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1.
Analysis of Progressive Neovascularization in Diabetic Retinopathy Using Widefield OCT Angiography.
Shiraki, A, Sakimoto, S, Eguchi, M, Kanai, M, Hara, C, Fukushima, Y, Nishida, K, Kawasaki, R, Sakaguchi, H, Nishida, K
Ophthalmology. Retina. 2022;(2):153-160
Abstract
PURPOSE To document enlarged neovascularization elsewhere (NVE) quantitatively and morphologically using widefield swept-source (SS) OCT angiography (OCTA) with vitreoretinal interface (VRI) slab images. DESIGN Retrospective, observational imaging study. PARTICIPANTS The study included 46 NVE examples in 25 eyes of 21 consecutive patients who demonstrated severe proliferative diabetic retinopathy with NVE between March 2018 and June 2020 at Osaka University Hospital. METHODS All patients underwent ophthalmologic examination, including ultra-widefield fluorescein angiography and widefield SS OCTA scans. MAIN OUTCOME MEASURES We evaluated the area and the vascular density (VD) of NVE lesions detected on five 12 × 12-mm2 or two 15 × 9-mm2 SS OCTA panoramic VRI slab images obtained at the first and final visits. RESULTS At baseline, the mean NVE area on OCTA was 1.85 ± 2.81 mm2, and the VD of the NVE lesions was 73.9 ± 14.6%. At the final visit, the mean NVE area on OCTA was 2.14 ± 3.14 mm2, and the mean VD of the NVE lesions was 65.3 ± 17.1%. The average NVE size change (square millimeters per month) was associated significantly with the ischemic index (P = 0.009). Growth of NVE area was classified into 2 patterns: round (61.8%) and ramified (38.2%). The round group tended to have a larger ischemic index at baseline than the ramified group (P = 0.0375). CONCLUSIONS We quantified the size and density of NVE lesions over time. The NVE size increase was associated significantly with the severity of ischemic changes. Furthermore, the round growth pattern was correlated significantly with the ischemic index. These findings suggest that the morphologic features of NVE are associated with more severe ischemia.
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A MULTITASK DEEP-LEARNING SYSTEM FOR ASSESSMENT OF DIABETIC MACULAR ISCHEMIA ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGES.
Yang, D, Sun, Z, Shi, J, Ran, A, Tang, F, Tang, Z, Lok, J, Szeto, S, Chan, J, Yip, F, et al
Retina (Philadelphia, Pa.). 2022;(1):184-194
Abstract
PURPOSE We aimed to develop and test a deep-learning system to perform image quality and diabetic macular ischemia (DMI) assessment on optical coherence tomography angiography (OCTA) images. METHODS This study included 7,194 OCTA images with diabetes mellitus for training and primary validation and 960 images from three independent data sets for external testing. A trinary classification for image quality assessment and the presence or absence of DMI for DMI assessment were labeled on all OCTA images. Two DenseNet-161 models were built for both tasks for OCTA images of superficial and deep capillary plexuses, respectively. External testing was performed on three unseen data sets in which one data set using the same model of OCTA device as of the primary data set and two data sets using another brand of OCTA device. We assessed the performance by using the area under the receiver operating characteristic curves with sensitivities, specificities, and accuracies and the area under the precision-recall curves with precision. RESULTS For the image quality assessment, analyses for gradability and measurability assessment were performed. Our deep-learning system achieved the area under the receiver operating characteristic curves >0.948 and area under the precision-recall curves >0.866 for the gradability assessment, area under the receiver operating characteristic curves >0.960 and area under the precision-recall curves >0.822 for the measurability assessment, and area under the receiver operating characteristic curves >0.939 and area under the precision-recall curves >0.899 for the DMI assessment across three external validation data sets. Grad-CAM demonstrated the capability of our deep-learning system paying attention to regions related to DMI identification. CONCLUSION Our proposed multitask deep-learning system might facilitate the development of a simplified assessment of DMI on OCTA images among individuals with diabetes mellitus at high risk for visual loss.
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NEW BIOMARKER QUANTIFYING THE EFFECT OF ANTI-VEGF THERAPY IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY ON ULTRAWIDE FIELD FLUORESCEIN ANGIOGRAPHY: RECOVERY Study.
