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Optical Coherence Tomography(OCT) is a non-invasive technique capturing cross-sectional area of the retina in micro-meter resolutions. It has been widely used as a auxiliary imaging reference to detect eye-related pathology and predict longitudinal progression of the disease characteristics. Retina layer segmentation is one of the crucial feature extraction techniques, where the variations of retinal layer thicknesses and the retinal layer deformation due to the presence of the fluid are highly correlated with multiple epidemic eye diseases like Diabetic Retinopathy(DR) and Age-related Macular Degeneration (AMD). However, these images are acquired from different devices, which have different intensity distribution, or in other words, belong to different imaging domains. This paper proposes a segmentation-guided domain-adaptation method to adapt images from multiple devices into single image domain, where the state-of-art pre-trained segmentation model is available. It avoids the time consumption of manual labelling for the upcoming new dataset and the re-training of the existing network. The semantic consistency and global feature consistency of the network will minimize the hallucination effect that many researchers reported regarding Cycle-Consistent Generative Adversarial Networks(CycleGAN) architecture., 16 pages, 10 figures

To correctly implement the dual-spectrometer SD-OCT, two numerical calibration methods are demonstrated that effectively compensate for the spectral misalignment between spectrometers. Significant improvements in the image contrast are observed through retinal imaging after spectral calibration.

Optical coherence tomography angiography (OCT-A) may help in the diagnosis of diabetic retinopathy (DR). The OCT-A field-of-view and the volume acquisition rate are limited by the number of samples. We explore the effect of reduced lateral sampling on DR classification with Deep Learning. © 2021 The Authors.

A fast and practical computational cross-calibration of multiple spectrometers is described. A signal correlation matrix (CM) can be constructed from paired B-scans in a multiple-spectrometer optical coherence tomography (OCT), where the wavelength-corresponding pixels are indicated by high cross correlation. The CM can be used to either guide the physical alignment of spectrometers or to numerically match the spectra in the post-process. The performance is comparable to the previously reported optimization approach, as demonstrated by the mirror tests, qualitative comparison of OCT and optical coherence tomography angiography (OCTA) images, and quantitative comparison of image metrics.

Megahertz-rate optical coherence tomography angiography (OCTA) is highly anticipated as an ultrafast imaging tool in clinical settings. However, shot-noise-limited sensitivity is inevitably reduced in high-speed imaging systems. In this Letter, we present a coherent buffer averaging technique for use with a Fourier-domain mode-locked (FDML) laser to improve OCTA contrast at 1060 nm MHz-rate retinal imaging. Full characterization of spectral variations among the FDML buffers and a numerical correction method are also presented, with the results demonstrating a 10-fold increase in the phase alignment among buffers. Coherent buffer averaging provided better OCTA contrast than the conventional multi-frame averaging approach with a faster acquisition time.

Optical coherence tomography (OCT) and OCT angiography (OCT-A) may benefit the screening of diabetic retinopathy (DR). This study investigated the effect of laterally subsampling OCT/OCT-A en face scans by up to a factor of 8 when using deep neural networks for automated referable DR classification. There was no significant difference in the classification performance across all evaluation metrics when subsampling up to a factor of 3, and only minimal differences up to a factor of 8. Our findings suggest that OCT/OCT-A can reduce the number of samples (and hence the acquisition time) for a volume for a given field of view on the retina that is acquired for rDR classification.

Corneal imaging is important for the diagnostic and therapeutic evaluation of many eye diseases. Optical coherence tomography (OCT) is extensively used in ocular imaging due to its non-invasive and high-resolution volumetric imaging characteristics. Optical coherence microscopy (OCM) is a technical variation of OCT that can image the cornea with cellular resolution. Here, we demonstrate a blue-light OCM as a low-cost and easily reproducible system to visualize corneal cellular structures such as epithelial cells, endothelial cells, keratocytes, and collagen bundles within stromal lamellae. Our blue-light OCM system achieved an axial resolution of 12 µm in tissue over a 1.2 mm imaging depth, and a lateral resolution of 1.6 µm over a field of view of 750 µm × 750 µm.

Fourier-domain mode-locked (FDML) laser sources allow OCT imaging systems with sweep rates reaching 1.6 MHz. However, physical limitations of conventional scanning systems require consideration. Resonant scanners fix imaging frequency, whereas galvanometer scanner (GS) systems require either raster scanning with large flyback that reduce usable data, or bi-directional scans that require many repeated scans. To overcome these limitations, we employed an effective 1.6 MHz stepped bi-directional scanning protocol, allowing 2 BM-scan OCT-angiography (OCTA) imaging using high-speed FDML. We present the ideal acquisition protocol and processing algorithm for optimum OCTA quality, with results demonstrating high vasculature contrast at 1.6 MHz scan rates.

