Arteriolar Caliber Research Articles

Associations of Retinal Vessel Geometry and Optical Coherence Tomography Angiography Metrics With Choroidal Metrics in Diabetic Retinopathy.

To elucidate the mechanism underlying changes in choroidal metrics (choroidal thickness [CT], choroidal vascularity index [CVI], and choriocapillaris [CC] flow deficit [FD]) observed in diabetic retinopathy (DR) and examine the association of choroidal metrics with both retinal vessel geometry and optical coherence tomography angiography (OCTA) metrics. Overall, 133 eyes of 133 patients were analyzed retrospectively. Retinal vessel geometry parameters were assessed using semiautomated software. The OCTA metrics and CT were calculated using automated algorithms provided by the manufacturer, whereas the CVI and CC-FD were calculated using ImageJ software from the binarized choroid B-scan image and the CC slab provided by the manufacturer, respectively. To assess the associations among choroidal metrics, retinal vessel geometry, and OCTA metrics, multivariable regression analyses were performed while controlling for clinical features and DR severity. In the multivariable linear regression analysis, CT (β = -399.84; P = 0.014) and CVI (β = -2.34; P = 0.021) showed significant associations with the arteriole-venule ratio, which is a ratio of central retinal arteriolar equivalent caliber with respect to central retinal venular equivalent caliber. The CC-FD showed a significant association with the fractal dimension of retinal arteriolar network (β = -2.90; P = 0.040). In contrast, the OCTA metrics showed no significant association with the choroidal metrics. The CT, CVI, and CC-FD in patients with DR were associated with retinal arteriolar geometry parameters rather than OCTA metrics, which indicates an association between choroidal changes and hemodynamic alterations in retinal arterioles and venules.

Retinal microvascular remodeling associates with adverse events in continuous-flow left ventricular assist device-supported patients

BackgroundContinuous-flow left ventricular assist device (cfLVAD) use is effective in supporting patients with end-stage heart failure (ESHF). Reduced flow pulsatility within the systemic circulation in cfLVAD-supported patients may lead to alterations within the microcirculation. Temporal changes in microvasculature in relation to adverse events in cfLVAD supported patients has not been studied. We aimed to profile changes within retinal microvasculature and its association with adverse events. MethodsRetinal photography was performed using Topcon TRC-NW8 non-mydriatic fundus camera in cfLVAD supported patients and ESHF control patients. Retinal measurements including arteriolar and venular caliber, fractal dimension, branching angle, and vessel tortuosity were evaluated using a validated semi-automated program. Demographic and adverse event data were documented. Results172 images were recorded from 48 patients (n=29 cfLVAD, n=19 ESHF, mean age 54.2 ± 11.9 years). There were significant trends in retinal arteriolar caliber (B = -0.53 µm, 95% CI: -0.96 – -0.10, p = 0.016) and retinal fractal dimension parameters (B = 0.014, 95% CI: 0.001 – 0.002, p = 0.016) in linear mixed model regressions. Amongst cfLVAD patients, there was a significant association between the incidence of gastrointestinal bleeding and stepwise increases in retinal arteriolar-venular caliber ratio (HR: 3.03, 95% CI: 2.06 – 4.45, p = 0.005), a measure of arteriolar narrowing. ConclusionsWe have observed for the first time that alterations in retinal microvasculature in cfLVAD-supported patients may be associated with gastrointestinal bleeding. While understanding these temporal changes may predict future adverse events in cfLVAD-supported patients, further multi-center studies are required to confirm the associations observed.

A Novel Method for the Measurement of Retinal Arteriolar Bifurcation.

The purpose of this research was to develop protocols for evaluating the bifurcation parameters of retinal arteriole and establish a reference range of normal values. In this retrospective study, we measured a total of 1314 retinal arteriolar bifurcations from 100 fundus photographs. We selected 200 from these bifurcations for testing inter-measurerand inter-method agreement. Additionally, we calculated the normal reference range for retinal arteriolar bifurcation parameters and analyzed the effects of gender, age, and anatomical features on retinal arteriolar bifurcation. The measurement method proposed in this study has demonstrated nearly perfect consistency among different measurers, with interclass correlation coefficient (ICC) for all bifurcation parameters of retinal arteriole exceeding 0.95. Among healthy individuals, the retinal arteriolar caliber was narrowest in young adults and increased in children, teenagers, and the elderly; retinal arteriolar caliber was greater in females than in males; and the diameter of the inferior temporal branch exceeded that of the superior temporal branch. The angle between the two branches of retinal arteriolar bifurcation was also greater in females than in males. When using the center of the optic disc as a reference point, the angle between the two branches of the retinal arteriole at the proximal or distal ends increased. In contrast, the estimated optimum theoretical values of retinal arteriolar bifurcation were not affected by these factors. The method for the measurement of retinal arteriolar bifurcation in this study was highly accurate and reproducible. The diameter and branching angle of the retinal arteriolar bifurcation were more susceptible to the influence of gender, age, and anatomical features. In comparison, the estimated optimum theoretical values of retinal arteriolar bifurcation were relatively stable. Video available for this article.

