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PURPOSE: To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography (OCTA) and retinal sensitivity measured by microperimetry across diabetic retinopathy severity. METHODS: Diabetic patients with and without retinopathy, and age matched non-diabetic controls, underwent OCTA imaging and microperimetry testing. Skeletonized vessel density (SVD) was computed from 3 mm x 3 mm OCTA images of the superficial capillary plexus, deep capillary plexus, and full retinal layer, excluding larger retinal vessels and the foveal avascular zone (FAZ). Pearson’s correlation was used to assess associations between average sensitivity and vessel density globally and in four parafoveal zones; centrally, average sensitivity was correlated with the FAZ area. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements. RESULTS: Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the FAZ areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this appeared to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities. CONCLUSIONS: Data from this study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in the parafovea of diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.

Background COVID-19, a highly contagious respiratory virus, presents unique challenges to ophthalmology practice as a high-volume, office-based specialty. In response to the COVID-19 pandemic, many operational changes were adopted in our ophthalmology clinic to enhance patient and provider safety while maintaining necessary clinical operations. The aim of this study was to evaluate how measures adopted during the pandemic period affected retina clinic performance and patient satisfaction, and to model future clinic flow to predict operational performance under conditions of increasing patient and provider volumes. Methods Clinic event timestamps and demographics were extracted from the electronic medical records of in-person retina encounters from March 15 to May 15, 2020 and compared with the same period in 2019 to assess patient flow through the clinical encounter. Patient satisfaction was evaluated by Press Ganey patient experience surveys obtained from randomly selected outpatient encounters. A discrete-events simulation was designed to model the clinic with COVID-era restrictions to assess operational performance under conditions of increasing patient and provider volumes. Results Retina clinic volume declined by 62 % during the COVID-19 health emergency. Average check-in-to-technician time declined 79 %, total visit length declined by 46 %, and time in the provider phase of care declined 53 %. Patient satisfaction regarding access nearly doubled during the COVID-period compared with the prior year (p p Conclusions Clinic throughput was optimized in response to the COVID-19 health emergency. Modeling these clinic changes can help plan for eventual volume increases in the setting of limits imposed in the COVID-era.

Many studies over the past 20 years have pursued the goal of preventing or deferring progression from early and intermediate age-related macular degeneration (AMD) to advanced AMD. The onset of neovascular AMD has been used as a primary endpoint in some prophylactic clinical trials because it is easy to assess and relatively well-defined. Nevertheless, the use of this endpoint for assessing progression of AMD lacks validation. The aims of this paper are to review the current practice of clinical trials investigating the prevention of progression of early or intermediate AMD to neovascular AMD, so-called prophylactic trials, as well as identify ongoing efforts to standardize endpoints and select the ideal population for such studies.

Purpose To identify optical coherence tomography angiography (OCTA) derived vessel metrics of the macula and optic nerve head (ONH) that predict diabetic retinopathy (DR) disease progression. Design Secondary analysis of clinical trial data Methods This was a sub-analysis of prospectively collected data from 73 subjects that participated in the TIME-2b Study (Aerpio Pharmaceuticals), a multi-center clinical trial for patients with moderate to severe DR treated with AKB-9778 and followed over a 12-month period. Eligible subjects were tested every 3 months with color fundus photography, spectral domain OCT and slit-lamp biomicroscopy. OCTA of the macula and ONH was obtained for a subset of patients enrolled at participating sites. En-face, full-depth retinal projections centered at the macula were analyzed for multiple metrics including foveal avascular zone (FAZ) area and perimeter, non-perfusion area, vessel density (VD) and presence of intraretinal microvascular abnormalities (IRMA). VD of the radial peripapillary capillaries was evaluated in four quadrants surrounding the optic disc for ONH images. Progression was defined as a ≥ 2-step increase in DR severity scale score or development of diabetic macular edema. Results Over a follow-up period of 12 months, 15 of 73 (20.5%) subjects progressed. At pre-treatment baseline, larger FAZ area, presence of IRMA, and reduced peripapillary VD in the superior temporal and inferior temporal regions were significantly associated with increased odds of progression. Conclusions FAZ area and temporal peripapillary VD are predictors of DR progression. OCTA metrics may improve progression risk assessment in DR when compared to established risk factors alone.

