Wide-field choriocapillaris mapping with 3.4 MHz adaptive optics-optical coherence tomography angiography.

The human choriocapillaris (CC) plays an essential role in supporting the overlying photoreceptor and retinal pigment epithelial cells and in maintaining overall retinal health. Disruption of CC structure and function is implicated in many retinal diseases, including age-related macular degeneration. Despite recent advances in ophthalmic imaging technologies, a full understanding of disease mechanisms remains elusive due to the inability to visualize CC microstructure.

3D-printed phantoms for measuring lateral resolution and contrast performance of ophthalmic adaptive optics imaging systems.

Adaptive optics (AO) imaging of the human retina is an emerging clinical technique that confers the highest possible spatial resolution of this tissue . To support consistent imaging performance across time and devices, we have designed and fabricated a robust and user-friendly phantom that can determine lateral resolution and contrast with 3D-printed microstructures approximating cone photoreceptors. We have carefully characterized multiple copies of this phantom via microscopic imaging and metrology, and we also demonstrated the phantom's utility with two different AO imaging modalities.

Label-free full-thickness imaging of porcine vagus nerve fascicular anatomy by polarization-sensitive optical coherence tomography.

Improving the efficacy of vagus nerve (VN) stimulation therapy requires a detailed understanding of the anatomical and functional organization of nerve fiber bundles and their fascicles. Variousimaging platforms have been optimized for this purpose. However, all existing tools with micrometer resolution require labeling to enhance the fascicle contrast, and this labeling is resource-intensive and time-consuming.

Identifying retinal pigment epithelium cells in adaptive optics-optical coherence tomography images with partial annotations and superhuman accuracy.

Retinal pigment epithelium (RPE) cells are essential for normal retinal function. Morphological defects in these cells are associated with a number of retinal neurodegenerative diseases. Owing to the cellular resolution and depth-sectioning capabilities, individual RPE cells can be visualized in vivo with adaptive optics-optical coherence tomography (AO-OCT).

Measurement of retinal blood flow precision in the human eye with multimodal adaptive optics imaging.

Impaired retinal blood flow (RBF) autoregulation plays a key role in the development and progression of several ocular diseases, including glaucoma and diabetic retinopathy. Clinically, reproducible RBF quantitation could significantly improve early diagnosis and disease management. Several non-invasive techniques have been developed but are limited for retinal microvasculature flow measurements due to their low signal-to-noise ratio and poor lateral resolution.

imaging of human retinal ganglion cells using optical coherence tomography without adaptive optics.

Retinal ganglion cells play an important role in human vision, and their degeneration results in glaucoma and other neurodegenerative diseases. Imaging these cells in the living human retina can greatly improve the diagnosis and treatment of glaucoma. However, owing to their translucent soma and tight packing arrangement within the ganglion cell layer (GCL), successful imaging has only been achieved with sophisticated research-grade adaptive optics (AO) systems.

Compact Linear Flow Phantom Model for Retinal Blood-Flow Evaluation.

Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique.

Quantification of Human Photoreceptor-Retinal Pigment Epithelium Macular Topography with Adaptive Optics-Optical Coherence Tomography.

Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques.

Revealing speckle obscured living human retinal cells with artificial intelligence assisted adaptive optics optical coherence tomography.

Background: In vivo imaging of the human retina using adaptive optics optical coherence tomography (AO-OCT) has transformed medical imaging by enabling visualization of 3D retinal structures at cellular-scale resolution, including the retinal pigment epithelial (RPE) cells, which are essential for maintaining visual function. However, because noise inherent to the imaging process (e.g.

Cellular-Level Visualization of Retinal Pathology in Multiple Sclerosis With Adaptive Optics.

Purpose: To apply adaptive optics-optical coherence tomography (AO-OCT) to quantify multiple sclerosis (MS)-induced changes in axonal bundles in the macular nerve fiber layer, ganglion cell somas, and macrophage-like cells at the vitreomacular interface.

Methods: We used AO-OCT imaging in a pilot study of MS participants (n = 10), including those without and with a history of optic neuritis (ON, n = 4), and healthy volunteers (HV, n = 9) to reveal pathologic changes to inner retinal cells and structures affected by MS.

Results: We found that nerve fiber layer axonal bundles had 38% lower volume in MS participants (1.

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.

Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in a small animal model.

Significance: Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions.

Deep learning-enabled volumetric cone photoreceptor segmentation in adaptive optics optical coherence tomography images of normal and diseased eyes.

Objective quantification of photoreceptor cell morphology, such as cell diameter and outer segment length, is crucial for early, accurate, and sensitive diagnosis and prognosis of retinal neurodegenerative diseases. Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional (3-D) visualization of photoreceptor cells in the living human eye. The current gold standard for extracting cell morphology from AO-OCT images involves the tedious process of 2-D manual marking.

Improved optical coherence tomography imaging of animal peripheral nerves using a prism nerve holder.

Significance: Modern optical volumetric imaging modalities, such as optical coherence tomography (OCT), provide enormous information about the structure, function, and physiology of living tissue. Although optical imaging achieves lateral resolution on the order of the wavelength of light used, and OCT achieves axial resolution on a similar micron scale, tissue optical properties, particularly high scattering and absorption, limit light penetration to only a few millimeters. In addition, imaging modalities are susceptible to significant motion artifacts due to cardiac and respiratory function.

