AV-casNet: Fully Automatic Arteriole-Venule Segmentation and Differentiation in OCT Angiography.

Automatic segmentation and differentiation of retinal arteriole and venule (AV), defined as small blood vessels directly before and after the capillary plexus, are of great importance for the diagnosis of various eye diseases and systemic diseases, such as diabetic retinopathy, hypertension, and cardiovascular diseases. Optical coherence tomography angiography (OCTA) is a recent imaging modality that provides capillary-level blood flow information. However, OCTA does not have the colorimetric and geometric differences between AV as the fundus photography does. Various methods have been proposed to differentiate AV in OCTA, which typically needs the guidance of other imaging modalities. In this study, we propose a cascaded neural network to automatically segment and differentiate AV solely based on OCTA. A convolutional neural network (CNN) module is first applied to generate an initial segmentation, followed by a graph neural network (GNN) to improve the connectivity of the initial segmentation. Various CNN and GNN architectures are employed and compared. The proposed method is evaluated on multi-center clinical datasets, including 3 ×3 mm2 and 6 ×6 mm2 OCTA. The proposed method holds the potential to enrich OCTA image information for the diagnosis of various diseases.

Disentangled Representation Learning for OCTA Vessel Segmentation With Limited Training Data.

Optical coherence tomography angiography (OCTA) is an imaging modality that can be used for analyzing retinal vasculature. Quantitative assessment of en face OCTA images requires accurate segmentation of the capillaries. Using deep learning approaches for this task faces two major challenges. First, acquiring sufficient manual delineations for training can take hundreds of hours. Second, OCTA images suffer from numerous contrast-related artifacts that are currently inherent to the modality and vary dramatically across scanners. We propose to solve both problems by learning a disentanglement of an anatomy component and a local contrast component from paired OCTA scans. With the contrast removed from the anatomy component, a deep learning model that takes the anatomy component as input can learn to segment vessels with a limited portion of the training images being manually labeled. Our method demonstrates state-of-the-art performance for OCTA vessel segmentation.

Anomaly segmentation in retinal images with poisson-blending data augmentation.

Diabetic retinopathy (DR) is one of the most important complications of diabetes. Accurate segmentation of DR lesions is of great importance for the early diagnosis of DR. However, simultaneous segmentation of multi-type DR lesions is technically challenging because of 1) the lack of pixel-level annotations and 2) the large diversity between different types of DR lesions. In this study, first, we propose a novel Poisson-blending data augmentation (PBDA) algorithm to generate synthetic images, which can be easily utilized to expand the existing training data for lesion segmentation. We perform extensive experiments to recognize the important attributes in the PBDA algorithm. We show that position constraints are of great importance and that the synthesis density of one type of lesion has a joint influence on the segmentation of other types of lesions. Second, we propose a convolutional neural network architecture, named DSR-U-Net++ (i.e., DC-SC residual U-Net++), for the simultaneous segmentation of multi-type DR lesions. Ablation studies showed that the mean area under precision recall curve (AUPR) for all four types of lesions increased by >5% with PBDA. The proposed DSR-U-Net++ with PBDA outperformed the state-of-the-art methods by 1.7%-9.9% on the Indian Diabetic Retinopathy Image Dataset (IDRiD) and 67.3% on the e-ophtha dataset with respect to mean AUPR. The developed method would be an efficient tool to generate large-scale task-specific training data for other medical anomaly segmentation tasks.

Multi-Scale Pathological Fluid Segmentation in OCT With a Novel Curvature Loss in Convolutional Neural Network.

