Abstract
Purpose :
The optoretinogram (ORG) has demonstrated promise for the non-invasive assessment of photoreceptor function. To realize its potential as a biomarker of retinal disease and response to therapy, it is critical to establish the factors that govern the variability of ORG across a healthy population. Here, we performed the normative characterization of the cone ORG, with the ultimate goal of establishing the sensitivity and specificity of ORG as a measure of cone function in disease.
Methods :
Cone ORGs were obtained in 20 healthy human subjects (age range: 19 - 50 yo) with a line-scan OCT over a 5°x3° field-of-view, dubbed a coarse-scale ORG (CoORG – Jiang et al. 2022). OCT volumes were processed to obtain cone outer segment (OS) length, and light-evoked changes in optical path length vs. time (ΔOPL) in the OS. Three nominal bleach strengths – 4.4e6, 8.8e6 and 14.2e6 photons/µm2 were used. The bleach strength of the stimulus at 532±5 nm was converted to effective photon density at the retina for each subject by incorporating stimulus spectrum & pulse width, anterior segment & macular pigment absorption, and each subject’s measured axial length & dilated pupil size. The inter- and intra-individual variation in ORG features were assessed for dependence on photon density, OS length and retinal eccentricity.
Results :
The previously described behavior of ΔOPL vs. time was observable with high inter-trial repeatability (±13.7 nm) for each subject. The ORG response amplitude and initial rate of change decreased with effective photon density at each eccentricity. Longer axial lengths and smaller dilated pupils contributed to a lower effective photon density and a corresponding decrease in ORG response. For the same photon density, ΔOPL decreased linearly with increasing eccentricity in a manner consistent with a decrease in OS length (mean R2 = 0.63, p<0.01). The slope of the linear decrease in maximum ΔOPL vs. OS length was dependent on bleach strength : 9.7 ± 0.6 nm/µm, 20.8 ± 2.0 nm/µm, 29.2 ± 3.4 nm/µm for nominal bleaches of 4.4e6, 8.8e6, and 14.2e6 photons/µm2 respectively.
Conclusions :
Two key factors - effective retinal photon density and OS length - explain the major variation in the normative cone ORG. To establish the ORG as a sensitive measure of cone function requires accounting for inter-individual differences in pupil size, axial length and eccentricity-dependent changes in OS length.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.