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Objective To evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). Design Interventional case series. Participants Patients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. Methods Eleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. Results AO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. Conclusion IRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Muller cell reactive gliosis were identified with AO-OCT.

Glaucoma was associated with axial bowing and rotation of Bruchs membrane opening (BMO) and anterior laminar insertion (ALI), skewed neural canal, and deeper anterior lamina cribrosa surface (ALCS). Longer axial length was associated with wider, longer, and more skewed neural canal and flatter ALCS.Investigate the effects of myopia and glaucoma in the prelaminar neural canal and anterior lamina cribrosa using 1060-nm swept-source optical coherence tomography.19 control (38 eyes) and 38 glaucomatous subjects (63 eyes).Participants were imaged with swept-source optical coherence tomography, and the images were analyzed for the BMO and ALI dimensions, prelaminar neural canal dimensions, and ALCS depth.Glaucomatous eyes had more bowed and nasally rotated BMO and ALI, more horizontally skewed prelaminar neural canal, and deeper ALCS than the control eyes. Increased axial length was associated with a wider, longer, and more horizontally skewed neural canal and a decrease in the ALCS depth and curvature.Our findings suggest that glaucomatous posterior bowing or cupping of lamina cribrosa can be significantly confounded by the myopic expansion of the neural canal. This may be related to higher glaucoma risk associated with myopia from decreased compliance and increased susceptibility to IOP-related damage of LC being pulled taut.

Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) are imaging technologies invented in the 1980s that have revolutionized the field of in vivo retinal diagnostics and are now commonly used in ophthalmology clinics as well as in vision science research. Adaptive optics (AO) technology enables high-fidelity correction of ocular aberrations, resulting in improved resolution and sensitivity for both SLO and OCT systems. The potential of gathering multi-modal cellular-resolution information in a single instrument is of great interest to the ophthalmic imaging community. Although similar instruments have been developed for imaging the human retina, developing such a system for mice will benefit basic science research and should help with further dissemination of AO technology. Here, we present our work integrating OCT into an existing mouse retinal AO-SLO system, resulting in a multi-modal AO-enhanced imaging system of the living mouse eye. The new system allows either independent or simultaneous data acquisition of AO-SLO and AO-OCT, depending on the requirements of specific scientific experiments. The system allows a data acquisition speed of 200 kHz A-scans/pixel rate for OCT and SLO, respectively. It offers ∼6 µm axial resolution for AO-OCT and a ∼1 µm lateral resolution for AO-SLO-OCT imaging.

PURPOSE To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes. METHODS We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers. RESULTS Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05). CONCLUSION Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.

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

The neurotrophin growth factors bind and activate two types of cell surface receptors: the tropomyosin receptor kinase (Trk) family and p75. TrkA, TrkB, and TrkC are bound preferentially by nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 (NT3), respectively, to activate neuroprotective signals. The p75 receptors are activated by all neurotrophins, and paradoxically in neurodegenerative disease p75 is upregulated and mediates neurotoxic signals. To test neuroprotection strategies, we engineered NT3 to broadly activate Trk receptors (mutant D) or to reduce p75 binding (mutant RK). We also combined these features in a molecule that activates TrkA, TrkB, and TrkC but has reduced p75 binding (mutant DRK). In neurodegenerative disease mouse models in vivo, the DRK protein is a superior therapeutic agent compared with mutant D, mutant RK, and wild-type neurotrophins and protects a broader range of stressed neurons. This work rationalizes a therapeutic strategy based on the biology of each type of receptor, avoiding activation of p75 toxicity while broadly activating neuroprotection in stressed neuronal populations expressing different Trk receptors. SIGNIFICANCE STATEMENT The neurotrophins nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 each can activate a tropomyosin receptor kinase (Trk) A, TrkB, or TrkC receptor, respectively, and all can activate a p75 receptor. Trks and p75 mediate opposite signals. We report the engineering of a protein that activates all Trks, combined with low p75 binding, as an effective therapeutic agent in vivo.