The segmentation of pathological fluid lesions in optical coherence tomography (OCT), including intraretinal fluid, subretinal fluid, and pigment epithelial detachment, is of great importance for the diagnosis and treatment of various eye diseases such as neovascular age-related macular degeneration and diabetic macular edema. Although significant progress has been achieved with the rapid development of fully convolutional neural networks (FCN) in recent years, some important issues remain unsolved. First, pathological fluid lesions in OCT show large variations in location, size, and shape, imposing challenges on the design of FCN architecture. Second, fluid lesions should be continuous regions without holes inside. But the current architectures lack the capability to preserve the shape prior information. In this study, we introduce an FCN architecture for the simultaneous segmentation of three types of pathological fluid lesions in OCT. First, attention gate and spatial pyramid pooling modules are employed to improve the ability of the network to extract multi-scale objects. Then, we introduce a novel curvature regularization term in the loss function to incorporate shape prior information. The proposed method was extensively evaluated on public and clinical datasets with significantly improved performance compared with the state-of-the-art methods.

Aqueous humor monocyte chemoattractant protein-1 predicted long-term visual outcome of proliferative diabetic retinopathy undergone intravitreal injection of bevacizumab and vitrectomy.

PURPOSE: We aim to investigate the risk factors associated with the prognosis of proliferative diabetic retinopathy (PDR) after a sequential treatment of intravitreal injection of bevacizumab (IVB) and pars plana vitrectomy (PPV). METHODS: In this cohort study, 63 eyes from 55 patients (21 females) diagnosed with PDR, who needed PPV for non-clearing vitreous hemorrhage or fibrovascular membrane proliferation were enrolled. All the eyes underwent IVB followed by PPV. Anterior chamber tap was performed at the beginning of both procedures to evaluate the concentration of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. RESULTS: Forty-seven patients (54 eyes) were followed over six months, averaging 12±5 (6-19) months. The concentration of VEGF significantly decreased after IVB (P<0.001), while other cytokines did not change significantly. The aqueous humor level of IL-8 after IVB (R = 0.378, P = 0.033), MCP-1 before (R = 0.368, P = 0.021) and after (R = 0.368, P = 0.038) IVB, and combined phacoemulsification (R = 0.293, P = 0.032) was correlated with the logMAR visual acuity at the last follow-up. Multivariate analysis showed that MCP-1 was the predictor for a worse visual outcome (B = 0.108, 95% CI 0.013-0.202; P = 0.027). CONCLUSIONS: MCP-1 was a predictor for the unfavorable visual outcome of PDR after IVB pretreatment and PPV.

Dilated retinal large vessels and capillaries associated with diabetic macular edema and photoreceptor loss respectively.

PURPOSE: Previously, we measured retinal large vessels and capillaries separately on optical coherence tomography angiography (OCTA). In the present study, we aim to evaluate the role of these parameters in association to diabetic macular edema (DME) and ellipsoid zone disruption (EZD). METHODS: In this cross-sectional study, 54 eyes from 31 patients (10 females, 31 Asians) with severe non-proliferative diabetic retinopathy (25 eyes) or proliferative diabetic retinopathy (PDR, 29 eyes) were enrolled. All eyes underwent 3 × 3 mm OCTA scans centered on the fovea. Perfusion density (PD), vessel length density (VLD), and vessel diameter index (VDI) were calculated for retinal large vessels and superficial capillaries separately. Other OCTA findings included suspended scattering particles in motion (SSPiM), number of microaneurysms (MA) in all retinal layers, and the area of foveal avascular zone (FAZ) of superficial capillary plexus. DME and EZD were evaluated on B-scans. Both univariate and multivariate analysis were performed. RESULTS: Of the 54 study eyes, 31 (57%) had DME and 21 (40%) had EZD. Multivariate regression model showed that PDR (ß = 27.8, 95% confidence interval (CI): 2.7-282.8, p = 0.005), more MA (ß = 2.5, 95% CI: 1.3-4.5, p = 0.003), and increased VDI of larger vessels (ß = 1.9, 95% CI: 1.0-3.5, p = 0.047) were risk factors for DME. As for EZD, presence of SSPiM (ß = 5.5, 95% CI: 1.2-26.1, p = 0.032) and increased VDI of capillaries (ß = 3.9, 95% CI: 1.1-13.8, p = 0.034) were risk factors. CONCLUSIONS: In eyes with diabetic retinopathy, dilation of retinal larger vessels was associated with macular edema, while dilation of retinal capillaries was associated with ellipsoid zone disruption.

