Optoretinography - Mechanisms and applications

Optoretinography (ORG) refers to the optical imaging of light-evoked neural activity, specifically in the retina. The general protocol involves using an imaging instrument, such as a scanning laser ophthalmoscope (SLO) or optical coherence tomography (OCT), to monitor the retinal response evoked by a visual stimulus. Advances in imaging technology, such as adaptive optics, high-speed and parallel recordings, and phase-resolved detection with SLO and OCT, have together enabled the recording of stimulus-evoked retinal events across a range of spatiotemporal resolution, from individual to collection cells, from milliseconds to minutes. The slow responses are attributed to changes in osmotic pressure and water movement, creating a shape change. The fast responses are attributed to shape changes due to voltage-dependent membrane tension that accompanies cell signaling via hyper- or depolarization. The cone ORG includes a rapid contraction followed by two slower elongation phases of the outer segment, each linked to specific stages of phototransduction. ORG has enabled classification of the cone types with high efficiency and precision, providing a detailed view of their spectral composition in the human macula. In patients with inherited retinal disease, ORG provides early detection of dysfunction in photoreceptors, evident even in clinically-defined healthy retinal areas. As a noninvasive, sensitive, and objective assay of retinal health, ORG holds promise for detecting disease progression and evaluating therapies.