Relationship between Functional and Structural Changes in Diabetic Vessels in Optical Coherence Tomography Angiography

PURPOSE To evaluate a fully automated local fractal dimension method to quantify vessel density and foveal avascular zone (FAZ) area in optical coherence tomography angiography (OCTA) images. METHODS Fifty-two healthy Asian Indian eyes underwent imaging prospectively with OCTA system. Superficial and deep retinal vascular plexus was imaged. Local fractal analysis was applied to the OCTA images. A scan area of 3 × 3 mm was selected in the superficial and deep retinal layers. Foveal avascular zone area and vessel density were quantified in circular and sectoral zones around the fovea. A unique contour map of vessel density and dropout zones was developed to perform regional comparisons. RESULTS Foveal avascular zone of superficial (0.35 ± 0.013 mm2) and deep (0.49 ± 0.012 mm2) retinal vascular plexus was segmented. The agreement between the manually segmented and local fractal dimension segmented FAZ area was 0.97 (95% confidence interval [CI]: 0.94-0.98) and did not change significantly with age (P = 0.94 and 0.21, respectively). The vessel density was greater in the deep than the superficial retinal vascular plexus (P < 0.0001). When the image was subdivided into sectors around the FAZ, inferior sector had greater vessel density than the others (temporal, superior, and nasal) in both superficial and deep retinal vascular plexus (P < 0.05). These observations were similar to recent studies on animal retinal vasculature map. CONCLUSIONS A novel implementation of local fractal dimension to calculate vessel density and FAZ area was demonstrated. Age did not impact vessel density but sectoral analyses showed greater vessel density in the inferior zone.

BackgroundTo analyze the changes in foveal avascular zone (FAZ) area, perimeter, and circularity in the superficial (SCP) and deep (DCP) capillary plexuses in eyes with diabetic macular edema (DME) treated with intravitreal anti-VEGF using optical coherence tomography angiography (OCTA).MethodsThis prospective observational study included 56 eyes from 32 patients with DME that received intravitreal anti-VEGF. OCTA images were obtained at baseline and 1, 3, and 6 months of follow-up. The outcome measures were FAZ area, perimeter, and circularity in both the SCP and DCP, as well as central subfield thickness (CST) and best-corrected visual acuity (BCVA).ResultsThe mean number of intravitreal anti-VEGF injections received during the observation period was 4.60 ± 0.82 (range: 3–6). The FAZ area, perimeter, and circularity were statistically unchanged at all observation points in both the SCP (p = 0.772, p = 0.405, p = 0.157, respectively) and the DCP (p = 0.620, p = 0.769, p = 0.481, respectively). Despite having no change in the FAZ parameters, there was still a statistically significant decrease in CST (p < 0.001) as well as a statistically significant increase in BCVA (p = 0.004) during the observation period.ConclusionsThe FAZ area, perimeter, and circularity in the SCP and DCP as measured by OCTA remained stable during the first 6 months of intravitreal anti-VEGF therapy in eyes with DME. While there were no significant changes in the FAZ, treatment with intravitreal anti-VEGF still resulted in decreased CST and improved BCVA.

OCT Angiography Biomarkers for Predicting Visual Outcomes after Ranibizumab Treatment for Diabetic Macular Edema

