Abstract

Noninvasive, objective, all-optical testing of neural function in the retina (optoretinography, or ORG) offers an opportunity to diagnose and stage blinding retinal diseases with greater sensitivity and speed than traditional functional methods. It has the potential to optimize endpoints in studies of medical interventions and increase the efficiency of clinical trials of emerging therapies. Unlike other functional tests, it offers precise correlation of function with disease-related structural changes, such as drusen, pseudodrusen, atrophy and photoreceptor degeneration. Thus in addition to providing a new set of biomarkers of retinal health and disease, it stands to enrich existing structural biomarkers. Recent efforts have demonstrated the feasibility of the ORG using full-field swept-source optical coherence tomography (FF-SS-OCT) and adaptive optics (AO) OCT. These methods have permitted investigation of functional responses at the cellular level, but at the expense of costly equipment, multiple expert personnel, and data volumes that preclude real-time feedback and require specialized data processing and storage equipment. However, the ORG’s significant potential to positively impact human health demands rapid translation of this technique into clinical research and eye care. Here we demonstrate a proto-clincial ORG system consisting of low-cost parts very similar to those found in the commercial OCT systems deployed in most ophthalmic care settings. By leveraging measurements of photoreceptor ORG responses using our high-resolution AO-OCT and AO-FF-SS-OCT systems, we designed a method for extracting these responses from a series of approximately 20 conventional OCT B-scans acquired within 50 milliseconds. Responses have been acquired from three experimental subjects and exhibit high test-retest repeatability and dependence on stimulus dose and retinal eccentricity. Results are available within minutes using non-optimized prototype software on a desktop PC.

© 2022 The Author(s)