We present an ideal acquisition protocol and processing algorithm for optimum OCT angiography quality using Fourier-domain mode-locked (FDML) laser, with results demonstrating high vasculature contrast at 1.6 MHz scan rates in the human retina.

PRECIS The peripapillary choriocapillaris (CC) was observed to be significantly impaired in normal tension glaucoma (NTG) subjects compared with normal controls using optical coherence tomography angiography (OCTA). PURPOSE The aim was to quantitatively evaluate the peripapillary CC in NTG, primary open-angle glaucoma (POAG), and control eyes using OCTA. MATERIALS AND METHODS Ninety eyes (30 controls, 30 NTG, and 30 POAG) from 73 patients were imaged using the Zeiss Plex Elite 9000. Five repeat 3×3 mm OCTA scans were acquired both nasally and temporally to the optic disc and subsequently averaged. Four CC flow deficit (FD) measures were calculated using the fuzzy C-means approach: FD density (FDD), mean FD size (MFDS), FD number (FDN), and FD area (FDA). RESULTS Temporal NTG CC parameters were associated with visual field index and mean deviation (P

Vision-robbing disorders are frequently characterized by their effects on vasculature and the retinal pigment epithelium (RPE). Polarization diversity detection (PDD) selectively visualizes the RPE to evaluate its structure and integrity. We present multi-contrast OCTA on small animal models for simultaneous RPE and vasculature display.

Two Photon Excited Fluorescence (TPEF) allows for high-resolution non-invasive retinal imaging, and benefits from guidance of Optical Coherence Tomography (OCT) and Sensorless Adaptive Optics (SAO). We present our progress on the use of SAO with OCT and TPEF for imaging the retina in mice.

Retinal microvasculature and the retinal pigment epithelium (RPE) play vital roles in maintaining the health and metabolic activity of the eye. Visualization of these retina structures is essential for pre-clinical studies of vision-robbing diseases, such as age-related macular degeneration (AMD). We have developed a quantitative multi-contrast polarization diversity OCT and angiography (QMC-PD-OCTA) system for imaging and visualizing pigment in the RPE using degree of polarization uniformity (DOPU), along with flow in the retinal capillaries using OCT angiography (OCTA). An adaptive DOPU averaging kernel was developed to increase quantifiable values from visual data, and QMC en face images permit simultaneous visualization of vessel location, depth, melanin region thickness, and mean DOPU values, allowing rapid identification and differentiation of disease symptoms. The retina of five different mice strains were measured in vivo, with results demonstrating potential for pre-clinical studies of retinal disorders.

PURPOSE To report a case of acute zonal occult outer retinopathy in which adaptive optics (AO) facilitated visualization of abnormal photoreceptors previously thought to be in an area of normal retina on conventional optical coherence tomography (OCT). METHODS Case report. RESULTS A 51-year-old woman presents with 11-month history of photopsias and scotoma in the temporal visual field of her left eye. Ocular imaging including fluorescein angiography, fundus autofluorescence and OCT suggested the diagnosis of acute zonal occult outer retinopathy in the left eye. Adaptive optics optical coherence tomography (AO-OCT) revealed photoreceptor abnormalities not previously identified in conventional OCT, in areas apparently normal on multimodal imaging. On enface and cross-sectional AO-OCT, round and evenly spaced hyperreflectivity corresponding to normal cone mosaic (Pattern 1) was adjacent to unevenly and disrupted cone hyperreflectivity (Pattern 2) and areas with hyporeflectivity or no cone reflectivity (Pattern 3). Cross-sectional AO-OCT of Patterns 2 and 3 also revealed attenuation of ellipsoid zone with loss of interdigitation zone. CONCLUSION Adaptive optics OCT documented cone photoreceptors in finer details than conventional OCT and revealed early changes in a patient with acute zonal occult outer retinopathy, in an area of the retina thought to be normal on conventional multimodal imaging. These findings may provide important insight into pathogenesis and progression of the disease.

