Arteriolar Caliber Research Articles

A stronger association of diabetes mellitus with impaired hyperaemia using a novel ECG-gated device compared with peripheral arterial tonometry

PurposeImpaired digital reactive hyperaemia and flicker-stimulated retinal vascular response are commonly reported risk markers of cardiovascular disease. This is the first study to determine the correlation of these risk markers with diabetes mellitus by comparing our novel flicker-modulated ECG-gated fundoscope with the EndoPAT2000 system.MethodsIn total, 119 controls and 120 participants with diabetes mellitus partook in this cross-sectional study. The EndoPAT2000 system assessed digital reactive hyperaemia under fasting conditions. A mydriatic ECG-gated fundoscope with a novel flicker module acquired digital retinal images of the left eye before, during and after flicker stimulation. An inhouse semi-automated software measured retinal vessel diameters using a validated protocol with two observers repeating measurements in a subset of 10 controls and 10 participants with diabetes mellitus. Intra- and inter-observer reliability analyses occurred by the interclass correlation coefficient. A receiver operating characteristic curve established associations of variables with diabetes mellitus.ResultsDiabetes mellitus was more strongly associated with flicker-stimulated retinal arteriolar calibre change from baseline (AUC 0.81, 95% CI 0.75–0.87, p < 0.0001) than reactive hyperaemia index. Median flicker-stimulated arteriolar calibre change from baseline (controls: 2.74%, IQR 1.07 vs diabetes mellitus: 1.64%, IQR 1.25, p < 0.0001) and reactive hyperaemia index (controls: 1.87, IQR 0.81 vs diabetes mellitus: 1.60, IQR 0.81, p = 0.003) were lower in diabetes mellitus than controls. Intra- and inter-observer reliability coefficients were high from 0.87 to 0.93.ConclusionsImpaired flicker-stimulated retinal arteriolar calibre change from baseline is more highly correlated with diabetes mellitus in this study than a reduced reactive hyperaemia index.

Normative data of retinal arteriolar and venular calibre measurements determined using confocal scanning laser ophthalmoscopy system - Importance and implications for study of cardiometabolic disorders.

Purpose:To determine and validate retinal vascular caliber measurements by using the confocal scanning laser ophthalmoscopy system. Retinal vasculature changes are often regarded as clinical markers for systemic disease.Methods:It was a prospective observational study conducted on 600 eyes of 300 normal subjects with no systemic or ocular illness from January 1, 2016 to June 30, 2017 in a tertiary referral eye center. Non-mydriatic infrared reflectance, blue reflectance, and blue peak blue autofluorescence fundus imaging were done on the confocal scanning laser ophthalmoscopy system. The dimensions of the retinal vessels were measured using inbuilt calipers at 1800 mm from the center of the optic disc. Internal and external dimensions were measured. Observer variation and its comparison using Image J software were assessed.Results:The median age was 29 years (18–50 years). Mean internal and external diameters for arterioles were 85.1 ± 12.4 mm and 105.0 ± 12.0 mm, and for venules were 133.8 ± 16.6 mm and 145.4 ± 16.1 mm, respectively. The mean internal and external wall thicknesses were 19.7 ± 8.0 mm and 11.0 ± 5.6 mm, and wall thickness-to-lumen ratios were 0.3 ± 0.1 and 0.1 ± 0.1, respectively. Arteriolar-to-venular ratio for lumen and vessel was 0.66 ± 0.1 and 0.74 ± 0.1, respectively. There was no statistically significant difference between age groups. Both inter- and intra-observer reproducibility was >95%. The Bland–Altman plot showed that the difference between measurements using both confocal scanning laser ophthalmoscopy and Image J software lies within the limits of agreement approximately 95% of the time.Conclusion:This is the first effort to develop a normative database by using a simple non-invasive confocal scanning laser ophthalmoscopy system with high observer reproducibility.

Retinal Microvascular Caliber and Incident Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis.