Distinctive Imaging Characteristics of Retinal and Cerebral Vessels between Central and Branch Retinal Vein Occlusion by MRI and AI-Based Image Analyzer

Retinal vessels have been good predictive and prognostic imaging biomarkers for systemic or eye diseases. Numerous studies have shown that the two retinal vein occlusion entities may correlate with cardiovascular and cerebrovascular events or primary open-angle glaucoma. This study aims to investigate if there is a disparity in the correlations between branch RVO (BRVO) and central RVO (CRVO) with systemic disorders or POAG, thus explaining the pathogenic difference between BRVO and CRVO. This retrospective case-control study enrolled 59 RVO subjects (118 eyes), including 25 CRVO and 34 BRVO subjects, who received routine eye and brain MRI examinations. The geometric characteristics of the caliber of the retinal and cerebral blood vessels and the optic nerve subarachnoid space width (ONSASW) were measured. Multivariable logistic regression analysis showed that ONSASW at 3 mm behind the globe (p = 0.044) and the relative retinal venular calibers (p = 0.031) were independent risk factors for the CRVO-affected eyes group in comparison with the BRVO-affected eyes group after adjusting for age, duration of hypertension, BMI, and IOP. In the CRVO-affected eyes, narrower relative retinal arteriolar calibers (p = 0.041) and wider relative venular calibers (p = 0.011) were independent risk factors compared with the CRVO-contralateral normal eyes when adjusting for IOP. We concluded that BRVO may be more associated with cerebrovascular diseases, and CRVO may be correlated with primary angle glaucoma. The geometric characteristics difference between the retinal and cerebrovascular may explain the pathological difference between CRVO and BRVO.

Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study.

Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.

Biomarkers of microvascular dysfunction and cerebral white matter connectivity: The Maastricht Study

AbstractBackgroundMicrovascular dysfunction may contribute to the development of various cerebral disorders, including cognitive dysfunction, dementia, and certain forms of depression. The suggested mechanism through which microvascular dysfunction contributes to these disorders is by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and cerebral white matter connectivity.MethodWe used cross‐sectional data from The Maastricht Study, a Dutch population‐based cohort (n = 4,326, mean±SD age 59.4±8.6 years, 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers (CRAE and CRVE), a composite score of flicker light‐induced retinal arteriolar and venular dilation response, and a composite score of plasma biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule‐1 (sICAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM‐1), soluble E‐selectin (sE‐selectin) and von Willebrand factor (vWF)). White matter connectivity was calculated from 3T diffusion MRI to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient and local efficiency) of cerebral white matter connections.ResultA higher endothelial dysfunction composite score was associated with a longer characteristic path length (beta per SD: 0.066 (95% confidence interval: 0.017; 0.114)) after adjustment for sociodemographic, lifestyle and cardiovascular factors, but not with any of the other white matter connectivity measures. All other measures of microvascular dysfunction were not associated with any of the connectivity measures after adjustments.ConclusionThe present study suggests that microvascular dysfunction, as quantified by a set of various measures, is not consistently associated with cerebral white matter connectivity. Only a composite score of plasma biomarkers of endothelial dysfunction was associated with a longer characteristic path length, with a longer characteristic path length being indicative for a topographically less integrated and less efficient cerebral network. Future cross‐sectional and longitudinal studies are needed to further understand the role of microvascular dysfunction in the development of cerebral disorders.

Influence of secondhand smoke exposure on the retinal vasculature of children in Hong Kong

BackgroundA recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children.MethodsThis is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables.ResultsHere we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001).ConclusionsExposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary.