Fan, W, Nittala, MG, Wykoff, CC, Brown, DM, Uji, A, Hemert, JV, Fleming, A, Robertson, G, Sadda, SR, Ip, M
Retina (Philadelphia, Pa.). 2022;(3):426-433
Abstract
PURPOSE To quantify changes of the retinal vascular bed area (RVBA) in mm2 on stereographically projected ultrawide field fluorescein angiography images in eyes with proliferative diabetic retinopathy after antivascular endothelial growth factor injection. METHODS This is a prospective, observational study. The early-phase ultrawide field fluorescein angiography images (Optos 200Tx) of 40 eyes with proliferative diabetic retinopathy and significant nonperfusion obtained at baseline and after six months (NCT02863354) were stereographically projected by correcting peripheral distortion. The global retinal vasculature on ultrawide field fluorescein angiography was extracted for calculating RVBA by summing the real size (mm2) of all the pixels automatically. RESULTS For the entire cohort, the global RVBA for the entire retina decreased from 67.1 ± 15.5 to 43.6 ± 18.8 mm2 after anti-VEGF treatment at six months (P < 0.001). In the subgroup receiving monthly anti-VEGF injections, the global RVBA decreased from 68.7 ± 16.2 to 33.9 ± 13.3 mm2 (P < 0.001). In the subgroup receiving anti-VEGF every three months, the global RVBA decreased from 65.6 ± 15.1 to 50.8 ± 19.3 mm2 (P = 0.004). CONCLUSION RVBA seems to be a new biomarker to indicate efficiency of retinal vascular changes after anti-VEGF injection. Eyes with proliferative diabetic retinopathy and significant nonperfusion demonstrate reduced RVBA after anti-VEGF treatment.
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Capillary density and caliber as assessed by optical coherence tomography angiography may be significant predictors of diabetic retinopathy severity.
Kushner-Lenhoff, S, Kogachi, K, Mert, M, Chu, Z, Shahidzadeh, A, Palejwala, NV, Wolfe, J, Itty, S, Drenser, KA, Capone, A, et al
PloS one. 2022;(1):e0262996
Abstract
PURPOSE To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. METHODS This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. RESULTS This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. CONCLUSION OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.
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Imaging the eye and its relevance to diabetes care.
Quinn, N, Jenkins, A, Ryan, C, Januszewski, A, Peto, T, Brazionis, L
Journal of diabetes investigation. 2021;(6):897-908
Abstract
Diabetes is a major cause of vision loss globally, yet this devastating complication is largely preventable. Early detection and treatment of diabetic retinopathy necessitates screening. Ocular imaging is widely used clinically, both for the screening and management of diabetic retinopathy. Common eye conditions, such as glaucoma, cataracts and retinal vessel thrombosis, and signs of systemic conditions, such as hypertension, are frequently revealed. As well as imaging by a skilled clinician during an eye examination, non-ophthalmic clinicians, such as general practitioners, endocrinologists, nurses and trained health workers, can also can carry out diabetic eye screening. This process usually comprises local imaging with remote grading, mostly human grading. However, grading incorporating artificial intelligence is emerging. In a clinical research context, retinal vasculature analyses using semi-automated software in many populations have identified associations between retinal vessel geometry, such as vessel caliber, and the risk of diabetic retinopathy and other chronic complications of type 1 and type 2 diabetes. Similarly, evaluation of corneal nerves by corneal confocal microscopy is revealing diabetes-related abnormalities, and associations with and predictive power for other chronic diabetes complications. As yet, the value of retinal vessel geometry and corneal confocal microscopy measures at an individual level is uncertain. In this article, targeting non-ocular clinicians and researchers, we review existent and emerging ocular imaging and grading tools, including artificial intelligence, and their associations between ocular imaging findings and diabetes and its chronic complications.
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Early Detection of Microvascular Impairments With Optical Coherence Tomography Angiography in Diabetic Patients Without Clinical Retinopathy: A Meta-analysis.
