Program Abstracts
Invited Session I: Optoretinography
Optoretinography: From Retinal Physiology to Clinical Biomarkers
Ram Sabesan, University of Washington
Ram Sabesan, University of Washington
Optoretinography (ORG) has emerged as a powerful approach for measuring light-evoked functional responses in the eye and bridging the gap between retinal structure and function. Broadly, ORG leverages existing optical imaging modalities, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), to measure stimulus-evoked neural activity non-invasively in the living human eye. When combined with adaptive optics, these techniques enable functional imaging at cellular resolution.
This presentation will provide an overview of recent advances in ORG and the insights they have provided into retinal physiology. Topics will include the fundamental properties of light-evoked responses in photoreceptors, as well as recent work linking these signals to phototransduction, outer retinal biomechanics, and coherent optical scattering. Together, these studies have begun to establish a unified framework for interpreting ORG measurements across imaging modalities. The presentation will also highlight the use of ORG as a sensitive biomarker of retinal disease, capable of detecting functional abnormalities before overt structural changes become apparent. Finally, it will conclude with a discussion of the remaining challenges, open questions, and opportunities for translating functional retinal imaging from the research laboratory into broader clinical practice.
Optoretinography and Beyond: Imaging Neural and Vascular Function in the Human Retina
Pedro Mecê, Institut Langevin, Paris
Pedro Mecê, Institut Langevin, Paris
Optoretinography (ORG) is emerging as a powerful approach for probing retinal function non-invasively. This presentation will highlight two complementary imaging strategies to extend cellular-resolution functional retinal imaging over large fields and at high speed.
We will first present time-domain full-field optical coherence tomography (FFOCT) for measuring stimulus-evoked photoreceptor responses over a 5° × 5° field at up to 500 Hz, with the aim of extending cellular ORG toward more scalable and clinically applicable measurements.
We will then consider retinal function from a broader physiological perspective. Neural activation is accompanied by vascular responses (neurovascular coupling) that regulate local blood supply and metabolic support, providing complementary information on retinal function. Adaptive-optics rolling-slit ophthalmoscopy (AO-RSO), a phase-contrast method developed in our group, provides cellular-scale imaging over approximately 4.5° × 3° at up to 200 Hz. Direct visualization and tracking of vessel walls over time reveal stimulus-evoked vasodilation during neurovascular coupling.
Together, these developments illustrate how functional retinal imaging may evolve from the measurement of photoreceptor activity toward a more integrated assessment of neural and vascular function, with potential applications in retinal and neurodegenerative disease.
Techniques and applications of optoretinography in combination with adaptive optics scanning laser ophthalmoscopy
Jessica Morgan, University of Pennsylvania
Jessica Morgan, University of Pennsylvania
Optoretinography is an emerging technique for high resolution assessment of retinal function through noninvasive imaging. This presentation will describe techniques and applications of optoretinography in combination with adaptive optics scanning laser ophthalmoscopy (AOSLO).
A custom-built, multimodal AOSLO was used to image the photoreceptors before, during, and after calibrated stimuli of 545 nm light were delivered to the retina. AOSLO videos were registered and cone intensities extracted. Population optoretinogram (ORG) measurements were made by normalizing, standardizing, and aggregating cones intensities to detect changes in cone intensities following stimulation. ORGs from patients with choroideremia and retinitis pigmentosa were compared with normal ORGs across retinal eccentricities.
In normal controls, the ORG was repeatable, decreased with eccentricity, and its action spectrum corresponded with the photopic luminosity function. In choroideremia patients, ORGs were severely reduced at all retinal locations in comparison to controls. Retinitis pigmentosa patients also exhibited severely reduced ORGs, especially at retinal locations approaching the transition zone of photoreceptor loss.
Optoretinography demonstrates promise as an objective biomarker of cone function in health and disease. Future applications of optoretinography include its use as a secondary outcome measure in clinical trials testing novel therapeutics for retinal disease.
Differential Coherence as an Optoretinographic Tool
Lawrence Sincich, The University of Alabama at Birmingham
Lawrence Sincich, The University of Alabama at Birmingham
Cone photoreceptors have stimulus-driven morphological changes that can alter their optical reflectance. In conjunction with adaptive optics, we are exploring how differential coherence imaging (DCI) may be used to measure positional shifts in reflective surfaces after stimulation with light in the living eye. Such shifts are expected to occur as interference effects from surface pairs lying within the coherence length of an imaging light source.
DCI images were created by subtracting successive frames during imaging with high (11.1 µm, λ = 840±10.5 nm) and low coherence (5 µm, λ ≈ 848±50 nm) sources of balanced intensity reflected from the eye. Imaging trials lasted 6 s, with a stimulus flashed for 0.5 s containing green light (543±11 nm, 0.9-20 µW). DCI reflectivity changes were compared to images processed from an adjacent area of unstimulated retina, acting as a control.
We found DCI signals—resolved at the single cone level—driven by visual stimulation in 3 tested subjects. DCI signals were detectable within 1 trial and are consistent with the movement of reflective surfaces positioned less than 10 µm apart. The signal likely arises from the inner/outer segment junction or from the outer segment tip adjacent to the retinal pigment epithelium. The DCI approach holds promise as a new optoretinographic tool for revealing photoreceptor responses.