Quantitative Volumetric Analysis of Retinal Ischemia with an Oxygen Diffusion Model and OCT Angiography.

Purpose: Retinal ischemia is a major feature of diabetic retinopathy (DR). Traditional nonperfused areas measured by OCT angiography (OCTA) measure blood supply but not ischemia. We propose a novel 3-dimensional (3D) quantitative method to derive ischemia measurements from OCTA data. Design: Cross-sectional study. Participants: We acquired 223 macular OCTA volumes from 33 healthy eyes, 33 diabetic eyes without retinopathy, 7 eyes with nonreferable DR, 17 eyes with referable but nonvision-threatening DR, and 133 eyes with vision-threatening DR. Methods: Each eye was scanned using a spectral-domain OCTA system (Avanti RTVue-XR, Visionix/Optovue, Inc) with 1.6-mm scan depth in a 3 × 3-mm region (640 × 304 × 304 voxels) centered on the fovea. For each scanned OCTA volume, a custom algorithm removed flow projection artifacts. We then enhanced, binarized, and skeletonized the vasculature in each OCTA volume and generated a 3D oxygen tension map using a zero-order kinetics oxygen diffusion model. Each volume was scaled to the average retina thickness in healthy controls after foveal registration and flattening of the Bruch's membrane. Finally, we extracted 3D ischemia maps by comparison with a reference map established from scans of healthy eyes using the same processing. To assess the ability of the ischemia maps to grade DR severity, we constructed receiver operating characteristic curves for diagnosing diabetes, referable DR, and vision-threatening DR. Main Outcome Measures: Spearman correlation coefficient and area under receiver operating characteristic curve (AUC) were used to quantify the ability of the ischemia maps to DR. Results: The ischemia maps showed that the ischemic tissues were at or near pathologically nonperfused areas, but not the normally nonvascular tissue, such as the foveal avascular zone. We found multiple novel metrics, including inferred 3D-oxygen tension, ischemia index, and ischemic volume ratio, were strongly correlated with DR severity. The AUCs of ischemia index measured were 0.94 for diabetes, 0.89 for DR, 0.88 for referable DR, and 0.85 for vision-threatening DR. Conclusions: A quantitative method to infer 3D oxygen tension and ischemia using OCTA in diabetic eyes can identify ischemic tissue that are more specific to pathologic changes in DR. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cascade Enhancement and Efficient Collection of Single Photon Emission under Topological Protection.

High emission rate, high collection efficiency, and immunity to defects are the requirements of implementing on-chip single photon sources. Here, we theoretically demonstrate that both cascade enhancement and high collection efficiency of emitted photons from a single emitter can be achieved simultaneously in a topological photonic crystal containing a resonant dielectric nanodisk. The nanodisk excited by a magnetic emitter can be regarded as a large equivalent magnetic dipole. The near-field overlapping between this equivalent magnetic dipole and edge state enables achieving a cascade enhancement of single-photon emission with a Purcell factor exceeding 4 × 103. These emitted photons are guided into edge states with a collection efficiency of more than 90%, which is also corresponding to quantum yield due to topological antiscattering and the absence of absorption. The proposed mechanism under topological protection has potential applications in on-chip light-matter interactions, quantum light sources, and nanolasers.

Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing.

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

Wide-field OCT angiography for non-human primate retinal imaging.

Optical coherence tomography (OCT) is a well-established research tool for vision research in animal models capable of providing in vivo imaging of the retina. Structural OCT can be enhanced using OCT angiography (OCTA) processing in order to provide simultaneously acquired, automatically co-registered vascular information. Currently available OCT. Currently available OCTA lack either large field of view or high resolution. In this study we developed a wide-field (60-degree), high-resolution (10.5-µm optical transverse) and high-sensitivity (104-dB) OCTA-enabled system for non-human primate imaging and with it imaged multiple disease models, including models of age-related macular degeneration (AMD), Bardet-Biedl Syndrome (BBS), and the CLN7 variant of Batten disease. We demonstrate clear visualization of features including drusen, ellipsoid zone loss, vascular retinopathy, and retinal thinning in these eyes.

Quantitative Evaluation of Type 1 and Type 2 Choroidal Neovascularization Components Under Treatment With Projection-Resolved OCT Angiography.