Zhang, B, Chou, Y, Zhao, X, Yang, J, Chen, Y
American journal of ophthalmology. 2021;:226-237
Abstract
PURPOSE To evaluate microvascular impairments with optical coherence tomography angiography (OCTA) in the eyes of diabetic patients with no diabetic retinopathy (NDR). DESIGN Systematic review and meta-analysis. METHODS The PubMed and Embase databases were comprehensively searched to identify studies comparing the microvascular changes between diabetic eyes without clinical retinopathy and healthy controls using OCTA. Data of interest were extracted and analyzed by Review Manager V.5.3 and Stata V.14.0. The weighted mean differences and their 95% confidence intervals were used to assess the strength of the association. RESULTS Forty-five cross-sectional studies involving 2241 diabetic and 1861 healthy eyes were ultimately included. OCTA unambiguously revealed that compared with the healthy control group, the NDR group manifested enlarged areas and increased perimeters of the foveal avascular zone, with decreased perfusion density (PD) in both superficial and deep capillary plexus of the macula (except parafoveal PD of the inner retina and foveal PD) and reduced radial peripapillary capillary PD. In addition, subgroup analyses according to the type of diabetes mellitus indicated that most of those differences became nonsignificant (except parafoveal PD in the deep capillary plexus) in type 1 diabetes mellitus, while in type 2 diabetes mellitus they remained statistically significant. CONCLUSION Our results suggested that retinal microvascular impairments might have occurred antecedent to clinically visible diabetic retinopathy and could be detected early by OCTA. However, those manifestations could be inconsistent according to the types of diabetes mellitus.
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EARLY RETINAL MICROVASCULAR ABNORMALITIES IN YOUNG ADULTS WITH TYPE 1 DIABETES MELLITUS WITHOUT CLINICALLY EVIDENT DIABETIC RETINOPATHY.
Chen, YJ, Khouri, AS, Zarbin, MA, Szirth, BC
Retina (Philadelphia, Pa.). 2021;(7):1478-1486
Abstract
PURPOSE To characterize the early retinal microvascular changes in young adults (age: 22.69 ± 3.50 years) with Type 1 diabetes mellitus without clinically detectable diabetic retinopathy using optical coherence tomography angiography and investigate the associated factors. METHODS A total of 36 participants with Type 1 diabetes mellitus (70 eyes) and 34 healthy controls (57 eyes) were retrospectively reviewed. The analyzed optical coherence tomography angiography indices included capillary vessel density, foveal avascular zone area/perimeter/acircularity index, and foveal vascular density, acquired in the 6 × 6-mm2 area centered on the fovea. The generalized estimation equations model was applied to compare the mean values and to study the associated factors. RESULTS In subjects with diabetes, statistically significant decreases were observed in parafoveal vessel density in both superficial and deep capillary plexuses, foveal avascular zone area/perimeter, and foveal vascular density when compared with controls (all P < 0.05). Higher glycated hemoglobin level was independently associated with the decrease of parafoveal vessel density as well as the increase of foveal avascular zone area/perimeter (all P < 0.05). Prepubescent onset of diabetes mellitus was also independently associated with the decrease of superficial parafoveal vessel density, foveal avascular zone area/perimeter, and foveal vascular density (P = 0.015, 0.011, 0.015, and 0.001, respectively). CONCLUSION In young adults with Type 1 diabetes mellitus lacking clinical signs of diabetic retinopathy, optical coherence tomography angiography revealed alterations in retinal microvasculature that were associated with glycated hemoglobin level and onset of diabetes mellitus related to puberty.
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Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield colour fundus photography and fluorescein angiography for detection of lesions in diabetic retinopathy.
Cui, Y, Zhu, Y, Wang, JC, Lu, Y, Zeng, R, Katz, R, Vingopoulos, F, Le, R, Laíns, I, Wu, DM, et al
The British journal of ophthalmology. 2021;(4):577-581
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Abstract
AIMS: To compare widefield swept-source optical coherence tomography angiography (WF SS-OCTA) with ultra-widefield colour fundus photography (UWF CFP) and fluorescein angiography (UWF FA) for detecting diabetic retinopathy (DR) lesions. METHODS This prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to October 2019. Proliferative DR, non-proliferative DR and diabetic patients with no DR were included. All patients were imaged with a WF SS-OCTA using a Montage 15×15 mm scan. UWF CFP and UWF FA were taken by a 200°, single capture retinal imaging system. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), neovascularisation elsewhere (NVE), neovascularisation of the optic disc (NVD) and non-perfusion areas (NPAs). All statistical analyses were performed using SPSS V.25.0. RESULTS One hundred and fifty-two eyes of 101 participants were included in the study. When compared with UWF CFP, WF SS-OCTA was found to be superior in detecting IRMAs (p<0.001) and NVE/NVD (p=0.007). The detection rates of MAs, IRMAs, NVE/NVD and NPAs in WF SS-OCTA were comparable with UWF FA images (p>0.05). Furthermore, when we compared WF SS-OCTA plus UWF CFP with UWF FA, the detection rates of MAs, IRMAs, NVE/NVD and NPAs were identical (p>0.005). Agreement (κ=0.916) between OCTA and FA in classifying DR was excellent. CONCLUSION WF SS-OCTA is useful for identification of DR lesions. WF SS-OCTA plus UWF CFP may offer a less invasive alternative to FA for DR diagnosis.
