Abstract
Purpose :
Photoreceptor photopigment density is a potentially attractive biomarker for detecting and tracking retinal diseases affecting photoreceptors. We recently 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) [1]. We hypothesize that inter-cone variability in our cone spectral sensitivities attributes to photopigment density variation. To test, we estimated relative photopigment density from AO-OCT spectral sensitivity measurements using a theoretical model of cone absorption.
Methods :
The Indiana AO-OCT system was used to acquire 5-s AO-OCT videos at a 10 Hz volume rate of a 1°×0.8° patch of cones at 3.8° temporal retina in one color-normal subject (age 28 y/o). AO-OCT cone optoretinograms were measured 2.5 s after stimulation with flashes of 450, 480, 520, 545, 570, 600, and 635 nm light from a supercontinuum laser. Two bright flashes (4.2-31.0 μW at cornea, <1.8 nm bandwidth, 60 ms duration) were used at each wavelength. Cones were classified into S, M and L cone types and responses were recorded for each combination of flash strength and wavelength. After compensating for lenticular absorption, we used our cone absorption model to fit a power law to individual cone responses and to extract fitting parameters that we used to compute spectral sensitivity and photopigment density.
Results :
Our mean spectral sensitivity measurements of 703 cones align to Stockman & Sharpe’s normalized cone fundamentals with a total least-squared error of 0.12, where 98% of this error is attributed solely to S cones. Confidence intervals were <0.36, <0.025 and <0.017 for S, M, and L cones, respectively. Across the three cone types, the standard deviation of individual cone photopigment relative densities about the mean is ±0.177. We also found that relative photopigment density at 3.8° decreased with increasing retinal eccentricity across the imaging patch with a slope of -0.19/° (p < .001). Both density distribution and eccentricity dependence are consistent with the literature.
Conclusions :
We can objectively measure relative photopigment number of individual cone photoreceptors at the cellular level in vivo with high sensitivity. These measurements may be of significant clinical interest.
[1] Bernucci, et al. IOVS (2022), 397 – F0435
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.