Longitudinal Changes in Optoretinography Provide an Early and Sensitive Biomarker of Outer Retinal Disease.

Objective: To examine whether optoretinography (ORG) can provide greater sensitivity for assessing the time-course of disease progression in Retinitis Pigmentosa (RP) compared to standard clinical imaging in a longitudinal study.

Design: Cohort study.

Participants: Five non-syndromic RP patients and 8 control subjects participated in the study.

Novel color via stimulation of individual photoreceptors at population scale.

We introduce a principle, Oz, for displaying color imagery: directly controlling the human eye's photoreceptor activity via cell-by-cell light delivery. Theoretically, novel colors are possible through bypassing the constraints set by the cone spectral sensitivities and activating M cone cells exclusively. In practice, we confirm a partial expansion of colorspace toward that theoretical ideal.

Genetic Reasons for Phenotypic Diversity in Neuronal Ceroid Lipofuscinoses and High-Resolution Imaging as a Marker of Retinal Disease.

Purpose: To describe the clinical characteristics, natural history, genetic landscape, and phenotypic spectrum of neuronal ceroid lipofuscinosis (NCL)-associated retinal disease.

Design: Multicenter retrospective cohort study complemented by a cross-sectional examination.

Subjects: Twelve pediatric subjects with biallelic variants in 5 NCL-causing genes (CLN3 lysosomal/endosomal transmembrane protein [], CLN6 transmembrane ER protein [], Major facilitator superfamily domain containing 8 [], Palmitoyl-protein thioesterase 1 ([], and tripeptidyl peptidase 1 []).

Optoretinography reveals rapid rod photoreceptor movement upon photoisomerization.

Rod photoreceptors are essential for vision under dim light conditions. The onset of rod-mediated vision is marked by the isomerization of rhodopsin. Here we demonstrate that human and rodent rods undergo a minute and rapid contraction of their outer segments immediately upon photoisomerization.

Longitudinal changes in optoretinography provide an early and sensitive biomarker of outer retinal disease.

Objective: To examine whether optoretinography (ORG) can provide greater sensitivity for assessing the time-course of disease progression in Retinitis Pigmentosa compared to standard clinical imaging in a longitudinal study.

Design: Cohort, longitudinal study.

Participants: Five non-syndromic RP patients and eight control subjects participated in the study.

Local variations in L/M ratio influence the detection and color naming of small spots.

The distribution of long-wavelength sensitive (L) and middle-wavelength sensitive (M) cones in the retina determines how different frequencies of incident light are sampled across space, and has been hypothesized to influence spatial and color vision. We asked whether the detection and color naming of small, short-duration increment stimuli depend on the relative numbers of L and M cones illuminated. Stimuli were corrected for optical aberrations by an adaptive optics system, and targeted to locations in the parafovea where cone spectral types were known.

Phase-restoring subpixel image registration: enhancing motion detection performance in Fourier-domain optical coherence tomography.

Phase-sensitive Fourier-domain optical coherence tomography (FD-OCT) enables , label-free imaging of cellular movements with detection sensitivity down to the nanometer scale, and it is widely employed in emerging functional imaging modalities, such as optoretinography (ORG), Doppler OCT, and optical coherence elastography. However, when imaging tissue dynamics , inter-frame displacement introduces decorrelation noise that compromises motion detection performance, particularly in terms of sensitivity and accuracy. Here, we demonstrate that the displacement-related decorrelation noise in FD-OCT can be accurately corrected by restoring the initial sampling points using our proposed Phase-Restoring Subpixel Image Registration (PRESIR) method.

Effects of long-term neural adaptation to habitual sspherical aberration on through-focus visual acuity in adults.

We investigated how long-term visual experience with habitual spherical aberration (SA) influences subjective depth of focus (DoF). Nine healthy cycloplegic eyes with habitual SAs of different signs and magnitudes were enrolled. An adaptive optics (AO) visual simulator was used to measure through-focus high-contrast visual acuity after correcting all monochromatic aberrations and imposing + 0.

Multimodal High-Resolution Imaging in Retinitis Pigmentosa: A Comparison Between Optoretinography, Cone Density, and Visual Sensitivity.

Purpose: Retinitis pigmentosa (RP), the most common inherited retinal disease, is characterized by progressive photoreceptor degeneration. It remains unknown to what extent surviving photoreceptors transduce light and support vision in RP. To address this, we correlated structure and functional measures using adaptive optics scanning laser ophthalmoscopy (AOSLO), adaptive optics microperimetry, and adaptive optics optical coherence tomography (AO-OCT)-based optoretinograms (ORGs).

Unique yellow shifts for small and brief stimuli in the central retina.

The spectral locus of unique yellow was determined for flashes of different sizes (<11 arcmin) and durations (<500 ms) presented in and near the fovea. An adaptive optics scanning laser ophthalmoscope was used to minimize the effects of higher-order aberrations during simultaneous stimulus delivery and retinal imaging. In certain subjects, parafoveal cones were classified as L, M, or S, which permitted the comparison of unique yellow measurements with variations in local L/M ratios within and between observers.

Effects of Neural Adaptation to Habitual Spherical Aberration on Depth of Focus.

We investigated how long-term visual experience with habitual spherical aberration (SA) influences subjective depth of focus (DoF). Nine healthy cycloplegic eyes with habitual SAs of different signs and magnitudes were enrolled. An adaptive optics (AO) visual simulator was used to measure through-focus high-contrast visual acuity after correcting all monochromatic aberrations and imposing +0.

Introduction to the Feature Issue on Adaptive Optics for Biomedical Applications.

The guest editors introduce a feature issue commemorating the 25th anniversary of adaptive optics in biomedical research.

