Perfusion Deficits in Diabetes Without Retinopathy Localize to the Perivenular Deep Capillaries Near the Fovea on OCT Angiography.

Purpose: To localize early capillary perfusion deficits in patients with diabetes mellitus (DM) without clinical diabetic retinopathy (DR) using averaged OCT angiography (OCTA). Design: Retrospective cross-sectional study. Participants: Patients with DM without DR and healthy controls. Methods: We measured perfusion deficits in the full retina, superficial capillary plexus (SCP), and deep capillary plexus (DCP) on averaged 3 × 3-mm OCTA images. Perfusion deficits were defined as the percentage of retinal tissue located >30 µm from blood vessels, excluding the foveal avascular zone (FAZ). One eye from each patient was selected based on image quality. We measured deficits in the parafoveal region, the 300 µm surrounding the FAZ, and 300 to 1000 µm surrounding the FAZ. If a capillary layer within one of these regions was significantly different in DM without DR compared with controls, we further characterized the location of perfusion deficit as periarteriolar, perivenular, or the capillaries between these 2 zones. Main Outcome Measures: Location of increased perfusion deficits in patients with DM without DR compared with controls. Results: Sixteen eyes from 16 healthy controls were compared with 16 eyes from 16 patients with DM without DR (age 45.1 ± 10.7 and 47.4 ± 15.2 years respectively, P = 0.64). Foveal avascular zone area and perfusion deficits in the entire parafovea and the 300 to 1000-µm ring around the FAZ were not significantly different between groups (P > 0.05 for all). Perfusion deficits in 300 µm around the FAZ were significantly increased in patients with DM without DR in full retinal thickness, SCP, and DCP (P < 0.05 for all). When analyzing the perivenular, periarteriolar, and capillary zones, only the perivenular DCP perfusion deficits were significantly increased (5.03 ± 2.92% in DM without DR and 2.73 ± 1.97% in controls, P = 0.014). Conclusions: Macular perfusion deficits in patients with DM without DR were significantly increased in the region nearest the FAZ, mainly at the perivenular deep capillaries. Further research on these early changes may improve our understanding of the capillaries most susceptible to vascular injury and disruption during diabetes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical Coherence Tomography Angiography of Volumetric Arteriovenous Relationships in the Healthy Macula and Their Derangement in Disease.

Purpose: To characterize relative arteriovenous connectivity of the healthy macula imaged by optical coherence tomography angiography (OCTA) using a new volumetric tool. Methods: OCTA volumes were obtained for 20 healthy controls (20 eyes). Two graders identified superficial arterioles and venules. We implemented a custom watershed algorithm to identify capillaries most closely connected to arterioles and venules by using the large vessels as seeds to flood the vascular network. We calculated ratios of arteriolar- to venular-connected capillaries (A/V ratios) and adjusted flow indices (AFIs) for superficial capillary plexuses (SCPs), middle capillary plexuses (MCPs), and deep capillary plexuses (DCPs). We also analyzed two eyes with proliferative diabetic retinopathy (PDR) and one eye with macular telangiectasia (MacTel) to evaluate the utility of this method in visualizing pathological vascular connectivity. Results: In healthy eyes, the MCP showed a greater proportion of arteriolar-connected vessels than the SCP and DCP (all P < 0.001). In the SCP, the arteriolar-connected AFI exceeded the venular-connected AFI, but this pattern reversed in the MCP and DCP, with higher venular-connected AFI (all P < 0.001). In PDR eyes, preretinal neovascularization originated from venules, whereas intraretinal microvascular abnormalities were heterogeneous, with some originating from venules and others representing dilated MCP capillary loops. In MacTel, diving SCP venules formed the epicenter of the outer retinal anomalous vascular network. Conclusions: Healthy eyes showed a higher MCP A/V ratio but relatively slower arteriolar vs. venular flow velocity in the MCP and DCP, which may explain deep retinal vulnerability to ischemia. In eyes with complex vascular pathology, our connectivity findings were consistent with histopathologic studies.

