Microvascular Abnormalities Research Articles

Study of Retinal and Choroidal Changes in Children with Sickle Cell Disease using Optical Coherence Tomography and Angiography

Abstract Background Sickle cell disease is known to cause vaso-occlusive peripheral retinopathy as a result of the microvascular insults that occur when sickled erythrocytes affect the retinal and choroidal blood flow. This leads to non-proliferative retinopathy (NPR) and proliferative retinopathy (PR) that can result in vision affection. While sickle cell retinopathy (SCR) in adult patients is well described, less is known about the retinal changes that occur in pediatric patients. To date, most studies have been of adults. Objective To screen children with sickle cell disease for the presence of retinal and choroidal changes and to compare the findings with age and sex matched controls by performing structural SD-OCT and OCTA and to correlate between findings. This aimed to assess the prevalence and age of onset of retinopathy among pediatric patients. Patients and Methods This cross sectional study was carried out from February 2020 to August 2020 on 30 eyes of patients attending outpatient clinic of Ophthalmology and Pediatric Departments of Ain Shams University Hospitals. Those patients were asked to participate and were enrolled in this study. The ethical standards stated by the ethical committee of Ain Shams University Hospitals were followed. Informed written consent was taken from guardians of all participants. Results There was a significant difference between the cases and control groups regarding the SCP and DCP vessel density, FAZ area, vascular disc density, central macular thickness, choroidal thickness, RNFL average thickness, IS/OS and C/D vertical ratio. However, there was no significant difference between the cases two groups regarding the GCC. There was a significant positive correlation between the retinal thickness and the vessel density in the SCP and DCP in the corresponding subfields. There was a positive statistically significant correlation between the Hb F level and the vessel density of the SCP and DCP. Also, there was a negative statistically significant correlation between the Hb F level and the FAZ. There was a negative statistically significant correlation between the Hb S level and the choroidal thickness, GCC and RNFL average thickness. There was also a statistically significant negative correlation between the disease duration and the temporal parafoveal retinal thickness. Conclusion SD-OCT and OCTA were able to detect areas of thinning and decreased vascular densities in asymptomatic sickle cell children. This study demonstrated a decreased vessel density on OCTA but a normal retinal thickness on SD-OCT in some of the parafoveal sucfields. This suggests that OCTA can detect microvascular abnormalities and retinopathy early even before it is visible on OCT. Further longitudinal studies are needed to examine the vascular densities and retinal and choroidal thinning in sickle cell disease children and their correlation with the various disease parameters.

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Patients with Systemic Sclerosis with and without Overlap Syndrome Show Similar Microvascular Abnormalities.

Introduction: Nailfold video capillaroscopy (NVC) is a useful tool for measuring capillary density (CD) and capillary morphology parameters and is mainly used in systemic sclerosis (SSc). Objective: We aimed to assess the prevalence of an SSc pattern and CD in different connective tissue diseases (CTDs). Methods: NVC was performed on 268 patients with CTDs. Control groups consisted of 104 healthy volunteers (HVs) and 36 primary Raynaud’s patients (PRPs). Results: Decreased CD was more prevalent in SSc, systemic lupus erythematosus (SLE), inflammatory myopathies (IIM), and overlap CTD patients compared with both controls. Average CD, the prevalence of decreased CD, and the prevalence of an SSc pattern did not differ significantly between SSc patients with (n = 39) and without (n = 50) overlap syndrome. An SSc pattern was significantly more prevalent in SLE (23%), SSc (82%), IIM (35%), and rheumatoid arthritis (17%) compared with both control groups. The prevalence of an elevated microangiopathy evaluation score (MES) was significantly higher in SLE, SSc, and IIM than in the HVs. Conclusion: The presence of another CTD in SSc did not influence CD or morphology. An SSc pattern may also be present in CTDs other than SSc. The MES is a useful instrument to distinguish between patients with CTDs and controls.

Optical Coherence Tomography Angiography Findings in Polycystic Ovary Syndrome.