To analyse macular microvascular alterations in myopic choroidal neovascularization (mCNV) and the efficiency of anti-vascular endothelial growth factor (anti-VEGF) therapy for mCNV by optical coherence tomography angiography (OCTA). A total of 123 patients were included in this retrospective study, divided into mCNV group, high myopia (HM) group, and normal group at the Affiliated Eye Hospital of Wenzhou Medical University from January 2017 to January 2019. Superficial vessel density, deep capillary density, foveal avascular zone (FAZ) area, A-circularity index (AI) and vessel density around the 300 µm width of the FAZ region density (FD) and the area of choroidal neovascularization (CNV) lesion (only for mCNV group) were measured on 3×3 mm2 OCTA images. FAZ area was corrected for axial length. Central macular thickness (CMT) was measured on OCT in mCNV group. Compared the parameters on OCTA of 3 groups and pre-anti-VEGF and post-anti-VEGF at 1, 2, 3, and 6mo follow-up in mCNV group. There were significant differences among 3 groups in superficial vessel density, deep capillary density and FD (P<0.05). FAZ area in HM group was smaller than normal group (P<0.05), but there was no significant difference between mCNV group and the other two group. AI increased in mCNV group (P<0.05). The mean CMT, area and flow area of CNV lesion decreased after treatment (P<0.05), while vessel density and FAZ didn't change. The mean CMT, area and flow area of CNV lesion statistically decreased after anti-VEGF treatment in mCNV group (P<0.05), while superficial vessel density, deep capillary density and FAZ area, AI and FD didn't change. The mean reduction ratio of lesions was 50.32% (7.07% to 100%). Lesion regression 100% was observed in 2 cases (4.88%). There was a negative correlation between the CNV lesion area and reduction ratio (r=-0.380, P=0.042) and the flow lesion area and reduction ratio (r=-0.402, P=0.030). Macular vessel density decreases, FAZ turns smaller and more irregular in mCNV eyes. Anti-VEGF therapy is efficient for mCNV without affecting vessel density and FAZ, but it is unable to completely eliminate CNV lesions in most cases. The bigger mCNV lesions have lower reduction ratio.

We aimed to assess the ability of deep learning (DL) and support vector machine (SVM) to detect a nonperfusion area (NPA) caused by retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA) images. The study included 322 OCTA images (normal: 148; NPA owing to RVO: 174 [128 branch RVO images and 46 central RVO images]). Training to construct the DL model using deep convolutional neural network (DNN) algorithms was provided using OCTA images. The SVM used a scikit-learn library with a radial basis function kernel. The area under the curve (AUC), sensitivity and specificity for detecting an NPA were examined. We compared the diagnostic ability (sensitivity, specificity and average required time) between the DNN, SVM and seven ophthalmologists. Heat maps were generated. With regard to the DNN, the mean AUC, sensitivity, specificity and average required time for distinguishing RVO OCTA images with an NPA from normal OCTA images were 0.986, 93.7%, 97.3% and 176.9 s, respectively. With regard to SVM, the mean AUC, sensitivity, and specificity were 0.880, 79.3%, and 81.1%, respectively. With regard to the seven ophthalmologists, the mean AUC, sensitivity, specificity and average required time were 0.962, 90.8%, 89.2%, and 700.6 s, respectively. The DNN focused on the foveal avascular zone and NPA in heat maps. The performance of the DNN was significantly better than that of SVM in all parameters (p < 0.01, all) and that of the ophthalmologists in AUC and specificity (p < 0.01, all). The combination of DL and OCTA images had high accuracy for the detection of an NPA, and it might be useful in clinical practice and retinal screening.

ObjectivesThe foveal avascular zone (FAZ) is a biomarker for quantifying diabetic macular ischemia (DMI), to automate the identification and quantification of the FAZ in DMI, using an improved U-Net convolutional neural network (CNN) and to establish a CNN model based on optical coherence tomography angiography (OCTA) images for the same purpose. Methods The FAZ boundaries on the full-thickness retina of 6 × 6 mm en face OCTA images of DMI and normal eyes were manually marked. Seventy percent of OCTA images were used as the training set, and ten percent of these images were used as the validation set to train the improved U-Net CNN with two attention modules. Finally, twenty percent of the OCTA images were used as the test set to evaluate the accuracy of this model relative to that of the baseline U-Net model. This model was then applied to the public data set sFAZ to compare its effectiveness with existing models at identifying and quantifying the FAZ area. Results This study included 110 OCTA images. The Dice score of the FAZ area predicted by the proposed method was 0.949, the Jaccard index was 0.912, and the area correlation coefficient was 0.996. The corresponding values for the baseline U-Net were 0.940, 0.898, and 0.995, respectively, and those based on the description data set sFAZ were 0.983, 0.968, and 0.950, respectively, which were better than those previously reported based on this data set. Conclusions The improved U-Net CNN was more accurate at automatically measuring the FAZ area on the OCTA images than the traditional CNN. The present model may measure the DMI index more accurately, thereby assisting in the diagnosis and prognosis of retinal vascular diseases such as diabetic retinopathy.

