spectral sensitivity measurements align well to Stockman & Sharpe’s well-recognized cone fundamentals with a total least-squared error of 0.12 and confidence intervals (CI) <0.36, <0.025 and <0.017 for S, M, and L cones, respectively. The substantive variability in individual cone spectral sensitivities once related to photopigment density exhibits a distribution of standard deviation=0.177 for a group of 703 cones. This indicates a two-fold difference in light sensitivity between the least sensitive cone (least amount of photopigment) and the most sensitive cone (largest amount of photopigment) for 95% of the cones measured. Furthermore, we found relative photopigment density decreased with increasing retinal eccentricity from nasal to temporal retina at 3.8° eccentricity with a slope of -0.24/° (p < .001). Both density distribution and eccentricity dependence are consistent with the literature.
|