Purpose: To evaluate the response of type 1 and type 2 macular neovascularization (MNV) components under anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration (AMD) using projection-resolved optical coherence tomography angiography (PR-OCTA). Methods: This retrospective study included eyes with treatment-naïve exudative AMD treated with anti-VEGF injections under a pro re nata (PRN) protocol over 1 year. Two-dimensional MNV areas and three-dimensional MNV volumes were derived from macular PR-OCTA scans using an automated convolutional neural network. MNV was detected as flow signal within the outer retinal slab. Type 1 components and type 2 components were analyzed separately. Results: Of 17 enrolled eyes, 12 eyes were pure type 1 MNV and five eyes were type 2 MNV. In eyes with pure type 1, the total (sum of type 1 and type 2 components) MNV area and volume did not change from baseline to 6 months or 12 months (P > 0.05). In eyes with type 2 MNV, the total MNV area significantly decreased from the baseline to 6 months (P = 0.0074) and 12 months (P = 0.014). The total type 2 MNV volume also decreased from baseline visit to visits at 6 months and at 12 months, nearing statistical signifiicance (P = 0.061 and P = 0.074). In eyes with type 2 MNV, the type 1 component increased from 0.093 mm2 to 0.30 mm2 (P = 0.058), and the type 2 component decreased from 0.37 mm2 at 6 months to 0 at 12 months (P = 0.0087). Conclusions: Type 1 and type 2 MNV may have different response under PRN anti-VEGF treatment over 1 year.

Multi-Plexus Nonperfusion Area Segmentation in Widefield OCT Angiography Using a Deep Convolutional Neural Network.

Purpose: To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR). Widefield OCTA en face images were generated by montaging the scans from these three regions. A projection-resolved OCTA algorithm was applied to remove projection artifacts at the voxel scale. A deep convolutional neural network with a parallel U-Net module was designed to detect NPAs and distinguish signal reduction artifacts from flow deficits in the superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Expert graders manually labeled NPAs and signal reduction artifacts for the ground truth. Sixfold cross-validation was used to evaluate the proposed algorithm on the entire dataset. Results: The proposed algorithm showed high agreement with the manually delineated ground truth for NPA detection in three retinal vascular plexuses on widefield OCTA (mean ± SD F-score: SVC, 0.84 ± 0.05; ICP, 0.87 ± 0.04; DCP, 0.83 ± 0.07). The extrafoveal avascular area in the DCP showed the best sensitivity for differentiating eyes with diabetes but no retinopathy (77%) from healthy controls and for differentiating DR by severity: DR versus no DR, 77%; referable DR (rDR) versus non-referable DR (nrDR), 79%; vision-threatening DR (vtDR) versus non-vision-threatening DR (nvtDR), 60%. The DCP also showed the best area under the receiver operating characteristic curve for distinguishing diabetes from healthy controls (96%), DR versus no DR (95%), and rDR versus nrDR (96%). The three-plexus-combined OCTA achieved the best result in differentiating vtDR and nvtDR (81.0%). Conclusions: A deep learning network can accurately segment NPAs in individual retinal vascular plexuses and improve DR diagnostic accuracy. Translational Relevance: Using a deep learning method to segment nonperfusion areas in widefield OCTA can potentially improve the diagnostic accuracy of diabetic retinopathy by OCT/OCTA systems.

Glaucomatous Focal Perfusion Loss in the Macula Measured by Optical Coherence Tomographic Angiography.

PURPOSE: To measure low perfusion area (LPA) and focal perfusion loss (FPL) in the macula using optical coherence tomography (OCT) angiography (OCTA) for glaucoma. DESIGN: Prospective, cross-sectional "case-control" comparison study. METHODS: A total of 60 patients with primary open-angle glaucoma (POAG) and 37 healthy participants were analyzed. AngioVue 6 × 6-mm high-definition (400 × 400 transverse pixels) macular OCTA scans were performed on one eye of each participant. Flow signal was calculated using the split-spectrum amplitude-decorrelation angiography algorithm. En face ganglion cell layer plexus (GCLP) and superficial vascular complex (SVC) images were generated. Using custom software, vessel density (VD) maps were obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 41 × 41 pixels. LPA was defined by local VD below 0.5 percentile over a contiguous area above 98.5 percentile of the healthy reference population. The FPL was the percentage VD loss (relative to normal mean) integrated over the LPA. RESULTS: Among patients with POAG, 30 had perimetric and 30 had preperimetric glaucoma. The LPAGCLP-VD was 0.16±0.38 mm2 in normal and 5.78±6.30 mm2 in glaucoma subjects (P < .001). The FPLGCLP-VD was 0.20%±0.47% in normal and 7.52%±8.84% in glaucoma subjects (P < .001). The perimetric glaucoma diagnostic accuracy, measured by the area under the receiver operating curve, was 0.993 for LPAGCLP-VD and 0.990 for FPLGCLP-VD. The sensitivities were, respectively, 96.7% and 93.3% at 95% specificity. The LPAGCLP-VD and FPLGCLP-VD had good repeatability (0.957 and 0.952 by intraclass correlation coefficient). Diagnostic accuracy was better than GCLP VD (AROC 0.950, sensitivity 83.3%) and OCT ganglion cell complex (GCC) thickness (AROC 0.927, sensitivity 80.0%) and GCC focal loss volume (AROC 0.957, sensitivity 80.0%). The LPAGCLP-VD and FPLGCLP-VD correlated well with central VF mean deviations (Pearson r = -0.716 and -0.705 respectively, both P < .001). CONCLUSION: Assessment of macular FPL using OCTA is useful in evaluating glaucomatous damage.