Macular Perfusion Deficits on OCT Angiography Correlate with Nonperfusion on Ultrawide-field Fluorescein Angiography in Diabetic Retinopathy.

OBJECTIVE: To evaluate the correlation between nonperfusion parameters on OCT angiography (OCTA) and ultrawide-field fluorescein angiography (UWF-FA) in subjects with diabetes mellitus (DM). DESIGN: Prospective, cross-sectional study. SUBJECTS: Subjects with DM and a wide range of diabetic retinopathy (DR) severity seen at a tertiary referral center. METHODS: We used averaged 3 × 3 mm OCTA scans to measure geometric perfusion deficit (GPD), vessel density, and vessel length density in the full retina, superficial capillary plexuses (SCPs), and deep capillary plexuses (DCPs). Nonperfusion was manually delineated on UWF-FA to quantify central, peripheral, and total retinal nonperfusion (mm2 and % area). MAIN OUTCOME MEASURES: Correlation between OCTA parameters and UWF-FA nonperfusion, and accuracy of these OCTA and UWF-FA parameters in detecting clinically referable eyes, using receiver operating characteristic (ROC) curve analysis, sensitivity, specificity, and area under the ROC curve (AUC). RESULTS: The study included 67 eyes (12 eyes with no signs of DR, 8 mild, 22 moderate, 14 severe nonproliferative DR, and 11 treatment-naive proliferative DR). There was a fair-to-moderate correlation between either central or total retinal nonperfusion on UWF-FA (mm2) and GPD in the SCP (r = 0.482 and r = 0.464, respectively) and DCP (r = 0.470 and r = 0.456, respectively). Receiver operating characteristic analysis showed the DCP GPD significantly superior to other OCTA parameters at the DCP with the largest overall AUC on OCTA for distinguishing referable DR (0.905). Furthermore, the GPD parameter had the largest AUC in each respective capillary layer compared with other parameters. Overall, the total UWF-FA nonperfusion area showed a comparable AUC (0.907) and performed significantly better than peripheral nonperfusion (P = 0.041). Comparing the AUC values between GPD and UWF-FA nonperfusion parameters showed no significant difference in discerning referable DR. CONCLUSIONS: Nonperfusion as quantified on OCTA (3 × 3 mm) correlated with UWF-FA parameters and both were comparable in detecting referable DR. These macular OCTA metrics, particularly DCP GPD, have the potential for gauging the overall ischemic status of the retina, with an important clinical role in identifying eyes with clinically referable DR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Macrophage-like Cells Are Increased in Patients with Vision-Threatening Diabetic Retinopathy and Correlate with Macular Edema.

Macrophage-like cells (MLCs) are potential inflammatory biomarkers. We previously showed that MLCs are increased in proliferative diabetic retinopathy (PDR) eyes. Vision-threatening diabetic retinopathy (VTDR) includes PDR, severe non-PDR (NPDR), and diabetic macular edema (DME). No prior data exist on MLCs in eyes with severe NPDR or DME. This prospective, cross-sectional optical coherence tomography-angiography (OCT-A) imaging study included 40 eyes of 37 participants who had NPDR classified as non-VTDR (n = 18) or VTDR (n = 22). Repeated OCT-A images were registered, averaged, and used to quantify the main outcome measures: MLC density and percent area. MLC density and percent area were correlated with clinical characteristics, NPDR stage, presence of DME, and OCT central subfield thickness (CST). In VTDR eyes, MLC density (2.6-fold, p < 0.001) and MLC percent area (2.5-fold, p < 0.01) were increased compared with non-VTDR eyes. Multiple linear regression analysis between MLC metrics and clinical characteristics found that MLC density was positively correlated with worse NPDR severity (p = 0.023) and higher CST values (p = 0.010), while MLC percent area was only positively associated with increased CST values (p = 0.006). MLCs are increased in patients with VTDR. Macular edema is the most strongly associated factor with increased MLC numbers in NPDR eyes.