Ultrahigh-speed multimodal adaptive optics system for microscopic structural and functional imaging of the human retina.

We describe the design and performance of a multimodal and multifunctional adaptive optics (AO) system that combines scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) for simultaneous retinal imaging at 13.4 Hz. The high-speed AO-OCT channel uses a 3.

Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics.

Choroideremia is an X-linked, blinding retinal degeneration with progressive loss of photoreceptors, retinal pigment epithelial (RPE) cells, and choriocapillaris. To study the extent to which these layers are disrupted in affected males and female carriers, we performed multimodal adaptive optics imaging to better visualize the in vivo pathogenesis of choroideremia in the living human eye. We demonstrate the presence of subclinical, widespread enlarged RPE cells present in all subjects imaged.

Weakly supervised individual ganglion cell segmentation from adaptive optics OCT images for glaucomatous damage assessment.

Cell-level quantitative features of retinal ganglion cells (GCs) are potentially important biomarkers for improved diagnosis and treatment monitoring of neurodegenerative diseases such as glaucoma, Parkinson's disease, and Alzheimer's disease. Yet, due to limited resolution, individual GCs cannot be visualized by commonly used ophthalmic imaging systems, including optical coherence tomography (OCT), and assessment is limited to gross layer thickness analysis. Adaptive optics OCT (AO-OCT) enables imaging of individual retinal GCs.

Cell - Vessel Mismatch in Glaucoma: Correlation of Ganglion Cell Layer Soma and Capillary Densities.

Purpose: The purpose of this study was to characterize the relationship between retinal ganglion cell layer (GCL) soma density and capillary density in glaucomatous eyes.

Methods: Six glaucoma subjects with known hemifield defects and 6 age-matched controls were imaged with adaptive optics - optical coherence tomography (AO-OCT) at 6 locations: 3 degrees, 6 degrees, and 12 degrees temporal to the fovea above and below the midline. GCL soma density and capillary density were measured at each location.

A Novel Fiber-Optic Confocal Laser Caliper Approach for Non-Contact Optical Characterization of Silk Fibroin Thin Films Created by Riboflavin Photo-Crosslinking.

Silk fibroin with its attractive combination of advanced properties is promising for regenerative treatments of corneal disorders. Novel photonics approach is used to characterize the thickness and refractive index of silk fibroin thin films photo-crosslinked with a natural photosensitizer Riboflavin.

Dissecting the microvascular contributions to diffuse correlation spectroscopy measurements of cerebral hemodynamics using optical coherence tomography angiography.

Diffuse correlation spectroscopy (DCS) is an emerging noninvasive, diffuse optical modality that purportedly enables direct measurements of microvasculature blood flow. Functional optical coherence tomography angiography (OCT-A) can resolve blood flow in vessels as fine as capillaries and thus has the capability to validate key attributes of the DCS signal. To characterize activity in cortical vasculature within the spatial volume that is probed by DCS and to identify populations of blood vessels that are most representative of the DCS signals.

Integrating adaptive optics-SLO and OCT for multimodal visualization of the human retinal pigment epithelial mosaic.

In vivo imaging of human retinal pigment epithelial (RPE) cells has been demonstrated through multiple adaptive optics (AO)-based modalities. However, whether consistent and complete information regarding the cellular structure of the RPE mosaic is obtained across these modalities remains uncertain due to limited comparisons performed in the same eye. Here, an imaging platform combining multimodal AO-scanning light ophthalmoscopy (AO-SLO) with AO-optical coherence tomography (AO-OCT) is developed to make a side-by-side comparison of the same RPE cells imaged across four modalities: AO-darkfield, AO-enhanced indocyanine green (AO-ICG), AO-infrared autofluorescence (AO-IRAF), and AO-OCT.

Persistent Dark Cones in Oligocone Trichromacy Revealed by Multimodal Adaptive Optics Ophthalmoscopy.

Dark cone photoreceptors, defined as those with diminished or absent reflectivity when observed with adaptive optics (AO) ophthalmoscopy, are increasingly reported in retinal disorders. However, their structural and functional impact remain unclear. Here, we report a 3-year longitudinal study on a patient with oligocone trichromacy (OT) who presented with persistent, widespread dark cones within and near the macula.

Quantification of Retinal Ganglion Cell Morphology in Human Glaucomatous Eyes.

Purpose: To characterize retinal ganglion cell morphological changes in patients with primary open-angle glaucoma associated with hemifield defect (HD) using adaptive optics-optical coherence tomography (AO-OCT).

Methods: Six patients with early to moderate primary open-angle glaucoma with an average age of 58 years associated with HD and six age-matched healthy controls with an average age of 61 years were included. All participants underwent in vivo retinal ganglion cell (RGC) imaging at six primary locations across the macula with AO-OCT.

Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum.

In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities.

Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics.

Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models with exogenous or transgenic labeling. While these studies provided a wealth of information on the delicate balance between neuroprotection and neurotoxicity within which these cells operate, extrapolation to human immune function has remained an open question.