White matter microstructural integrity is associated with retinal vascular caliber in adolescents with bipolar disorder

ObjectiveReduced white matter integrity is observed in bipolar disorder (BD), and is associated with cardiovascular risk in adults. This topic is underexplored in youth, and in BD, where novel microvascular measures may help to inform understanding of the vascular-brain connection. We therefore examined the association of retinal vascular caliber with white matter integrity in a cross-sectional sample of adolescents with and without BD. MethodsEighty-four adolescents (n = 42 BD, n = 42 controls) completed retinal imaging, yielding arteriolar and venular caliber. Diffusion tensor imaging measured white matter fractional anisotropy (FA). Multiple linear regression tested associations between retinal vascular caliber and FA in regions-of-interest; corpus callosum, anterior thalamic radiation, uncinate fasciculus, and superior longitudinal fasciculus. Complementary voxel-wise analyses were performed. ResultsArteriolar caliber was elevated in adolescents with BD relative to controls (F(1,79) = 6.15, p = 0.02, η2p = 0.07). In the overall sample, higher venular caliber was significantly associated with lower corpus callosum FA (β = −0.24, puncorrected = 0.04). In voxel-wise analyses, higher arteriolar caliber was significantly associated with lower corpus callosum and forceps minor FA in the overall sample (β = −0.46, p = 0.03). A significant diagnosis-by-venular caliber interaction on FA was noted in 5 clusters including the right retrolenticular internal capsule (β = 0.72, p = 0.03), corticospinal tract (β = 0.72, p = 0.04), and anterior corona radiata (β = 0.63, p = 0.04). In each instance, venular caliber was more positively associated with FA in BD vs. controls. ConclusionRetinal microvascular measures are associated with white matter integrity in BD, particularly in the corpus callosum. This study was proof-of-concept, designed to guide future studies focused on the vascular-brain interface in BD.

Retinopathy is associated with impaired cognition in patients undergoing peritoneal dialysis

Objective Previous studies have shown a relationship between retinopathy and cognition including population with and without chronic kidney disease (CKD) but data regarding peritoneal dialysis (PD) are limited. This study aims to investigate the relationship between retinopathy and cognitive impairment in patients undergoing peritoneal dialysis (PD). Methods In this observational study, we recruited a total of 107 participants undergoing PD, consisting of 48 men and 59 women, ages ranging from 21 to 78 years. The study followed a cross-sectional design. Retinal microvascular characteristics, such as geometric changes in retinal vascular including tortuosity, fractal dimension (FD), and calibers, were assessed. Retinopathy (such as retinal hemorrhage or microaneurysms) was evaluated using digitized photographs. The Modified Mini-Mental State Examination (3MS) was performed to assess global cognitive function. Results The prevalence rates of retinal hemorrhage, microaneurysms, and retinopathy were 25%, 30%, and 43%, respectively. The mean arteriolar and venular calibers were 63.2 and 78.5 µm, respectively, and the corresponding mean tortuosity was 37.7 ± 3.6 and 37.2 ± 3.0 mm−1. The mean FD was 1.49. After adjusting for age, sex, education, mean arterial pressure, and Charlson index, a negative association was revealed between retinopathy and 3MS scores (regression coefficient: −3.71, 95% confidence interval: −7.09 to −0.33, p = 0.03). Conclusions Retinopathy, a condition common in patients undergoing PD, was associated with global cognitive impairment. These findings highlight retinopathy, can serve as a valuable primary screening tool for assessing the risk of cognitive decline.

Preconception maternal retinal arteriolar narrowing and fetal growth throughout pregnancy: A prospective cohort study.

To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth. A hospital-based, prospective preconception cohort including 369 women with a singleton live birth. We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit. We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11-13, 18-21, 24-28, and 32-34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH-21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24-28 weeks and 32-34 weeks of gestation, after full adjustment. Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (-0.34; 95% CI -0.66 to -0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (-0.41; 95% CI -0.90 to -0.001) and fetal FL (-0.55; 95% CI -1.00 to -0.10) between 24-28 weeks and 32-34 weeks of gestation, respectively. Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex.

To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements. The between-device difference in CRAE (9.5 µm; 95% confidence interval, 8.0-11.1 µm) was larger than the between-device difference in CRVE (2.9 µm; 95% confidence interval, 1.3-4.5 µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4.8 to 23.9 µm for CRAE and -12.0 to 17.8 µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83-0.92) and 0.91 (95% confidence interval, 0.86-0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002). Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.

The role of retinal vessel geometry as an indicator of systemic arterial stiffness assessed by cardio-ankle vascular index.