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. The retina allows for visualization of a microvascular bed that shares similarities with the cerebral microvasculature. We investigated the associations between baseline retinal arteriolar and venular calibers (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively) and incident depressive symptoms in the Multi-Ethnic Study of Atherosclerosis (MESA). We used longitudinal data on 4,366 participants (mean age = 63.2 years; 48.5% women, 28.4% Black) without baseline depressive symptoms. Depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale score ≥16 and/or use of antidepressant medication, were determined between 2002 and 2004 (baseline; MESA visit 2) and at 3 follow-up examinations conducted every 1.5–2 years thereafter. Fundus photography was performed at baseline. After a mean follow-up period of 6.1 years, 21.9% (n = 958) had incident depressive symptoms. After adjustment for sociodemographic, lifestyle, and cardiovascular factors, a 1–standard-deviation larger baseline CRVE was associated with a higher risk of depressive symptoms (hazard ratio = 1.10, 95% confidence interval: 1.02, 1.17), and a 1–standard-deviation larger baseline CRAE was not statistically significantly associated with incident depressive symptoms (hazard ratio = 1.04, 95% confidence interval: 0.97, 1.11). In this study, larger baseline CRVE, but not CRAE, was associated with a higher incidence of depressive symptoms.

Thyroid Status and Brain Circulation: The Rotterdam Study.

ContextWhether thyroid dysfunction is related to altered brain circulation in the general population remains unknown.ObjectiveWe determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly people.MethodsThis was a population-based study of 3 subcohorts of the Rotterdam Study, starting in 1989, 2000, and 2006. A total of 5142 participants (mean age, 63.8 years; 55.4% women), underwent venipuncture to measure serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/minute). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non)linear regression models.ResultsFT4 (in pmol/L) levels had an inverse U-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion than middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P nonlinearity = .002) was up to –2.44 mL (95% CI –4.31; –0.56). Higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to –2.46 µm, 95% CI –4.98; 0.05 for lower FT4).ConclusionThese results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through suboptimal brain circulation that is potentially modifiable.

Retinal blood vessel calibre and vascular ageing in a general Spanish population: A EVA study.

The aim of this work was to analyse the association of the retinal arteriolar calibre and the arteriole/venule index (AV index) with vascular ageing in a general population without previous cardiovascular disease. Descriptive cross-sectional study. A total of 482 individuals without cardiovascular disease (mean age: 55.6±14.2years) were selected by random sampling, stratified by age and sex. The retinal arteriolar calibre was measured using digital fundus images of the back of the eye captured with a validated, semiautomatized and computer-assisted software (Index calculator). Vascular ageing was defined using three criteria based on the values of: (1) Carotid-femoral Pulse Wave Velocity (cfPWV), (2) Brachial-ankle Pulse Wave Velocity (baPWV) and (3) Carotid Intima-Media Thickness. The AV index and arteriolar calibre show a negative correlation with age, arterial pressure, cardiovascular risk and parameters of vascular structure and function (p<0.001 in all cases). We found lower mean values of the AV index and arteriolar calibre in the individuals with early vascular ageing compared to those with healthy vascular ageing. AV index was negatively correlated with cfPWV ((β=-2.9; 95% CI (-4.7; -1.1)), baPWV ((β=-3.2; 95% CI (-5.4; -0.9)) and vascular ageing index ((β=-1.7; 95% CI (-2.7; -0.7)). Arteriolar calibre showed a negative correlation with baPWV (β=-0.1; 95% CI (-0.2; -0.1)). In the logistic regression analysis, lower values of AV index ((OR=0.01; 95% CI (0.01-0.10), OR=0.03; 95% CI (0.01-0.11) and OR=0.09; 95% CI (0.01-0.67)) were associated with EVA defined with cfPWV, baPWV and vascular ageing index respectively, and lower values of arteriolar calibre ((OR=0.71; 95% CI (0.55-0.91)) were associated with EVA defined with vascular ageing index. Lower values of AV index and retinal arteriolar calibre were associated with vascular ageing in a general Spanish population without previous cardiovascular disease.

