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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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2.
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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FOVEAL MÜLLER CELL CONE AS A PROGNOSTIC OPTICAL COHERENCE TOMOGRAPHY BIOMARKER FOR INITIAL RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CYSTOID DIABETIC MACULAR EDEMA.
Choi, M, Yun, C, Oh, JH, Kim, SW
Retina (Philadelphia, Pa.). 2022;(1):129-137
Abstract
PURPOSE To investigate the effect of the foveal Müller cell cone structure on the anatomical and functional response to intravitreal bevacizumab treatment in patients with diabetic macular edema. METHODS In 93 treatment-naive eyes with center-involved cystic type diabetic macular edema, spectral-domain optical coherence tomography scans of baseline were retrospectively evaluated to determine the foveal Müller cell cone structure and prognostic features including length of disorganization in the retinal inner layers and ellipsoid zone disruption. The area and circularity of the foveal avascular zone of the superficial and deep capillary plexus 1 month after intravitreal bevacizumab treatment were evaluated using optical coherence tomography angiography. RESULTS Destruction of the foveal Müller cell cone structure and a large foveal avascular zone in the deep capillary plexus (mm2) correlated strongly with a poor anatomical response (CST > 250 µm) at 1 month after first intravitreal bevacizumab (Exp [B] = 29.444, P = 0.002 and Exp [B] = 12.419, P = 0.013, respectively). A destroyed Müller cell cone structure (P = 0.008) and length of ellipsoid zone disruption (P < 0.001) at baseline were associated with poor visual acuity at 1 month after the first intravitreal bevacizumab. CONCLUSION The foveal Müller cell cone structure correlates with the response to initial antivascular endothelial growth factor treatment.
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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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EXTENDED FIELD IMAGING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FOR THE STUDY OF RETINAL AND CHOROIDAL CHANGES AFTER RADIATION THERAPY FOR CHOROIDAL MELANOMA: Comparison With Wide-Field Angiography.
Preziosa, C, Corvi, F, Staurenghi, G, Pellegrini, M
Retina (Philadelphia, Pa.). 2021;(2):373-380
Abstract
PURPOSE Radiation retinopathy is a common side effect of ocular radiotherapy with no long-term effective therapy. Optical coherence tomography angiography (OCTA) and wide-field fluorescein angiography (FA) are widely used for the study of radiation maculopathy and peripheral nonperfusion, respectively. We investigated the role of extended field imaging (EFI-OCTA) for the study of retinal and choroidal alterations after radiotherapy for choroidal melanoma. METHODS Cross-sectional observational study of 20 eyes of 20 patients diagnosed with radiation retinopathy. All patients underwent a complete imaging evaluation including FA and indocyanine green angiography (ICGA) with 55° and 102° lens (Spectralis Heidelberg Engineering, Heidelberg, Germany). Optical coherence tomography angiography imaging was performed with the Zeiss PlexElite 9000 Swept Source OCTA (Carl Zeiss Meditec, Dublin, CA) using a 12 × 12-mm volume scan pattern centered on the fovea and a +20.00-diopter lens specifically designed to obtain EFI examination. The imaging methods were then compared in terms of visible field of view, extension of nonperfused areas, and vessel density. RESULTS The mean extension ratio of EFI-OCTA compared to OCTA without EFI, FA/ICGA 55° and FA/ICGA 102° was, respectively, 1.98 ± 0.02, 1.21 ± 0.01 and 0.36 ± 0.003. The mean extension of retinal and choroidal nonperfused areas evaluated by EFI-OCTA (63.03 ± 48.21 and 38.63 ± 30.83 mm2) were significantly higher than with OCTA without EFI (40.40 ± 34.87 and 24.26 ± 21.82 mm2, P < 0.001) but lower than with FA/ICGA 102° (140.7 ± 69.23 and 108.3 ± 69.51 mm2, P < 0.001). No significant differences were found between mean extension of retinal and choroidal ischemic areas measured with EFI-OCTA and FA/ICGA 55° (69.64 ± 51.92 and 47.23 ± 33.59 mm2). The mean vessel density of EFI-OCTA (retina and choroid segmentation) was significantly different compared to OCTA without EFI (P < 0.05). Retinal vessel density was negatively correlated to retinal extension of nonperfused areas (r = -0.5, P = 0.02), and choroidal vessel density was negatively correlated to choroidal nonperfused areas (r = -0.6, P = 0.003) measured with EFI-OCTA. CONCLUSION In our series, EFI-OCTA captured larger areas than OCTA without EFI and FA/ICGA with 55° lens. EFI-OCTA images showed a good definition of retinal and choroidal vascular changes after radiotherapy, suggesting a possible role of this safe and noninvasive imaging technique in the follow-up of patients with radiation retinopathy.
