Arteriole-to-venule Ratio Research Articles

Retinal and Macular Changes in Pregnant Women of Advanced Maternal Age: A Retrospective Study.

Aims/Background Pregnancy may cause physiological and pathological changes in multiple organs in a woman's body, including the heart, liver, and eyes. With rapid advances in societies and economies, the proportion of advanced maternal age (AMA) women has significantly increased. Here, we aimed to investigate the changes in arteriole retinal diameter, venule diameter, macular layer thickness, and arteriole to venule ratio (AVR) in this population. Methods This retrospective case-control study included 523 pregnant women (1046 eyes) and was performed on both eyes. In total, 318 subjects were included in the AMA group, and 205 subjects were included in the non-AMA group. Nonmydriatic fundus photography and optical coherence tomography (OCT) were performed on the same day, and the results were analyzed for the central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), AVR, and macular thickness (9 subfields) by integrative vessel analysis and automatic OCT software. Results In both eyes, the CRAE was significantly lower in the AMA group than that in the non-AMA group (p < 0.05; respectively). The CRVE in the AMA group was higher than that in the non-AMA group (p < 0.001; respectively). Compared to the non-AMA group, the AMA group exhibited a significant reduction in macular thickness within the inner nasal, outer nasal, and inner temporal subfields of both eyes (p < 0.05; respectively). Age was significantly correlated with CRVE and AVR in both eyes of pregnant women (CRVE: p < 0.0001; AVR: p < 0.01). Conclusion This study reports variations in the diameter of the retinal vasculature and the thickness of the macula in women of AMA. It is important to consider these changes when interpreting the adverse eye outcomes experienced by women of AMA.

Comparative analysis of retinal microvascular parameters in healthy individuals with or without carotid artery stenosis or plaque.

To evaluate the correlations between retinal microvascular changes and carotid artery stenosis (CAS) with and without plaques using fundus photography. Patients who had undergone bilateral carotid ultrasonography and bilateral fundus photography were divided into the following groups based on the carotid intima-media thickness (IMT) determined via ultrasonography in this retrospective, observational study: the control and CAS (comprising CAS with and without plaque subgroups) groups. The following retinal indicators were determined via fundus photography based on a deep learning algorithm: the arteriole-to-venule ratio (AVR), whole retinal fractal dimension (FD), arteriolar fractal dimension (AFD), venular fractal dimension (VFD), vascular density (VD), and VD within 3 mm (VD3mm) and 5 mm (VD5mm) from the macular fovea. The correlations between these indicators and IMT were also assessed. In total, 715 participants, comprising 313 participants with CAS (CAS group; 91 with plaque and 222 without plaque) and 402 participants without CAS (control group), participated in this study. AFD, VFD, and FD in the CAS group were significantly lower than those in the control group (all p < 0.001). VD, VD3mm, and VD5mm showed significant differences between the groups (all p < 0.05). VFD in the CAS with plaque group was lower than that in the group without plaque (p = 0.014). VD3mm, and VD5mm showed significantly negative correlations with IMTmin in the CAS subgroup. AFD, VFD, FD, VD, VD3 mm, and VD5 mm decreased, and fundus photography based on deep learning algorithm may provide new approaches for screening of CAS.

Deep Learning‐Enabled Vasculometry Depicts Phased Lesion Patterns in High Myopia Progression