Macrophage-like cells are still detectable on the retinal surface after posterior vitreous detachment.

The identity of vitreoretinal interface macrophage-like cells (MLCs) remains unknown and potential candidates include retinal microglia, perivascular macrophages, monocyte-derived macrophages, and/or vitreal hyalocytes. Since hyalocytes are detectable on the posterior vitreous surface after vitreous extraction in animals, we imaged patients with and without posterior vitreous detachment (PVD) to determine if hyalocytes are the principal MLC component. We performed repeated foveal-centered 3 × 3 mm OCT-A images from 21 eyes (11 no PVD and 10 PVD eyes). Images were registered, segmented, and averaged. The OCT slab from 0 to 3 microns above the internal limiting membrane was used to detect MLCs. We calculated MLC density and distribution in relation to the superficial vascular plexus for 3 vascular regions-on vessels, perivascular, and non-vascular. MLC density was 1.8-fold greater in the PVD group compared to the no PVD group (P = 0.04). MLCs in eyes with PVD were increased 1.9-fold on-vessel (P = 0.07), 1.9-fold in the perivascular region (P = 0.12), and 2.2-fold in non-vascular areas (P = 0.22). MLC density was not severely reduced after PVD, suggesting that the majority of MLCs are not vitreal hyalocytes. PVD status is an important parameter in future MLC studies.

Deep Capillary Geometric Perfusion Deficits on OCT Angiography Detect Clinically Referable Eyes with Diabetic Retinopathy.

PURPOSE: To evaluate the sensitivity (SN) and specificity (SP) of OCT angiography (OCTA) parameters for detecting clinically referable eyes with diabetic retinopathy (DR) in a cohort of patients with diabetes mellitus (DM). DESIGN: Retrospective, cross-sectional study. SUBJECTS: Patients with DM with various levels of DR. METHODS: We measured vessel density, vessel length density (VLD), and geometric perfusion deficits (GPDs) in the full retina, superficial capillary plexus (SCP), and deep capillary plexus (DCP) on 3 × 3-mm OCTA images. Geometric perfusion deficit was recently described as retinal tissue located further than 30 µm from blood vessels, excluding the foveal avascular zone (FAZ). We modified the GPD metric by including the FAZ as an additional variable. Clinically referable eyes were defined as moderate nonproliferative DR (NPDR) or worse retinopathy, or diabetic macular edema (DME). One eye from each patient was selected for the analysis based on image quality. We used a binary logistic regression model to adjust for covariates. MAIN OUTCOME MEASURES: Sensitivity, SP, and area under the curve (AUC). RESULTS: Seventy-one of 150 included eyes from 150 patients (52 with DM without DR, 27 with mild NPDR, 16 with moderate NPDR, 10 with severe NPDR, 30 with proliferative DR, and 15 with DME) had clinically referable DR. Geometric perfusion deficit metric that included the FAZ performed better than GPD in detecting referable DR in the SCP (P = 0.025) but not the DCP or full retina (P > 0.05 for both). Deep capillary plexus GPD had the largest AUC for detecting clinically referable eyes (AUC = 0.965, SN = 97.2%, SP = 84.8%), which was significantly larger than the AUC for vessel density of any layer (P < 0.05 for all) but not DCP VLD (P = 0.166). The cutoff value of 2.5% for DCP GPD resulted in a highly sensitive test for detecting clinically referable eyes without adjusting for covariates (AUC = 0.955, SN = 97.2%, SP = 79.7%). CONCLUSIONS: Vascular parameters in OCTA, especially in the DCP, have the potential to identify eyes that warrant further evaluation. Geometric perfusion deficits may better distinguish these clinically referable eyes with DR than standard vessel density parameters.