To compare the ability of wide-field optical coherence tomography angiography (WF-OCTA) to that of ultra-wide field fluorescein angiography (UWF-FA) and ultra-wide-field color fundus photography (UWF-CP) to detect retinal neovascularization (NV) in eyes with proliferative diabetic retinopathy (PDR). In this cross-sectional study, naive patients with active PDR underwent UWF-FA and UWF-CP using the Optos 200Tx and WF-OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000. NV was defined on OCTA when the co-registered B-scan with flow overlay of the vitreoretinal interface (VRI) segmentation showed extraretinal proliferation. Three masked readers examined the UWF-FA, UWF-CP, and WF-OCTA independently for the presence of NV. Statistical analysis was performed to compare the diagnostic accuracy of the 3 wide-field imaging modalities using OCT B-scan as the reference standard. In 82 eyes with PDR, neovascularization of the disc (NVD) was detected in 13 eyes by UWF-CP, 35 eyes with UWF-FA, and 37 eyes with OCTA using the VRI slab. Upon review of the 2500 OCT B-scans with superimposed flow overlay of each eye, NVD was confirmed in 37 eyes. The sensitivity and specificity of NVD detection were 35.1% and 97.8%, respectively for UWF-CP; 94.6% and 100%, respectively, for UWF-FA; and 100% and 100% for WF-OCTA. One hundred ninety-six foci of neovascularization elsewhere (NVE) were identified with the OCT B-scan with superimposed flow overlay. UWF-CP analysis was able to detect 62 foci of NVE of the 196 confirmed by B-scan (31.6% detection rate). An additional 11 foci of NVE seen on UWF-CP were not confirmed by B-Scan (15% false positive rate). There were 182 foci of NVE identified by UWF-FA (detection rate 91.3%), while WF-OCTA detected 196 retinal NVEs (detection rate 100%). The rate of false positives for both UWF-FA and WF-OCTA was low (

Background The purpose of this study was to investigate the association between diabetic retinopathy (DR) severity and macular choriocapillaris (CC) flow deficit percentage (FD %) in different macular regions using swept-source optical coherence tomography angiography (SS-OCTA). Methods Diabetic patients with SS-OCTA images were graded by severity and retrospectively assessed. CC FD % was calculated in four different regions of the OCTA image: inner, middle, outer, and full-field region. The generalized estimating equations (GEE) approach for clustered eye data was used to determine effect size and significance of age and disease severity on FD % for each region. Results 160 eyes from 90 total diabetic patients met inclusion criteria. Out of 90 patients, 33 had no DR, 17 had mild nonproliferative DR (NPDR), 8 had moderate NPDR, 10 had severe NPDR and 22 had proliferative DR. Age and DR severity had a significant positive association with FD % for each region studied with a greater effect in the two centermost regions. The increase in flow deficit percentage per year of age by region was: inner 0.12 (p Conclusions Topographic analysis of the CC FD % in diabetic eyes suggests that CC flow impairment corresponds to DR severity, with all studied regions of the CC significantly affected. There was greater regional impairment due to age and disease severity in the inner and middle regions.

Intravitreal antivascular endothelial growth factor (anti-VEGF) treatment has drastically improved the visual and anatomical outcomes in patients with diabetic macular edema (DME); however, success is not always guaranteed, and a proportion of these eyes demonstrate persistent DME (pDME) despite intensive treatment. While standardized criteria to define these treatment-resistant eyes have not yet been established, many studies refer to eyes with no clinical response or an unsatisfactory partial response as having pDME. A patient is considered to have pDME if the retinal thickness improves less than 10-25% after 6 months of treatment. A range of treatment options have been recommended for eyes with pDME, including switching anti-VEGF agents, using corticosteroids and/or antioxidant drugs in adjunct with anti-VEGF therapy, and vitrectomy. In addition, multimodal imaging of DME eyes may be advantageous in predicting the responsiveness to treatment; this is beneficial when initiating alternative therapies. We explore the literature on persistent DME regarding its defining criteria, incidence, the baseline biological markers that may be useful in anticipating the response to treatment, and the available treatment options.

Diabetic retinopathy is one of the leading causes of blindness worldwide. Optical coherence tomography angiography (OCTA) is a non-invasive technology that provides depth-resolved images of the chorioretinal vasculature and allows for the understanding of the changes in vasculature with diabetic retinopathy. Not only can it provide qualitative information, but OCTA can also provide quantitative information about the vasculature in patients with diabetic retinopathy. Macular vessel density is one of the quantitative metrics that can be obtained from OCTA images. This is a repeatable and non-subjective measurement that can provide valuable insight into the pathophysiology of diabetic retinopathy. In this non-systematic review, the measurement of macular vessel density in diabetic retinopathy and the reasons for its importance in the diagnosis and management of patients with diabetes and varying severities of diabetic retinopathy is discussed.

