Subretinal Aspects of the Optoretinographic Response

Optoretinography (ORG) detects stimulus-evoked, nanometer-scale changes in the optical path length of photoreceptors, hypothesized to reflect osmotic water shifts into and out of the outer segments (OS), as well as electrostatic effects of opsin photoisomerization. The aim of this study was to measure parallel changes in the subretinal space (SRS), which may reflect changes in the SRS volume. The results of these experiments could affect interpretations of the photoreceptor ORG, which make testable hypotheses about the SRS volume. Moreover, because water movement in the outer retina is impeded in a number of diseases of the outer retina, this method could represent a novel biomarker of outer retinal health.

A custom swept-source optical coherence tomography system (100 kHz, 1060 nm) was used to image the eyes of four healthy subjects. After dilation and dark adaptation, serial B-scans were acquired over 125 ms at 400 Hz, with a stimulus flash delivered after 40 ms. From the resulting series, relative phase velocities between layers were calculated for three compartments: OS, supracone space (SCS), and ciliary zone (CZ).

Light stimulation produced rapid, layer-specific responses. Following stimulation, the OS contracted briefly and then elongated, the SCS elongated and subsequently contracted, and the CZ exhibited a response similar to the OS but with lower amplitude. These responses were temporally coordinated across layers, suggesting coupled structural and fluid dynamics within the outer retina.

Visible light induces rapid, reversible structural changes across multiple outer retinal layers, including the spaces surrounding the photoreceptor outer segments. Noninvasive measurement of these responses may improve understanding of the biophysical sources of the ORG signal and provide a probe of outer retinal functional integrity.