To evaluate microstructure and vascularity of macula and optic disc in polycystic ovary syndrome (PCOS) by optical coherence tomography (OCT) and OCT angiography (OCTA). Descriptive study. Department of Ophthalmology and Department of Obstetrics and Gynecology, University of Health Sciences, Yüksek lhtisas Training and Research Hospital, Bursa, Turkey between January and June 2019. Fifty-nine patients with PCOS and 35 healthy controls were enrolled in the study. Foveal avascular zone (FAZ), the capillary density assessed in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the macula and was also measured in optic disc using the OCTA. The thicknesses of the retinal nerve fiber (RNFL), ganglion cell complex (GCC), and macula were measured by OCT. The capillary density in the macula and optic disc region were not a significant difference between the PCOS patients and healthy controls.The parafoveal superior, inferior, and temporal quadrant thickness was significantly higher in the study group compared to control group (p=0.047, p=0.033,and p=0.033, respectively). In patients with PCOS, there were negative correlations between IR and inferior RNFL, total and superior GCC thickness (r=-0.29 p= 0.027, r=-0.27 p=0.050, r=-0.31 p=0.029, respectively). Although no microvascular macular abnormalities were seen in PCOS patients, the parafoveal thickness significantly increased in all quadrants, except the nasal quadrant. In patients with PCOS, IR, dyslipidemia may affect the structural integrity of the retina. Further longitudinal follow-up studies are needed to determine whether PCOS has any effect on OCTA findings. Key Words: Polycystic ovary syndrome, Retina, Optical coherence tomography, Optical coherence tomography angiography.

Quantitative Optical Coherence Tomography Angiography Biomarkers for Alport Syndrome

Purpose: The aim of this study was to evaluate microvascular abnormalities of patients with Alport syndrome (AS) using optical coherence tomography angiography (OCT-A) quantitative biomarkers. Methods: This was cross sectional, prospective evaluation of consecutive patients with AS and healthy subjects. AS diagnosis was performed by the genetic test. All participants underwent a retinal vasculature evaluation by spectral-domain optical coherence tomography (SD-OCT) and OCT-A of the macula. Quantitative analysis included whole vascular density, foveal avascular zone area, fractal dimension (FD), and lacunarity (LAC). Results: Ninety-four eyes were included in this study, 45 eyes from patients with AS and 49 eyes from healthy subjects. The pathogenic mutation in the COL4A5 gene on the chromosome X was found in 14 patients; the pathogenic autosomal recessive mutations in the COL4A3 gene were found in 9 patients. Quantitative evaluation demonstrated a significant difference between AS and healthy subjects on LAC of the superficial capillary plexus and deep capillary plexus (DCP) (p < 0.001 and p < 0.001, respectively) and on FD in the DCP (p < 0.001). Conclusion: The DCP Alport patients have a higher vessel nonuniformity than DCP of healthy subjects. We hypothesize that endothelial cell lesion in the setting of low resistance at the DCP circuit could lead to long-term structural disorganization.

Effectiveness and side effects of immunomodulatory agents for complex regional pain syndrome

The main causes of Complex regional pain syndrome (CRPS) are not fully understood. However, it usually emerges following a surgery or an injury to a limb. Inflammation, musculoskeletal, neuronal, and microvascular abnormalities have been found to contribute to the progression of the disease. Immune cells activation, especially with regards to the early phases of the disease is also indicated in the literature. Accordingly, efforts were directed to manage and enhance such responses, aiming to enhance the outcomes by introducing many immunomodulatory agents for managing patients with CRPS and relieving the associated pain. In this literature review, we have discussed the effectiveness and safety of common immunomodulatory agents for CRPS. We have mainly reviewed the roles of glucocorticoids, TNF-α antagonists, bisphosphonates, and intravenous immunoglobulins administration. Glucocorticoids were among the first reported modalities in the management of the syndrome. However, their use is approached with caution because of their potential systemic side effects. Bisphosphonates and TNF-α antagonists also have validated efficacies and should be administered within the early inflammatory phases to achieve better outcomes. Intravenous immunoglobulins are not adequately validated among the current studies, and evidence shows that they might be useful for a certain subgroup. Therefore, further investigations are required to formulate stronger evidence.