PurposeTo investigate the potential phases in myopic retinal vascular alterations for further elucidating the mechanisms underlying the progression of high myopia (HM). MethodsFor this retrospective study, participants diagnosed with high myopia at Beijing Tongren Hospital were recruited. Based on bionic mechanisms of human vision, an intelligent image processing model was developed and utilized to extract and quantify the morphological characteristics of retinal vasculatures in different regions measured by papilla-diameter (PD), including vascular caliber, arteriole-to-venule ratio (AVR), tortuosity, the angle of the vascular arch (AVA), the distance of the vascular arch (DVA), density, fractal dimension, and venular length. In addition, the optic disc and the area of peripapillary atrophy (PPA) were also quantified. The characteristics of the overall population, as well as patients aged less than 25 years old, were compared by different genders. Univariate and multiple linear regression analyses were conducted to investigate the correlation of retinal vasculature parameters with PPA width, and detailed trends of the vascular indicators were analyzed to explore the potential existence of staged morphological changes. FindingsThe study included 14,066 fundus photographs of 5775 patients (aged 41.2 ± 18.6 years), of whom 7379 (61.2 %) were female. The study included 12,067 fundus photographs of 5320 patients (aged 41.2 ± 18.6 years). Significant variations in the morphological parameters of retinal vessels were observed between males and females. After adjusting for age and sex, multiple linear regression analysis showed that an increased PPA width ratio was associated with lower AVA (1PD), DVA (1PD), vascular caliber (0.5–1.0 PD), tortuosity (0.5–1.0 PD), density and fractal dimension (all P < 0.001, Spearman’s ρ < 0). Overall, the changes in retinal vascular morphology showed two phases: tortuosity (0.5–1.0PD) and AVA (1PD) decreased rapidly in the first stage but significantly more slowly in the second stage, while vascular density and fractal dimension showed a completely opposite trend with an initial slow decline followed by a rapid decrease. ConclusionsThis study identified two distinct phases of retinal vascular morphological changes during the progression of HM. Traction lesions were predominant in the initial stage, while atrophic lesions were predominant in the later stage. These findings provide further insight into the development mechanism of HM from the perspective of retinal vasculature.

Characteristics of retinal image associated with premature ovarian insufficiency: a case- control study

PurposeTo establish an early clinical diagnosis model based on the retinal vascular features associated with POI, supplying a non-invasive way for accurately and early predicted the risk of POI.MethodsA total of 78 women with spontaneous POI and 48 healthy women were recruited from the Affiliated Shenzhen Maternity & Child Healthcare Hospital in the study. Retinal characteristics were analyzed using an automated retinal image analysis system. Binary logistic regression was used to identify POI cases and develop predictive models.ResultsCompared to the normal group, the POI group had larger central retinal artery equivalent (CRAE) (P = 0.006), central retinal vein equivalent (CRVE) (P = 0.001), index of venules asymmetry (Vasym) (P = 0.000); larger bifurcation angles of arterioles (Aangle) (P = 0.001), bifurcation coefficient of venule (BCV) (P = 0.001) and more obvious arteriovenous nipping (Nipping) (P = 0.005), but lower arteriole-to-venule ratio (AVR) (P = 0.012). In the POI group, the odds ratio (OR) of Vasym was 6.72e-32 (95% C.I. 4.62e-49–9.79e-15, P = 0.000), the OR of BCV was 5.66e-20 (95% C.I. 1.93e-34–.0000, P = 5.66e-20) and the OR of Nipping was 6.65e-06 (95% C.I. 6.33e-10–.0698, P = 0.012). Moreover, the area under the ROC curve for the binary logistic regression with retinal characteristics was 0.8582, and the fitting degree of regression models was 60.48% (Prob > chi-square = 0.6048).ConclusionThis study demonstrated that retinal image analysis can provide useful information for POI identification and certain characteristics may help with early clinical diagnosis of POI.