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CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME AND POSTERIOR OCULAR INVOLVEMENT: Case Series of 11 Patients and Literature Review.
Morel, N, Bonnet, C, Mehawej, H, Le Guern, V, Pérard, L, Roumier, M, Brezin, A, Godeau, B, Haroche, J, Benhamou, Y, et al
Retina (Philadelphia, Pa.). 2021;(11):2332-2341
Abstract
PURPOSE To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome. METHODS Retrospective case series of patients presenting with catastrophic antiphospholipid syndrome and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at catastrophic antiphospholipid syndrome diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best-corrected visual acuity. RESULTS This study included 23 patients (11 cases treated by the authors and 12 published case reports); 21 (91%) of them female. Their median age at diagnosis was 28 years (range, 16-79 years). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n = 11, 48%), or retinal vasculitis (n = 1, 4%). Final best-corrected visual acuity was not significantly worse than the best-corrected visual acuity at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months (range, 2-132 months), nearly half the patients (n = 11, 48%) had permanent vision loss including best-corrected visual acuity of <20/400 for 4 patients. CONCLUSION Posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.
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Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea.
Pollreisz, A, Reiter, GS, Bogunovic, H, Baumann, L, Jakob, A, Schlanitz, FG, Sacu, S, Owsley, C, Sloan, KR, Curcio, CA, et al
Investigative ophthalmology & visual science. 2021;(2):26
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Abstract
PURPOSE To refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes. METHODS In a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas. RESULTS Sixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold. CONCLUSIONS Normalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.
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Relationship of Topographic Distribution of Geographic Atrophy to Visual Acuity in Nonexudative Age-Related Macular Degeneration.
Shen, LL, Sun, M, Ahluwalia, A, Young, BK, Park, MM, Toth, CA, Lad, EM, Del Priore, LV
Ophthalmology. Retina. 2021;(8):761-774
Abstract
PURPOSE To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA. DESIGN Retrospective analysis of a multicenter, prospective, randomized controlled trial. PARTICIPANTS The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. METHODS We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model. MAIN OUTCOME MEASURES Geographic atrophy area in macular subfields and VA. RESULTS The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm2 vs. 1.10 ± 1.62 mm2; P = 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm2 vs. 1.03 ± 1.53 mm2; P < 0.001). Total GA area correlated poorly with VA (r2 = 0.07). Among GA areas in 9 subfields, only GA area in the central zone was associated independently with VA (P < 0.001). We determined 1 mm as the optimal diameter for the central zone in which GA area correlated best with VA (r2 = 0.45). On average, full GA coverage of the central 1-mm diameter zone corresponded to 34.8 letters' decline in VA. The VA decline rate was comparable between eyes with initial noncentral and central GA before GA covered the entire central 1-mm diameter zone (2.7 letters/year vs. 2.8 letters/year; P = 0.94). CONCLUSIONS The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.
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Effect of Aflibercept on Diabetic Retinopathy Severity and Visual Function in the RECOVERY Study for Proliferative Diabetic Retinopathy.
