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Zawadzki, R. J.

Publications and source records attributed to Zawadzki, R. J..

9 recordsLinked to original sources
bioRxiv2026

Dark adaptation of cone photoreceptor responses is revealed by optoretinography

Dark adaptation is the essential process that restores visual sensitivity following exposure to bright light, yet the underlying mechanisms remain incompletely understood. Here, we propose a method for assessing dark adaptation in cones using optoretinography (ORG) based on adaptive optics optical coherence tomography (AO-OCT). ORG quantifies cone functional response by monitoring nano-scale changes in the cones outer segment occurring over hundreds of milliseconds after visible stimulation. This method consists of sequential measurements of stimulus-evoked cone responses over the course of minutes of dark adaptation. Each response captures optical path length changes in single photoreceptor outer segments over milliseconds during a multi-minute recovery period following a strong photopigment bleach. We parameterized cone ORG responses and proposed an exponential model linking ORG dynamics to pigment regeneration. Parameters of the ORG response exhibited exponential decay behavior during dark adaptation, and were thus fit with exponential functions and quantified by the resulting decay parameter{tau} . Parameters capturing the amplitude of the ORG responses recovered more slowly than those capturing temporal dynamics of the responses. This difference is consistent with distinct contributions from photopigment regeneration and downstream phototransduction processes. Recovery speed varied by two-to threefold among three normal subjects, suggesting substantial inter-subject physiological diversity. Processes within the cone, including pigment regeneration, are thought to underlie the gains in photopic visual sensitivity that occur in the dark. These findings highlight ORG as an objective and sensitive assay of those cellular mechanisms. While the ORG itself has shown promise as a biomarker of the health of the photoreceptor response to light, the results of this study show that it may also be useful for probing the health of the intra- and intercellular homeostatic mechanisms that support it.

neuroscience↗
bioRxiv2025

Subretinal aspects of the optoretinographic response

1Water movement in the living human retina and its regulation are important components of the tissues structural integrity, optical properties, and homeostasis. In the outer retina there is a continuous flow of water from the subretinal space, through the retinal pigmented epithelium, and into the choroid. This flow is disrupted acutely in disorders such as retinal detachment and central serous retinopathy, and is also known to reduce dramatically with age and age-related macular degeneration. Optoretiongraphy is an emerging technique for measuring neural function in the retina by monitoring nanometer-scale deformations of the membranes of photoreceptors. These deformations have been hypothetically attributed, in part, to osmotic shifts that cause water to move into and out of the photoreceptor outer segment after light stimulation. In the present work, we describe a method for measuring changes in the lengths of the cone outer segment and subretinal space in parallel and results showing that light stimuli change the volume of the subretinal space. These results are consistent with earlier ex vivo measurements of its light-induced hydration. The magnitude of the latter changes depend on the rate of water clearance from the subretinal space, and thus may serve as an indicator of the health of the water transport system. In addition, they may help us understand the mechanisms underlying the photoreceptor optoretinogram. These findings add to a growing understanding of the ways in which light exposure leads to transient reconfigurations of the outer retinal layers lasting milliseconds to hours.

neuroscience↗
bioRxiv2025

Insight into human photoreceptor function: modeling optoretinographic responses to diverse stimuli

Optoretinography is an emerging method for detecting and measuring functional responses from neurons in the living human retina. Its potential applications are significant and broad, spanning clinical assessment of retinal disease, investigation of fundamental scientific questions, and rapid evaluation of experimental therapeutics for blinding retinal diseases. Progress in all these domains hinges on the development of robust methods for quantifying observed responses in relation to visible stimuli. In this work, we describe a novel optoretinographic imaging platform-full-field swept-source optical coherence tomography with adaptive optics, measure cone responses in two healthy volunteers to a variety of stimulus patterns, and propose a simple model for predicting and quantifying responses to those stimuli. TeaserThe function of human retinal neurons is quantified by the light they reflect, opening a new frontier in visual health

physiology↗
bioRxiv2022

Velocity-based optoretinography for clinical applications

Optoretinography (ORG) is an emerging tool for testing neural function in the retina. Unlike existing methods, it is noninvasive, objective, and provides information about retinal structure and function at once. As such, it has great potential to transform ophthalmic care and clinical trials of novel therapeutics designed to restore or preserve visual function. Recent efforts have demonstrated the feasibility of the ORG using state-of-the-art optical coherence tomography systems. These methods measure the stimulus-evoked movement of subcellular features in the retina, using the phase of the reflected light to monitor their position. Here we present an alternative approach that monitors the velocity of these features instead. This conceptual shift has significant implications for the nascent field of optoretinography. By avoiding the need to track specific cells over time, it obviates costly and laborious aspects of the position-based approaches, such as adaptive optics, digital aberration correction, real-time tracking, and three-dimensional segmentation and registration. We used this novel velocity-based approach to measure the photoreceptor ORG responses in three healthy subjects. The resulting responses were reproducible and exhibited dependence on dose and retinal eccentricity. The position of the relevant structures was reconstructed through numerical integration of velocity.