URINARY PROTEOMIC SIGNATURE OF THE RETINAL MICROVASCULATURE

Objective: The retinal vasculature provides a window into the body's microcirculation. Variations in retinal vessel diameters have been associated with adverse cardiovascular outcomes, such as stroke and coronary heart disease. As the pathogenesis of retinal microvascular diameter changes remain poorly understood, this study aimed to provide novel insights by characterizing the urinary proteomic signature of the retinal microvasculature. Design and method: The central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriole-to venule-ratio (AVR) were measured from digitized retinal photographs of 562 randomly recruited Flemish participants (mean age, 48.9 years; 50.9% women). The urinary proteome was analyzed using capillary electrophoresis coupled with mass spectrometry. Multivariable linear regression analysis identified significant urinary peptides with adjustment for age, sex, body mass index, smoking, hypertension, plasma glucose, total and HDL cholesterol, eGFR, and history of cardiovascular disease. Reactome pathway enrichment analysis was performed to interpret the proteomic signature. Results: Table 1 shows participant characteristics. Of the 359 peptides analyzed, 19 were significantly associated with CRAE after adjusting for potential confounders and multiple testing (Table 2). In the proteomic profile, 14 peptides (74%) were fragments of collagen I, III, and XI proteins, while the remaining peptides were fragments of the fibrinogen alpha chain (11%), xylosyltransferase 1 (5%), S100 calcium-binding protein A9 (5%), and hemoglobin subunit alpha (5%) proteins. Pathway analysis showed that these proteins were predominantly involved in endothelial cell proliferation and migration, collagen formation and degradation, and cell-extracellular matrix interactions (Figure 1). No peptides were significantly associated with CRVE and AVR following adjustment. Conclusions: This study revealed a novel urinary proteomic signature as a potential biomarker of retinal arteriolar narrowing. The signature suggests fibrosis and neovascularization may be involved in retinal microvascular diameter changes. Further investigation may help elucidate the pathophysiologic mechanisms underlying the relationship between microvascular and macrovascular disease.

Retinal vessel architecture and geometry are not impaired in normal-tension glaucoma

To investigate the associations between retinal vessel parameters and normal-tension glaucoma (NTG). We conducted a case–control study with a prospective cohort, allowing to record 23 cases of NTG. We matched NTG patient with one primary open-angle glaucoma (POAG) and one control per case by age, systemic hypertension, diabetes, and refraction. Central retinal artery equivalent (CRAE), central retinal venule equivalent (CRVE), Arteriole-To-Venule ratio (AVR), Fractal Dimension and tortuosity of the vascular network were measured using VAMPIRE software. Our sample consisted of 23 NTG, 23 POAG, and 23 control individuals, with a median age of 65 years (25–75th percentile, 56–74). No significant differences were observed in median values for CRAE (130.6 µm (25–75th percentile, 122.8; 137.0) for NTG, 128.4 µm (124.0; 132.9) for POAG, and 135.3 µm (123.3; 144.8) for controls, P = .23), CRVE (172.1 µm (160.0; 188.3), 172.8 µm (163.3; 181.6), and 175.9 µm (167.6; 188.4), P = .43), AVR (0.76, 0.75, 0.74, P = .71), tortuosity and fractal parameters across study groups. Vascular morphological parameters were not significantly associated with retinal nerve fiber layer thickness or mean deviation for the NTG and POAG groups. Our results suggest that vascular dysregulation in NTG does not modify the architecture and geometry of the retinal vessel network.

Evaluation of Retinal Vascularity Index in Patients with COVID-19: A Case-Control Study.

The purpose of this study was to evaluate the impact of COVID-19 infection on retinal microvasculature by topographically mapping the retinal arteriole-to-venule ratio (AVR). In a comparative cross-sectional case-control study, fundus photos were obtained in COVID-19-infected patients and healthy controls. AVT was measured over 16 points across the retina using retinal vascularity index (RVI)-a novel semi-automated computerized parameter based on retinal vasculature. A total of 51 COVID-19-positive patients and 65 healthy controls were enrolled in the study. Overall, the mean RVI of all 16 points across the retina was 0.34 ± 0.02 in patients with COVID-19 and 0.33 ± 0.02 in control subjects (p = 0.64). Out of the 16 points being measured, three points had a statistically significant greater value in patients with COVID compared to normal controls. Localised greater RVI values were found in some of the points in COVID-19-positive patients, which likely indicates a more focal change of the vasculature.

Relationship of Retinal Vessel Caliber with Age-Related Macular Degeneration.