Panretinal handheld OCT angiography for pediatric retinal imaging.

Comprehensive visualization of retina morphology is essential in the diagnosis and management of retinal diseases in pediatric populations. Conventional imaging techniques often face challenges in effectively capturing the peripheral retina, primarily due to the limitations in current optical designs, which lack the necessary field of view to characterize the far periphery. To address this gap, our study introduces a novel ultra-widefield optical coherence tomography angiography (OCTA) system. This system, specifically tailored for pediatric applications, incorporates an ultrahigh-speed 800 kHz swept-source laser. The system's innovative design achieves a 140° field of view while maintaining excellent optical performance. Over the last 15 months, we have conducted 379 eye examinations on 96 babies using this system. It demonstrates marked efficacy in the diagnosis of retinopathy of prematurity, providing detailed and comprehensive peripheral retinal angiography. The capabilities of the ultra-widefield handheld OCTA system in enhancing the clarity and thoroughness of retina vascularization assessments have significantly improved the precision of diagnoses and the customization of treatment strategies. Our findings underscore the system's potential to advance pediatric ophthalmology and broaden the scope of retinal imaging.

Isolated Retinal Neovascularization in Retinopathy of Prematurity: Clinical Associations and Prognostic Implications.

OBJECTIVE: Isolated retinal neovascularization (IRNV) is a common finding in patients with stage 2 and 3 retinopathy of prematurity (ROP). This study aimed to further classify the clinical course and significance of these lesions (previously described as "popcorn" based on clinical appearance) in patients with ROP as visualized with ultrawidefield OCT (UWF-OCT). DESIGN: Single center, retrospective case series. PARTICIPANTS: Images were collected from 136 babies in the Oregon Health and Science University neonatal intensive care unit. METHODS: A prototype UWF-OCT device captured en face scans (>140°), which were reviewed for the presence of IRNV along with standard zone, stage, and plus classification. In a cross-sectional analysis we compared demographics and the clinical course of eyes with and without IRNV. Longitudinally, we compared ROP severity using a clinician-assigned vascular severity score (VSS) and compared the risk of progression among eyes with and without IRNV using multivariable logistic regression. MAIN OUTCOME MEASURES: Differences in clinical demographics and disease progression between patients with and without IRNV. RESULTS: Of the 136 patients, 60 developed stage 2 or worse ROP during their disease course, 22 of whom had IRNV visualized on UWF-OCT (37%). On average, patients with IRNV had lower birth weights (BWs) (660.1 vs. 916.8 g, P = 0.001), gestational age (GA) (24.9 vs. 26.1 weeks, P = 0.01), and were more likely to present with ROP in zone I (63.4% vs. 15.8%, P < 0.001). They were also more likely to progress to stage 3 (68.2% vs. 13.2%, P < 0.001) and receive treatment (54.5% vs. 15.8%, P = 0.002). Eyes with IRNV had a higher peak VSS (5.61 vs. 3.73, P < 0.001) and averaged a higher VSS throughout their disease course. On multivariable logistic regression, IRNV was independently associated with progression to stage 3 (P = 0.02) and requiring treatment (P = 0.03), controlling for GA, BW, and initial zone 1 disease. CONCLUSIONS: In this single center study, we found that IRNV occurs in higher risk babies and was an independent risk factor for ROP progression and treatment. These findings may have implications for OCT-based ROP classifications in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visualizing features with wide-field volumetric OCT angiography.