Retinal image measurements and their association with chronic kidney disease in Chinese patients with type 2 diabetes: the NCD study.

AIMS: Retinal and renal microcirculations are known to share similar physiological changes during early diabetes because of abnormal glucose metabolism and other processes. The retinal vasculature therefore may serve as potential biomarker for the early identification of those at high risk of chronic kidney disease (CKD) in diabetes. METHODS: Data from 1925 patients (aged 49.0 ± 10.3) with type 2 diabetes were analyzed. Various retinal image measurements (RIMs) were collected using a validated fully automated computer program. Multiple logistic regressions were performed to investigate the correlation between RIMs and CKD. RESULTS: In logistic regression adjusting for multiple variables, wider venular calibers in the central and middle zones and narrower arteriolar caliber in the central zone were associated with CKD (p < 0.001, p = 0.020, and p < 0.001, respectively). Increased arteriolar tortuosity was associated with CKD (p = 0.035). Multiple image texture measurements were also significantly associated with CKD. CONCLUSIONS: Renal dysfunction in type 2 diabetes was associated with various retinal image measurements. These non-invasive image measurements may serve as potential biomarkers for the early identification and monitoring of individuals at high risk of CKD in the course of diabetes.

Spectral-Domain OCT Analysis of Risk Factors for Macular Atrophy Development in the HARBOR Study for Neovascular Age-Related Macular Degeneration.

PURPOSE: To identify baseline risk factors for macular atrophy (MA) development in HARBOR via a longitudinal assessment of monthly spectral-domain (SD)-OCT scans. Previous analyses of MA in HARBOR examined data from color fundus photography (CFP) and fluorescein angiography (FA). DESIGN: Retrospective, post hoc analysis of SD-OCT images from HARBOR (ClinicalTrials.gov identifier, NCT00891735), a phase 3, multicenter, prospective, randomized, double-blind, active treatment-controlled clinical trial. PARTICIPANTS: Patients (N = 1097) with subfoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD) treated with intravitreal ranibizumab 0.5 mg monthly (n = 275), 0.5 mg pro re nata (PRN) after 3 loading doses (n = 275), 2.0 mg monthly (n = 274), or 2.0 mg PRN (n = 273). METHODS: Evaluable SD-OCT macular cube scans from patients with 24 months of follow-up (N = 941) were examined monthly from baseline to month 24 by masked reading center-trained graders. Atrophy diagnosis criteria were consistent with those proposed by the Classification of Atrophy Meetings (CAM) group: hypertransmission of light into the choroid, loss of retinal pigment epithelium, and loss of outer retinal layers. Multivariable proportional hazards regression was performed for time to atrophy development. MAIN OUTCOME MEASURES: Risk factors for MA as determined by time to MA development over 24 months of treatment. RESULTS: Baseline risk factors for MA were confirmed from prior analyses that used CFP and FA data: absence of subretinal fluid, presence of intraretinal cysts, presence of Type 3 neovascularization, and presence of atrophy in the fellow eye. This analysis of SD-OCT data identified new baseline risk factors for MA: higher central drusen volume, lower choroidal thickness, presence of nascent atrophy, presence of reticular pseudodrusen, and increased central foveal thickness. Ranibizumab treatment regimen and dose level were not found to be risk factors for MA development. CONCLUSIONS: In this analysis of a major nAMD trial using CAM atrophy criteria, new baseline risk factors for MA development were identified using an SD-OCT dataset. Risk factors for MA development identified by prior analyses were confirmed. Monthly treatment with ranibizumab 0.5 mg was not found to be a risk factor for MA development over 24 months.

OCT Risk Factors for Development of Late Age-Related Macular Degeneration in the Fellow Eyes of Patients Enrolled in the HARBOR Study.

