Coarse-scale optoretinography (CoORG) with extended field-of-view for normative characterization

Optoretinography (ORG) has the potential to be an effective biomarker for light-evoked retinal activity owing to its sensitive, objective, and precise localization of retinal function and dysfunction. Many ORG implementations have used adaptive optics (AO) to localize activity on a cellular scale. However, the use of AO restricts field-of-view (FOV) to the isoplanatic angle, necessitating the montaging of multiple regions-of-interest to cover an extended field. In addition, subjects with lens opacities, increased eye movements and decreased mobility pose challenges for effective AO operation. Here, we developed a coarse-scale ORG (CoORG) system without AO, which accommodates FOVs up to 5.5 deg. in a single acquisition. The system is based on a line-scan spectral domain OCT with volume rates of up to 32 Hz (16,000 B-frames per second). For acquiring ORGs, 5.5 deg. wide OCT volumes were recorded after dark adaptation and two different stimulus bleaches. The stimulus-evoked optical phase change was calculated from the reflections encasing the cone outer segments and its variation was assessed vs. eccentricity in 12 healthy subjects. The general behavior of ΔOPL vs. time mimicked published reports. High trial-to-trial repeatability was observed across subjects and with eccentricity. Comparison of ORG between CoORG and AO-OCT based ORG at 1.5°, 2.5°, and 3.5° eccentricity showed an excellent agreement in the same 2 subjects. The amplitude of the ORG response decreased with increasing eccentricity. The variation of ORG characteristics between subjects and versus eccentricity was well explained by the photon density of the stimulus on the retina and the outer segment length. Overall, the high repeatability and rapid acquisition over an extended field enabled the normative characterization of the cone ORG response in healthy eyes, and provides a promising avenue for translating ORG for widespread clinical application.