Velocity-based optoretinography for clinical applications

Optoretinography (ORG) is an emerging tool for testing neural function in the retina. Unlike existing methods, it is noninvasive and objective, and provides information about retinal structure and function at once. As such, it has great potential to transform ophthalmic care and clinical trials of novel therapeutics designed to restore or preserve visual function. Recent efforts have demonstrated the feasibility of ORG using state-of-the-art optical coherence tomography systems. These methods measure the stimulus-evoked movement of subcellular features in the retina, using the phase of reflected light to monitor their positions. Here we present an alternative approach that monitors the velocity of these features instead. This conceptual shift has significant implications for the nascent field of ORG. By avoiding the need to track specific cells over time, it obviates costly and laborious aspects of position-based approaches, such as adaptive optics, digital aberration correction, real-time tracking, and three-dimensional segmentation and registration. We used this velocity-based approach to measure the photoreceptor ORG responses in three healthy subjects. The resulting responses were reproducible and exhibited dependence on dose and retinal eccentricity. The possibility of reconstructing the position signal through numerical integration of velocity was explored.