Purpose Evaluate the relationship between retinal vascular caliber and age-related macular degeneration (AMD) severity or progression. Methods A retrospective secondary analysis of 1172 fundus photographs and clinical data from the prospective Age-Related Eye Disease Study (AREDS). Central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were measured using the Parr–Hubbard–Knudtson formula. Univariate and multivariate regressions were used to determine the association of CRAE, CRVE, and AVR with age, sex, smoking status, presence of cilioretinal artery, and AMD severity at baseline and 5 years using the 9-step AMD severity score. Results Only CRAE and CRVE were higher in men (P < 0.001), current smokers (P < 0.001), and the eyes with a cilioretinal artery (P=0.009 − 0.043). AMD severity was greater in older patients (P=0.001), current smokers (P=0.012), the eyes without a cilioretinal artery (P=0.001), and lower AVR (P=0.034) on multivariate regression but was not influenced by CRAE or CRVE (P=0.240 − 0.500). Choroidal neovascularization (CNV) presence was associated with older age (P=0.003) and absence of a cilioretinal artery (P=0.009), while central geographic atrophy (CGA) was associated with narrower CRAE (P=0.002) and possibly AVR (P=0.046). None of the retinal vessel parameters were predictive of AMD severity score or new onset of CNV or CGA at 5 years. Conclusion A lower arteriole-to-venule ratio may be associated with AMD severity, with narrower arterioles seen in the eyes with geographic atrophy, suggesting a role of the retinal vasculature in AMD pathophysiology. This trial is registered with ClinicalTrials.gov Identifier: NCT00000145.

CHANGES IN RETINAL VESSEL DIAMETER ARE ASSOCIATED WITH CEREBRAL MICROBLEEDS IN NEUROLOGICALLY ASYMPTOMATIC INDIVIDUALS WITH TYPE 1 DIABETES

Objective: We observed recently that a third of asymptomatic individuals with type 1 diabetes (T1D) showed signs of cerebral small-vessel disease in brain magnetic resonance imaging (MRI). Here, we aimed to explore the relationship between an easily applicable quantitative measure of retinal vessel diameters (RVD) and cerebrovascular changes in these individuals. Design and method: We included 188 individuals with type 1 diabetes and 30 healthy sex and age matched (49% males, median age 40 years) controls. Any neurological signs or symptoms were exclusion criteria. All subjects underwent a clinical and biochemical work-up, as well as brain MRI. Both retinas were phenotyped by measuring the width of all vessels located 0.5 to 1.0 disc diameters from the disc margin by a computer-assisted method (IVAN software). Summarized estimates for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) represented average retinal vessel diameters. The arteriole-to-venule ratio (AVR) was calculated as an additional estimate of early retinal vascular pathology. Associations between blood pressure (BP), cerebral microbleeds (CMBs), white-matter hyperintensities (Fazekas classification), and CRAE, CRVE, and AVR were assessed with non-parametric tests and linear regression models. Results: No difference in CRAE, CRVE, or AVR were found between individuals with type 1 diabetes and controls. An expected correlation between BP and CRAE (p = 0.01) was observed. Median AVR was lower among individuals with T1D and cerebral microbleeds (p = 0.02) compared to those without. A correlation between AVR and the number of CMBs (p = 0.035) was also found. Further, median CRAE was lower among those with &gt; 10 CMBs (p = 0.039) compared to those without. We observed no correlations between RVD and white-matter hyperintensities. Conclusions: Individuals with CMBs had lower CRAE and AVR suggesting that early vascular changes in the retinal are indicative of cerebrovascular pathology in middle aged individuals with T1D.

Longitudinal Effect of Bariatric Surgery on Retinal Microcirculation and Target Organ Damage: the BASTOD Study.

Obesity is associated with increased cardiovascular risk. Bariatric surgery (BS) improves the clinical and metabolic profile. Retinal caliber changes could precede cardiovascular events. Different studies have shown an improvement in retinal caliber after BS. The aim of this study was to examine retinal caliber and other cardiovascular target organ damage before and after BS. Monocentric, prospective cohort study at the Montpellier University Hospital. Biologic features, vessel stiffness, echocardiograph variables, and retinal caliber at baseline and 6 and 12months were assessed in consecutive patients with class 2 or 3 obesity undergoing BS. A mixed linear model adjusted for age and sex was used. We included 88 patients (75 women). The mean (SD) age was 43years (11) and mean (SD) baseline weight 117 (21) Kg. Mean changes in the first year after BS were - 5.1µm in central retinal vein equivalent (CRVE) (p < 0.0001), + 0.02 in arteriole-to-venule ratio (AVR) (p < 0.0001), - 1.4mmol/L in glycemia (p < 0.0001), - 1.0mg/L in natural logarithm of C-reactive protein (p < 0.0001), and - 54.0g in left ventricular mass (p = 0.0005). We observed no significant improvement in arterial stiffness markers. Predictors of improvement in CRVE were high baseline weight (p = 0.030), male sex (p = 0.025), and no diabetes history (p Dynamic links between variations = 0.047). The retinal microvascular phenotype improved during the first year after bariatric surgery, with decreased CRVE and increased AVR. Factors associated with retinal microvascular plasticity were male sex, high baseline weight, and absence of diabetes. Longitudinal assessment of retinal vascular calibers may offer new insights into the pathophysiology of subclinical vascular processes.