To investigate the effect of image averaging on qualitative and quantitative assessments of optical coherence tomography angiography (OCTA) images from eyes of patients with branch retinal vein occlusion (BRVO). Macular OCTA images of 33 eyes of 33 patients with BRVO were obtained using the HS100 HR-SD-OCT system (Canon, Inc.). For each eye, five OCTA cube scans were obtained with a 3 × 3mm scan protocol, and the data were averaged and compounded into a single high image quality cube data using built-in software. Pre- and post-averaging images were compared qualitatively and quantitatively in superficial capillary plexus (SCP) and deep capillary plexus (DCP) OCTA image slabs. After averaging, all OCTA images showed marked improvement in image quality with less background noise and better vessel continuity. The number of microaneurysms in both the SCP and DCP was larger in single images than in averaged images. A significant increase in the detection rate of capillary telangiectasia in the DCP was noted after image averaging. The number of eyes with disrupted foveal avascular zone (FAZ) decreased significantly after averaging (P = .0253). Five eyes (15.2%) with a disrupted FAZ on the single image showed an intact FAZ after averaging. Vessel length density (VLD) and fractal dimension (FD) significantly decreased and vessel diameter index (VDI) increased after averaging, while significant changes were not observed in vessel density (VD) in both the SCP and DCP. In the SCP, lower VD, VLD, and fractal dimension were significantly correlated with worse visual acuity. OCTA averaging has a significant effect on qualitative and quantitative assessments in eyes with BRVO.

To evaluate the changes in foveal avascular zone (FAZ) area and the retinal capillary density after a single intravitreal anti-VEGF injection for macular edema secondary to diabetic retinopathy or retinal vein occlusion. In this prospective noncomparative case series, 18 eyes of 15 patients with diabetic macular edema (13 eyes) or macular edema secondary to central retinal vein occlusion (5 eyes) were included. Optical coherence tomography angiography (OCTA) images were obtained, and retinal capillary vessel density and FAZ area were measured in the foveal and parafoveal regions at the level of the superficial (SCP) and deep retinal capillary plexus (DCP) before and at the first visit after intravitreal injection. The mean interval between baseline and follow up OCTA was 32.5 ± 9.4 (range, 21-50) days. Foveal and parafoveal vessel density in the SCP and DCP were not significantly different before and after intravitreal injection (all P > 0.1), nor was FAZ area (P = 0.48 and P = 0.42, respectively). No significant difference was found between eyes with diabetic macular edema and those with retinal vein occlusion with respect to the mean change of vessel density and FAZ area (all P > 0.05). In this pilot study, retinal capillary density and FAZ area remained statistically unchanged in the short-term after a single intravitreal injection of an anti-VEGF agent.

The Foveal Avascular Zone (FAZ) is of clinical importance since the retinal vascular arrangement around the fovea changes with retinal vascular diseases and in high myopic eyes. Therefore, it is important to segment and quantify the FAZs accurately. Using a novel location-aware deep learning method the FAZ boundary was segmented in en-face optical coherence tomography angiography (OCTA) images. The FAZ dimensions were compared the parameters determined using four methods: (1) device in-built software (Cirrus 5000 Angioplex), (2) manual segmentation using Image J software by an experienced clinician, and (4) the new method (new location-aware deep-learning method). The parameters were measured from OCTA data from healthy subjects (n=34) and myopic patients (n=66). For this purpose, FAZ location was manually delineated in en-face OCTA images of dimensions 420x420 pixels corresponding to 6mm x 6mm. A modified UNet segmentation with an additional channel from a Gaussian distribution around the likely location of the FAZ was designed and trained using 100 manually segmented OCTA images. The predicted FAZ and the related parameters were then obtained using a test dataset consisting of 100 images. For analysis, two strategies were applied. The segmentation of FAZ was compared using the Dice coefficient and Structural Similarity Index (SSIM) to determine the effectiveness of the proposed deep learning method when compared to the other three methods. Furthermore, to provide deeper insight, a set of FAZ dimensions namely area, perimeter, circularity index, eccentricity, perimeter, major axis, minor axis, inner circle radius, circumcircle radius, the maximum and minimum boundary dimensions, and orientation of major axis were compared between the 3 methods. Finally, vessel-related parameters including tortuosity, vessel diameter index (VDI) and vessel avascular density (VAD) were calculated and compared. The high myopic eyes exhibited a narrowing the FAZ area and perimeter. The currently developed algorithm does not correct for axial length variations. This analysis should be extended with a larger number of images in each group of myopia as well as correcting for axial length variations.