Optical coherence tomography (OCT) and its extension OCT angiography (OCTA) have become essential clinical imaging modalities due to their ability to provide depth-resolved angiographic and tissue structural information non-invasively and at high resolution. Within a field of view, the anatomic detail available is sufficient to identify several structural and vascular pathologies that are clinically relevant for multiple prevalent blinding diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and vein occlusions. The main limitation in contemporary OCT devices is that this field of view is limited due to a fundamental trade-off between system resolution/sensitivity, sampling density, and imaging window dimensions. Here, we describe a swept-source OCT device that can capture up to a 12 × 23-mm field of view in a single shot and show that it can identify conventional pathologic features such as non-perfusion areas outside of conventional fields of view. We also show that our approach maintains sensitivity sufficient to visualize novel features, including choriocapillaris morphology beneath the macula and macrophage-like cells at the inner limiting membrane, both of which may have implications for disease.

Optimizing numerical k-sampling for swept-source optical coherence tomography angiography.

High-quality swept-source optical coherence tomography (SS-OCT) requires accurate k-sampling, which is equally vital for optical coherence tomography angiography (OCTA). Most SS-OCT systems are equipped with hardware-driven k-sampling. However, this conventional approach raises concerns over system cost, optical alignment, imaging depth, and stability in the clocking circuit. This work introduces an optimized numerical k-sampling method to replace the additional k-clock hardware. Using this method, we can realize high axial resolution (4.9-µm full-width-half-maximum, in air) and low roll-off (2.3 dB loss) over a 4-mm imaging depth. The high axial resolution and sensitivity achieved by this simple numerical method can reveal anatomic and microvascular structures with structural OCT and OCTA in both macular and deeper tissues, including the lamina cribrosa, suggesting its usefulness in imaging retinopathy and optic neuropathy.

Real-time line-field optical coherence tomography for cellular resolution imaging of biological tissue.

A real-time line-field optical coherence tomography (LF-OCT) system is demonstrated with image acquisition rates of up to 5000 B-frames or 2.5 million A-lines per second for 500 A-lines per B-frame. The system uses a high-speed low-cost camera to achieve continuous data transfer rates required for real-time imaging, allowing the evaluation of future applications in clinical or intraoperative environments. The light source is an 840 nm super-luminescent diode. Leveraging parallel computing with GPU and high speed CoaXPress data transfer interface, we were able to acquire, process, and display OCT data with low latency. The studied system uses anamorphic beam shaping in the detector arm, optimizing the field of view and sensitivity for imaging biological tissue at cellular resolution. The lateral and axial resolution measured in air were 1.7 µm and 6.3 µm, respectively. Experimental results demonstrate real-time inspection of the trabecular meshwork and Schlemm's canal on ex vivo corneoscleral wedges and real-time imaging of endothelial cells of human subjects in vivo.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

Interpretable Diabetic Retinopathy Diagnosis Based on Biomarker Activation Map.

OBJECTIVE: Deep learning classifiers provide the most accurate means of automatically diagnosing diabetic retinopathy (DR) based on optical coherence tomography (OCT) and its angiography (OCTA). The power of these models is attributable in part to the inclusion of hidden layers that provide the complexity required to achieve a desired task. However, hidden layers also render algorithm outputs difficult to interpret. Here we introduce a novel biomarker activation map (BAM) framework based on generative adversarial learning that allows clinicians to verify and understand classifiers' decision-making. METHODS: A data set including 456 macular scans were graded as non-referable or referable DR based on current clinical standards. A DR classifier that was used to evaluate our BAM was first trained based on this data set. The BAM generation framework was designed by combing two U-shaped generators to provide meaningful interpretability to this classifier. The main generator was trained to take referable scans as input and produce an output that would be classified by the classifier as non-referable. The BAM is then constructed as the difference image between the output and input of the main generator. To ensure that the BAM only highlights classifier-utilized biomarkers an assistant generator was trained to do the opposite, producing scans that would be classified as referable by the classifier from non-referable scans. RESULTS: The generated BAMs highlighted known pathologic features including nonperfusion area and retinal fluid. CONCLUSION/SIGNIFICANCE: A fully interpretable classifier based on these highlights could help clinicians better utilize and verify automated DR diagnosis.

Perfused and Nonperfused Microaneurysms Identified and Characterized by Structural and Angiographic OCT.

