Characterizing cone spectral classification by optoretinography

Abstract

Light propagation in photoreceptor outer segments is affected by photopigment absorption and the phototransduction amplification cascade. Photopigment absorption has been studied using retinal densitometry, while recently, optoretinography (ORG) has provided an avenue to probe changes in outer segment optical path length due to phototransduction. With adaptive optics (AO), both densitometry and ORG have been used for cone spectral classification based on the differential bleaching signatures of the three cone types. Here, we characterize cone classification by ORG, implemented in an AO line-scan optical coherence tomography (OCT), and compare it against densitometry. The cone mosaics of five color normal subjects were classified using ORG showing high probability (∼0.99), low error (<0.22%), high test-retest reliability (∼97%), and short imaging durations (< 1 hour). Of these, the cone spectral assignments in two subjects were compared against AO-scanning laser opthalmoscope densitometry. High agreement (mean: 91%) was observed between the two modalities in these two subjects, with measurements conducted 6-7 years apart. Overall, ORG benefits from higher sensitivity and dynamic range to probe cone photopigments compared to densitometry, and thus provides greater fidelity for cone spectral classification.

Parafoveal cone function in choroideremia assessed with adaptive optics optoretinography

“…Prior studies have established the ORG as a physiological response in stimulated photoreceptors 29 , 30 , 34 , 51 , but it remains to be established whether the ORG is correlated with vision. As a subjective procedure requiring participant input, responses to microperimetry stimuli require perception, and thus threshold sensitivity measurements represent function of the full visual system.…”

Unique yellow shifts for small and brief stimuli in the central retina

“…Unique yellow was measured at the fovea using a staircase procedure in eight subjects; four of these subjects (10001R, 20075L, 20206R, and 20210L) also participated in the foveal hue scaling experiment. In the parafovea (∼1.5° to 2° eccentricity), unique yellow was determined for four subjects (10001R, 10003L, 20053R, and 20236R) whose parafoveal cone mosaics were spectrally classified via adaptive optics optical coherence tomography (AO-OCT)–based optoretinography ( Pandiyan et al., 2020 ; Pandiyan et al., 2022 ). Subject 20210L, who participated in the foveal measurements, had also been classified using optoretinography but was unavailable for parafoveal unique yellow measurements.…”

“…Stimulus locations, extracted by locating the digital crosses inserted in the raw video frames to mark the retinal locus of stimulus delivery, were then registered to R-SLAM–generated retinal maps so that stimulus deliveries for all trials could be plotted in a common coordinate system for each subject. Additionally, cone spectral identity labels were transferred from AO-OCT images to the R-SLAM–generated retinal maps using custom software ( Pandiyan et al., 2022 ).…”

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 ).…”