Increased retinal venular calibre in acute infections

Population-based studies have demonstrated that increased retinal venular calibre is a risk factor for cardiac disease, cardiac events and stroke. Venular dilatation also occurs with diabetes, obesity, dyslipidemia and autoimmune disease where it is attributed to inflammation. This study examined whether the inflammation associated with infections also affected microvascular calibre. Participants with infections and CRP levels > 100 mg/L were recruited from the medical wards of a teaching hospital and assisted to complete a demographic and vascular risk factor questionnaire, and to undergo non-mydriatic retinal photography (Canon CR5-45NM, Japan). They were then treated with appropriate antibiotics, and underwent repeat retinal imaging when their CRP levels had fallen to less than 100 mg/L. Retinal images were examined for arteriole and venular calibre using validated semi-automated software based on Knudtson’s modification of the Parr-Hubbard formula (IVAN, U Wisconsin). Differences in inflammatory markers and calibre were examined using the paired t-test for continuous variables. Determinants of calibre were calculated from multiple linear regression analysis. Forty-one participants with respiratory (27, 66%), urinary (6, 15%), skin (5, 12%), or miscellaneous (3, 7%) infections were studied. After antibiotic treatment, participants’ mean CRP levels fell from 172.9 ± 68.4 mg/L to 42.2 ± 28.2 mg/L (p < 0.0001) and mean neutrophil counts fell from 9 ± 4 × 109/L to 6 ± 3 × 109/L (p < 0.0001). The participants’ mean venular calibre (CRVE) decreased from 240.9 ± 26.9 MU to 233.4 ± 23.5 MU (p = 0.0017) but arteriolar calibre (CRAE) was unchanged (156.9 ± 15.2 MU and 156.2 ± 16.0 MU, p = 0.84). Thirteen additional participants with infections had a CRP > 100 mg/L that persisted at review (199.2 ± 59.0 and 159.4 ± 40.7 mg/L, p = 0.055). Their CRAE and CRVE were not different before and after antibiotic treatment (p = 0.96, p = 0.78). Hospital inpatients with severe infections had retinal venular calibre that decreased as their infections resolved and CRP levels fell after antibiotic treatment. The changes in venular calibre with intercurrent infections may confound retinal vascular assessments of, for example, blood pressure control and cardiac risk.

Neurostructural correlates of retinal microvascular caliber in adolescent bipolar disorder.

Vascular-brain associations are well established in adults but neglected in youth and psychiatric populations, who are at greater cardiovascular risk. We therefore examined the association of retinal vascular caliber with regional brain structure in adolescents with and without bipolar disorder (BD). One hundred and three adolescents (n=51 BD, n=52 healthy control [HC]) completed retinal fundus imaging, yielding arteriolar and venular diameters, followed by T1-weighted 3-Tesla MRI. Region of interest (ROI) analyses examined ventrolateral prefrontal cortex (vlPFC) and ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, and hippocampus, complemented by vertex-wise analyses. Linear regression assessed the association between retinal measures and brain structure, adjusting for covariates including age, sex, BMI, and intracranial volume (ICV). In the overall sample, arteriolar caliber was negatively associated with ACC volume (β=-0.20, p uncorrected =.046) and surface area (β=-0.19, p uncorrected =.049). There were no other significant ROI findings. Vertex-wise analyses detected several significant positive bilateral associations of arteriovenous ratio (AVR) with volume and surface area in regions including rostral middle frontal gyrus (left p=.001; right p=.006), isthmus cingulate cortex (left and right p<.001), and left precuneus (p<.001). Significant negative associations were also observed for AVR (p=.03) and arteriolar caliber (p=.01), including a cluster encompassing the left rostral middle frontal gyrus and orbitofrontal cortical thickness. In the sole retinal-by-diagnosis interaction, greater AVR was more strongly associated with lower volume in the left middle temporal and fusiform gyri in BD versus HC (p=.004). This study provides evidence that vascular-brain associations are already evident in adolescence, suggesting that optimizing cardiovascular health may benefit the brain. This may be particularly relevant in BD and other brain disorders. Future research focusing on subpopulations where vascular-brain associations may be especially strong, for whom vascular-related interventions may be most indicated, is warranted.