PURPOSE: Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR. METHODS: We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in en face OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection. MAIN OUTCOME MEASURES: OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow. RESULTS: We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP. CONCLUSIONS: OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Early Sign of Retinal Neovascularization Evolution in Diabetic Retinopathy: A Longitudinal OCT Angiography Study.

Purpose: To assess whether the combination of en face OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal neovascularization (RNV) in eyes with diabetic retinopathy (DR). Design: Retrospective, longitudinal study. Participants: Patients with DR that had at least 2 visits. Methods: We obtained wide-field OCTA scans of 1 eye from each participant and generated en face OCT, en face OCTA, and cross-sectional OCTA. We identified eyes with RNV sprouts, defined as epiretinal hyperreflective materials on en face OCT with flow signals breaching the internal limiting membrane on the cross-sectional OCTA without recognizable RNV on en face OCTA and RNV fronds, defined as recognizable abnormal vascular structures on the en face OCTA. We examined the corresponding location from follow-up or previous visits for the presence or progression of the RNV. Main Outcome Measures: The characteristics and longitudinal observation of early signs of RNV. Results: From 71 eyes, we identified RNV in 20 eyes with the combination of OCT and OCTA, of which 13 (65%) were photographically graded as proliferative DR, 6 (30%) severe nonproliferative DR, and 1 (5%) moderate nonproliferative diabetic retinopathy. From these eyes, we identified 38 RNV sprouts and 26 RNV fronds at the baseline. Thirty-four RNVs (53%) originated from veins, 24 (38%) were from intraretinal microabnormalities, and 6 (9%) were from a nondilated capillary bed. At the final visit, 53 RNV sprouts and 30 RNV fronds were detected. Ten eyes (50%) showed progression, defined as having a new RNV lesion or the development of an RNV frond from an RNV sprout. Four (11%) RNV sprouts developed into RNV fronds with a mean interval of 7.0 months. Nineteen new RNV sprouts developed during the follow-up, whereas no new RNV frond was observed outside an identified RNV sprout. The eyes with progression were of younger age (P = 0.014) and tended to be treatment naive (P = 0.07) compared with eyes without progression. Conclusions: Longitudinal observation demonstrated that a combination of en face OCT and cross-sectional OCTA can identify an earlier form of RNV before it can be recognized on en face OCTA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Single-shot OCT and OCT angiography for slab-specific detection of diabetic retinopathy.

In this study, we present an optical coherence tomographic angiography (OCTA) prototype using a 500 kHz high-speed swept-source laser. This system can generate a 75-degree field of view with a 10.4 µm lateral resolution with a single acquisition. With this prototype we acquired detailed, wide-field, and plexus-specific images throughout the retina and choroid in eyes with diabetic retinopathy, detecting early retinal neovascularization and locating pathology within specific retinal slabs. Our device could also visualize choroidal flow and identify signs of key biomarkers in diabetic retinopathy.

OCT angiography and its retinal biomarkers [Invited].

Optical coherence tomography angiography (OCTA) is a high-resolution, depth-resolved imaging modality with important applications in ophthalmic practice. An extension of structural OCT, OCTA enables non-invasive, high-contrast imaging of retinal and choroidal vasculature that are amenable to quantification. As such, OCTA offers the capability to identify and characterize biomarkers important for clinical practice and therapeutic research. Here, we review new methods for analyzing biomarkers and discuss new insights provided by OCTA.

Perfused and Nonperfused Microaneurysms Identified and Characterized by Structural and Angiographic OCT.

Purpose: Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored. Design: Retrospective, cross-sectional study. Participants: A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR. Methods: We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in en face OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection. Main Outcome Measures: OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow. Results: We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP. Conclusions: OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Retina 2023;■:1-8 © 2023 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Optical coherence tomography split-spectrum amplitude-decorrelation optoretinography.

This pilot study reports the development of optical coherence tomography (OCT) split-spectrum amplitude-decorrelation optoretinography (SSADOR) that measures spatially resolved photoreceptor response to light stimuli. Using spectrally multiplexed narrowband OCT, SSADOR improves sensitivity to microscopic changes without the need for cellular resolution or optical phase detection. Therefore, a large field of view (up to 3 × 1 mm2 demonstrated) using conventional OCT instrument design can be achieved, paving the way for clinical translation. SSADOR promises a fast, objective, and quantifiable functional biomarker for photoreceptor damage in the macula.