Changes of retinal structure and function in patients with internal carotid artery stenosis

BackgroundTo investigate the structural and functional changes of the retina in patients with different degrees of internal carotid artery (ICA) stenosis.MethodsThis cross-sectional study included patients with varying degrees ICA stenosis. Clinical characteristics of 41 patients were collected after being divided into four groups according to the ICA stenosis indicated by computed tomographic angiography (Group 0: without ICA stenosis, Group 1: ipsilateral slight ICA stenosis, Group 2: ipsilateral moderate ICA stenosis, Group 3: ipsilateral severe ICA stenosis). Retinal vessel caliber (RVC) was measured quantitatively with the Integrative Vessel Analysis software. The retinal sensitivity was examined with the MP-3 microperimeter. The relationships among central retinal artery equivalent (CRAE), central retinal vein equivalent, arteriole to venule ratio (AVR), mean retinal sensitivity (MS) and ICA stenosis degree were analysed.ResultsThe CRAE in Group 3 were significantly smaller compared with Group 0, Group 1 and Group 2 (P < 0.001, P < 0.001, P = 0.002). Significant decrease was found between Group 3 with other groups in MS at fovea (P < 0.001, P < 0.001, P = 0.002). Moreover, there was a positive correlation found between MS and CRAE (Beta = 0.60, P < 0.001 at fovea; Beta = 0.64, P < 0.001 at 2 degree; Beta = 0.60, P < 0.001 at 4 degree; Beta = 0.55, P < 0.001 at 8 degree; Beta = 0.53, P < 0.001 at 12 degree).ConclusionsThe present study revealed smaller CRAE and AVR in ipsilateral severe ICA stenosis patients. And the MS decreased in patients with severe ICA stenosis. In addition, MS had a positive correlation with CRAE.

Retinal vascular caliber in patients with newly diagnosed iron deficiency anemia

BackgroundTo evaluate the retinal vascular caliber using fundus photography in patients with newly diagnosed iron deficiency anemia (IDA). MethodsThis study included 56 eyes of 28 female patients with IDA and the 56 eyes of 28 age- and sex-matched healthy participants. Retinal vascular calibers were measured using image analysis software from fundus photographs. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and arteriole-to-venule ratio (AVR) were compared between groups. Linear regression analysis was used to quantify the relative impact of hemoglobin level on CRAE, CRVE, and AVR. ResultsThe CRAE was significantly narrower in patients with IDA. However, no such difference appeared between groups in CRVE. AVR was significantly lower among patients with IDA than in the control group. Linear regression analysis revealed that in patients with IDA, hemoglobin level was associated with CRAE and CRVE but not with AVR. Among non-anemic individuals, there was also no association between hemoglobin level and CRAE, CRVE, or AVR. ConclusionsOur results showing that the CRAE is significantly narrower in patients with IDA than in healthy non-anemic individuals suggests that vascular caliber may reflect early microvascular alterations resulting from IDA. Added to that, hemoglobin level was associated with CRAE and CRVE in our linear regression analysis of patients with IDA. Certain changes in retinal vascular caliber are also clearly associated with high blood pressure, cardiovascular risk, and mortality. It may be critical to identify all alterations in retinal vascular caliber in order to prevent potential ocular and systemic disorders in patients with IDA.