Objectives:To investigate the association between optical coherence tomography angiography (OCTA) findings and inner retinal thickness (IRT) in diabetic patients.Materials and Methods:This retrospective study included 23 eyes of 23 diabetic patients with retinopathy (group 1), 30 eyes of 30 diabetic patients without retinopathy (group 2), and 27 eyes of 27 non-diabetic age-matched controls (group 3). Foveal avascular zone (FAZ) area (mm2), average vessel density (%) in the parafoveal region, and average IRT in the parafoveal region (μm) were calculated using 6x6 mm OCTA images. Correlations between IRT and OCTA findings were analyzed.Results:The mean FAZ area was 0.32±0.11 mm2 in group 1, 0.29±0.08 mm2 in group 2, and 0.22±0.09 mm2 in group 3. There were statistically significant differences between groups 1 and 3 (p<0.001) and between groups 2 and 3 (p=0.001). Average IRT was 108.02±9.42 µm in group 1, 110.12±11.01 µm in group 2, and 114.41±5.21 µm in group 3, with statistically significant differences between groups 1 and 3 (p=0.003) and between groups 2 and 3 (p=0.014). In both group 1 and group 2, average IRT was correlated with FAZ area (r=-0.320 and -0.512, respectively).Conclusion:The inner retina is significantly thinner in diabetic patients with and without retinopathy compared to controls. Quantitative OCTA findings and IRT are correlated in diabetic patients, suggesting that both structures are compromised in patients with diabetes with or without retinopathy. Microvascular changes in FAZ detected by OCTA might precede neurodegenerative changes.

PurposeThe purpose of this study was to evaluate specifically in type 1 diabetes mellitus (DM) individuals the relationship between perifoveal superficial capillary plexus (SCP) parameters assessed by optical coherence tomography angiography (OCTA) and diabetic retinopathy (DR) grade.MethodsCross-sectional analysis of a large scale prospective OCTA trial cohort (ClinicalTrials.gov NCT03422965). A total of 1186 eyes (593 individuals), 956 type 1 DM eyes (478 patients), and 230 control eyes (115 healthy volunteers) were included in this study. DR stage was graded according to the International Classification. OCTA imaging was performed with a commercially available device (Cirrus HD-OCT). Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) area, perimeter and circularity measurements were quantified in the SCP and receiver operating characteristic (ROC) curves were constructed for each OCTA parameter.ResultsVD and PD (in both 3 × 3 and 6 × 6 mm captures) were inversely associated with DR stage (P < 0.001 in all cases) in a multiple regression analysis after controlling by age, gender, signal strength index, axial length, and DM duration. Greater FAZ area and perimeter and conversely lower circularity measurements were observed as DR severity increased in both scanning protocols (P < 0.05 in all cases).ConclusionsIn type 1 DM individuals, OCTA provides an objective, continuous, and reliable method for accurate quantification of VD, PD, and FAZ parameters in the SCP, which ultimately correlate with DR stages.Translational RelevanceObjective OCTA measurements of the retinal microvasculature could substitute the clinical DR classification in patients with type 1 DM, identify patients at risk of DR progression, and inform treatment decisions to modify the evolution of the disease.