Longer-Term Soy Nut Consumption Improves Vascular Function and Cardiometabolic Risk Markers in Older Adults: Results of a Randomized, Controlled Cross-Over Trial

Abstract Objectives Soy foods may contribute to the beneficial effects of plant-based diets on cardiovascular disease (CVD) risk. However, their effects on vascular function have hardly been investigated. The objective was to investigate if longer-term soy nut consumption improves vascular function and cardiometabolic health in older adults. Methods Twenty-three apparently healthy participants (60–70 years; BMI between 20–30 kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67 g of soy nuts daily providing 25.5 g soy protein) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Volunteers followed the Dutch food-based dietary guidelines. At baseline and at 8 and 16 weeks anthropometric measurements and fasting blood samples were collected. Markers of vascular function (i.e., endothelial function, arterial stiffness, and microvascular structure) were assessed at week 16. Results No serious adverse events were reported and the soy nut regime was well tolerated. Body weight remained stable. Serum isoflavone concentrations, a marker of compliance, increased after the intervention period (daidzein: 128.3 ng/mL; 95% CI: 72.6–183.9 ng/mL; P &amp;lt; 0.001 and genistein: 439.8 ng/mL 95% CI: 246.7–632.9 ng/mL; P &amp;lt; 0.001). The brachial artery flow-mediated vasodilation (FMD) response increased by 1.49 pp (95% CI: 0.03–2.95 pp; P = 0.046) following the soy intervention, but no effect was found on the carotid artery reactivity (CAR) response. Arterial stiffness, assessed by carotid-to-femoral pulse wave velocity (PWVc-f), was unchanged. Retinal arteriolar calibers (CRAE), a measure for microvascular structure, tended to improve by 1.42 mm (95% CI: −0.05–2.90 mm; P = 0.059). Soy consumption also lowered serum LDL-cholesterol concentrations by 0.17 mmol/L (95% CI: 0.02–0.32 mmol/L; P = 0.027). HDL-cholesterol and triacylglycerol (TAG) did not change. Finally, office SBP and DBP decreased by 4 mmHg (95% CI: 0–8 mmHg; P = 0.034) and 2 mmHg (95% CI: 1–4 mmHg; P = 0.005), respectively. Conclusions A longer-term daily intake of soy nuts improved endothelial function, office blood pressure, and serum LDL-cholesterol concentrations, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Funding Sources This study was supported by a grant from the Alpro Foundation.

Effect of ECG-gating Retinal Photographs on Retinal Vessel Caliber Measurements in Subjects with and without Type 2 Diabetes

ABSTRACT Purpose/Aim of this study: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes. Materials and Methods: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules. Results: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88–1.17% vs ECG-gated: 0.39, 95%CI 0.29–0.49%, p < .0001) than venular (ungated 0.62, 95%CI 0.53–0.73% vs ECG-gated: 0.26, 95%CI 0.19–0.35%, p < .0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively. Conclusion: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements.

Correlation between retinal vascular parameters and cystatin C in patients with type 2 diabetes.

To investigate the relationship between retinal vascular parameters and cystatin C in patients with type 2 diabetes in northwestern China. This was a cross-sectional study of 1689 patients with type 2 diabetes. A validated fully automated computer program was used to extract retinal vascular parameters from the entire vascular tree. Multiple logistic regression analyses were conducted to investigate the relationship between these vascular measurements and cystatin C. For retinal vascular geometrical measurements, smaller arteriolar fractal dimension was related to high cystatin C after adjusting for multiple variables (odds ratio [OR] 0.149, 95% CI 0.042-0.532). For retinal vascular caliber measurements, narrower central and middle arteriolar calibers were related to high cystatin C after adjusting for multiple variables (central: OR 0.922, 95% CI 0.886-0.960; middle: OR 0.940, 95% CI 0.901-0.981). Wider central, middle and peripheral venular calibers were associated with high cystatin C after adjusting for multiple variables (central: OR 1.058, 95% CI 1.003-1.117; middle: OR 1.094, 95% CI 1.040-1.150; peripheral: OR 1.075, 95% CI 1.023-1.130). Multiple retinal vascular geometrical and caliber measurements are associated with cystatin C in type 2 diabetic patients. Further studies are needed to explore whether these retinal vascular changes can predict the incidence and progress of diabetic nephropathy.

The performance of an integrated model including retinal information in predicting childhood hypertension.

