Quantification of vascular changes in macular telangiectasia type 2 with AngioTool software.

PURPOSE: To compare AngioTool (AT) vascular parameters (VP) between MacTel2 eyes and normal eyes. Secondary outcome measures were to correlate VP with BCVA and to analyze VP between various grades of Simple MacTel Classification. METHODS: This is a retrospective study. SD OCTA images of the superficial vascular complex (SVC) and deep capillary complex (DVC) were exported into Image J and AT. The explant area (EA), vessel area (VA), vessel percentage area (VPA), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL), total number of endpoints (TNE) and mean E lacunarity (MEL) were studied. RESULTS: Group 1 had 120 MacTel2 eyes. Group 2 had 60 age-matched normal eyes. All VP were significantly different between the two groups except EA and TNE in both complexes. None of the VP had a correlation with BCVA. Interquadrant analysis (IQA) in SVC and DVC showed statistical significance in VPA, AVL and JD and in AVL, TNE, JD, VPA respectively. Post hoc analysis in SVC and DVC showed statistical significance in TNJ, JD, TVL and AVL between grade 1 and grade 3, and in VA, VPA, TNJ, JD, TVL and MEL between grade 0 and grade 3 respectively. CONCLUSION: VP were affected in MacTel2 eyes. VP did not correlate with BCVA. Occurrence of pigmentation is an important event in the progression of disease. AT may provide quantitative markers to measure disease progression.

Comparison of Changes in Retinal Vascular Parameters and Density in Patients with Moyamoya Disease: A Retrospective Study.

INTRODUCTION: This study aimed to compare retinal vascular parameters and density in patients with moyamoya disease using the optical coherence tomography angiography. METHODS: This clinical trial totally enrolls 78 eyes from 39 participants, and all these patients with moyamoya disease (N = 13) are set as experimental group and participants with health who matched with age and gender are considered as the control group (N = 26). Then all these participants receive optical coherence tomography angiography detection. Participants' general data are collected and analyzed. Skeleton density (SD) value, vessel density (VD) value, fractal dimension (FD) value, vessel diameter index (VDI) value, foveal avascular zone (FAZ) value are analyzed. RESULTS: A total of 39 participants are included in this study. The SD value in the experimental group was significantly lower than that in control group (0.175 [0.166, 0.181] vs. 0.184 [0.175, 0.188], p = 0.017). Similarly, the VD value in the experimental group was significantly lower than that in the control group (0.333 [0.320, 0.350] vs. 0.354 [0.337, 0.364], p = 0.024). Additionally, the FD value in the experimental group was significantly lower than that in the control group (2.088 [2.083, 2.094] vs. 2.096 [2.090, 2.101], p = 0.022). As for the VDI and FAZ, VDI and FAZ values in the experimental group were lower than those in the control group, there was no significant difference in VDI and FAZ values between the two groups. CONCLUSIONS: Our study, using non-invasive and rapid OCTA imaging, confirmed decreased retinal vascular parameters and density in patients with moyamoya disease.

Relationship between nonperfusion area from widefield optical coherence tomography angiography and macular vascular parameters in diabetic retinopathy.

PURPOSE: To evaluate the relationship between the nonperfusion area (NPA) from widefield optical coherence tomography angiography (OCTA) and macular vascular parameters in diabetic retinopathy (DR). METHODS: In total, 51 eyes from 51 patients with proliferative DR (PDR) or moderate/severe non-PDR were included. Widefield OCTA using the Zeiss Plex Elite 9000 was performed. A semi-automatic algorithm calculated the percentages of the NPA within the total image. Macular OCTA (3 × 3 mm and 6 × 6 mm area) was scanned using the RTVue-XR Avanti. Vessel density (VD) was automatically separated into the superficial (SCP) and deep capillary plexus (DCP), and foveal avascular zone (FAZ) measurements were computed according to the parafoveal (1-3 mm) and perifoveal (3-6 mm) regions. RESULTS: A negative correlation was found between the average VD of the SCP and DCP obtained 3 × 3 mm and 6 × 6 mm area and the NPA. Multiple regression analysis revealed that the temporal-perifoveal region most negatively correlated with the NPA (r = - 0.55, p < 0.0001). No correlation was found between FAZ measurements and DR severity (area, p = 0.07; perimeter, p = 0.13). CONCLUSION: Diabetic macular nonperfusion was significantly associated with the NPA from widefield OCTA. In particular, the temporal-perifoveal DCP disorder may be a sensitive indicator of wide NPA.

Cardiovascular health and retinal microvascular geometry in Australian 11-12 year-olds.

Traditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults. Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associated with cardiovascular health from childhood. In a population-based cross-sectional study in children (n = 1126, mean age 11.4 years, 50.3% girls), we examined associations of cardiovascular risk factors and pre-clinical arterial phenotypes with retinal geometric parameters. Cardiovascular parameters included body mass index (BMI), an inflammatory marker (GlycA), low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, systolic (SBP) and diastolic blood pressure, large artery functional (pulse wave velocity, PWV and carotid arterial elasticity) and structural (carotid intima-media thickness) phenotypes. Retinal geometric parameters (fractal dimension (Df) and tortuosity) were quantified from retinal images. Multivariable regression models were performed and adjusted for potential confounders. Higher values for BMI, SBP and PWV showed weak associations with lower (i.e. worse) arteriolar but not venular Df (standardized mean difference (SMD) ranging from -0.07 to -0.09, 95% CIs -0.15 to -0.01). Higher HDL was associated with greater arteriolar Df (SMD 0.07, 95% CI 0.01 to 0.13). Only higher SBP was associated with higher (i.e. worse) arteriolar but not venular tortuosity (SMD 0.09, 95% CI 0.02 to 0.16). In generally healthy children, some risk factors and pre-clinical arterial phenotypes show small associations with retinal geometric parameters. In childhood, emerging relationships between microvascular parameters and cardiometabolic risk may be better described by retinal vascular caliber than by geometric parameters.

Comparison of two different optical coherence tomography angiography devices in detecting healthy versus glaucomatous eyes - an observational cross-sectional study.

BACKGROUND: To understand the differences between two different optical coherence tomography angiography (OCTA) devices in detecting glaucomatous from healthy eyes by comparing their vascular parameters, diagnostic accuracy and test-retest reliability. METHODS: A cross-sectional observational study was performed on healthy and glaucoma subjects, on whom two sets of OCTA images of optic disc and macula were acquired using both AngioVue (Optovue, USA) and Swept Source (Topcon, Japan) OCTA devices during one visit. A novel in-house software was used to calculate the vessel densities. Diagnostic accuracy of the machines in differentiating healthy versus glaucomatous eyes was determined using area under the receiver operating characteristic curve (AUROC) and test-retest repeatability of the machines was also evaluated. RESULTS: A total of 80 healthy and 38 glaucomatous eyes were evaluated. Glaucomatous eyes had reduced mean vessel density compared to healthy controls in all segmented layers of the optic disc and macula using AngioVue (p ≤ 0.001). However, glaucomatous eyes had higher mean vessel density on optic disc scans using Swept Source, with lack of statistically significant difference between healthy and glaucomatous eyes. The AUROC showed better diagnostic accuracy of AngioVue (0.761-1.000) compared to Swept Source (0.113-0.644). The test-retest reliability indices were generally better using AngioVue than Swept Source. CONCLUSIONS: AngioVue showed better diagnostic capability and test-retest reliability compared to Swept Source. Further studies need to be undertaken to evaluate if there is any significant difference between the various machines in diagnosing and monitoring glaucoma.

A Multi-Stage Approach for Cardiovascular Risk Assessment from Retinal Images Using an Amalgamation of Deep Learning and Computer Vision Techniques.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. Early detection and effective risk assessment are crucial for implementing preventive measures and improving patient outcomes for CVDs. This work presents a novel approach to CVD risk assessment using fundus images, leveraging the inherent connection between retinal microvascular changes and systemic vascular health. This study aims to develop a predictive model for the early detection of CVDs by evaluating retinal vascular parameters. This methodology integrates both handcrafted features derived through mathematical computation and retinal vascular patterns extracted by artificial intelligence (AI) models. By combining these approaches, we seek to enhance the accuracy and reliability of CVD risk prediction in individuals. The methodology integrates state-of-the-art computer vision algorithms and AI techniques in a multi-stage architecture to extract relevant features from retinal fundus images. These features encompass a range of vascular parameters, including vessel caliber, tortuosity, and branching patterns. Additionally, a deep learning (DL)-based binary classification model is incorporated to enhance predictive accuracy. A dataset comprising fundus images and comprehensive metadata from the clinical trials conducted is utilized for training and validation. The proposed approach demonstrates promising results in the early prediction of CVD risk factors. The interpretability of the approach is enhanced through visualization techniques that highlight the regions of interest within the fundus images that are contributing to the risk predictions. Furthermore, the validation conducted in the clinical trials and the performance analysis of the proposed approach shows the potential to provide early and accurate predictions. The proposed system not only aids in risk stratification but also serves as a valuable tool for identifying vascular abnormalities that may precede overt cardiovascular events. The approach has achieved an accuracy of 85% and the findings of this study underscore the feasibility and efficacy of leveraging fundus images for cardiovascular risk assessment. As a non-invasive and cost-effective modality, fundus image analysis presents a scalable solution for population-wide screening programs. This research contributes to the evolving landscape of precision medicine by providing an innovative tool for proactive cardiovascular health management. Future work will focus on refining the solution's robustness, exploring additional risk factors, and validating its performance in additional and diverse clinical settings.

A comparison of two optical coherence tomography-angiography devices in pseudoexfoliation glaucoma versus primary open-angle glaucoma and healthy subjects.