Nailfold Capillaroscopy Abnormalities Correlate With Disease Activity in Adult Dermatomyositis.

Objectives: The aim of this study was to determine the relationship between disease activity in adult patients with dermatomyositis (DM) and other biomarkers of disease activity such as C-reactive protein creatinine kinase and nailfold video capillaroscopy (NVC).Methods: We performed a prospective single center study of 15 adult patients with DM. Study participants underwent two assessments at least 9 months apart including clinical, laboratory and NVC evaluations. Patients received immunosuppressive medications for their dermatomyositis, and ongoing disease activity was measured by the Myositis Intention to Treat Index (MITAX). NVC evaluation included assessment of capillary density, capillary apical diameter (mm), and the number of microhemorrhages per digit.Results: Microvascular abnormalities were present in most DM patients. Of these, capillary density (4.71 vs. 6.84, p = 0.006) and mean apical diameter (56.09 vs. 27.79 μm, p = 0.003) significantly improved over the study period in concordance with improving disease control (MITAX 8.53 vs. 2.64, p = 0.002). Longitudinal analysis demonstrated that capillary density was independently associated with MITAX (β = −1.49 [CI −2.49, −0.33], p = 0.013), but not other parameters such as C-reactive protein and creatinine kinase.Conclusions: Nailfold capillary density is a dynamic marker of global disease activity in adult DM. NVC may be utilized as a non-invasive point-of-care tool to monitor disease activity and inform treatment decisions in patients with DM.

Updated review on the pathophysiology of Chagas cardiomyopathy.

More than 110 years after Chagas disease discovery, some aspects of the mechanisms involved in the physiopathology of heart damage are still unknown. Previously, Trypanosoma cruzi was considered to be the only cause of myocardial injury. Currently, there are other known mechanisms involved in the physiopathology of Chagas heart disease, including the immune-inflammatory response, autoimmunity, microvascular abnormalities and nerve damage, which are interrelated and contribute to cardiac damage. Nowadays, the parasite is the main cause of cardiac damage during the acute stage of Chagas disease and the one that initiates the complex physiopathological network that triggers the other mentioned mechanisms. The consequence of these pathophysiological mechanisms is progressive deterioration of cardiac function that ultimately establishes Chronic Chagasic cardiomyopathy. The aim of this review is to describe and discuss the main physiopathological mechanisms that are currently being postulated with respect to cardiac damage in T. cruzi infection.

IMAGE EVALUATION OF ARTIFICIAL INTELLIGENCE-SUPPORTED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGING USING OCT-A1 DEVICE IN DIABETIC RETINOPATHY.

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.

Effects of the Topical Administration of Semaglutide on Retinal Neuroinflammation and Vascular Leakage in Experimental Diabetes.

Background: An unexpected increase in the rate of severe diabetic retinopathy was observed in the Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN)-6 clinical trial. Although this effect was attributed to a rapid decrease in blood glucose levels, a direct deleterious effect of semaglutide on the retina could not be ruled out. In order to shed light on this issue, we have performed a study aimed at testing the direct effect of semaglutide administered by eye drops on retinal neuroinflammation and microvascular abnormalities using the db/db mouse model. Methods: Eye drops containing semaglutide (0.33 mg/mL; 5 μL once/daily) or vehicle (PBS; 5 μL once daily) were administered for 15 days. Results: We found that semaglutide significantly reduced glial activation, as well as the retinal expression of Nuclear factor kB (NF-κB), proinflammatory cytokines (IL-1β, IL-6, IL-18) and Intercellular Adhesion Molecule (ICAM)-1. In addition, semaglutide prevented the apoptosis of cells from the retinal ganglion layer and activated the protein kinase B (AKT) pathway. Finally, a dramatic decrease in vascular leakage was observed in db/db mice treated with semaglutide. All these findings were observed without any change in blood glucose levels and, therefore, can be directly attributed to semaglutide. Conclusions: These experimental findings point to a beneficial rather than a deleterious effect of semaglutide on the retina of subjects with diabetes.