NEW METHOD FOR REDUCING ARTIFACTUAL FLOW DEFICITS CAUSED BY COMPENSATION TECHNIQUES IN THE CHORIOCAPILLARIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To mitigate artifactual choriocapillaris flow deficits in optical coherence tomography angiography, which are a side effect of inverse structural optical coherence tomography compensation. METHODS: In a modified algorithm, we set pixels in the original structural optical coherence tomography that were greater than one SD above the mean intensity (hyperreflective regions) to the mean pixel intensity of the image to remove hyporeflective regions in the inverse slab. We compared this algorithm to the original using flow deficit density and multiscale structural similarity index obtained from three distinct thresholding methods (local Phansalkar, global MinError (I), and global Li). RESULTS: We included 16 eyes of 16 healthy subjects (31.1 ± 6.9 years, 10 females). Using the modified optical coherence tomography correction, flow deficit density was lower compared with the original algorithm using Phansalkar (P < 0.001) but higher using Li thresholding (P = 0.049). Multiscale structural similarity index was increased after applying the modified algorithm with all three thresholding methods (P < 0.001), indicating a closer relationship to the original optical coherence tomography angiography scan. CONCLUSION: We demonstrate a new method that significantly reduced the introduction of artifactual flow deficits in the choriocapillaris during postprocessing. Given the improved multiscale structural similarity index, we believe our algorithm more accurately represents the choriocapillaris.

Macrophage-Like Cell Density Is Increased in Proliferative Diabetic Retinopathy Characterized by Optical Coherence Tomography Angiography.

Purpose: To quantitatively characterize macrophage-like cells (MLCs) at the vitreoretinal interface in different severity stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Methods: The study included 72 eyes of 72 subjects: 18 healthy controls, 22 diabetes mellitus (DM) without DR, 17 nonproliferative DR (NPDR), and 15 proliferative DR (PDR). We obtained repeated (average, 6.5; range, 3-10) macular OCTA scans for each eye. We registered and averaged the 3-µm OCT slab above the vitreoretinal interface to visualize MLCs. Using a semiautomated method, we binarized and quantified MLCs and compared MLC densities among groups. We also evaluated MLC distribution relative to underlying superficial capillary plexus vasculature and quantified MLCs overlying blood vessels within the perivascular 30-µm watershed region and within ischemic zones (defined as >30 µm from the nearest vessel). Results: MLC density was 2.8- to 3.8-fold higher in PDR compared with all other groups (P < 0.05 for all). MLC density in PDR was most increased in perivascular areas (3.3- to 4.2-fold; P < 0.05 vs. all) and on blood vessels (3.0- to 4.0-fold; P < 0.05 vs. all), and elevated to a lesser extent in ischemic areas (2.3- to 3.4-fold; P < 0.05 vs. all). MLCs were more likely to localize on blood vessels in DM without DR, NPDR, and PDR (P < 0.05 for all), but not healthy eyes. Conclusions: MLC density was significantly increased in PDR. MLCs clustered on blood vessels in diabetic but not in healthy eyes. Further studies are needed to confirm the origin, identity, and function of MLCs during DR.

Assessment of retinal microvascular health by optical coherence tomography angiography among persons with HIV.

Microvasculopathy may link HIV-related chronic inflammation and premature multimorbidity. In this proof-of-concept study, we used optical coherence tomography angiography (OCTA) to evaluate the retina as a convenient assessment of microvascular health among persons with HIV (PWH) undergoing surveillance ophthalmic care at Emory from 2018 to 2021. Among patients with longstanding HIV, OCTA identified microvascular abnormalities even among eyes without clinical retinal disease. Retinovascular evaluation by OCTA is a feasible, noninvasive technique for assessing microvasculopathy among PWH.

Exploring the Relationship Between Multilayered Choroidal Neovascularization and Choriocapillaris Flow Deficits in AMD.