Purpose To quantitatively and qualitatively evaluate the microvascular and structural abnormalities associated with inner retinal dimpling after internal limiting membrane peeling for full-thickness macular holes using sequential en face optical coherence tomography (OCT) and OCT angiography. Methods Thirteen eyes of 13 patients with idiopathic full-thickness macular holes were enrolled in the study. Patients were treated with pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. Subjects were evaluated preoperatively and at postoperative Months 1, 3, and 6. At each visit, patients underwent a comprehensive ophthalmologic examination, en face OCT and OCT angiography. The morphology and number and proportionate area of inner retinal dimples were analyzed. Vessel density of the superficial vascular complex at all visits was also measured. Results Inner retinal dimples were identified 1 month after surgery in all cases. The number and proportionate area of inner retinal dimples significantly increased over the follow-up period (P = 0.05). Preoperative vessel density of the superficial vascular complex was 17.9 ± 1.9 and did not change significantly over the follow-up period (P = 0.15). Conclusion Inner retinal dimples are identified with en face OCT as early as the first month after internal limiting membrane peeling for idiopathic full-thickness macular holes and progressively increase in number and proportionate area in the subsequent 3 to 6 months after surgery. This may be the result of progressive deturgescence of the nerve fiber layer in the postoperative period.

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.

We are investigating Two Photon Excited Fluorescence (TPEF) as a non-invasive imaging technique for retinal imaging due to its axial sectioning ability. We combined TPEF with Optical Coherence Tomography (OCT) and Sensorless Adaptive Optics (SAO) to obtain co-registered multi-volume averaged images. © 2021 The Authors.

PurposeInvestigate the effects of myopia and glaucoma in the prelaminar neural canal and anterior lamina cribrosa using 1060-nm swept-source optical coherence tomographyDesignRetrospective, cross-sectional studyMethodsSettingClinical practicePatient or study population19 controls (38 eyes); 38 glaucomatous subjects (63 eyes). Inclusion criteria for glaucomatous subjects: i) optic disc neural rim loss; ii) peripapillary nerve fibre layer (NFL) loss on spectral domain optical coherence tomography (SD-OCT); iii) glaucomatous visual field defect with an abnormal pattern standard deviation (PIntervention or observation proceduresSwept-source optical coherence tomographyMain Outcome Measure(s)Bruchs membrane opening (BMO) and anterior laminar insertion (ALI) dimension, prelaminar neural canal dimension, anterior lamina cribrosa surface (ALCS) depthResultsGlaucomatous eyes had more bowed and nasally rotated BMO and ALI, more horizontally skewed prelaminar neural canal, and deeper ALCS than the control eyes. Increased axial length was associated with a wider, longer, and more horizontally skewed neural canal, and decrease in the ALCS depth and curvature.ConclusionOur findings suggest that glaucomatous posterior bowing or cupping of lamina cribrosa can be significantly confounded by the myopic expansion of the neural canal. This may be related to higher glaucoma risk associated with myopia from decreased compliance and increased susceptibility to IOP-related damage of LC being pulled taut.

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.

Moyamoya (MM) disease is a chronic cerebrovascular disease that can lead to progressive stenosis of the terminal portions of the internal carotid arteries and their proximal branches. We sought to investigate and quantify retinal vascular changes in patients with MM vasculopathy (MMV) using optical coherence tomography angiography (OCTA) compared to healthy controls. Our findings reveal retinal microvascular changes in patients with MMV and highlights the potential of OCTA imaging for the detection of subclinical retinal pathology.

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.

PReCIS:: The Bruch membrane opening (BMO) was posteriorly bowed and the degree of nonplanarity increased in stable and progressive glaucoma subjects. BMO became more posterior relative to the Bruch membrane (BM) in control and both stable and progressive glaucoma subjects. Purpose To investigate longitudinal changes in morphologic characteristics of the BMO in control and glaucomatous subjects. Materials and methods A total of 53 myopic eyes (17 control, 6 suspect, 20 stable glaucoma, and 10 progressing glaucoma) were followed for an average of 4.2±1.4 years and imaged at the baseline and 2 follow-up appointments using a 1060 nm swept-source optical coherence tomography system. BM and BMO were segmented, and 4 morphometric BMO parameters (area, ellipse ratio, nonplanarity, and depth) were measured. Results There were no significant changes in BMO area or ellipse ratio for all groups. BMO nonplanarity was shown to increase in the glaucoma groups. BMO depth relative to BM increased in all groups except the suspects (control: 8.1 µm/y, P=0.0001; stable glaucoma: 3.5 µm/y, P=0.0001; progressing glaucoma: 14.0 µm/y, P=0.0026). In linear mixed-model analysis, axial length was positively associated with BMO area in all groups except for progressing glaucoma, and with BMO nonplanarity in stable glaucoma. It was not a significant factor to the slopes of the BMO parameters in the ANCOVA analysis of slopes. Conclusions Longitudinally, BMO increased in nonplanarity in the glaucoma eyes, and its axial position relative to BM became more posterior in both control and glaucoma eyes.