Optical coherence tomography (OCT) has become an essential tool in the evaluation of glaucoma, typically through analyzing retinal nerve fiber layer changes in circumpapillary scans. Three-dimensional OCT volumes enable a much more thorough analysis of the optic nerve head (ONH) region, which may be the site of initial glaucomatous optic nerve damage. Automated analysis of this region is of great interest, though large anatomical variations and the termination of layers make the requisite peripapillary layer and Bruch’s membrane opening (BMO) segmentation a challenging task. Several machine learning-based segmentation methods have been proposed for retinal layer segmentation, and a few for the ONH region, but they typically depend on either heavily averaged or pre-processed B-scans or a large amount of annotated data, which is a tedious task and resource-intensive. We evaluated a semi-supervised adversarial deep learning method for segmenting peripapillary retinal layers in OCT B-scans to take advantage of unlabeled data. We show that the use of a generative adversarial network and unlabeled data can improve the performance of segmentation. Additionally, we use a Faster R-CNN architecture to automatically segment the BMO. The proposed methods are then used for the 3D morphometric analysis of both control and glaucomatous ONH volumes to demonstrate the potential for clinical utility.

Contrast for imaging the retinal microvasculature and the retinal pigment epithelium (RPE) is essential for pre-clinical studies of vision-robbing diseases. By integrating polarization diversity detection (PDD) with OCT angiography (OCTA), we have developed a novel quantitative multi-contrast OCT for imaging pigment in the RPE as well as flow in the retinal capillaries. An adaptive filter was developed for degree of polarization uniformity (DOPU) processing to provide improved measurements of melanin region thickness in tilted retina. The retinas of three mouse strains were imaged in vivo, with results demonstrating potential for simultaneous mapping of vasculature and melanin distribution in the RPE.

The present paper introduces a numerical calibration method for the easy and practical implementation of multiple spectrometer-based spectral-domain optical coherence tomography (SD-OCT) systems. To address the limitations of the traditional hardware-based spectrometer alignment across more than one spectrometer, we applied a numerical spectral calibration algorithm where the pixels corresponding to the same wavelength in each unit are identified through spatial- and frequency-domain interferometric signatures of a mirror sample. The utility of dual spectrometer-based SD-OCT imaging is demonstrated through in vivo retinal imaging at two different operation modes with high-speed and dual balanced acquisitions, respectively, in which the spectral alignment is critical to achieve improved retinal image data without any artifacts caused by misalignment of the spectrometers.

The aim was to quantitatively compare retinal vascular detail as seen on optical coherence tomography angiography (OCTA) and matched histology in the human eye. 13 normal human donor eyes were used. The central retinal artery was cannulated after which human packed red blood cells were perfused through the retinal vasculature. Retinal vessels were imaged using a custom-built OCTA device during red blood cell perfusion. The eye was subsequently perfused with endothelial cell antibodies and the flat-mounted retina studied histologically using a confocal scanning laser microscope. Qualitative and quantitative comparisons of retinal vascular information as seen on OCTA and histology from the same region of interest were performed. Gradable OCTA images were acquired from 4 of 13 eyes with mean postmortem-to-OCTA imaging time of 4.5 ± 1.3 h 23 pairs of OCTA-histology matched images were evaluated. The retinal arteries and veins had similar pixel intensity on OCTA images. The diameter of retinal veins was significantly greater than its paired artery on OCTA (P 0.001). The density of vascular structures on OCTA (40.2% ± 10.1%) was significantly less than matched histology (52.1% ± 9.3%, P 0.001). Mean capillary diameter on OCTA (10.2 ± 2.4 μm) was significantly greater than histology (8.2 ± 2.4 μm; P 0.001). This is the first study to directly compare OCTA against histology from the same human eye. OCTA visualizes many of the vascular structures in the human retinal circulation but does not exactly match what is seen on histologic examination.

Two-Photon Excited Fluorescence (TPEF) is a common modality for volumetric imaging within a biological sample. The molecule-specific contrast of TPEF imaging of the retina enables novel in vivo studies of disease and retina physiology. Furthermore, retinal studies can be aided by imaging the relevant cells, which can be fluorescently labelled with fluorophores such as GFP. The multiphoton absorption suppresses the out-of-focus background signal and improves with the axial sectioning without a confocal aperture in the optical detection path. Imaging the retina with near infrared (NIR) light is ideal since the retina contain visual pigments that are sensitive to visible wavelengths and NIR light has less scattering within biological tissue than shorter wavelengths. However, high pulse energy is required to generate the TPEF, yet minimizing the incident exposure energy is required for non-invasive imaging. TPEF signal intensity increases quartically with the spot size, which leads to high sensitivity to aberrations that distribute the energy deposition of the focused light1. For retinal imaging, decreasing the spot size requires the imaging beam to fill a larger area of the eye, which corresponds to an increase in the aberration amplitudes and often results in low TPEF. Recent research has demonstrated improvements to the TPEF signal for retinal imaging using AO for aberrations correction2,3,4.