Coarse-scale optoretinography (CoORG) with extended field-of-view for normative characterization.

Optoretinography (ORG) has the potential to be an effective biomarker for light-evoked retinal activity owing to its sensitive, objective, and precise localization of retinal function and dysfunction. Many ORG implementations have used adaptive optics (AO) to localize activity on a cellular scale. However, the use of AO restricts field-of-view (FOV) to the isoplanatic angle, necessitating the montaging of multiple regions-of-interest to cover an extended field.

Characterizing cone spectral classification by optoretinography.

Light propagation in photoreceptor outer segments is affected by photopigment absorption and the phototransduction amplification cascade. Photopigment absorption has been studied using retinal densitometry, while recently, optoretinography (ORG) has provided an avenue to probe changes in outer segment optical path length due to phototransduction. With adaptive optics (AO), both densitometry and ORG have been used for cone spectral classification based on the differential bleaching signatures of the three cone types.

Suprathreshold Contrast Perception Is Altered by Long-term Adaptation to Habitual Optical Blur.

Purpose: To investigate whether visual experience with habitual blur alters the neural processing of suprathreshold contrast in emmetropic and highly aberrated eyes.

Methods: A large stroke adaptive optics system was used to correct ocular aberrations. Contrast constancy was assessed psychophysically in emmetropic and keratoconic eyes using a contrast matching paradigm.

Improvement of neural contrast sensitivity after long-term adaptation in pseudophakic eyes.

An adaptive optics (AO) system was used to investigate the effect of long-term neural adaptation to the habitual optical profile on neural contrast sensitivity in pseudophakic eyes after the correction of all aberrations, defocus, and astigmatism. Pseudophakic eyes were assessed at 4 and 8 months postoperatively for changes in visual performance. Visual benefit was observed in all eyes at all spatial frequencies after AO correction.

Human cone elongation responses can be explained by photoactivated cone opsin and membrane swelling and osmotic response to phosphate produced by RGS9-catalyzed GTPase.

Human cone outer segment (COS) length changes in response to stimuli bleaching up to 99% of L- and M-cone opsins were measured with high resolution, phase-resolved optical coherence tomography (OCT). Responses comprised a fast phase (∼5 ms), during which COSs shrink, and two slower phases (1.5 s), during which COSs elongate.

Interferometric imaging of thermal expansion for temperature control in retinal laser therapy.

Precise control of the temperature rise is a prerequisite for proper photothermal therapy. In retinal laser therapy, the heat deposition is primarily governed by the melanin concentration, which can significantly vary across the retina and from patient to patient. In this work, we present a method for determining the optical and thermal properties of layered materials, directly applicable to the retina, using low-energy laser heating and phase-resolved optical coherence tomography (pOCT).

Cortical distance unifies the extent of parafoveal contour interactions.

It is well known that crowding, the disruptive influence of flanking items on identification of targets, is the primary limiting factor to object identification in the periphery, while limits in the fovea are more determined by the ability to resolve individual items. Whether this is a dichotomous or merely a quantitative difference, and the transition between these two regimes, has remained unexplained. Here, using an adaptive optics system for optimal control of optical and stimulus factors, we measured threshold acuity for identification of Tumbling Es flanked by bars at a variety of flanker spacings and eight eccentricities in the parafovea.

Reflective mirror-based line-scan adaptive optics OCT for imaging retinal structure and function.

Line-scan OCT incorporated with adaptive optics (AO) offers high resolution, speed, and sensitivity for imaging retinal structure and function . Here, we introduce its implementation with reflective mirror-based afocal telescopes, optimized for imaging light-induced retinal activity (optoretinography) and weak retinal reflections at the cellular scale. A non-planar optical design was followed based on previous recommendations with key differences specific to a line-scan geometry.

Correcting intra-volume distortion for AO-OCT using 3D correlation based registration.

Adaptive optics (AO) based ophthalmic imagers, such as scanning laser ophthalmoscopes (SLO) and optical coherence tomography (OCT), are used to evaluate the structure and function of the retina with high contrast and resolution. Fixational eye movements during a raster-scanned image acquisition lead to intra-frame and intra-volume distortion, resulting in an inaccurate reproduction of the underlying retinal structure. For three-dimensional (3D) AO-OCT, segmentation-based and 3D correlation based registration methods have been applied to correct eye motion and achieve a high signal-to-noise ratio registered volume.

High-speed adaptive optics line-scan OCT for cellular-resolution optoretinography.

Optoretinography-the non-invasive, optical imaging of light-induced functional activity in the retina-stands to provide a critical biomarker for testing the safety and efficacy of new therapies as well as their rapid translation to the clinic. Optical phase change in response to light, as readily accessible in phase-resolved OCT, offers a path towards all-optical imaging of retinal function. However, typical human eye motion adversely affects phase stability.

The optoretinogram reveals the primary steps of phototransduction in the living human eye.

Photoreceptors initiate vision by converting photons to electrical activity. The onset of the phototransduction cascade is marked by the isomerization of photopigments upon light capture. We revealed that the onset of phototransduction is accompanied by a rapid (<5 ms), nanometer-scale electromechanical deformation in individual human cone photoreceptors.

Effect of cone spectral topography on chromatic detection sensitivity.

The spatial and spectral topography of the cone mosaic set the limits for detection and discrimination of chromatic sinewave gratings. Here, we sought to compare the spatial characteristics of mechanisms mediating hue perception against those mediating chromatic detection in individuals with known spectral topography and with optical aberrations removed with adaptive optics. Chromatic detection sensitivity in general exceeded previous measurements and decreased monotonically for increasingly skewed cone spectral compositions.