Retinal vascular morphology and blood flow characteristics of patients with various degrees of intracranial internal carotid artery stenosis

To explore the retinal vascular morphology and blood flow characteristics of patients with varying degrees of intracranial internal carotid artery (IICA) stenosis. A total of 280 eligible patients were divided into non-stenosis (n=39), mild stenosis (n=80), moderate stenosis (n=83) and severe stenosis groups (n=49). Hemodynamic indices of the posterior ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) in the dark zone of optic nerve were detected using color Doppler ultrasonography. CRA equivalent (CRAE), central retinal vein equivalent (CRVE) and arteriole-to-venule ratio (AVR) within 0.5-1.0 PD from the optic disc rim to the center of the fundus image were measured using IVAN software. The diagnostic values of PCA peak systolic velocity (PSV) and end-diastolic velocity (EDV) for severe IICA stenosis were evaluated by receiver operating characteristic (ROC) curves. The blood flow parameters (PSV and EDV) of the OA, CRA and PCA in the severe stenosis group were the lowest (P<0.05). The PSV and EDV of the OA, CRA and PCA had significant negative correlations with severe IICA stenosis, and PCA PSV was more sensitive in the presence of the same index. The areas under the ROC curves for PCA PSV and EDV were 0.722 and 0.761, respectively, indicating that PCA PSV and EDV had high diagnostic values. There is no correlation between retinal vascular morphology and IICA stenosis. Severe IICA stenosis has significant negative correlations with ocular the blood flow parameters PSV and EDV, and PCA PSV is most sensitive with the same index, thus being a potential predictive index.

Study on the Interaction between the Characteristics of Retinal Microangiopathy and Risk Factors for Cerebral Small Vessel Disease.

Objective This study was designed to explore the characteristics of retinal microangiopathy in patients with cerebral small vessel disease (CSVD) and clarify its interaction with the risk factors for CSVD. Methods Sixty patients with CSVD and 15 healthy individuals were enrolled. Demographic data, risk factors, and medical history were recorded, and magnetic resonance imaging was performed to detect and analyze the characteristics of retinal microangiopathy in the two groups. The interaction among retinal microangiopathy, vascular risk factors, and total imaging load of CSVD was compared. Results (1) Hypertension, standard deviation of systolic blood pressure (SBPSD), standard deviation of blood glucose (SDBG), and atherogenic index of plasma (AIP) were independent vascular risk factors for CSVD. (2) Statistically significant differences in hypertension, SBPSD, SDBG, and AIP were observed between the two groups in terms of the total imaging burden of CSVD (p < 0.05). (3) Multivariate logistic linear regression showed that CSVD was associated with a wider central retinal vein equivalent (CRVE) (p = 0.015), a smaller arteriole-to-venule ratio (AVR) (p = 0.001), and a higher incidence of vessel tortuosity (p = 0.027). (4) When the total imaging burden of CSVD ranges from 0 to 4 points, the CRVE is larger, the AVR is smaller, and the incidence of vascular tortuosity is higher, with a statistically significant difference (p < 0.05). (5) The characteristics of retinal microangiopathy were correlated with hypertension, SBPSD, SDBG, and AIP (p < 0.05). (6) An association was observed between the characteristics of retinal microangiopathy and vascular risk factors and the total imaging burden of CSVD (p < 0.05). Conclusions (1) Hypertension, SBP variability, BG fluctuation, and AIP are independent vascular risk factors for CSVD. (2) Retinal microvessels are changed in patients with CSVD, and venous dilatation, decreased arteriovenous ratio, and vascular tortuosity are the main characteristics of the disease. (3) The characteristics of retinal microangiopathy are interactively correlated with the total imaging load and risk factors for CSVD and can be used as indicators of the severity of CSVD.

Correlation Between Retinal Microvascular Abnormalities and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes.