PURPOSE: To evaluate the relationship between OCT features and progression to late age related-macular degeneration (AMD) in the fellow eyes of patients enrolled in the Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular AMD (HARBOR) (ClinicalTrials.gov identifier, NCT00891735). DESIGN: Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. PARTICIPANTS: Evaluable patients (n = 501) with macular neovascularization (MNV) secondary to neovascular AMD and early or intermediate AMD in the fellow eye. METHODS: Volume OCT scans from 501 fellow eyes of 501 patients with MNV were reviewed. Baseline OCT features that were assessed included intraretinal hypereflective foci (IHRF), hyporeflective foci (hRF) within drusenoid lesions (DLs), subretinal drusenoid deposits (SDDs), and drusen volume (DV) of 0.03 mm3 or more. OCT images obtained at months 6, 12, 18, and 24 were graded by masked graders for late AMD (defined as MNV, complete retinal pigment epithelium and photoreceptor atrophy [cRORA], or both). Participant demographic characteristics (age, gender, and smoke exposure) and baseline OCT features were correlated with progression to late AMD. MAIN OUTCOME MEASURES: Incidence of late AMD, hazard ratio (HR) for demographics, and OCT risk factors. RESULTS: At month 24, 33.13% of eyes (166/501) demonstrated late AMD: 20.96% (105/501) demonstrated cRORA, whereas 12.18% (61/501) demonstrated MNV. Baseline demographic factors were not associated significantly with development of late AMD, whereas significant associations were identified for all OCT features. Intraretinal hypereflective foci had an HR of 5.21 (95% confidence interval [CI], 3.29-8.26), hRF within DLs had an HR of 2.42 (95% CI, 1.74-3.38), SDD had an HR of 1.95 (95% CI, 1.34-2.82), and DV of 0.03 mm3 or more had an HR of 1.46 (95% CI, 1.03-2.07). The correlation remained significant when considering only the progression to cRORA and MNV alone, except for DV, which was not associated significantly with progression to MNV. CONCLUSIONS: We confirmed that 4 previously reported OCT risk factors were associated with progression to late AMD in the fellow eyes of patients newly diagnosed with MNV. Although outcomes of more than 2 years were not evaluated, these findings may help to identify high-risk AMD patients.

Automated quantification of superficial retinal capillaries and large vessels for diabetic retinopathy on optical coherence tomographic angiography.

Optical coherence tomography angiography (OCTA) is a relatively new technique with capillary-level resolution, which has shown great potential for the diagnosis of diabetic retinopathy (DR). A fully automatic algorithm for the quantitative measurement of microcirculatory changes in sight-threatening DR is presented. The foveal avascular zone (FAZ) segmentation was improved with a graph-theoretic method and the large vessels and capillaries were separately identified and analyzed. The method was evaluated in healthy and diabetic eyes with various stages of retinopathy. Results showed that, compared with the healthy group, the diabetic group showed a significantly larger large vessel density, but a significantly smaller capillary density (P < .001). Circularity of FAZ was significantly smaller while nonperfusion area was significantly larger in the diabetic group. The combined variable of all image metrics reached an area under the ROC of 0.853 (95% CI, 0.784-0.923) for mild to moderate nonproliferative DR and 0.950 (95% CI, 0.922-0.979) for proliferative DR. Microvascular and FAZ changes with various DR stages can be accurately delineated using the developed automatic program. Quantitative metrics on OCTA serve as potential biomarkers for the staging of DR.

Influence of Axial Length on Parafoveal and Peripapillary Metrics from Swept Source Optical Coherence Tomography Angiography.

Purpose: To assess the effect of axial length (AL) on the quantification of superficial vessel density of both macular and disc region using swept source optical coherence tomography angiography (SSOCTA). Methods: This is a cross-sectional clinical study. Seventy-five eyes from 75 Chinese healthy participants (56 females) with a mean age of 26.6 ± 6.8 (range 19-50) years were included in this study. All eyes were imaged with SSOCTA, using a 3 × 3mm scan pattern centered on the macular and optic disc, respectively, and the superficial layer was used for evaluation. The image size was corrected with AL using Bennett formula. Outcome measurements included perfusion density (PD), vessel length density (VLD) in parafoveal and disc regions, averaged peripapillary large vessel diameter and area of foveal avascular zone (FAZ). Image processing and measurements was performed using Image J software. Multivariate regression analysis adjusting for age and signal strength was used to assess the influence of AL on the metrics. Results: AL was the only predictive factor for parafoveal PD (ß = -0.273, P = .047) and VLD (ß = -0.396, P = .003). There was no correlation between AL and area of FAZ, large vessel diameter, or the vessel density on any location in disc region. Age was the only predictor for PD (ß = -0.287, P = .024) and VLD (ß = -0.289, P = .023) on optic nerve head. Conclusions: AL was negatively correlated with superficial parafoveal microvasculature, but not correlated with peripapillary capillaries, suggesting that the inner retina stretches more in the distal end of the disc with increased AL.

