Toward a clinical optoretinogram: a review of noninvasive, optical tests of retinal neural function

Abstract

The past few years have witnessed rapid development of the optoretinogram-a noninvasive, optical measurement of neural function in the retina, and especially the photoreceptors (Ph). While its recent development has been rapid, it represents the culmination of hundreds of experiments spanning decades.Early work showed measurable and reproducible changes in the optical properties of retinal explants and suspensions of Ph, and uncovered some of the biophysical and biochemical mechanisms underlying them.That work thus provided critical motivation for more recent work based on clinical imaging platforms, whose eventual goal is the improvement of ophthalmic care and streamlining the discovery of novel therapeutics.The first part of this review consists of a selective summary of the early work, and identifies four kinds of stimulus-evoked optical signals that have emerged from it: changes in light scattered from the membranous discs of the Ph's outer segment (OS), changes in light scattered by the front and back boundaries of the OS, rearrangement of scattering material in and near the OS, and changes in the OS length. In the past decade, all four of these signals have continued to be investigated using imaging systems already used in the clinic or intended for clinical and translational use. The second part of this review discusses these imaging modalities, their potential to detect and quantify the signals of interest, and other factors influencing their translational promise. Particular attention is paid to phase-sensitive optical coherence tomography (OCT) with adaptive optics (AO), a method in which both the amplitude and the phase of light reflected from individual Ph is monitored as visible stimuli are delivered to them. The record of the light's phase is decoded to reveal a reproducible pattern of deformation in the OS, while the amplitude reveals changes in scattering and structural rearrangements. The method has been demonstrated in a few labs and has been used to measure responses from both rods and cones. With the ability to detect responses to stimuli isomerizing less than 0.01% of photopigment, this technique may prove to be a quick, noninvasive, and objective way to measure subtle disease-related dysfunction at the cellular level, and thus to provide an entirely new and complementary biomarker for retinal disease and recovery.

Functional Optical Coherence Tomography for Intrinsic Signal Optoretinography: Recent Developments and Deployment Challenges

“…The retina is thin, transparent, and stratified into distinct cellular layers. Since the stimulus-evoked retinal activity was found to alter intrinsic optical properties at different layers, OCT has been actively investigated for depth-resolved IOS imaging ( 22 , 34 ). Both time-domain and Fourier-domain OCT systems have been demonstrated for IOS imaging.…”

Evaluation of the effectiveness of the decision support algorithm for physicians in retinal dystrophy using machine learning methods

“…Электроретинография представляет собой метод электрофизиологического тестирования, при котором регистрируется электрический отклик сетчатки при её стимуляции коротким стимулом света или изменением пространственной организации яркости (паттернами) [3]. В отличие от хорошо изученных сигналов электрокардиограммы, представляющих собой продолжающуюся активность миокарда, для снятия электроретинограммы необходимо стимулировать сетчатку светом, чтобы вызвать синхронизированную активность ретинальных клеток, ведущую, таким образом, к генерации ответа электроретинограммы [4].…”

Optical coherence tomography in healthy human subjects in the setting of prolonged dark adaptation

“…Many studies have shown the utility of OCT for studying retinal structural changes, especially in the context of dark adaptation, though the dark adaptation periods in these and other clinical studies were done over short periods of time only 21 . To the best of our knowledge, the longest studied period of dark adaptation in human subjects has been 30 min 22 .…”