Retinal swelling due to the accumulation of fluid is associated with the most vision-threatening retinal diseases. Optical coherence tomography (OCT) is the current standard of care in assessing the presence and quantity of retinal fluid and image-guided treatment management. Deep learning methods have made their impact across medical imaging, and many retinal OCT analysis methods have been proposed. However, it is currently not clear how successful they are in interpreting the retinal fluid on OCT, which is due to the lack of standardized benchmarks. To address this, we organized a challenge RETOUCH in conjunction with MICCAI 2017, with eight teams participating. The challenge consisted of two tasks: fluid detection and fluid segmentation. It featured for the first time: all three retinal fluid types, with annotated images provided by two clinical centers, which were acquired with the three most common OCT device vendors from patients with two different retinal diseases. The analysis revealed that in the detection task, the performance on the automated fluid detection was within the inter-grader variability. However, in the segmentation task, fusing the automated methods produced segmentations that were superior to all individual methods, indicating the need for further improvements in the segmentation performance.

The central role of the cardiovascular system is to maintain adequate capillary perfusion. The spatially and temporally heterogeneous nature of capillary perfusion has been reported in some organs. However, such heterogeneous perfusion properties have not been sufficiently explored in the retina. Arguably, spatial and temporal heterogeneity of capillary perfusion could be more predominant in the retina than that in other organs. This is because the retina is one of the highest metabolic demand neural tissues yet it has a limited blood supply due to optical requirements. In addition, the unique heterogeneous distribution of retinal neural cells within different layers and regions, and the significant heterogeneity of intraretinal oxygen distribution and consumption add to the complexity. Retinal blood flow distribution must match consumption of nutrients such as oxygen and glucose within the retina at the cellular level in order to effectively maintain cell survival and function. Sophisticated local blood flow control in the microcirculation is likely required to control the retinal capillary perfusion to supply local retinal tissue and accommodate temporal and spatial variations in metabolic supply and demand. The authors would like to update the knowledge of the retinal microvessel and capillary network and retinal oxidative metabolism from their own studies and the work of others. The coupling between blood supply and energy demands in the retina is particularly interesting. We will mostly describe information regarding the retinal microvessel network and retinal oxidative metabolism relevant to the spatial and temporal heterogeneity of capillary perfusion. We believe that there is significant and necessary spatial and temporal heterogeneity and active regulation of retinal blood flow in the retina, particularly in the macular region. Recently, retinal optical coherence tomography angiography (OCTA) has been widely used in ophthalmology, both experimentally and clinically. OCTA could be a valuable tool for examining retinal microvessel and capillary network structurally and has potential for determining retinal capillary perfusion and its control. We have demonstrated spatial and temporal heterogeneity of capillary perfusion in the retina both experimentally and clinically. We have also found close relationships between the smallest arterioles and capillaries within paired arterioles and venules and determined the distribution of smooth muscle cell contraction proteins in these vessels. Spatial and temporal heterogeneity of retinal capillary perfusion could be a useful parameter to determine retinal microvessel regulatory capability as an early assay for retinal vascular diseases. This topic will be of great interest, not only for the eye but also other organs. The retina could be the best model for such investigations. Unlike cerebral vessels, retinal vessels can be seen even at the capillary level. The purpose of this manuscript is to share our current understanding with the readers and encourage more researchers and clinicians to investigate this field. We begin by reviewing the general principles of microcirculation properties and the spatial and temporal heterogeneity of the capillary perfusion in other organs, before considering the special requirements of the retina. The local heterogeneity of oxygen supply and demand in the retina and the need to have a limited and well-regulated retinal circulation to preserve the transparency of the retina is discussed. We then consider how such a delicate balance of metabolic supply and consumption is achieved. Finally we discuss how new imaging methodologies such as optical coherence tomography angiography may be able to detect the presence of spatial and temporal heterogeneity of capillary perfusion in a clinical setting. We also provide some new information of the control role of very small arterioles in the modulation of retinal capillary perfusion which could be an interesting topic for further investigation.