Repeatability and Reproducibility of Quantification of Superficial Peri-papillary Capillaries by four Different Optical Coherence Tomography Angiography Devices.

This study was performed to test the repeatability and reproducibility of measurements of peri-papillary capillaries from four optical coherence tomography angiography (OCTA) devices. 109 healthy eyes were imaged with four OCTA devices (Spectralis, Optovue, Triton and Cirrus). A 3 × 3 mm scan pattern centered on the disc was repeated twice by each device. En face images of superficial capillary plexus were screened and processed for calculation. Vessel length density (VLD) was calculated on four equally divided parts of a ring between two concentric circles manually centered on the disc. General linear model (GLM) was used to test the impact of device and location on VLD. Intraclass correlation coefficient (ICC) of VLD between repeated scans was calculated. Of 218 acquisitions, 36%, 92%, 76% and 88% were eligible for analysis from Spectralis, Optovue, Triton and Cirrus, respectively. ICC was 0.94, 0.90, 0.84 and 0.87 for the four devices. GLM showed measurements significantly varied among devices (P < 0.001) and locations (P < 0.001). Pairwise comparison showed Triton = Spectralis >Optovue >Cirrus, and temporal = nasal >superior = inferior in measuring capillary VLD. This study revealed the repeatability of measuring peri-papillary capillaries was high for all four devices, while the reproducibility among the machines was unfavorable.

Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration.

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch's membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

Quantity of Intraretinal Hyperreflective Foci in Patients With Intermediate Age-Related Macular Degeneration Correlates With 1-Year Progression.

Purpose: The purpose of this study was to evaluate the correlation between quantity of intraretinal hyperreflective foci (HRF) in the eye with intermediate AMD and progression to late AMD. Methods: Volume optical coherence tomography (OCT) scans from 114 eyes of 114 patients were retrospectively reviewed. HRF were assessed both qualitatively and quantitatively. Five sequential en face slabs from midretina were thresholded to isolate the HRF. These five slabs were recombined, and HRF area was measured in the whole 6 × 6-mm image (HRFTOT) and within the central 3-mm (HRF3mm) and 5-mm (HRF5mm) regions. These measurements were correlated with the development of late AMD (defined as choroidal neovascularization [CNV] and/or complete RPE and photoreceptor atrophy [cRORA]) after 1 year of follow-up. Results: HRF area in all three regions showed significant correlations with progression to late AMD: R = 0.610 for HRF3mm, R = 0.622 for HRF5mm, and R = 0.614 for HRFTOT (all P < 0.001). Correlations remained significant with progression to cRORA alone, though not for progression to CNV alone. While qualitative assessment of HRF (i.e., presence of HRF: yes or no) also showed a significant correlation with progression to late AMD (R = 0.454, P < 0.001) and atrophy alone (R = 0.445, P < 0.001), they were weaker than by HRF quantification. Conclusions: The area of HRF from en face OCT in eyes with intermediate AMD correlates with the 1-year risk of progression to late AMD, and in particular with the development of atrophy.

Multiple enface image averaging for enhanced optical coherence tomography angiography imaging.