neuroscience↗
bioRxiv2021

Investigating the causes of stimulus-evoked changes in cone reflectance using a combined adaptive optics SLO-OCT system

In vivo functional imaging of human photoreceptors is an emerging field, with compelling potential applications in basic science, translational research, and clinical management of ophthalmic disease. Measurements of light-evoked changes in the photoreceptors has been successfully demonstrated using adaptive optics (AO) coherent flood illumination (CFI), AO scanning light ophthalmoscopy (SLO), AO optical coherence tomography (OCT), and full-field OCT with digital AO (dAO). While the optical principles and data processing of these systems differ greatly, and while these differences manifest in the resulting measurements, we believe that the underlying physiological processes involved in each of those techniques are likely the same. AO-CFI and AO-SLO systems are more widely used than OCT systems. However, those systems produce only two-dimensional images and so, less can be said about the anatomical and physiological origins of the observed signal. OCT signal, on the other hand, provides 3D imaging but at a cost of high volume of data, making it impractical to clinical purposes. In light of this, we employed a combined AO-OCT-SLO system-with point-for-point correspondence between the OCT and SLO images-to measure functional responses simultaneously with both and investigate SLO retinal functional biomarkers based on OCT response. The resulting SLO images reveal reflectance changes in the cones which are consistent with those previously reported using AO-CFI and AO-SLO. The resulting OCT volumes show phase changes in the cone outer segment (OS) consistent with those previously reported by us and others. We recapitulate a model of the cone OS previously proposed to explain AO-CFI reflectance changes, and show how this model can be used to predict the signal in AO-SLO. The limitations of the model is also discussed in this manuscript.

bioengineering↗
bioRxiv2020

Kilohertz retinal FF-SS-OCT and flood imaging with hardware-based adaptive optics

A retinal imaging system was designed for full-field (FF) swept-source (SS) optical coherence tomography (OCT) with cellular resolution. The system incorporates a real-time adaptive optics (AO) subsystem and a very high speed CMOS sensor, and is capable of acquiring volumetric images of the retina at rates up to 1 kHz. While digital aberration correction (DAC) is an attractive potential alternative to AO, it has not yet been shown to provide resolution of cones in the fovea, where early detection of functional deficits is most critical. Here we demonstrate that FF-SS-OCT with hardware AO permits resolution of foveal cones, with volume rates adequate to measure light-evoked changes in photoreceptors. With the reference arm blocked, the system can operate as kilohertz AO flood illumination fundus camera with adjustable temporal coherence and is expected to allow measurement of light-evoked changes caused by common path interference in photoreceptor outer segments (OS). In this work, we describe the systems optical design, characterize its performance, and demonstrate its ability to produce images of the human photoreceptor mosaic.

bioengineering↗
bioRxiv2018

Functional retinal imaging using adaptive optics swept-source OCT at 1.6MHz

Objective optical assessment of photoreceptor function may permit earlier diagnosis of retinal disease than current methods such as perimetry, electrophysiology, and clinical imaging. In this work, we describe an adaptive optics (AO) optical coherence tomography (OCT) system designed to measure functional responses of single cones to visible stimuli. The OCT subsystem consisted of a raster-scanning Fourier-domain mode-locked laser that acquires A-scans at 1.64MHz with a center wavelength of 1063nm, and an AO subsystem providing diffraction-limited imaging. Analysis of serial volumetric images revealed phase changes of cone photoreceptors consistent with outer segment elongation and proportional to stimulus intensity, as well as other morphological changes in the outer segment and retinal pigment epithelium.

bioengineering↗
bioRxiv2018

Aperture Phase Modulation with Adaptive Optics: A Novel Approach for Speckle Reduction and Structure Extraction in Optical Coherence Tomography

AbstractSpeckle is an inevitable consequence of the use of coherent light in optical coherence tomography (OCT), and often acts as noise that obscures micro-structures of biological tissue. We here present a novel method of suppressing speckle noise intrinsically compatible with adaptive optics (AO) in OCT system: by modulating the phase inside the imaging system pupil aperture with a segmented deformable mirror, thus producing minor perturbations in the point spread function (PSF) to create un-correlated speckle pattern between B-scans, and further averaging to wash out the speckle but maintain the structures. It is a well-controlled and universal method which can efficiently determine the optimal range of phase modulation that minimizing speckle noise while maximizing image resolution and signal strength for different systems and/or samples. As an active method, its effectiveness and efficiency were demonstrated by both ex-vivo non-biological and in-vivo biological applications.

bioengineering↗