Purpose: We used optical coherence tomography angiography to test the hypothesis that more complex, multilayered choroidal neovascular (CNV) membranes in AMD are associated with worse flow deficits (FD) in the choriocapillaris. Methods: Retrospective, cross-sectional study including 29 eyes of 29 subjects with neovascular AMD. En face choriocapillaris images were compensated for signal attenuation using the structural OCT slab and signal normalization based on a cohort of healthy subjects. We binarized the choriocapillaris using both local Phansalkar and global MinError(I) methods and quantified FD count, FD density, and mean FD size in the entire area outside the CNV, in the 200-µm annulus surrounding the CNV, and in the area outside the annulus. We used projection-resolved optical coherence tomography angiography to quantify CNV complexity, including highest CNV flow height, number of flow layers, and flow layer thickness. We explored the relationship between CNV complexity and choriocapillaris FD using Spearman correlations. Results: The highest CNV flow signal significantly correlated with lower FD count (P < 0.01), higher FD density (P < 0.05), and higher mean FD size (P < 0.05) in the area outside the annulus and the entire area outside the CNV using both Phansalkar and MinError(I). Within the annulus, CNV complexity was not consistently correlated with choriocapillaris defects. Conclusions: CNV vascular complexity is correlated with choriocapillaris FD outside the CNV area, providing evidence for the importance of choriocapillaris dysfunction in neovascular AMD, as well as the potential role of choroidal ischemia in the pathogenesis of complex CNV membranes.

Parafoveal vessel changes in primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography angiography.

PURPOSE: To evaluate parafoveal and peripapillary perfusion in healthy, glaucoma suspect, normal-tension glaucoma, and primary open-angle glaucoma subjects. PATIENTS AND METHODS: This was a retrospective cross-sectional study with optical coherence tomography angiography imaging with RTVue XR Avanti (Optovue, Inc., Fremont, CA) of 56 eyes (14 healthy, 14 glaucoma suspect, 16 normal-tension glaucoma, and 12 primary open-angle glaucoma) at a tertiary academic referral center. Parafoveal and peripapillary superficial vessel density and parafoveal superficial retinal thickness were the main parameters of interest. Area under receiver operating characteristic curves were calculated. RESULTS: There were significant decreases in parafoveal superficial vessel density in primary open-angle (40.06±4.54%, P<0.001) and normal-tension glaucoma (42.82±5.16%, P=0.010) but not suspect eyes (45.72±4.37%, P=0.916) compared to healthy eyes (48.10±2.82%). Similarly, decreases were observed in parafoveal inner retinal thickness in primary open-angle (83.19±14.29 µm, P<0.001) and normal-tension glaucoma eyes (94.97±12.44 µm, P=0.035), but not suspect eyes (99.93±9.00 µm, P=0.648), compared to healthy controls (107.00±9.55 µm). Only primary open-angle glaucoma eyes displayed significant changes in peripapillary vessel density (37.63±7.19%) compared to healthy controls (49.12±2.80%, P<0.001). Further statistical adjustment for sex and age revealed a significant decrease in parafoveal vessel density in suspects relative to controls (P=0.039). Diagnostic accuracy of parafoveal vessel density was high with an area under the curve of 0.833±0.073 for normal-tension glaucoma and 0.946±0.049 for primary open-angle glaucoma. CONCLUSION: Parafoveal vessel density was significantly reduced in glaucomatous eyes, with good diagnostic accuracy. These findings provide further evidence that these changes may be useful in the diagnosis and monitoring of disease in glaucoma patients.

Hemodynamic Response of the Three Macular Capillary Plexuses in Dark Adaptation and Flicker Stimulation Using Optical Coherence Tomography Angiography.