Image degradation due to wavefront aberrations can be corrected with adaptive optics (AO). In a typical AO configuration, the aberrations are measured directly using a Shack-Hartmann wavefront sensor and corrected with a deformable mirror in order to attain diffraction limited performance for the main imaging system. Wavefront sensor-less adaptive optics (SAO) uses the image information directly to determine the aberrations and provide guidance for shaping the deformable mirror, often iteratively. In this report, we present a Deep Reinforcement Learning (DRL) approach for SAO correction using a custom-built fluorescence confocal scanning laser microscope. The experimental results demonstrate the improved performance of the DRL approach relative to a Zernike Mode Hill Climbing algorithm for SAO.

We present novel approaches of implementing state-of-the-art deep learning techniques for the processing of optical coherence tomography angiography (OCT-A) images for the classification of diabetic retinopathy (DR) severity. The effects of feature-engineering on a deep neural network’s classification performance is compared against unprocessed OCT-A images. We investigate the effects of lower axial resolution (simulated by using a narrower spectral bandwidth) on the classification of DR severity, and the recovery of lost features using a generative adversarial network. We also explore the relationship between DR severity classification and lateral resolution.

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

Real time rendering of en face optical coherence tomography (OCT) and OCT-angiography (OCTA) of arbitrary retinal layers in ophthalmic imaging sessions can be used to increase the yield rate of high-quality acquisitions, provide real-time feedback during image-guided surgeries and compensate aberrations in sensorless adaptive optics (AO) OCT and OCTA. However, real-time en face visualizations rely critically on the accurate segmentation of retinal layers in the three-dimensional OCT volumes. Here, we demonstrate a compact deep-learning architecture that segmented batches of OCT B-scans and produced the corresponding OCT and OCTA projections within only 41 ms. The short latency was possible due to a low complexity neural network structure, CNN compression using TensorRT, and the use of Tensor Cores on GPU hardware to accelerate the computation of convolutions. Inferencing of the original U-net was accelerated by 21 times without reducing the accuracy. To the best our knowledge, our work is the first demonstration of an ophthalmic imager with embedded artificial intelligence (AI) providing real-time feedback.

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.

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer., Graphical abstract Image, graphical abstract

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.

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaques in the brain detectable by highly invasive in vivo brain imaging or in post-mortem tissues. A non-invasive and inexpensive screening method is needed for early diagnosis of asymptomatic AD patients. The shared developmental origin and similarities with the brain make the retina a suitable surrogate tissue to assess Aβ load in AD. Using curcumin, a FluoroProbe that binds to Aβ, we labeled and measured the retinal fluorescence in vivo and compared with the immunohistochemical measurements of the brain and retinal Aβ load in the APP/PS1 mouse model. In vivo retinal images were acquired every 2 months using custom fluorescence scanning laser ophthalmoscopy (fSLO) after tail vein injections of curcumin in individual mice followed longitudinally from ages 5 to 19 months. At the same time points, 1-2 mice from the same cohort were sacrificed and immunohistochemistry was performed on their brain and retinal tissues. Results demonstrated cortical and retinal Aβ immunoreactivity were significantly greater in Tg than WT groups. Age-related increase in retinal Aβ immunoreactivity was greater in Tg than WT groups. Retinal Aβ immunoreactivity was present in the inner retinal layers and consisted of small speck-like extracellular deposits and intracellular labeling in the cytoplasm of a subset of retinal ganglion cells. In vivo retinal fluorescence with curcumin injection was significantly greater in older mice (11-19 months) than younger mice (5-9 months) in both Tg and WT groups. In vivo retinal fluorescence with curcumin injection was significantly greater in Tg than WT in older mice (ages 11-19 months). Finally, and most importantly, the correlation between in vivo retinal fluorescence with curcumin injection and Aβ immunoreactivity in the cortex was stronger in Tg compared to WT groups. Our data reveal that retina and brain of APP/PS1 Tg mice increasingly express Aβ with age. In vivo retinal fluorescence with curcumin correlated strongly with cortical Aβ immunohistochemistry in Tg mice. These findings suggest that using in vivo fSLO imaging of AD-susceptible retina may be a useful, non-invasive method of detecting Aβ in the retina as a surrogate indicator of Aβ load in the brain.

Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care. A hallmark of AD is the deposition of amyloid-β (Aβ)-containing senile neuritic plaques and neurofibrillary tangles composed of hyperphosporylated tau in the brain. However, current in vivo methods to quantify Aβ in the brain are invasive, requiring radioactive tracers and positron emission tomography. Toward development of alternative methods to assess AD progression, we focus on the retinal manifestation of AD pathology. The retina is an extension of the central nervous system uniquely accessible to light-based, non-invasive ophthalmic imaging. However, earlier studies in human retina indicate that the literature is divided on the presence of Aβ in the AD retina. To help resolve this disparity, this study assessed retinal tissues from neuropathologically confirmed AD cases to determine the regional distribution of Aβ in retinal wholemounts and to inform on future retinal image studies targeting Aβ. Concurrent post-mortem brain tissues were also collected. Neuropathological cortical assessments including neuritic plaque (NP) scores and cerebral amyloid angiopathy (CAA) were correlated with retinal Aβ using immunohistochemistry, confocal microscopy, and quantitative image analysis. Aβ load was compared between AD and control (non-AD) eyes. Our results indicate that levels of intracellular and extracellular Aβ retinal deposits were significantly higher in AD than controls. Mid-peripheral Aβ levels were greater than central retina in both AD and control eyes. In AD retina, higher intracellular Aβ was associated with lower NP score, while higher extracellular Aβ was associated with higher CAA score. Our data support the feasibility of using the retinal tissue to assess ocular Aβ as a surrogate measure of Aβ in the brain of individuals with AD. Specifically, mid-peripheral retina possesses more Aβ deposition than central retina, and thus may be the optimal location for future in vivo ocular imaging.

Purpose The purpose of this study was to compare perfusion parameters of the parafovea with scans outside the parafovea to find an area most susceptible to changes secondary to diabetic retinopathy (DR). Methods Patients with different DR severity levels as well as controls were included in this cross-sectional clinical trial. Seven standardized 3 × 3 mm areas were recorded with Swept Source Optical Coherence Tomography Angiography: one centered on the fovea, three were temporal to the fovea, and three nasally to the optic disc. The capillary perfusion density (PD) of the superficial capillary complex (SCC) and deep capillary complex (DCC) as well as the fractal dimension (FD) were generated. Statistical analyses were done with R software. Results One hundred ninety-two eyes (33 controls, 51 no-DR, 41 mild DR, 37 moderate/severe DR, and 30 proliferative DR), of which 105 patients with diabetes and 25 healthy controls were included (59 ± 15 years; 62 women). Mean PD of the DCC was significantly less in patients without DR (parafovea = 0.48 ± 0.03; temporal = 0.48 ± 0.02; and nasal = 0.48 ± 0.03) compared to controls (parafovea = 0.49 ± 0.02; temporal = 0.50 ± 0.02; and nasal = 0.50 ± 0.03). With increasing DR severity, PD and FD of the SCC and DCC further decreased. Conclusions Capillary perfusion of the retina is affected early by diabetes. PD of the DCC was significantly reduced in patients with diabetes who did not have any clinical signs of DR. The capillary network outside the parafovea was more susceptible to capillary perfusion deficits compared to the capillaries close to the fovea. Trial registration clinicaltrial.gov, NCT03765112, https://clinicaltrials.gov/ct2/show/NCT03765112?term=NCT03765112&rank=1.

Segmentation of retinal layers in optical coherence tomography (OCT) is an essential step in OCT image analysis for screening, diagnosis, and assessment of retinal disease progression. Real-time segmentation together with high-speed OCT volume acquisition allows rendering of en face OCT of arbitrary retinal layers, which can be used to increase the yield rate of high-quality scans, provide real-time feedback during image-guided surgeries, and compensate aberrations in adaptive optics (AO) OCT without using wavefront sensors. We demonstrate here unprecedented real-time OCT segmentation of eight retinal layer boundaries achieved by 3 levels of optimization: 1) a modified, low complexity, neural network structure, 2) an innovative scheme of neural network compression with TensorRT, and 3) specialized GPU hardware to accelerate computation. Inferencing with the compressed network U-NetRT took 3.5 ms, improving by 21 times the speed of conventional U-Net inference without reducing the accuracy. The latency of the entire pipeline from data acquisition to inferencing was only 41 ms, enabled by parallelized batch processing. The system and method allow real-time updating of en face OCT and OCTA visualizations of arbitrary retinal layers and plexuses in continuous mode scanning. To the best our knowledge, our work is the first demonstration of an ophthalmic imager with embedded artificial intelligence (AI) providing real-time feedback.

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.