Background: The roles of the retinal microvasculature and the retinal pigment epithelium (RPE) in maintaining the health and metabolic activity of the retina lend great clinical value to their high-resolution visualization. Methods: By integrating polarization diversity detection (PDD) into multi-scale and -contrast sensorless adaptive optics optical coherence tomography (MSC-SAO-OCT), we have developed a novel multi-contrast SAO OCT system for imaging pigment in the RPE as well as flow in the retinal capillaries using OCT angiography (OCTA). Aberration correction was performed based on the image quality using transmissive deformable optical elements. Results: MSC-SAO-OCTA imaging was performed at multiple fields-of-view (FOVs) with adjustable numerical aperture (NA). Retinal flow and RPE structural images for in vivo healthy and pathological human posterior eyes were demonstrated to show clinical feasibility of the system. Conclusions: High-resolution imaging of retinal vasculature at both large and small FOVs, as well as characterization of RPE topology and deformation, enables more sophisticated and concise investigation of retinal pathologies for in vivo human imaging. MSC imaging may permit detection and analysis of even subtle deformations in the RPE layer using a single instrument.

Two-photon excited fluorescence (TPEF) imaging of the retina is a developing technique that provides non-invasive compound-specific measurements from the retina. In this report, we demonstrate high-resolution TPEF imaging of the mouse retina using sensorless adaptive optics (SAO) and optical coherence tomography (OCT). A single near-infrared light source was used for simultaneous multi-modal imaging with OCT and TPEF. The image-based SAO could be performed using the en face OCT or the TPEF for aberration correction. Our results demonstrate OCT and TPEF for angiography. Also, we demonstrate non-invasive cellular-resolution imaging of fluorescently labelled cells and the Retinal Pigment Epithelium (RPE) mosaic.

In this study we describe our novel Multi-Scale and multi-Mode Sensorless Adaptive Optics OCT system (MSM-SAO-OCT). Our system expands upon our previously reported work by introducing a zoomable collimator, phase calibration interferometer, and polarization diversity detection module. By using a zoomable collimator into the system setup, we allow an adjustable probing beam diameter without the need to change the optical setup, permitting imaging with both low and high lateral resolution (18 µm – 6 µm) at various Fields of View (FOV) within diffraction limited resolution. By employing SAO optimization algorithm, different morphological structures and microvasculature in a retina were clearly visualized after wavefront aberration correction with dual deformable optical elements – Variable Focus Lens (VFL) for defocus and a Multi-Actuator Adaptive Lens (MAL) for two astigmatisms. For retinal vasculature imaging, MSM-SAO-OCT system generates flow-specific contrast as measuring amplitude of complex variance from the multiple OCT B-scans from the same transverse location after stabilizing OCT signals in a phase using a static interference signal from phase calibration interferometer. In addition, the use of polarization diversity detection allows to create Degree Of Polarization Uniformity (DOPU) contrast using for visualization of the Retinal Pigment Epithelium (RPE) with its inherent tissue characteristic (polarization scrambling). In order to demonstrate functionality and clinical utility of the MSM-SAO-OCT system, in vivo human retinal imaging was performed on research subjects, and imaging results are presented and discussed.

High quality visualization of the retinal microvasculature can improve our understanding of the onset and development of retinal vascular diseases, especially Diabetic Retinopathy (DR), which is a major cause of visual morbidity and is increasing in prevalence. Optical Coherence Tomography Angiography (OCT-A) images are acquired over multiple seconds and are particularly susceptible to motion artifacts, which are more prevalent when imaging individuals with DR whose ability to fixate is limited due to deteriorating vision. The sequential acquisition and averaging of multiple OCT-A images can be performed for removing motion artifact and increasing the contrast of the vascular network. As motion artifacts often irreversibly corrupt OCT-A images of DR eyes, a robust registration pipeline is needed before feature preserving image averaging can be performed. In this report we present an improvement upon a novel method for the acquisition, processing, segmentation, registration, and averaging of sequentially acquired OCT-A images, to correct for motion artifacts in images of DR eyes. Image discontinuities caused by rapid micro-saccadic movements and image warping due to smoother reflex movements were corrected by strip-wise affine registration and subsequent local similarity-based non-rigid registration. Where our previous work was limited by the need for at least one image containing no motion artifact, thus reducing its clinical relevance, this novel template-less method stitches together partial images to form complete, motion-free images. These techniques significantly improve image quality, increasing the value for clinical diagnosis and increasing the range of patients for whom high quality OCT-A images can be acquired.