Purpose: To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA). Methods: Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA. Parafoveal vessel density and adjusted flow index (AFI) were calculated for superficial (SCP), middle (MCP), and deep capillary plexuses (DCP), and then compared between conditions after adjusting for age, refractive error, and scan quality. SCP vessel length density (VLD) was also evaluated. Between-condition capillary images were aligned and subtracted to identify differences. We then analyzed images from 10 healthy subjects during the transition from dark adaptation to ambient light. Results: SCP vessel density was significantly higher while SCP VLD was significantly lower during ambient light and flicker compared to dark adaptation. There was a significant positive mean value for DCP "flicker minus dark or light," suggesting more visible vessels during flicker due to changes in flow, dilation, or vessel recruitment. We found a significant, transient increase in SCP and decrease in both MCP and DCP vessel density during the transition from dark to light. Conclusions: We show evidence suggesting constriction of deeper vessels and dilation of large SCP vessels during the transition from dark to light. This contrasts to redistribution of blood flow to deeper layers during dark adaptation and flicker stimulation.

CHARACTERIZATION AND CORRELATION OF "JAMPOL DOTS" ON ADAPTIVE OPTICS WITH FOVEAL GRANULARITY ON CONVENTIONAL FUNDUS IMAGING.

PURPOSE: To describe features characteristic of multiple evanescent white dot syndrome (MEWDS) using adaptive optics scanning laser ophthalmoscopy (AOSLO). METHODS: Six women (seven eyes) who presented with MEWDS between June 2014 and April 2017 underwent ophthalmologic examinations and multimodal imaging including infrared, AOSLO, and spectral domain optical coherence tomography. RESULTS: Bright hyperreflective lesions on AOSLO throughout the course of MEWDS could be correlated to the hyperreflective dots of foveal granularity on infrared imaging without apparent corresponding changes on spectral domain optical coherence tomography. During the acute phase of MEWDS, extrafoveal hyperreflective dots were also visible on AOSLO and infrared and were associated with accumulations of hyperreflective material above the retinal pigment epithelium on spectral domain optical coherence tomography. CONCLUSION: Foveal granularity on conventional fundus imaging could be correlated with hyperreflective lesions visible on AOSLO. We hypothesize that these hyperreflective lesions, "Jampol dots," are the foveal corollaries of the same process associated with the classic "dot" lesions in MEWDS. Based on the intact photoreceptor mosaic on AOSLO, we surmise that this material is accumulating at the level of the retinal pigment epithelium.

MULTIMODAL IMAGING OF ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ADAPTIVE OPTICS SCANNING LASER OPHTHALMOSCOPY.

PURPOSE: To report a case of acute exudative polymorphous vitelliform maculopathy including the findings of optical coherence tomography angiography and adaptive optics scanning laser ophthalmoscopy. METHODS: Findings on clinical examination, color fundus photography, spectral-domain optical coherence tomography, infrared reflectance, autofluorescence, optical coherence tomography angiography, and adaptive optics scanning laser ophthalmoscopy. RESULTS: A 54-year-old white man with no significant medical history and history of smoking presented with bilateral multiple serous and vitelliform detachments consistent with acute exudative polymorphous vitelliform maculopathy. Extensive infectious, inflammatory, and malignancy workup was negative. Spectral-domain optical coherence tomography showed thickened, hyperreflective ellipsoid zone, subretinal fluid, and focal as well as diffuse subretinal hyperreflective material corresponding to the vitelliform lesions. Optical coherence tomography angiography showed normal retinal and choroidal vasculature, whereas adaptive optics scanning laser ophthalmoscopy showed circular focal "target" lesions at the level of the photoreceptors in the area of foveal detachment. CONCLUSION: Multimodal imaging is valuable in evaluating patients with acute exudative polymorphous vitelliform maculopathy.

Comparison of Zeiss Cirrus and Optovue RTVue OCT Angiography Systems: A Quantitative and Qualitative Approach Examining the Three Capillary Networks in Diabetic Retinopathy.