Evaluation of the effect of the severity of diabetic retinopathy on microvascular abnormalities and vascular density using optical coherence tomography angiography.

To quantify and to study the relationship between retinal microvascular changes and different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). This prospective observational study included the eyes of patients with different stages of DR. OCTA was performed in all eyes using a 9 × 9mm protocol. We analyzed the superficial and deep retinal capillary plexuses, for the following OCTA parameters: number of microaneurysms (MA), number of intraretinal microvascular abnormalities (IRMA), the total surface of capillary non-perfusion (CNP) areas, and vascular density (VD). The association between those parameters and the severity of DR was studied. A total of 70 eyes of 45 patients were included. The number of MA in the superficial capillary plexus (SCP) showed a significant association with DR severity (p = 0.03). The number of IRMA and the total surface of CNP areas were associated with the severity of DR in both plexuses (p = 0.019 in the SCP and p = 0.044 in the DCP for IRMA; p < 0.001 in the SCP and p = 0.001 in the DCP for CNP areas). The VD decreased significantly with the severity of DRin the DCP (p = 0.04). The number of vascular abnormalities andthe surface of CNP areas were significantly associated with the severity of DR. The decrease in vascular density in the DCP with increasing disease severity suggests that the DCP is more vulnerable to vascular changes than the SCP. Those parameters might be tools for a future DR severity scale based on OCTA. In addition to its capability of detecting vascular changes in DR non-invasively, OCTA may also serve as a valuable tool to graduate DR.

Peripheral arterial filling time and peripheral retina fluorescence features in ultra-widefield angiography.

To evaluate the peripheral arterial filling time (PAFT) and venous filling time (VFT) in eyes without known diseases that may influence filling process using ultra-widefield (UWF) fluorescein angiography (FA), and to review the peripheral retina fluorescence features. A total of 30 eyes of 30 patients were retrospectively reviewed in this observational study. UWF-FA was performed using Optos 200Tx. PAFT and VFT was recorded. The interval between the arterial or venous filling completion and the previous photo was documented. The appearance of the far peripheral retina was described as either granular background fluorescence or mottled fluorescent band or vascular leakage. Terminal vascular patterns was described as loop pattern or branching pattern. Microvascular abnormalities such as arteriovenous shunting, vessels crossing the horizontal raphe, right angle vessels, terminal networks, capillary nonperfusion, drusen or microaneurysms were evaluated. The normal limits of PAFT was 3.397-8.984s and 4.399-11.753s for VFT. The appearance of the far peripheral retina, defined as granular background (63%), mottled fluorescence (20%), or vascular leakage (17%), was symmetrical between both eyes. Capillary nonperfusion (23%) and microaneurysms (40%) were more frequently found in eyes with loop pattern than in eyes with branching pattern. Other peripheral signs such as right-angle vessels (73%), and terminal networks (80%) were commonly seen on UWF-FA in the normal peripheral retina. The main courses of retinal artery and vein filling time are overlapping with each other on UWF-FA. Notably, the arterial filling process is completed in the arteriovenous phase rather than the traditionally named arterial phase. There are various manifestations in the peripheral retina of normal eyes.

Long-term outcome of a Chinese cohort idiopathic retinitis, vasculitis, aneurysms, and neuroretinits (IRVAN) patients.