Optical coherence tomography (OCT) is a powerful tool in ophthalmology that provides in vivo morphology of the retinal layers and their light scattering properties. The directional (angular) reflectivity of the retinal layers was investigated with focus on the scattering from retinal pigment epithelium (RPE). The directional scattering of the RPE was studied in three mice strains with three distinct melanin concentrations: albino (BALB/c), agouti (129S1/SvlmJ), and strongly pigmented (C57BL/6J). The backscattering signal strength was measured with a directional OCT system in which the pupil entry position of the narrow OCT beam can be varied across the dilated pupil of the eyes of the mice. The directional reflectivity of other retinal melanin-free layers, including the internal and external limiting membranes, and Bruch’s membrane (albinos) were also measured and compared between the strains. The intensity of light backscattered from these layers was found highly sensitive to the angle of illumination, whereas the inner/outer segment (IS/OS) junctions showed a reduced sensitivity. The reflections from the RPE are largely insensitive in highly pigmented mice. The differences in directional scattering between strains shows that directionality decreases with an increase in melanin concentrations in RPE, suggesting increasing contribution of Mie scattering by melanosomes.

High resolution visualization of optical coherence tomography (OCT) and OCT angiography (OCT-A) data is required to fully take advantage of the imaging modality’s three-dimensional nature. However, artifacts induced by patient motion often degrade OCT-A data quality. This is especially true for patients with deteriorated focal vision, such as those with diabetic retinopathy (DR). We propose a novel methodology for software-based OCT-A motion correction achieved through serial acquisition, volumetric registration, and averaging. Motion artifacts are removed via a multi-step 3D registration process, and visibility is significantly enhanced through volumetric averaging. We demonstrate that this method permits clear 3D visualization of retinal pathologies and their surrounding features, 3D visualization of inner retinal capillary connections, as well as reliable visualization of the choriocapillaris layer.

Retinal microvasculature and the retinal pigment epithelium (RPE) play vital roles in maintaining the health and metabolic activity of the eye. Visualization of these retina structures is essential for pre-clinical studies of vision-robbing diseases, such as age-related macular degeneration (AMD). We have developed a quantitative multi-contrast polarization diversity OCT and angiography (QMC-PD-OCTA) system for imaging and visualizing pigment in the RPE using degree of polarization uniformity (DOPU), along with flow in the retinal capillaries using OCT angiography (OCTA). An adaptive DOPU averaging kernel was developed to increase quantifiable values from visual data, and QMC en face images permit simultaneous visualization of vessel location, depth, melanin region thickness, and mean DOPU values, allowing rapid identification and differentiation of disease symptoms. The retina of five different mice strains were measured in vivo, with results demonstrating potential for pre-clinical studies of retinal disorders.

Automated measurements of the human cone mosaic requires the identification of individual cone photoreceptors. The current gold standard, manual labeling, is a tedious process and can not be done in a clinically useful timeframe. As such, we present an automated algorithm for identifying cone photoreceptors in adaptive optics optical coherence tomography (AO-OCT) images. Our approach fine-tunes a pre-trained convolutional neural network originally trained on AO scanning laser ophthalmoscope (AO-SLO) images, to work on previously unseen data from a different imaging modality. On average, the automated method correctly identified 94% of manually labeled cones when compared to manual raters, from twenty different AO-OCT images acquired from five normal subjects. Voronoi analysis confirmed the general hexagonal-packing structure of the cone mosaic as well as the general cone density variability across portions of the retina. The consistency of our measurements demonstrates the high reliability and practical utility of having an automated solution to this problem.

We demonstrate the utility of a novel scanning method for optical coherence tomography angiography (OCTA). Although raster scanning is commonly used for OCTA imaging, a bidirectional approach would lessen the distortion caused by galvanometer-based scanners as sources continue to increase sweep rates. As shown, a unidirectional raster scan approach has a lower effective scanning time than bidirectional approaches; however, a strictly bidirectional approach causes contrast variation along the B-scan direction due to the non-uniform time interval between B-scans. Therefore, a stepped bidirectional approach is introduced and successfully applied to retinal imaging in normal controls and in a pathological subject with diabetic retinopathy.