The objective of this study was to examine the association of an integrated model (composed of retinal arteriolar caliber, height, and sex) with blood pressure (BP) among a group of Chinese children, and assess the predictive value of the integrated model for childhood hypertension. This study included 1460 candidates aged 12.634 ± 0.420 years. Height, weight, waist circumference, and BP were obtained and ophthalmological measurements were taken. The computer-imaging program (IVAN, University of Wisconsin, Madison, WI) was used to measure calibers of retinal vessels. Receiver-operating characteristic curve (ROC) analyses were performed to assess the accuracy of the integrated model as a diagnostic test of elevated BP in children. The accuracy of the integrated model (assessed by area under the curve) for identifying elevated BP was 0.777 (95% confidence interval: 0.742-0.812). The optimal threshold of the integrated model for defining hypertension was 0.153, and the calculation formula for the specific predictive risk was: Logit (p/1 - p) = -5.666 - 0.261 × retinal arteriolar caliber + 0.945 × sex + 0.438 × height. In identifying elevated BP, the sensitivity and specificity were 0.711 and 0.736, respectively. The model containing eye message is a comprehensive and relatively effective index to identify elevated BP in 12-year-old children, which can offer assistance to further understand childhood microcirculation disease. We firstly incorporated retinal vascular diameter, sex, and height into one integrated model to identify hypertension in 12-year-old children. The current discrimination of hypertension in children is difficult. There have been some studies to simplify the diagnosis of children's hypertension, but they were limited to anthropometric measurements. We proposed a composed model containing microcirculation information to predict childhood hypertension. Based on the knowledge that microcirculation is not only a means to study the manifestations but also early pathogenic correlates of hypertension, the combined model containing microcirculation message as a method may provide new insights into the diagnosis of childhood hypertension.

Alterations in retinal and choroidal thickness following nonarteritic anterior ischemic optic neuropathy.

To show alterations of retinal arteriolar caliber (RAC), retinal venular caliber (RVC), retinal nerve fiber layer thickness (RNFLT), peripapillary choroidal thickness (ppCT), and central macular thickness (CMT) in acute and chronic phases of nonarteritic anterior ischemic optic neuropathy (NAION). Forty-one eyes of 41 patients with NAION were included in this retrospective study. RAC, RVC, RNFLT, ppCT, and CMT measurements were performed via spectral-domain optical coherence tomography in the acute and chronic phases of NAION. RVC, RNFLT, ppCT, and CMT were significantly thinner in the chronic phase compared to the acute phase (p < 0.001), whereas RAC remained similar throughout the visits (p = 0.26). The visual acuity difference between the acute and chronic phases was not correlated with the changes of RAC, RVC, RNFLT, ppCT, or CMT. RVC, RNFLT, ppCT, and CMT decreases in the chronic phase when compared to the acute phase of NAION, whereas RAC does not change significantly.

Retinal arteriolar calibre and venular fractal dimension predict progression of proliferative diabetic retinopathy 6 months after panretinal photocoagulation: a prospective, clinical interventional study

ObjectiveWe examined the hypothesis that baseline retinal vascular geometry in patients with proliferative diabetic retinopathy (PDR) predicts disease activity 6 months after panretinal photocoagulation (PRP).Methods and analysisWe included 47 eyes...

Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study

BackgroundAssociations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD.MethodsRetinal microvascular parameters (fractal dimension [FD] – a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background.ResultsLower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03–1.34 for arterioles and OR 1.24, CI 1.05–1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR.ConclusionsThis study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria.

Six-year incidence and systemic associations of retinopathy in a multi-ethnic Asian population without diabetes

PurposeWe described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes.MethodsWe included 4374 participants with non-diabetes from a population-based cohort,...