To evaluate the clinical characteristics and treatment outcomes of idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN) in a cohort of Chinese patients. The clinical history, imaging evaluation, treatment and outcomes of 42 eyes in 21 patients diagnosed with IRVAN in a 15-year period were reviewed. Most patients were females (90%) ranged from 15 to 58years old. The initial decimal best corrected visual acuity (BCVA) of the patients ranged from light perception (LP) to 1.5 (0.55 ± 0.38). Eighteen eyes were in stage 2; 21 eyes in stage 3; and 1 in stage 5 at the initial visits according to the present staging system. Two eyes had vitreoretinal fibrovascular proliferation (FVP) and tractional retinal detachment (RD) at the initial visit. Intra-retinal microvascular abnormality (IRMA) was found in 7 eyes. Thirty-four eyes received retinal photocoagulation, 27 of which were pan-retinal photocoagulation (PRP). Total of 8 PPV were performed for VH, vitreoretinal FVP and RD, and macular epimembrane. Aneurysms on the head of optic nerve and artery bifurcations disappeared in 8 eyes and decreased in number in 2 eyes 1year after photocoagulation. However, the BCVA of the patients did not have significant difference from that at the initial visits (P = 0.534). Seven eyes suffered severe visual impairment (BCVA ≤ 0.1) due to vitreoretinal FVP and tractional RD (3), exudative maculopathy (2), paracentral acute middle maculopathy (PAMM)(1), and neovascular glaucoma (NVG) (1). We found that IRVAN have a predilection to female gender. Vitreoretinal FVP and tractional RD and exudative maculopathy are major causes of severe visual impairment in IRVAN patients. We propose to revise the present staging system to include vitreoretinal FVP and RD in the staging of IRVAN patients.

Foveal Remodeling of Retinal Microvasculature in Parkinson's Disease.

BackgroundRetinal microvascular alterations have been previously described in Parkinson’s disease (PD) patients using optical coherence tomography angiography (OCT-A). However, an extensive description of retinal vascular morphological features, their association with PD-related clinical variables and their potential use as diagnostic biomarkers has not been explored.MethodsWe performed a cross-sectional study including 49 PD patients (87 eyes) and 40 controls (73 eyes). Retinal microvasculature was evaluated with Spectralis OCT-A and cognitive status with Montreal Cognitive Assessment. Unified PD Rating Scale and disease duration were recorded in patients. We extracted microvascular parameters from superficial and deep vascular plexuses of the macula, including the area and circularity of foveal avascular zone (FAZ), skeleton density, perfusion density, vessel perimeter index, vessel mean diameter, fractal dimension (FD) and lacunarity using Python and MATLAB. We compared the microvascular parameters between groups and explored their association with thickness of macular layers and clinical outcomes. Data were analyzed with General Estimating Equations (GEE) and adjusted for age, sex, and hypertension. Logistic regression GEE models were fitted to predict diagnosis of PD versus controls from microvascular, demographic, and clinical data. The discrimination ability of models was tested with receiver operating characteristic curves.ResultsFAZ area was significantly smaller in patients compared to controls in superficial and deep plexuses, whereas perfusion density, skeleton density, FD and lacunarity of capillaries were increased in the foveal zone of PD. In the parafovea, microvascular parameters of superficial plexus were associated with ganglion cell-inner plexiform layer thickness, but this was mainly driven by PD with mild cognitive impairment. No such associations were observed in controls. FAZ area was negatively associated with cognition in PD (non-adjusted models). Foveal lacunarity, combined with demographic and clinical confounding factors, yielded an outstanding diagnostic accuracy for discriminating PD patients from controls.ConclusionParkinson’s disease patients displayed foveal microvascular alterations causing an enlargement of the vascular bed surrounding FAZ. Parafoveal microvascular alterations were less pronounced but were related to inner retinal layer thinning. Retinal microvascular abnormalities helped discriminating PD from controls. All this supports OCT-A as a potential non-invasive biomarker to reveal vascular pathophysiology and improve diagnostic accuracy in PD.

Retinal microvascular parameters are not associated with diabetes in the Northern Ireland Cohort for the Longitudinal Study of Ageing

