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

Abstract

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.

Parafoveal cone function in choroideremia assessed with adaptive optics optoretinography

“…Optoretinography has recently emerged as a technique for measuring photoreceptor function in the living human retina 29 – 35 , 37 , 39 , 47 . In the present study, ORG signals in parafoveal retina were successfully obtained using AOSLO in both normal-sighted participants and those diagnosed with CHM.…”

“…ORG amplitudes in previous studies likewise have shown similar ranges across individuals, with ORG amplitudes in some cases varying by a factor of two 30 , 31 . The cause of this inter-subject variability is unknown though possible contributing factors include outer segment length, axial length, and dilated pupil size 39 in additional to biological variables such as age and sex. In the present study, the normal-sighted participant with the lowest ORG amplitude was female.…”

“…At the level of individual cells, ORG measurements have shown increasing ORG responses with increasing stimuli irradiance and have enabled classification of cone types in the trichromatic mosaic 29 , 32 – 34 . Studies of optoretinography largely have been confined to proof of concept studies in normal sighted individuals 29 – 39 . To our knowledge, there has only been one report of optoretinography applied to retinal disease 40 .…”

Intensity-based optoretinography reveals sub-clinical deficits in cone function in retinitis pigmentosa

“…pORGs are determined using the argument (or phase) of the complex OCT signal, and are typically calculated by determining the change in phase as referenced to the cone boundary. This is then related to the change in optical path length ( 29 – 35 ). Conversely, iORGs are created from changes in the amplitude of backscattered light from photoreceptors using adaptive optics flood illumination ophthalmoscopes ( 26 , 36 ) adaptive optics scanning light ophthalmoscopes (AOSLOs) ( 25 , 37 , 38 ), and OCTs ( 39 – 43 ).…”

Light-evoked deformations in rod photoreceptors, pigment epithelium and subretinal space revealed by prolonged and multilayered optoretinography

“…Although a few studies have extracted phase-sensitive ORG signals from speckle patterns by spatial averaging, this approach could not maintain the spatial heterogeneity (20)(21)(22). It was unclear how the actual nanoscopic tissue movement could be interpreted from the phase component of speckle patterns or how other tissues such as the retinal pigment epithelium (RPE) and the Bruch's membrane (BrM) behave in response to light stimuli, as their signals are mixed in these speckle patterns.…”