Association of reduced retinal arteriolar tortuosity with depression in older participants from the Northern Ireland Cohort for the Longitudinal Study of Ageing

IntroductionThe retina shares similar anatomical and physiological features with the brain and subtle variations in retinal microvascular parameters (RMPs) may reflect similar vascular variation in the brain. The aim of this study was to assess associations between RMPs and measures of depression in the Northern Ireland Cohort for the Longitudinal Study of Ageing.MethodsRMPs (arteriolar and venular caliber, fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Depression was characterised by the Centre for Epidemiologic Studies Depression Scale (CES-D) in the absence of mild cognitive impairment or use of anti-depressive medications. Associations between depression and RMPs were assessed by regression analyses with adjustment for potential confounders.ResultsData were available for 1376 participants of which 113 (8.2%) and 1263 (91.8%) were classified with and without depression. Participants had a mean age of 62.0 ± 8.4 yrs., 52% were female, and 8% were smokers. Individuals with depression had a higher CES-D score than those without (22.0 ± 6.2 versus 4.4 ± 3.9). Lower values of arteriolar tortuosity were significantly associated with depression, before and after adjustment for potential confounders (odds ratio = 0.79; 95% confidence intervals: 0.65, 0.96; P = 0.02).ConclusionDecreased retinal arteriolar tortuosity, a measure of the complexity of the retinal microvasculature was associated with depression in older adults independent of potential confounding factors. Retinal measures may offer opportunistic assessment of microvascular health associated with outcomes of depression.

Microvascular changes at different stages of chronic kidney disease.

Patients with progressing chronic kidney disease (CKD) are more likely to experience cardio‐ and cerebrovascular events than progressing to end‐stage renal disease. The authors explored whether retinal microvascular calibers differed with the degree of renal impairment and between the standard and extended optic disk and may serve as a simple additional tool for risk stratification in this highly vulnerable patient cohort. The authors analyzed central retinal arteriolar and venular equivalent calibers (CRAE, CRVE) at different retinal zones (zone B&C) using digital retinal imaging in hypertensive patients with stage 2 (n = 66) or stage 3 CKD (n = 30). Results were adjusted for age, sex, HbA1c, and 24‐hour diastolic blood pressure. Mean eGFR was 77.7 ± 8.9 and 48.8 ± 7.9 ml/min/1.73 m2 for stage 2 and 3 CKD, respectively. CRAE and CRVE in zones B and C were significantly lower in patients with stage 3 CKD compared to patients with stage 2 CKD (CRAE‐B:141.1 ± 21.4 vs. 130.5 ± 18.9 µm, p = .030; CRAE‐C:137.4 ± 19.4 vs 129.2 ± 18.2 µm, p = .049; CRVE‐B:220.8 ± 33.0 vs. 206.0 ± 28.4 µm, p = .004; and CRVE‐C:215.9 ± 33.0 vs. 201.2 ± 25.1µm, p = .003). In patients with stage 2 CKD, CRAE‐B was higher than CRAE‐C (141.1 ± 21.4 vs. 137.4 ± 19.4µm, p < .001). In contrast, such a difference was not found in patients with stage 3 CKD. CRAE of both retinal zones correlated with eGFR for the entire cohort. In patients with stage 3 CKD, retinal narrowing is more pronounced compared to patients with stage 2 CKD. Whether the novel observation of difference in arteriolar caliber between zones B and C in stage 2 CKD could serve as an early marker of CKD progression warrants further investigation.

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

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. 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. 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. 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.

Retinal Vascular Caliber Association with Nonperfusion and Diabetic Retinopathy Severity Depends on Vascular Caliber Measurement Location

To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. Retrospective image review. Adults with diabetes mellitus. All images from subjects with same-day UWF fluorescein angiography (FA) and color imaging were evaluated. Predominantly peripheral lesions (PPL) and DR severity were graded from UWF color images. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an optic disc centered inner and outer zone. Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. Two hundred eighty-five eyes of 193 patients (24.9% mild nonproliferative DR [NPDR], 22.8% moderate NPDR, 37.5% severe NPDR and 14.7% proliferative DR [PDR]) were reviewed. No significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (quartile 1) were associated with a 1.7- to 2.4-fold nonperfusion increase across all retinal regions compared to the remaining eyes (P = 0.002 [PP] to 0.048 [FP]). In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (mild NPDR: 10% vs PDR: 31%, P = 0.007). This association was not observed when measured within the inner zone (P= 0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (quartile 1) was more common in eyes with PPL compared to eyes without PPL (34.1% vs 20.8%, P = 0.017) as were thicker outer venular calibers (quartile 4) (33% vs 21.3%, P = 0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7±26.5μm vs 123.0 ± 29.5μm, P = 0.001). The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.

A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.