Changes in visibility of the Henle fiber layer and photoreceptor bands of the human retina with illumination directionality have been reported in OCT clinical imaging. These are a direct consequence of the changes in back scattering due to fibrous tissue orientation and to waveguiding properties of the photoreceptors respectively. Here we report the preliminary results of a study on the effects of retinal images acquired with OCT of illumination directionality in the mouse retina. The quantitative assessment of the reflectivity of retinal layers of a BALB/c and WT pigmented mice was performed in-vivo using a swept-source optical coherence tomography system. The intensities of backscattered signals from different outer retinal layers were measured and compared.

Adaptive optics has been applied to retinal imaging in order to resolve the cellular features. We are investigating wavefront sensorless adaptive optics (WSAO) for Optical Coherence Tomography and Scanning Laser Ophthalmoscopy, using the image quality to guide the aberration correction. In this report we investigate characterizations of the open loop performance.

Adaptive optics optical coherence tomography (AO-OCT) systems capable of 3D high resolution imaging have been applied to posterior eye imaging in order to resolve the fine morphological features in the retina. Human cone photoreceptors have been extensively imaged and studied for the investigation of retinal degeneration resulting in photoreceptor cell death. However, there are still limitations of conventional approaches to AO in the clinic, such as relatively small field-of-view (FOV) and the complexities in system design and operation. In this research, a recently developed phase-resolved Sensorless AO Swept Source based OCT (SAO-SS-OCT) system which is compact in size and easy to operate is presented. Owing to its lens-based system design, wide-field imaging can be performed up to 6° on the retina. A phase stabilization unit was integrated with the OCT system. With the phase stabilized OCT signal, we constructed retinal micro-vasculature image using a phase variance technique. The retinal vasculature image was used to align and average multiple OCT volumes acquired sequentially. The contrast-enhanced photoreceptor projection image was then extracted from the averaged volume, and analyzed based on its morphological features through a novel photoreceptor structure evaluation algorithm. The retinas of twelve human research subjects (10 normal and 2 pathological cases) were measured in vivo. Quantitative parameters used for evaluating the cone photoreceptor mosaic such as cell density, cell area, and mosaic regularity are presented and discussed. The SAO-SS-OCT system and the proposed photoreceptor evaluation method has significant potential to reveal early stage retinal diseases associated with retinal degeneration.

Optical Coherence Tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. A limitation of the performance and utilization of the OCT systems has been the lateral resolution. Through the combination of wavefront sensorless adaptive optics with dual variable optical elements, we present a compact lens based OCT system that is capable of imaging the photoreceptor mosaic. We utilized a commercially available variable focal length lens to correct for a wide range of defocus commonly found in patient eyes, and a multi-actuator adaptive lens after linearization of the hysteresis in the piezoelectric actuators for aberration correction to obtain near diffraction limited imaging at the retina. A parallel processing computational platform permitted real-time image acquisition and display. The Data-based Online Nonlinear Extremum seeker (DONE) algorithm was used for real time optimization of the wavefront sensorless adaptive optics OCT, and the performance was compared with a coordinate search algorithm. Cross sectional images of the retinal layers and en face images of the cone photoreceptor mosaic acquired in vivo from research volunteers before and after WSAO optimization are presented. Applying the DONE algorithm in vivo for wavefront sensorless AO-OCT demonstrates that the DONE algorithm succeeds in drastically improving the signal while achieving a computational time of 1 ms per iteration, making it applicable for high speed real time applications.

High quality visualization of the retinal microvasculature can improve our understanding of the onset and development of retinal vascular diseases, which are a major cause of visual morbidity and are increasing in prevalence. Optical Coherence Tomography Angiography (OCT-A) images are acquired over multiple seconds and are particularly susceptible to motion artifacts, which are more prevalent when imaging patients with pathology whose ability to fixate is limited. The acquisition of multiple OCT-A images sequentially can be performed for the purpose of removing motion artifact and increasing the contrast of the vascular network through averaging. Due to the motion artifacts, a robust registration pipeline is needed before feature preserving image averaging can be performed. In this report, we present a novel method for a GPU-accelerated pipeline for acquisition, processing, segmentation, and registration of multiple, sequentially acquired OCT-A images to correct for the motion artifacts in individual images for the purpose of averaging. High performance computing, blending CPU and GPU, was introduced to accelerate processing in order to provide high quality visualization of the retinal microvasculature and to enable a more accurate quantitative analysis in a clinically useful time frame. Specifically, image discontinuities caused by rapid micro-saccadic movements and image warping due to smoother reflex movements were corrected by strip-wise affine registration estimated using Scale Invariant Feature Transform (SIFT) keypoints and subsequent local similarity-based non-rigid registration. These techniques improve the image quality, increasing the value for clinical diagnosis and increasing the range of patients for whom high quality OCT-A images can be acquired.