PURPOSE: To investigate the effect of multiple enface image averaging on image quality of the optical coherence tomography angiography (OCTA). METHODS: Twenty-one normal volunteers were enrolled in this study. For each subject, one eye was imaged with 3 × 3 mm scan protocol, and another eye was imaged with the 6 × 6 mm scan protocol centred on the fovea using the ZEISS Angioplex™ spectral-domain OCTA device. Eyes were repeatedly imaged to obtain nine OCTA cube scan sets, and nine superficial capillary plexus (SCP) and deep capillary plexus (DCP) were individually averaged after registration. RESULTS: Eighteen eyes with a 3 × 3 mm scan field and 14 eyes with a 6 × 6 mm scan field were studied. Averaged images showed more continuous vessels and less background noise in both the SCP and the DCP as the number of frames used for averaging increased, with both 3 × 3 and 6 × 6 mm scan protocols. The intensity histogram of the vessels dramatically changed after averaging. Contrast-to-noise ratio (CNR) and subjectively assessed image quality scores also increased as the number of frames used for averaging increased in all image types. However, the additional benefit in quality diminished when averaging more than five frames. Averaging only three frames achieved significant improvement in CNR and the score assigned by certified grades. CONCLUSION: Use of multiple image averaging in OCTA enface images was found to be both objectively and subjectively effective for enhancing image quality. These findings may of value for developing optimal OCTA imaging protocols for future studies.

Comparison of short-wavelength blue-light autofluorescence and conventional blue-light autofluorescence in geographic atrophy.

BACKGROUND/AIMS: To systematically compare the intermodality and inter-reader agreement for two blue-light confocal fundus autofluorescence (FAF) systems. METHODS: Thirty eyes (21 patients) with a diagnosis of geographic atrophy (GA) were enrolled. Eyes were imaged using two confocal blue-light FAF devices: (1) Spectralis device with a 488 nm excitation wavelength (488-FAF); (2) EIDON device with 450 nm excitation wavelength and the capability for 'colour' FAF imaging including both the individual red and green components of the emission spectrum. Furthermore, a third imaging modality (450-RF image) isolating and highlighting the red emission fluorescence component (REFC) was obtained and graded. Each image was graded by two readers to assess inter-reader variability and a single image for each modality was used to assess the intermodality variability. RESULTS: The 95% coefficient of repeatability (1.35 mm2 for the 488-FAF-based grading, 8.13 mm2 for the 450-FAF-based grading and 1.08 mm2 for the 450-RF-based grading), the coefficient of variation (1.11 for 488-FAF, 2.05 for 450-FAF, 0.92 for 450-RF) and the intraclass correlation coefficient (0.994 for 488-FAF, 0.711 for 450-FAF, 0.997 for 450-RF) indicated that 450-FAF-based and 450-RF-based grading have the lowest and highest inter-reader agreements, respectively. The GA area was larger for 488-FAF images (median (IQR) 2.1 mm2 (0.8-6.4 mm2)) than for 450-FAF images (median (IQR) 1.0 mm2 (0.3-4.3 mm2); p<0.0001). There was no significant difference in lesion area measurement between 488-FAF-based and 450-RF-based grading (median (IQR) 2.6 mm2 (0.8-6.8 mm2); p=1.0). CONCLUSION: The isolation of the REFC from the 450-FAF images allowed for a reproducible quantification of GA. This assessment had good comparability with that obtained with 488-FAF images.

Distinctive Analysis of Macular Superficial Capillaries and Large Vessels Using Optical Coherence Tomographic Angiography in Healthy and Diabetic Eyes.