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IMAGE EVALUATION OF ARTIFICIAL INTELLIGENCE-SUPPORTED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGING USING OCT-A1 DEVICE IN DIABETIC RETINOPATHY.
Kawai, K, Uji, A, Murakami, T, Kadomoto, S, Oritani, Y, Dodo, Y, Muraoka, Y, Akagi, T, Miyata, M, Tsujikawa, A
Retina (Philadelphia, Pa.). 2021;(8):1730-1738
Abstract
PURPOSE To investigate the effect of denoise processing by artificial intelligence (AI) on the optical coherence tomography angiography (OCTA) images in eyes with retinal lesions. METHODS Prospective, observational, cross-sectional study. Optical coherence tomography angiography imaging of a 3 × 3-mm area involving the lesions (neovascularization, intraretinal microvascular abnormality, and nonperfusion area) was performed five times using OCT-HS100 (Canon, Tokyo, Japan). We acquired AI-denoised OCTA images and averaging OCTA images generated from five cube scan data through built-in software. Main outcomes were image acquisition time and the subjective assessment by graders and quantitative measurements of original OCTA images, averaging OCTA images, and AI-denoised OCTA images. The parameters of quantitative measurements were contrast-to-noise ratio, vessel density, vessel length density, and fractal dimension. RESULTS We studied 56 eyes from 43 patients. The image acquisition times for the original, averaging, and AI-denoised images were 31.87 ± 12.02, 165.34 ± 41.91, and 34.37 ± 12.02 seconds, respectively. We found significant differences in vessel density, vessel length density, fractal dimension, and contrast-to-noise ratio (P < 0.001) between original, averaging, and AI-denoised images. Both subjective and quantitative evaluations showed that AI-denoised OCTA images had less background noise and depicted vessels clearly. In AI-denoised images, the presence of fictional vessels was suspected in 2 of the 35 cases of nonperfusion area. CONCLUSION Denoise processing by AI improved the image quality of OCTA in a shorter time and allowed more accurate quantitative evaluation.
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Diabetic vascular hyperpermeability: optical coherence tomography angiography and functional loss assessments of relationships among retinal vasculature changes.
Arima, M, Nakao, S, Kaizu, Y, Wada, I, Yamaguchi, M, Fujiwara, K, Akiyama, M, Stitt, AW, Sonoda, KH
Scientific reports. 2021;(1):4185
Abstract
Our study assessed the influence of vascular permeability on vascular flow density (FD)-correlated retinal sensitivity (RS) in DR. In this cross-sectional, prospective, consecutive study, RS in the extrafoveal macula of DR patient was measured by microperimetry. FD was measured in the total, superficial, and deep capillary plexus layers (TCP, SCP, and DCP) by optical coherence tomography angiography. All measurement points were classified into four categories according to intensity of fluorescein leakage and FD, and the RS reduction was compared. A stratified analysis by retinal thickness (RT) was also performed. Fourteen eyes (14 patients) were enrolled. FDs at 207 RS measurement points were analyzable. For TCP, SCP and DCP, the leakage did not decrease RS at points where FD was maintained. The greater the leakage, the smaller the RS reduction at points with low FD in TCP (P = .020). Points with high leakage showed a significant smaller RS reduction than points with low leakage (P = .001 for TCP, P = .040 for SCP, and P = .046 for DCP) only in areas with low RT and low FD. Our results suggested that vascular hyperpermeability may inhibit the RS reduction in the non-edematous ischemic diabetic retina.