PURPOSE: To compare peripapillary vascular parameters derived from two optical coherence tomography angiography devices in pseudoexfoliation glaucoma, primary open-angle glaucoma, and healthy controls and to evaluate their diagnostic accuracy. METHODS: Observational, cross-sectional study. In total, 20 eyes with pseudoexfoliation glaucoma, 20 primary open-angle glaucoma eyes matched by peripapillary retinal nerve fiber layer thickness, and 20 control eyes were recruited. Participants underwent standard automated perimetry and peripapillary retinal nerve fiber layer analysis by Optovue and Cirrus optical coherence tomography. Vascular parameters provided by Angiovue and Angioplex optical coherence tomography angiography were compared. Their diagnostic accuracy and correlation with structural and functional parameters were assessed. RESULTS: All peripapillary optical coherence tomography angiography vascular parameters were significantly different among groups (all p < 0.05). The whole image capillary density and peripapillary capillary density by Angiovue were significantly lower in pseudoexfoliation glaucoma compared with primary open-angle glaucoma (p = 0.009 and p = 0.001, respectively). Conversely, vascular parameters by Angioplex were not statistically different between primary open-angle glaucoma and pseudoexfoliation glaucoma. A good correlation was found using Angiovue between whole image capillary density and visual field mean deviation (0.758, p < 0.001), peripapillary capillary density and visual field mean deviation (0.729, p = 0.001), and peripapillary capillary density and peripapillary retinal nerve fiber layer thickness in eyes with pseudoexfoliation glaucoma (0.716, p = 0.001). Angiovue parameters showed higher area under the receiver operating characteristic curves than Angioplex to discriminate among groups. CONCLUSION: Only Angiovue detected a significantly lower capillary density in pseudoexfoliation glaucoma compared to primary open-angle glaucoma at similar glaucoma damage. Both, Angiovue and Angioplex demonstrated a decreased capillary density in glaucoma eyes compared to healthy eyes. Furthermore, Angiovue-derived vascular parameters showed better correlation with functional and structural parameters and a higher diagnostic capacity to discriminate among groups compared to Angioplex.

Combination of vatalanib and a 20-HETE synthesis inhibitor results in decreased tumor growth in an animal model of human glioma.

BACKGROUND: Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic treatments, such as vatalanib, have been added as an adjuvant to control angiogenesis and tumor growth. However, evidence of progressive tumor growth and resistance to antiangiogenic treatment has been observed. To counter the unwanted effect of vatalanib on GBM growth, we have added a new agent known as N-hydroxy-N'-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. The aims of the studies were to determine 1) whether the addition of HET0016 can attenuate the unwanted effect of vatalanib on tumor growth and 2) whether the treatment schedule would have a crucial impact on controlling GBM. METHODS: U251 human glioma cells (4×10(5)) were implanted orthotopically. Two different treatment schedules were investigated. Treatment starting on day 8 (8-21 days treatment) of the tumor implantation was to mimic treatment following detection of tumor, where tumor would have hypoxic microenvironment and well-developed neovascularization. Drug treatment starting on the same day of tumor implantation (0-21 days treatment) was to mimic cases following radiation therapy or surgery. There were four different treatment groups: vehicle, vatalanib (oral treatment 50 mg/kg/d), HET0016 (intraperitoneal treatment 10 mg/kg/d), and combined (vatalanib and HET0016). Following scheduled treatments, all animals underwent magnetic resonance imaging on day 22, followed by euthanasia. Brain specimens were equally divided for immunohistochemistry and protein array analysis. RESULTS: Our results demonstrated a trend that HET0016, alone or in combination with vatalanib, is capable of controlling the tumor growth compared with that of vatalanib alone, indicating attenuation of the unwanted effect of vatalanib. When both vatalanib and HET0016 were administered together on the day of the tumor implantation (0-21 days treatment), tumor volume, tumor blood volume, permeability, extravascular and extracellular space volume, tumor cell proliferation, and cell migration were decreased compared with that of the vehicle-treated group. CONCLUSION: HET0016 is capable of controlling tumor growth and migration, but these effects are dependent on the timing of drug administration. The addition of HET0016 to vatalanib may attenuate the unwanted effect of vatalanib.

Vascular alterations in the sprague-dawley rat mandible during intravenous bisphosphonate therapy.

Long-term use of intravenous bisphosphonates, such as zoledronic acid (zoledronate), has been linked to bisphosphonate-related osteonecrosis of the jaw (BRONJ). Invasive dental surgery seems to trigger the bone necrosis in most cases. To determine the effects of zoledronic acid on the vascular structure of the rat mandible. Extracted of the mandibular first molar in rats that received 2 IV injections of zoledronate (20 µg/kg), 4 weeks apart. Zoledronate-treated rats (n = 18) were then compared to a control group of untreated rats (n = 18). At the fourth, eighth, and 12th week after molar extraction, 8 rat mandibles from each group were perfused with 35% radiopaque triphenylbismuth in methyl methacrylate via carotid artery perfusion. Mandibles were harvested and examined by micro-CT to assess the spatial and dimensional changes of the vasculature as a result of zoledronate treatment. The micro-CT analysis showed that zoledronic acid-treated rats had blood vessels that were thicker, less connected, and less ordered than control rats that were not exposed to zoledronic acid. This study demonstrated that treatment with zoledronic acid in rats is associated with vascular changes in alveolar bone. Further studies are underway to explore whether these vascular changes contribute to the pathogenesis of BRONJ.