Background and Purpose: Diabetic retinopathy (DR) is one of the common microvascular complications in diabetes. The total magnetic resonance imaging (MRI) burden of cerebral small vessel disease (CSVD) tends to be increased in diabetic patients and is a marker of microvascular disease; however, the relationship between DR and CSVD is unclear. This study aimed to explore the relationship between retinal microvascular abnormalities and the total MRI burden of CSVD in patients with type 2 diabetes.Methods: Data were collected from patients with type 2 diabetes who were hospitalized between December 2019 and November 2020 in Changzhou Second People’s Hospital affiliated to Nanjing Medical University. All patients underwent retinal photography and cerebral MRI. The central retinal artery equivalent (CRAE), the central retinal venous equivalent (CRVE), and arteriole-to-venule ratio (AVR) were calculated using Image J software to determine the retinal vascular calibers for each patient. The total MRI burden score for CSVD was determined, and the relationship between retinal microvascular abnormalities and the total MRI burden of CSVD was analyzed.Results: Of the 151 diabetic patients included in the study, 84 (55.6%) had no diabetic retinopathy (NDR), 27 (17.9%) had mild DR, and 40 (26.5%) had moderate, or severe non-proliferative DR (grouped together for this study as “more than mild DR”). In patients with more than mild DR, the proportion of moderate to severe burden of CSVD was 75%, which was higher than in patients with mild DR (48.1%) or NDR (26.2%). Patients with moderate to severe burden of CSVD were more likely than those with mild burden of CSVD to have narrowed retinal arterioles (105.24 ± 8.42 μm vs. 109.45 ± 7.93 μm), widened retinal venules (201.67 ± 16.25 μm vs. 193.95 ± 13.54 μm), and lower arteriole-to-venule ratio (0.52 ± 0.05 vs. 0.57 ± 0.04) (P < 0.05 for all). The degree of DR (r = 0.465, P < 0.001) and CRVE (r = 0.366, P < 0.001) were positively correlated with the total MRI burden of CSVD. Multivariate logistic regression analysis indicated that, after adjustments were made for age, smoking, alcohol consumption, hypertension, and other factors, more than mild DR (OR, 4.383; P = 0.028), CRAE (OR, 0.490; P = 0.031), and CRVE (OR, 1.475; P = 0.041) were independently associated with moderate to severe burden of CSVD.Conclusion: Retinal microvascular abnormalities in patients with type 2 diabetes are associated with the presence of cerebral small vessel lesions. The degree of DR and retinal vessel changes can be used as predictors of intracranial microcirculation lesions.

Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke

Objective: To explore the relationship between the total cerebral small vessel disease (CSVD) score and retinal vessel diameters in patients with mild stroke. Methods: The patients with mild stroke who were hospitalized in the Second People's Hospital of Changzhou, Nanjing Medical University from March to December 2019 were continuously collected (National Institutes of Health Stroke Scale score≤3 points). All patients completed the head magnetic resonance imaging and retinal fundus photography examination, and then the retinal arteriovenous diameter was measured semi-automatically based on the pictures. According to the total CSVD score (0-4 points), the patients were divided into 5 groups. The baseline characteristics of the patients were compared. Moreover, the correlation of total CSVD with retinal blood vessel diameters were analyzed by spearman and linear regression. Results: A total of 206 patients were enrolled. There were 69, 51, 41, 30, and 15 patients with 0, 1, 2, 3, and 4 points, respectively. In CSVD subgroups, there were significant differences in age, duration of hypertension and diabetes (all P<0.05). The central retinal artery equivalent (CRAE), (CSVD scores 0-4 were (126±12) μm, (118±11) μm, (108±11) μm, (99±8) μm, (90±7) μm, P<0.001) and arteriole-to-venule ratio (AVR) (CSVD scores 0-4 were 0.65±0.05, 0.60±0.04, 0.56±0.04, 0.49±0.03, 0.44±0.02, P<0.001) were different in CSVD subgroups. With the increase of CSVD score, the diameter of artery and AVR became smaller. The total CSVD was significantly correlated with AVR by Spearman correlation analysis (r= 0.818, P<0.001). By constructing a linear regression equation model, the coefficient of determination of the total CSVD score (R2=0.694) was higher than that of lacunes, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space. After adjusting for age, course of hypertension and diabetes, and different types of CSVD, further multiple linear regression analysis revealed that the total CSVD score was still an independent related factor of AVR (β=-0.039, P<0.001, 95%CI=-0.051--0.028). Conclusions: Total CSVD score is negatively correlated with retinal artery diameters and AVR. Additionally, the total CSVD score can better reflect the degree of cerebral microvascular lesions than single type CSVD.