BACKGROUND AND OBJECTIVES: Construct a method for visualizing the middle capillary plexus (MCP) using Zeiss optical coherence tomography angiography (OCTA) and compare to established segmentation methods using the Optovue system. PATIENTS AND METHODS: Twenty eyes with diabetic retinopathy were imaged. Visualization of the MCP, image artifacts, preservation of pathological changes, foveal avascular zone (FAZ) area, and vessel length density (VLD) were compared between devices. RESULTS: The authors successfully segmented the superficial (SCP), MCP, and deep (DCP) capillary plexuses on both devices. More images artifacts were detected on Optovue. Microaneurysms and telangiectatic vessels were better visualized in the MCP on the Optovue. FAZ area showed a strong correlation between the two instruments (r2= 0.666; P < .0001). The SCP had lower VLD compared to the MCP and DCP on both devices. CONCLUSION: The authors provide an objective and consistent method for manual segmentation using Zeiss OCTA to visualize the three retinal capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e198-e205.].

Prevalence of Subclinical CNV and Choriocapillaris Nonperfusion in Fellow Eyes of Unilateral Exudative AMD on OCT Angiography.

PURPOSE: To determine the prevalence of subclinical choroidal neovascularization (CNV) in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and to quantify choriocapillaris nonperfusion adjacent to CNV. METHODS: We retrospectively reviewed all patients with AMD who underwent OCTA and identified eyes with unilateral exudative AMD. We determined the presence of subclinical CNV on custom en face macular slabs of the outer retina and choriocapillaris and confirmed on cross-sectional scans. Two graders quantified the percent choriocapillaris area of nonperfusion (PCAN) in the entire choriocapillaris slab as well as in the "halo" zone (200 µm) surrounding subclinical and exudative CNV lesions. RESULTS: Of 140 AMD patients who underwent OCTA, 34 had unilateral exudative AMD, with five of the 34 fellow eyes (14.7%) having subclinical CNV. Compared with PCAN in the entire slab (10.333 ± 4.288%), we found that "halo" PCAN, surrounding CNV, was significantly higher (13.045 ± 5.809%; P < 0.001). Further, there was a trend for higher PCAN in exudative CNV eyes (15.267 ± 7.230%) compared with their fellow subclinical CNV eyes (10.823 ± 3.365%, P = 0.115). CONCLUSIONS: There is a notable prevalence of subclinical CNV in fellow eyes with unilateral exudative CNV, and significantly greater choriocapillaris nonperfusion adjacent to all CNV lesions. We identified a trend for increased choriocapillaris nonperfusion in exudative AMD eyes as compared with their fellow subclinical CNV eyes, which deserves further study. TRANSLATIONAL RELEVANCE: OCTA can be useful in clinical practice to detect subclinical CNV and study choriocapillaris dysfunction.

Statistical Model of Optical Coherence Tomography Angiography Parameters That Correlate With Severity of Diabetic Retinopathy.

Purpose: To determine whether combining quantitative optical coherence tomography angiography (OCTA) parameters can achieve high sensitivity and specificity to distinguish eyes with nonproliferative diabetic retinopathy (NPDR) from those with proliferative diabetic retinopathy (PDR) as well as eyes with diabetes and no DR (NoDR) from those with clinical DR (any DR). Methods: This cross-sectional study included 28 eyes (17 patients) with NoDR, 54 eyes (34 patients) with NPDR, and 56 eyes (36 patients) with PDR. OCTA images were processed to quantify the foveal avascular zone (FAZ) area, acircularity, vessel density, skeletonized vessel density, fractal dimension, and intersections and average vessel diameter for the superficial (SCP) and the deep capillary plexus (DCP). Binary logistic regression models were used to identify the OCTA parameters that best distinguished DR severity groups. The area (AUC) under the receiver operating characteristic (ROC) curves, and sensitivity and specificity were calculated for each model. Results: The regression model identified the SCP FAZ area, DCP vessel density, and acircularity as parameters that best distinguished between DR severity groups. ROC curves for NPDR versus PDR had an AUC of 0.845 (P < 0.001) and sensitivity and specificity of 86% and 70%, respectively. ROC curves for NoDR versus any DR showed an AUC of 0.946 (P < 0.001) with sensitivity of 89% and specificity of 96%, with comparable results when explored in males and females separately. Conclusions: We identified a set of OCTA parameters with high sensitivity and specificity for distinguishing between groups based on DR severity, suggesting potential clinical application for OCTA as a screening tool for DR.