Alagorie, AR, Velaga, S, Nittala, MG, Yu, HJ, Wykoff, CC, Sadda, SR
Ophthalmology. Retina. 2021;(5):409-419
Abstract
PURPOSE To evaluate the effect of intravitreal aflibercept on diabetic retinopathy (DR) severity and visual function in patients with proliferative DR (PDR) without diabetic macular edema (DME). DESIGN Prospective, longitudinal, multicenter clinical trial. PARTICIPANTS Forty eyes of 40 patients with PDR and no DME were enrolled in this study. Patients were randomized into monthly and quarterly 2-mg aflibercept injection cohorts and were treated over a period of 12 months. METHODS All patients underwent ultra-widefield fundus imaging including pseudocolor and fluorescein angiography using an Optos 200Tx device. MAIN OUTCOME MEASURES Severity of DR at baseline, month 6, and month 12 was evaluated using the DR severity scale (DRSS). The DRSS scores were correlated with the 25-item Visual Function Questionnaire (VFQ-25) and 39-item Visual Function Questionnaire (VFQ-39) scores at baseline and month 12. RESULTS Mean age of the patients was 48.2 years (range, 25-75 years), mean duration of diabetes mellitus was 16.1 years (range, 2-36 years), and median glycated hemoglobin level was 8.8% (IQR, 7.4%-10%). Both monthly and quarterly groups demonstrated a statistically significant regression in DRSS from baseline to month 12 (P < 0.001). The monthly group demonstrated a statistically significant greater regression of DRSS score at the month 6 visit compared with the quarterly group (P = 0.019). However, the difference between the two groups became statistically insignificant at month 12 visit (P = 0.309). Also no difference was found in mean VFQ-25 and VFQ-39 composite scores between the monthly and quarterly groups at month 12 (P = 0.947 and P = 0.921, respectively). The improvement in mean VFQ-25 and VFQ-39 composite scores at month 12 was correlated significantly with improvement in DRSS score (r = 0.384 and P = 0.039, and r = 0.361 and P = 0.046, respectively). CONCLUSIONS In this study of eyes with PDR without DME, both monthly and quarterly aflibercept injection groups showed significant improvement in DR severity at month 12 compared with baseline. The improvement in DRSS score was associated with an improvement in VFQ-25 and VFQ-39 composite score.
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SUSPENDED SCATTERING PARTICLES IN MOTION MAY INFLUENCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VESSEL DENSITY METRICS IN EYES WITH DIABETIC MACULAR EDEMA.
Maltsev, DS, Kulikov, AN, Kazak, AA, Freund, KB
Retina (Philadelphia, Pa.). 2021;(6):1259-1264
Abstract
PURPOSE To study the effect of the suspended scattering particles in motion (SSPiM) on optical coherence tomography angiography (OCTA) vessel density metrics in eyes with diabetic macular edema (DME). METHODS Thirty-four eyes with DME from 27 patients (16 men and 11 women; 61.4 ± 9.6 years) with DME were included in this retrospective cohort study. Among these eyes, 19 (55.9%) showed the SSPiM artifact on OCTA. All participants received 3-mm and 6-mm optical coherence tomography angiography (OCTA) imaging. Perfusion density and skeletonized vessel density were calculated for the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), and these were compared between eyes with and without SSPiM. Additionally, foveal vessel density in a 300-µm-wide region around the foveal avascular zone (FVD) was evaluated on 3-mm OCTA scans. The main outcome measures were vessel density in the SCP and the DCP. RESULTS Among the 3-mm OCTA images, there was no statistically significant difference in SCP vessel density in eyes with and without SSPiM (P = 0.98). Vessel density in the DCP (P = 0.001 and P = 0.028 for perfusion and skeletonized vessel density, respectively) and FVD (P = 0.03) on 3-mm OCTA scans were significantly higher in DME eyes with SSPiM than in those without SSPiM. There were no statistically significant differences in vessel density in SCP and DCP between eyes with and without SSPiM based on 6-mm OCTA scans. CONCLUSION The presence of SSPiM may lead to an overestimation of DCP vessel density in eyes with DME when 3-mm OCTA scans are used for analysis.