BackgroundThe retinal microvasculature offers unique non-invasive evaluation of systemic microvascular abnormalities. Previous studies reported associations between retinal microvascular parameters (RMPs) and diabetes. The aim of this study was to assess associations between RMPs and diabetes in a cross-sectional analysis of older persons from the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).MethodsRMPs (central retinal arteriolar/venular equivalents, arteriolar to venular ratio, fractal dimension, and tortuosity) were measured from optic disc-centred fundus images using semi-automated software. Associations were assessed between RMPs and diabetes status with adjustment for potential confounders.ResultsData were included for 1762 participants with 209 classified as having diabetes. Participants had a mean age of 62.1 ± 8.5 years, and 54% were female. As expected, participants with diabetes had significantly higher mean glycated haemoglobin A1c compared to participants without diabetes (57.4 ± 17.6 mmol/mol versus 37.0 ± 4.2 mmol/mol, respectively). In unadjusted and minimally adjusted regression, arteriolar to venular ratio, arteriolar tortuosity and venular tortuosity were significantly associated with diabetes (minimally adjusted odds ratio [OR] = 0.85; 95% confidence intervals [CIs] 0.73, 0.99; P = 0.04, OR = 1.18; 95% CI 1.02, 1.37; P = 0.03 and OR = 1.20; 95% CI 1.04, 1.38; P = 0.01, respectively), although all failed to remain significant following adjustment for potential confounders. No additional associations between other RMPs and diabetes were detected.ConclusionDespite previously reported associations between diabetes and RMPs, our study failed to corroborate these associations in an older community-based cohort.

Assessment of Left Ventricular Systolic Function by Speckle Tracking in Diabetic Patients Receiving Direct Acting Antiviral Drugs for Chronic HCV

Background: Diabetes mellitus [DB] is a well-known risk factor for cardiovascular disease. The co-existence of DM and microvascular abnormalities could lead to hypertrophy of left ventricle (LV) with diastolic and/or systolic dysfunction. However, early stages of the disease are asymptomatic due to its chronic nature and the effective control of diabetes. Aim of the work: This clinical cohort aimed to assess left ventricular systolic function in DM patients, receiving direct acting antiviral (DAA) drugs for chronic hepatitis-C virus by speckle tracking. Subjects and methods: This clinical cohort included 90 patients who were divided into three equal groups. Patients were recruited from Hepatology Outpatient Clinic of Kafr El-Shaikh University hospital, who were sent to the cardiovascular department for evaluation. Patients were evaluated just before, one month and three months after starting therapy. Results: No one in control group had diastolic dysfunction compared to 10.0% and 16.7% in DAAs and Non-DAAs groups, respectively. Conventional echocardiography returned statistically non-significant difference except significant increase of LVESD, IVST and LVPWT in study groups than control groups. However, the difference between DAAs and Non-DAAs groups was statistically non-significant. The basic strain parameters returned significant lower values at different windows in control than study groups. The strains were reduced in the follow up visits (first and third months) in DAAs groups, but not significantly reduced in non-DAAs group. Acute myocardial infarction was reported among one patient in non-DAAs group compared to none in DAAs group. Conclusion: The speckle tracking is a useful tool for early detection of subclinical left ventricular dysfunction in HCV diabetic patients and could be used for following up of response DAA treatment. DAAs therapy is associated with improvement, not of HCV disease, but also of cardiac dysfunction

Retinal Microvasculature in Schizophrenia.

PurposeSchizophrenia is associated with alterations in neural structure and function of the retina that are similar to changes seen in the retina and brain in multiple neurodegenerative disorders. Preliminary evidence suggests that retinal microvasculature may also be compromised in schizophrenia. The goal of this study was to determine, using optical coherence tomography angiography (OCTA), whether 1) schizophrenia is associated with alterations in retinal microvasculature density; and 2) microvasculature reductions are associated with retinal neural layer thinning and performance on a measure of verbal IQ.Patients and MethodsTwenty-eight outpatients with schizophrenia or schizoaffective disorder and 37 psychiatrically healthy control subjects completed OCT and OCTA exams, and the Wechsler Test of Adult Reading.ResultsSchizophrenia patients were characterized by retinal microvasculature density reductions, and enlarged foveal avascular zones, in both eyes. These microvascular abnormalities were generally associated with thinning of retinal neural (macular and peripapillary nerve fiber layer) tissue (but the data were stronger for the left than the right eye) and lower scores on a proxy measure of verbal IQ. First- and later-episode patients did not differ significantly on OCTA findings.ConclusionThe retinal microvasculature impairments seen in schizophrenia appear to be a biomarker of overall brain health, as is the case for multiple neurological conditions. Additional research is needed, however, to clarify contributions of social disadvantage and medical comorbidities to the findings.