Adaptive optics has been successfully applied to cellular resolution imaging of the retina, enabling visualization of the characteristic mosaic patterns of the outer retina. Wavefront sensorless adaptive optics (WSAO) is a novel technique that facilitates high resolution ophthalmic imaging; it replaces the Hartmann-Shack Wavefront Sensor with an image-driven optimization algorithm and mitigates some the challenges encountered with sensor-based designs. However, WSAO generally requires longer time to perform aberrations correction than the conventional closed-loop adaptive optics. When used for in vivo retinal imaging applications, motion artifacts during the WSAO optimization process will affect the quality of the aberration correction. A faster converging optimization scheme needs to be developed to account for rapid temporal variation of the wavefront and continuously apply corrections. In this project, we investigate the Databased Online Nonlinear Extremum-seeker (DONE), a novel non-linear multivariate optimization algorithm in combination with in vivo human WSAO OCT imaging. We also report both hardware and software updates of our compact lens based WSAO 1060nm swept source OCT human retinal imaging system, including real time retinal layer segmentation and tracking (ILM and RPE), hysteresis correction for the multi-actuator adaptive lens, precise synchronization control for the 200kHz laser source, and a zoom lens unit for rapid switching of the field of view. Cross sectional images of the retinal layers and en face images of the cone photoreceptor mosaic acquired in vivo from research volunteers before and after WSAO optimization are presented.

Polarization-sensitive optical coherence tomography (PS-OCT) and second harmonic generation (SHG) microscopy are two imaging modalities with different resolutions, field-of-views (FOV), and contrasts, while they both have the capability of imaging collagen fibers in biological tissues. PS-OCT can measure the tissue birefringence which is induced by highly organized fibers while SHG can image the collagen fiber organization with high resolution. Articular cartilage, with abundant structural collagen fibers, is a suitable sample to study the correlation between PS-OCT and SHG microscopy. Qualitative conjecture has been made that the phase retardation measured by PS-OCT is affected by the relationship between the collagen fiber orientation and the illumination direction. Anatomical studies show that the multilayered architecture of articular cartilage can be divided into four zones from its natural surface to the subchondral bone: the superficial zone, the middle zone, the deep zone, and the calcified zone. The different zones have different collagen fiber orientations, which can be studied by the different slopes in the cumulative phase retardation in PS-OCT. An algorithm is developed based on the quantitative analysis of PS-OCT phase retardation images to analyze the microstructural features in swine articular cartilage tissues. This algorithm utilizes the depth-dependent slope changing of phase retardation A-lines to segment structural layers. The results show good consistency with the knowledge of cartilage morphology and correlation with the SHG images measured at selected depth locations. The correlation between PS-OCT and SHG microscopy shows that PS-OCT has the potential to analyze both the macro and micro characteristics of biological tissues with abundant collagen fibers and other materials that may cause birefringence.

Vision researchers often use small animals due to the availability of many transgenic strains that model human diseases or express biomarkers. Adaptive optics (AO) enables non-invasive single-cell imaging in a living animal but often results in high system complexity. Sensorless AO (SAO) can provide depth-resolved aberration correction with low system complexity. We present a multi-modal sensorless AO en face retina imaging system that includes optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy (SLO), and fluorescence detection. We present a compact lens-based imaging system design that allows for a 50-degree maximum field of view (FOV), which can be reduced to the region of interest to perform SAO with the modality of choice. The system performance was demonstrated on wild type mice (C57BL/6J), and transgenic mice with GFP labeled cells. SAO SLO was used for imaging microglia (Cx3cr1-GFP) over ~1 hour, where dynamics of the microglia branches were clearly observed. Our results also include volumetric cellular imaging of microglia throughout the inner retina.