To investigate the microstructure of cystoid macular edema (CME) in retinitis pigmentosa (RP) and the associated vascular changes using optical coherence tomography (OCT) angiography. In this retrospective study, we included 42 eyes of 21 patients with RP and age-similar normally sighted controls who underwent both OCT and optical coherence tomography angiography. Using OCT, spatial distribution of CME and the retinal layer, which CME located, was examined. Optical coherence tomography angiography images of the superficial capillary plexus and deep capillary plexus were obtained. Foveal and parafoveal flow densities in each layer and foveal avascular zone area were measured. Of the 42 eyes with RP, 32 had CME. All CMEs were located in the inner nuclear layer and limited to the parafovea. The outer nuclear layer/ganglion cell layer was involved in 12 eyes (37.5%). Compared with RP without CME, RP with CME (RP-CME) did not show significant differences in flow density or extent of vascular disruption within the superficial capillary plexus, deep capillary plexus, or foveal avascular zone areas. RP-CME was mostly located in the inner nuclear layer of the parafoveal macula, without vascular disruption in optical coherence tomography angiography. Our findings may support the hypothesis that the pathogenesis of RP with CME differs from retinal vascular CME triggered by compromised deep capillary plexus.

To analyze optical coherence tomography angiography images in ocular ischemic syndrome (OIS) before and after carotid artery stenting. We report the case of an 80-year-old man with a history of hypertension and diabetes mellitus who developed OIS in the right eye due to right internal carotid artery stenosis 2 years earlier. After visual acuity declined in the left eye 2 years later, a neurosurgeon discovered left internal carotid artery stenosis, which led to the diagnosis of OIS in the left eye as well. After carotid artery stenting, improvements were observed in both visual acuity and blood flow as assessed by laser speckle flowgraphy. The area of the foveal avascular zone and density of the retinal vessel at the level of the superficial and deep retinal layers were analyzed using optical coherence tomography angiography before and after treatment. Mean superficial foveal avascular zone area was 0.29 mm2 before treatment, decreasing by 29.97% to 0.20 mm2 after treatment. Mean deep foveal avascular zone area was 1.72 mm2 before treatment, decreasing by 20.35% to 1.37 mm2 after treatment. Superficial or deep vessel density increased by 33.4% and 34.3% after treatment, respectively. Optical coherence tomography angiography confirmed foveal avascular zone area reduction and increased vessel density in all retinal layers after carotid artery stenting for OIS. These findings suggest that optical coherence tomography angiography may be useful for evaluating blood flow and treatment efficacy in OIS.

To assess the diagnostic ability of foveal avascular zone (FAZ) parameters to discriminate glaucomatous eyes with visual field defects (VFDs) in different locations (central vs. peripheral) from normal eyes. Totally, 125 participants were separated into 3 groups: normal (n=45), glaucoma with peripheral VFD (PVFD, n=45), and glaucoma with central VFD (CVFD, n=35). The FAZ area, perimeter, and circularity and parafoveal vessel density were calculated from optical coherence tomography angiography images. The diagnostic ability of the FAZ parameters and other structural parameters was determined according to glaucomatous VFD location. Associations between the FAZ parameters and central visual function were evaluated. A larger FAZ area and longer FAZ perimeter were observed in the CVFD group than in the PVFD and normal groups. The FAZ area, perimeter, and circularity were better in differentiating glaucomatous eyes with CVFDs from normal eyes [areas under the receiver operating characteristic curves (AUC), 0.78 to 0.88] than in differentiating PVFDs from normal eyes (AUC, 0.51 to 0.64). The FAZ perimeter had a similar AUC value to the circumpapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer thickness for differentiating eyes with CVFDs from normal eyes (all P>0.05, the DeLong test). The FAZ area was significantly correlated with central visual function (β=-112.7, P=0.035, multivariate linear regression). The FAZ perimeter had good diagnostic capability in differentiating glaucomatous eyes with CVFDs from normal eyes, and may be a potential diagnostic biomarker for detecting glaucomatous patients with CVFDs.

To investigate the effect of denoise processing by artificial intelligence (AI) on the optical coherence tomography angiography (OCTA) images in eyes with retinal lesions. 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. 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. Denoise processing by AI improved the image quality of OCTA in a shorter time and allowed more accurate quantitative evaluation.