Age-related features of the organization of the microcirculatory bed of the bulbar conjunctiva

Objective: Analysis of age-related changes of microcirculatory bed of bulbar conjunctiva.Methods: 46 individuals of both sexes, divided into 5 age groups according to WHO recommendations, were examined. Biomicroscopy of bulbar conjunctiva was performed using a non-mydriatic retinal camera TOPCON TRC-NW8F (Japan); the obtained images were processed with a mea‑ suring device of automated analysis system ImageScope (Leica, Germany).Results: The average diameter of arterioles, arterioleto-venule ratio (AVR) and specific density of capillaries were the largest, and the diameter of venules was the smallest among the subjects aged 18–44 years. The most sensitive indicators of the state of microcirculatory bed were AVR and the specific density of capillaries, the values of which in the group of 45–59-year-olds were 10–11% lower than in people aged 18–24 and 25–44 years. Differences in other indicators between people aged 18-24 and 45–59 years were not significant. Between the groups of 60–74 and 75–86-year-old participants of the study, pronounced differences (about 18%) were found only in the specific density of capillaries: compared with 18–24 and 45–59-year-olds, this indicator decreased by almost 1.5 times, AVR – only by a third, and changes in the average diameter of arterioles and venules did not exceed 9–12%. Elderly people more often demonstrated arteriolar spasm, their uneven caliber, avascular fields and other disorders of the structure of the micro‑ circulatory bed.Conclusions: As the body ages, in the microcirculatory bed of the bulbar conjunctiva, the number of atypical vascular formations increases, the diameter of the arterioles decreases, the AVR and the specific density of capillaries decrease, the diameter of the venules increases.

Quantitative measurements of enlarged perivascular spaces in the brain are associated with retinal microvascular parameters in older community-dwelling subjects.

Perivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people. We analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors. In 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume β=-0.170, count β=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size increased with decreasing FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa β=-0.137, FDv β=-0.139, p<0.01; width: FDa β=-0.144, FDv β=-0.158, p<0.01; size: FDa β=-0.157, FDv β=-0.162, p<0.01). Increase in PVS number and size visible on MRI reflect arteriolar narrowing and lower retinal arteriole and venule branching complexity, both markers of impaired microvascular health. Computationally-derived PVS metrics may be an early indicator of failing vascular health and should be tested in longitudinal studies.

Factors Associated With Retinal Vessel Diameters in an Elderly Population: the Thessaloniki Eye Study.

To identify the factors associated with retinal vessel diameters in the population of the Thessaloniki Eye Study. Cross-sectional population-based study (age ≥ 60 years). Subjects with glaucoma, late age-related macular degeneration, and diabetic retinopathy were excluded from the analyses. Retinal vessel diameters were measured using the IVAN software, and measurements were summarized to central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole to venule ratio (AVR). The analysis included 1614 subjects. The hypertensive group showed lower values of CRAE (P = 0.033) and AVR (P = 0.0351) compared to the normal blood pressure (BP) group. On the contrary, the group having normal BP under antihypertensive treatment did not have different values compared to the normal BP group. Diastolic BP (per mm Hg) was negatively associated with CRAE (P < 0.0001) and AVR (P < 0.0001), while systolic BP (per mm Hg) was positively associated with CRAE (P = 0.001) and AVR (P = 0.0096). Other factors significantly associated included age, sex, alcohol, smoking, cardiovascular disease history, ophthalmic medication, weight, and IOP; differences were observed in a stratified analysis based on BP medication use. Our study confirms previous reports about the association of age and BP with vessel diameters. The negative correlation between BP and CRAE seems to be guided by the effect of diastolic BP as higher systolic BP is independently associated with higher values of CRAE. The association of BP status with retinal vessel diameters is determined by diastolic BP status in our population. Multiple other factors are also independently associated with retinal vessel diameters.

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confidence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03 µm (CI, −1.96 to −0.11; P = 0.028) and −0.007 (CI, −0.011 to −0.002; P = 0.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates −0.91 µm (CI, −1.82 to −0.01; P = 0.048) and −0.006 (95% CI, −0.011 to −0.001; P = 0.014), respectively. Circulating inactive dp–ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.