Purpose. A newly developed high-penetration Doppler optical coherence angiography (HP-OCA) with a 1-μm probe beam for noninvasive investigation of vascular pathology of exudative macular diseases is introduced. A descriptive case series is presented to discuss the clinical utility of HP-OCA. Methods. Eleven eyes of 10 subjects with exudative macular disease, including two eyes with myopic choroidal neovascularization (mCNV); four eyes with AMD; and five eyes with polypoidal choroidal vasculopathy (PCV) were investigated. Two Doppler scanning modes (bidirectional and high-sensitive) of HP-OCA were used for the investigation. HP-OCA provides depth-resolved and en face angiograms and a structural OCT noninvasively. The HP-OCA images were compared with fluorescein angiography (FA); indocyanine green angiography (ICGA); and color fundus images. Results. The abnormal vasculature patterns observed with high-sensitive HP-OCA presented high similarity to the midphase of ICGA. Several abnormal Doppler signals were observed in the en face high-sensitive HP-OCA and were colocated with FA leakage. This colocation was found in one eye with mCNV, four eyes with AMD, and one eye with PCV. Doppler tomogram of the bidirectional mode showed abnormal Doppler signals in three of five PCV cases beneath the pigment epithelium detachment. With the high-sensitive mode, Doppler signals were found beneath the elevated retinal pigment epithelium in all untreated cases. Conclusions. HP-OCA revealed depth-resolved abnormal vasculatures in exudative macular diseases. The en face HP-OCA images showed high similarity with FA and ICGA images. These results suggest HP-OCA can be used for noninvasive and three-dimensional angiography in a clinical routine.

In this report, which is an international collaboration of OCT, adaptive optics, and control research, we demonstrate the Data-based Online Nonlinear Extremum-seeker (DONE) algorithm to guide the image based optimization for wavefront sensorless adaptive optics (WFSL-AO) OCT for in vivo human retinal imaging. The ocular aberrations were corrected using a multi-actuator adaptive lens after linearization of the hysteresis in the piezoelectric actuators. The DONE algorithm succeeded in drastically improving image quality and the OCT signal intensity, up to a factor seven, while achieving a computational time of 1 ms per iteration, making it applicable for many high speed applications. We demonstrate the correction of five aberrations using 70 iterations of the DONE algorithm performed over 2.8 s of continuous volumetric OCT acquisition. Data acquired from an imaging phantom and in vivo from human research volunteers are presented.

The visibility of retinal microvasculature in optical coherence tomography angiography (OCT-A) images is negatively affected by the small dimension of the capillaries, pulsatile blood flow, and motion artifacts. Serial acquisition and time-averaging of multiple OCT-A images can enhance the definition of the capillaries and result in repeatable and consistent visualization. We demonstrate an automated method for registration and averaging of serially acquired OCT-A images. Ten OCT-A volumes from six normal control subjects were acquired using our prototype 1060-nm swept source OCT system. The volumes were divided into microsaccade-free en face angiogram strips, which were affine registered using scale-invariant feature transform keypoints, followed by nonrigid registration by pixel-wise local neighborhood matching. The resulting averaged images were presented of all the retinal layers combined, as well as in the superficial and deep plexus layers separately. The contrast-to-noise ratio and signal-to-noise ratio of the angiograms with all retinal layers (reported as average ± standard deviation ) increased from 0.52 ± 0.22 and 19.58 ± 4.04 ?? dB for a single image to 0.77 ± 0.25 and 25.05 ± 4.73 ?? dB , respectively, for the serially acquired images after registration and averaging. The improved visualization of the capillaries can enable robust quantification and study of minute changes in retinal microvasculature.

Optical coherence tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. Although the axial resolution of OCT system, which is a function of the light source bandwidth, is sufficient to resolve retinal features at a micrometer scale, the lateral resolution is dependent on the delivery optics and is limited by ocular aberrations. Through the combination of wavefront sensorless adaptive optics and the use of dual deformable transmissive optical elements, we present a compact lens-based OCT system at an imaging wavelength of 1060 nm for high resolution retinal imaging. We utilized a commercially available variable focal length lens to correct for a wide range of defocus commonly found in patient’s eyes and a novel multi-actuator adaptive lens for aberration correction to achieve near diffraction limited imaging performance at the retina. With a parallel processing computational platform, high resolution cross-sectional and en face retinal image acquisition and display was performed in real time. In order to demonstrate the system functionality and clinical utility, we present images of the photoreceptor cone mosaic and other retinal layers acquired in vivo from research subjects.