Human Parafoveal Capillary Vascular Anatomy and Connectivity Revealed by Optical Coherence Tomography Angiography.

Purpose: To assess the connection among arterioles, venules, and capillaries in three retinal capillary plexuses using optical coherence tomography angiography (OCTA). Methods: This was a prospective, cross-sectional, observational study including 20 eyes of 10 healthy subjects. En face and cross-sectional OCTA images were segmented to study the superficial (SCP), middle (MCP), and deep capillary plexuses (DCP). Using thin slabs and manual segmentation within the three plexuses, we examined the connections between the large-caliber superficial vessels within a 3 × 3 mm2 OCTA scan (arterioles and venules) and the smaller capillaries in each plexus. Results: Twenty eyes of 10 healthy subjects (5 females; average age of 30.8 ± 6.3 years) were included in the analysis. We identified vascular interconnections linking the superficial arterioles and venules with capillaries in each plexus (SCP, MCP, and DCP). We found capillaries in the DCP crossed the horizontal raphe. Conclusions: Our findings show that each of the three capillary plexuses in the parafovea has its own feeding arteriolar supply and draining venules, supporting a physiologic model in which each plexus controls its own oxygenated blood supply to match the metabolic needs of each distinct retinal neurovascular unit.

Projection-Resolved OCT Angiography of Microvascular Changes in Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy.

Purpose: To identify the microvascular changes associated with paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) and to improve our understanding of the relevant involvement of the three retinal capillary plexuses using projection-resolved optical coherence tomography angiography (PR-OCTA). Methods: This was a retrospective study of 18 eyes with AMN or PAMM imaged with OCTA. We used cross-sectional PR-OCTA to localize reduced flow signal to the superficial (SCP), middle (MCP), or deep capillary plexus (DCP) or choriocapillaris that corresponded to inner retinal PAMM or outer retinal AMN lesions on OCT. Results: Five eyes with AMN showed outer retinal disruption on OCT associated with reduced DCP flow signal. All three eyes with AMN and follow-up had recovery of DCP flow. Thirteen eyes with PAMM showed middle retinal disruption on OCT associated with reduced flow signal in both the MCP and DCP. Of these, five also had reduced flow signal in the SCP. All 10 eyes with PAMM and follow-up showed variable recovery of flow signal in one or more plexuses. PAMM reperfusion was primarily arterial in nature. Three eyes with PAMM and no evidence of MCP reperfusion experienced severe thinning of the inner nuclear layer (INL), while seven eyes with robust MCP flow signal recovery showed relative preservation of INL thickness. Conclusions: Using PR-OCTA, we found that AMN was associated with reduced DCP flow signal, while PAMM was associated with reduced MCP and DCP flow signal and occasionally the SCP. The MCP appears to be important in sustaining INL thickness in these eyes.

Solitary retinal hemangioblastoma findings in OCTA pre- and post-laser therapy.

PURPOSE: To report optical coherence tomography angiography (OCTA) findings pre- and post-thermal laser therapy of a rare, asymptomatic, unilateral, isolated retinal hemangioblastoma. OBSERVATIONS: A 40-year-old asymptomatic Caucasian man was found to have an isolated, unilateral retinal hemangioblastoma after referral for possible retinal hole. Comparison of OCTAs pre- and post-thermal laser therapy demonstrated a significant reduction of blood flow toward and within the lesion, in addition to contraction of the lesion and constriction of the accompanying feeder vessels. A 4-month follow-up OCTA showed marked reduction of lesion size, and caliber of treated vessels. CONCLUSIONS AND IMPORTANCE: Non-invasive OCTA imaging of a retinal hemangioblastoma demonstrated decreased blood flow signal and vessel caliber after treatment. OCTA shows potential as a new tool to improve our understanding of the effectiveness of therapy in these lesions.