Purpose: To quantify and evaluate macular superficial capillaries and large vessels separately using an optical coherence tomographic angiography (OCTA)-based automatic segmentation algorithm. Methods: In this cross-sectional study, all eyes were scanned using an OCTA device with 3 × 3 mm cube centered on the fovea. Retinal large vessels (arterioles/venules) were automatically segmented from superficial vasculature en-face images. All images were normalized, binarized, and skeletonized for quantification. Metrics of retinal capillaries were calculated by subtracting the measurements of large vessels from total vasculature. Perfusion density (PD), vessel length density (VLD), and vessel diameter index (VDI) within Early Treatment Diabetic Retinopathy Study (ETDRS) 3-mm ring were calculated for total superficial vasculature, large vessels (PDlarge, VLDlarge, and VDIlarge) and capillaries (PDcap, VLDcap, and VDIcap), respectively. Results: Fifty-nine eyes from 59 healthy participants (mean age, 45 ± 14 years, 36 females) and 118 eyes from 67 patients with diabetes mellitus (mean age, 57 ± 10 years, 28 females) were included. The diabetic cohort included four subgroups (35 eyes without diabetic retinopathy, 30 eyes with mild to moderate nonproliferative diabetic retinopathy [NPDR], 27 eyes with severe NPDR, and 26 eyes with PDR). Linear regression showed that all above metrics were correlated with the disease stage (from healthy state to PDR), and the ß value was -0.76, 0.24, -0.78, 0.80, 0.30, 0.77, -0.81, 0.16, and -0.82 for VD, VDlarge, VDcap, VDI, VDIlarge, VDIcap, VLD, VLDlarge, and VLDcap, respectively. Conclusions: Retinal capillaries and large vessels responded differently in the context of diabetes. VLD of capillary is a potentially reliable metric in diabetic retinopathy staging.

Subfoveal choroidal thickness predicts macular atrophy in age-related macular degeneration: results from the TREX-AMD trial.

BACKGROUND: Our purpose was to evaluate the relationship between subfoveal choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with age-related macular degeneration (AMD). METHODS: This was a prospective, multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial (NCT01648292) with treatment-naïve neovascular AMD (NVAMD) in at least one eye were included. SCT was measured by certified reading center graders at baseline using spectral domain optical coherence tomography (SDOCT). The baseline SCT was correlated with the presence of MA at baseline and development of incident MA by month 18. Generalized estimating equations were used to account for information from both eyes. RESULTS: Baseline SCT in eyes with MA was statistically significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04) and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and non-MA developers revealed a statistically significant difference (P = 0.03). Receiver operating characteristic curve (ROC) analysis showed the cut-off threshold of SCT for predicting the development of MA in cases without MA at baseline was 124 µm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among eyes without MA at baseline, those with baseline SCT ≤124 µm were 4.3 times more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P = 0.005) than those with baseline SCT >124 µm. CONCLUSIONS: Eyes with AMD and MA had less SCT than those without MA. Eyes with less baseline SCT also appear to be at higher risk to develop MA within 18 months.

Effects of VEGF levels on anti-VEGF therapy for patients with idiopathic choroidal neovascularization.

The objective of this study is to investigate the levels of vascular endothelial growth factor (VEGF) and other cytokines in aqueous humor of patients with idiopathic choroidal neovascularization (CNV) and their effects together with central retinal thickness (CRT) on the response to intravitreal injection of anti-VEGF antibody ranibizumab. This clinical study recruited 32 eyes from 32 patients with CNV under or besides fovea. VEGF, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 levels were detected in aqueous humor (0.1 ml) sampled during intravitreal injection. Aqueous humor controls were from nine cataract patients without any systemic disorders. The VEGF levels in aqueous humor were negatively related (r = -0.373, p = 0.035) to CRT, which was positively related (r = 0.743, p < 0.001) to the number of injections. The VEGF levels before treatment and during the third injection in four patients with three or more injections were 13.42 ± 8.50 and 5.75 ± 3.68 (p = 0.055), respectively. The average best corrected visual acuity (BCVA) before and 12 months after treatment were 57.03 ± 16.15 and 75.16 ± 11.78 (p < 0.001), and the average CRT before and 12 months after treatment were 352.09 ± 84.15 and 251.13 ± 63.96 (p < 0.001), respectively. The visual improvement was negatively related (r = -0.815, p < 0.001) to the visual baseline, and the vision 12 months after treatment was positively related (r = 0.581, p < 0.001) to that before treatment. No severe ocular or systemic complication appeared during treatment and follow-ups for all the patients. Intravitreal injection of anti-VEGF antibody ranibizumab is safe and effective for the treatment of idiopathic CNV through decreasing CRT. The patients with larger CRT baseline need more injections of ranibizumab.