A Stepwise Increase In Epicardial Fat Volume Is Associated With Increased Microvascular And Macrovascular Abnormalities

Introduction: It has been reported that an increase in epicardial fat volume (EFV) has been associated with an increase in cardiovascular structural and functional abnormalities (CVSFA). The purpose of the study was to assess whether a stepwise increase in EFV is associated with an increase in microvascular and macrovascular abnormalities, as assessed by the Early Cardiovascular Health Assessment Scoring System (ECVHAS).

Developing a normative database for retinal perfusion using optical coherence tomography angiography.

Visualizing and characterizing microvascular abnormalities with optical coherence tomography angiography (OCTA) has deepened our understanding of ocular diseases, such as glaucoma, diabetic retinopathy, and age-related macular degeneration. Two types of microvascular defects can be detected by OCTA: focal decrease because of localized absence and collapse of retinal capillaries, which is referred to as the non-perfusion area in OCTA, and diffuse perfusion decrease usually detected by comparing with healthy case-control groups. Wider OCTA allows for insights into peripheral retinal vascularity, but the heterogeneous perfusion distribution from the macula, parapapillary area to periphery hurdles the quantitative assessment. A normative database for OCTA could estimate how much individual's data deviate from the normal range, and where the deviations locate. Here, we acquired OCTA images using a swept-source OCT system and a 12×12 mm protocol in healthy subjects. We automatically segmented the large blood vessels with U-Net, corrected for anatomical factors such as the relative position of fovea and disc, and segmented the capillaries by a moving window scheme. A total of 195 eyes were included and divided into 4 age groups: < 30 (n=24) years old, 30-49 (n=28) years old, 50-69 (n=109) years old and >69 (n=34) years old. This provides an age-dependent normative database for characterizing retinal perfusion abnormalities in 12×12 mm OCTA images. The usefulness of the normative database was tested on two pathological groups: one with diabetic retinopathy; the other with glaucoma.

Mucopolysaccharide polysulfate promotes microvascular stabilization and barrier integrity of dermal microvascular endothelial cells via activation of the angiopoietin-1/Tie2 pathway

BackgroundMucopolysaccharide polysulfate (MPS) is a heparinoid and MPS-containing formulations are widely used as moisturizers for dry skin and to treat peripheral vascular insufficiency. Although MPS has therapeutic effects in skin diseases with microvascular abnormalities, the effects of MPS on microvascular function remain incompletely understood. ObjectiveThe aim of this study was to evaluate the functional activities of MPS on human pericytes (HPC) and human dermal microvascular endothelial cells (HDMEC) in vitro, and on microvascular permeability of the skin. MethodsThe protein expression of angiopoietin (Ang)-1 in HPC, and platelet-derived growth factor-BB (PDGF-BB) and phosphorylated tyrosine-protein kinase receptor 2 (Tie2) in HDMEC were measured in the presence or absence of MPS. The vascular barrier was evaluated by the expressions of claudin-5 and vascular endothelial (VE)-cadherin, and transendothelial electrical resistance (TEER). ResultsIn HPC, MPS dose-dependently enhanced Ang-1 secretion, which activated Tie2 in HDMEC. In HDMEC, MPS significantly increased the production of PDGF-BB, which is important for the recruitment of HPC to the vascular endothelium, and significantly increased the phosphorylation of Tie2, which results in the activation of the Ang-1/Tie2 signaling . MPS significantly increased the expression of tight junction protein claudin-5 and TEER in the HDMEC. Moreover, the intradermal injection of MPS prevented vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. ConclusionWe found that MPS promoted microvascular stabilization and barrier integrity in HDMEC via Ang-1/Tie2 activation. These results suggest that MPS might improve microvascular abnormalities in various diseases accompanied by disturbances in Ang-1/Tie2 signaling.