Phase-based optoretinographic measurements of cones with a raster-scanning adaptive optics OCT are highly repeatable

Optoretinography (ORG) is a class of methods that use noninvasive, all-optical techniques to measure stimulus-evoked responses in the retina. By conveying functional and structural information at once, it offers a valuable complement to existing functional assays such as visual acuity, visual fields, and electroretinography. Whether employed in basic scientific research or clinical testing, the utility of ORG depends on its sensitivity to changes in the cone response. This sensitivity depends in part on the intrinsic variation of photoreceptor responses. In ORG studies using adaptive optics (AO), single cone responses are sometimes reported, but more often the responses of many cones are pooled in a defined field of view (FOV) to convey an average cone response with improved signal-to-noise ratio (SNR). In this study, we quantify repeatability of cellular-resolution ORG measurements made with adaptive optics (AO) optical coherence tomography (OCT). First, we describe a model-fitting method for parameterizing and quantifying the ORG responses. Next, using model-derived parameters, we investigate two kinds of repeatability: among repeated measurements of individual cones and among repeated measurements of the pooled responses of cones in a 1° field of view. Repeated measurements of individual cones exhibited good consistency in the ORG amplitude. Although responses among neighboring cones can differ greatly, pooled responses of cones from the same field of view were highly repeatable for maximum outer segment elongation and the elongation rate. Both kinds of repeatability were assessed using the same data sets; test-retest pairs were acquired within 30-minute windows in an effort to isolate measurement noise from physiological changes that may be more appropriately considered signal. These findings demonstrate AO-OCT-ORG's potential value in detecting changes in cone response due to experimental or therapeutic interventions, and its value in measuring longitudinal disease-related changes in response.