Purpose To report a case of presumed ocular sarcoidosis initially presenting with features of multiple evanescent white dot syndrome (MEWDS) with atypical optical coherence tomography angiography (OCTA) findings. Observations A 23 year-old woman presented with a unilateral central scotoma, photophobia, and decreased visual acuity after a viral illness. Examination of the right eye revealed multiple round white macular spots and stippled granularity at the fovea. Multimodal imaging with fluorescein angiography (FA), indocyanine green angiography (ICG), fundus autofluorescence (FAF), and optical coherence tomography (OCT) was consistent with a diagnosis of MEWDS. However, OCTA demonstrated choriocapillaris (CC) flow deficits, which is not typical for MEWDS. The clinical course was initially consistent with MEWDS, with spontaneous recovery of symptoms over ensuing months. The patient presented five months later with floaters and a central scotoma. Examination showed panuveitis, and systemic evaluation revealed an elevated angiotensin converting enzyme (ACE) and hilar lymphadenopathy on chest x-ray consistent with presumed sarcoidosis. Conclusions and Importance A case of MEWDS atypically demonstrated CC flow deficits on OCTA and subsequently presented as uveitis secondary to presumed sarcoidosis. Atypical features in MEWDS may be a sign of another disorder masquerading early on as MEWDS and ought to prompt further investigation.

Purpose To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions. Design Observational descriptive study. Participants Thirty-two participants with normal and pathologic retina examination results. Methods Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae. Main Outcomes Measures Description of HMM module-obtained macula images. Results From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane. Conclusions In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.

Understanding the precision of measurements on and across optical coherence tomography angiography (OCTA) devices is critical for tracking meaningful change in disease. The purpose of this study is to investigate the repeatability and reproducibility of vessel area density and vessel skeleton density measurements from various commercial OCTA devices in diabetic eyes. Patients were imaged three consecutive times each on three different OCTA devices. En face OCTA images of the superficial capillary plexus, deep capillary plexus, and full retinal layer were exported for analysis. Vessel area density and vessel skeleton density were calculated. The coefficient of repeatability (CoR) was calculated to assess the repeatability of these measurements, and linear mixed models were utilized to assess the reproducibility of these measurements. Forty-four eyes from 27 diabetic patients were imaged. Normalized CoR values ranged between 3.44 and 6.65% when calculated for vessel area density and between 1.35 and 23.39% when calculated for vessel skeleton density. When stratified by disease severity, the swept-source OCTA device consistently produced the smallest CoR values for vessel area density in the full retinal layer. Vessel area density measurements were repeatable across the two spectral-domain devices in the full retinal layer when all severities were combined, as well as in diabetic patients without retinopathy, mild nonproliferative diabetic retinopathy (NPDR), and moderate NPDR. Vessel area density measured in the full retinal layer may be a more precise measure than vessel skeleton density to follow diabetic retinopathy patients both on the same device and across devices.

Purpose Microperimetry (MP) allows for measurement of retinal sensitivity at precise locations and is now commonly employed as a clinical trial endpoint. Test–retest reliability is important when evaluating treatment effects in patients with geographic atrophy (GA). This study aimed to determine the test–retest variability of MP in patients with moderate to severe GA using the MAIA MP device. Methods In this prospective study, patients with a confirmed diagnosis of foveal-involving GA were enrolled. Participants performed three MP assessments of a selected eye over two visits with the Macular Integrity Assessment (MAIA) 2 instrument (Centervue, Padova, Italy) utilizing a wide 30° grid, consisting of 93 stimuli (Goldmann III) using a 4-2 representation strategy, encompassing the entire area of GA and beyond. Mean retinal sensitivity (MS) was expressed as an average threshold value (dB) for the entire field tested. Coefficients of Repeatability at a 95% level (CoR95) were calculated for Point Wise Sensitivity (PWS). Fixation stability (FS) was assessed by evaluating the area of an elliptical representation encompassing 95% of the cloud of fixation points (CFP) dataset generated by the MAIA MP, known as the bivariate contour ellipse area (BCEA). Results A total of 8 subjects were enrolled (21 tests), with six subjects completing 3 MP assessments. BCVA in these patients ranged from 20/100 to 20/800. The mean area of GA was 18.7 ± 12.3 mm2. The average time to complete one MP assessment was 13 min 9 s and mean BCEA@95% was 38.5 ± 19.3°2. The MS was 14.3 ± 4.5 dB. No significant increase in MS was noted between testing pairs 1&2 and 2&3. The preferred retinal locus was maintained in the same quadrant on successive tests. The mean CoR95 for PWS were similar for testing pairs 1&2 (± 3.50 dB) and 2&3 (± 3.40). Conclusion Microperimetry using a wide grid can be reliably performed in a reasonable amount of time in patients with moderate and severe vision loss secondary to GA. There was no learning effect seen between sequential assessments when analyzing MS or PWS. A change of approximately 4 dB in PWS provides a threshold for considering a true change in this patient cohort.