Abstract
Purpose :
Optoretinography (ORG) has emerged as an effective biomarker for light-evoked retinal activity owing to its sensitive, objective, and precise localization of function and dysfunction. ORG implementations have typically used adaptive optics (AO) to localize activity on a cellular scale, at the cost of a limited field size. Here, we report on the development of a coarse-scale ORG (CoORG) system without AO and its use for normative characterization of the ORG across the human macula.
Methods :
The system is based on a line-scan spectral domain OCT with illumination centered at 840±20nm. A high-speed camera enables the capture of up to 5.5° field-of-view OCT volumes at rates up to 32Hz (16,000 B-scans/sec). Such volumes were acquired after 1 min. dark adaptation and a stimulus flash centered at 532±5nm. Three stimulus bleach strengths were used and five repeat trials were obtained in each condition. The time evolution of OCT phase converted to change in optical path length (ΔOPL) in the cone outer segment (COS) provided an ORG trace and its variation was assessed vs. eccentricity and bleach strength in 12 normal subjects (ages: 26-41 yrs). In two subjects, AO-OCT based ORGs were compared against CoORG at the same eccentricities.
Results :
High inter-trial repeatability was observed across subjects and eccentricity (std: ±10 nm). Comparison of ORG between CoORG and AO-OCT at 1.5°, 2.5°, and 3.5° showed good agreement. The magnitude of ΔOPL and its rate of change vs. time increased with bleach strength, and decreased vs. eccentricity. On average, at stimulus photon density of 8.8e6 photons/μm2, saturated ΔOPL ranged from 755 nm±113 nm at 0.5° to 491 nm±32 nm at 4.5°; at 4.4e6 photons/μm2, saturated ΔOPL ranged from 486 nm±58 nm at 0.5° to 367 nm±61 nm. At each bleach strength, the change in saturated ΔOPL was well-predicted and linearly correlated with subjects’ COS length within the central 5° (R2>0.53, p<0.01). The slope of this linear relation defined the % increase in COS length due to bleach, equal to 3.4%, 2.1%, and 1.1% for stimulus photon density of 14.2e6, 8.8e6 & 4.4e6 photons/μm2 respectively.
Conclusions :
The CoORG offers high repeatability and rapid imaging over an extended field, enabling the normative characterization of the cone ORG response in healthy eyes and providing an avenue for translating ORG for widespread clinical application.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.