Shining light on photoreceptors: A minireview on the development and clinical applications of optoretinography.

Retinal diseases often result in photoreceptor dysfunction and cell death, leading to progressive vision impairment and eventual blindness. Clinical management can benefit from assessing photoreceptor mediated visual function, such as for progression monitoring. Meanwhile, therapeutic development requires accurate and reliable vision end points. The emerging optoretinography (ORG) technologies promise noninvasive, objective, and highly sensitive markers of photoreceptor function. ORG is an umbrella term that covers several imaging modalities that use intrinsic optical signal, i.e., without dyes or labeling agents, to quantify photoreceptor responses to light. Early studies showed stimulus-evoked light scattering and morphological changes in isolated photoreceptor and retina, which provided the experimental foundation for subsequent inquires in vivo. Technology advancements allowed for optically quantifying photoreceptor light responses in live human subjects using two-dimensional (2D) fundus photography and 3D optical coherence tomography (OCT). The integration of adaptive optics (AO) with OCT enabled direct measurements of outer segment length changes of individual human photoreceptors, revealing essential steps of the phototransduction cascades. In an effort to enlarge measurement field of view, ease imaging workflow, and improve accessibility, more recent studies investigated ORG techniques without the need to resolve or track individual cells. Clinical ORG imaging culminated in demonstrating highly sensitive and reliable detection of photoreceptor dysfunction in patients with degenerative retinal diseases. Ongoing development of both AO and non-AO ORG approaches promises to advance our understanding of phototransduction and the visual processing pathway, while establishing a powerful clinical tool for assessing vision.