To determine whether retinal vessel geometry is associated with systemic arterial stiffness, as determined by the cardio-ankle vascular index (CAVI). This single-center retrospective cross-sectional study included 407 eyes of 407 subjects who underwent routine health exams, including CAVI and fundus photography. Retinal vessel geometry was measured using a computer-assisted program (Singapore "I" Vessel Assessment). Subjects were classified into two groups based on CAVI values: high CAVI (≥9) or low CAVI (<9). The main outcome measures included the association of retinal vessel geometry and CAVI value evaluated using multivariable logistic regression models. Three hundred forty-three subjects (343, 84.3%) were in the low CAVI group, and 64 (15.7%) subjects were in the high CAVI group. Multivariable logistic linear regression analyses adjusted for age, sex, body mass index, smoking status, mean arterial pressure, and the presence of hypertension, diabetes mellitus, and dyslipidemia showed a significant association between high CAVI values and the following retinal vessel geometry parameters: central retinal arteriolar equivalent caliber (CRAE; adjusted odds ratio [AOR], 0.95; 95% confidence interval [CI], 0.89-1.00; P = 0.043), fractal dimension of arteriolar network (FDa; AOR, 4.21 × 10-4; 95% CI, 2.32 × 10-7-0.77; P = 0.042), and arteriolar branching angle (BAa; AOR, 0.96; 95% CI, 0.93-0.99; P = 0.007). Increased systemic arterial stiffness had a significant association with retinal vessel geometry related to arterial narrowing (CRAE), less branching complexity of the arterial tree (FDa), and acute arteriolar bifurcation (BAa).

Longer-term mixed nut consumption improves brain vascular function and memory: A randomized, controlled crossover trial in older adults

Nut consumption may reduce age-related cognitive decline, but underlying mechanisms are unclear. To investigate in older adults longer-term effects of mixed nut consumption on brain vascular function, which may underlie improvements in cognitive performance. Twenty-eight healthy individuals (age [mean±SD]: 65±3 years; BMI: 27.9±2.3kg/m2) were included in a randomized, single-blinded, cross-over trial with a 16-week intervention (60g/d mixed nuts: walnuts, pistachio, cashew, and hazelnuts) and control period (no nuts), separated by 8 weeks of washout. Participants followed the Dutch food-based dietary guidelines. At the end of each period, cerebral blood flow (CBF), a marker of brain vascular function, was quantified using arterial spin labeling magnetic resonance imaging. Effects on endothelial function, arterial stiffness, and the retinal microvasculature were also assessed. Cognitive performance was measured using the Cambridge Neuropsychological Test Automated Battery. Body weight remained stable during the study. As compared to the control period, the mixed nut intervention resulted in a higher regional CBF in the right frontal and parietal lobes (treatment effect: 5.0±6.5mL/100g/min; P<0.001), left frontal lobe (5.4±7.1mL/100g/min; P<0.001), and bilateral prefrontal cortex (5.6±6.6mL/100g/min; P<0.001). Carotid artery reactivity (0.7PP; 95%CI: 0.2 to 1.2; P=0.007), brachial flow-mediated vasodilation (1.6PP; 95%CI: 1.0 to 2.2; P<0.001) and retinal arteriolar calibers were higher (2μm; 95%CI: 0 to 3; P=0.037), and carotid-to-femoral pulse wave velocity lower (-0.6m/s; 95%CI:-1.1 to-0.1; P=0.032). Further, visuospatial memory (-4 errors [16%]; 95%CI:-8 to 0; P=0.045) and verbal memory (+1 correct [16%]; 0 to 2; P=0.035) improved, but executive function and psychomotor speed did not change. Longer-term mixed nut consumption as part of a healthy diet beneficially affected brain vascular function, which may relate to the observed beneficial effects on memory in older adults. Moreover, different characteristics of the peripheral vascular tree also improved.

The relationship of retinal vessel calibres with cardiovascular risk factors in apparently healthy young eyes

AbstractPurpose: Although retinal vascular calibre has been linked to increased cardiovascular (CV) risk, it remains unclear whether retinal vascular morphologic changes are already evident in young adults and correlate with modifiable CV risk factors. The purpose of this study was to explore the relationship of retinal arteriolar and venular calibre with CV risk factors and ocular parameters in healthy young subjects.Methods: A cross‐sectional study was performed in 52 apparently healthy subjects (mean 21.6 ± 2.2 years of age). Retinal vascular calibres were measured from fundus photographs using semi‐automated imaging software and expressed as central retinal arteriolar (CRAE) or venular (CRVE) equivalent and arterio‐venous ratio (AVR). CV risk factors and ocular parameters were assessed. Forward stepwise multiple linear regression analysis was used to detect the independent relationship between retinal vascular calibre and CV and ocular parameters.Results: Means for CRAE and CRVE were 191 ± 15.4 μm and 209 ± 15.8 μm respectively. The mean CRAE but not CRVE was significantly higher in women than in men (p = 0.009). Systolic blood pressure (SBP) and spherical equivalent were significant contributing factors to CRAE (SBP: p &lt; 0.001; SE: p = 0.021). However, CRVE was not significantly predicted by CV risk factors or ocular parameters. SBP was the only one independent contributor to AVR (p = 0.018).Conclusions: In young adults, higher SBP was found to be related to narrower retinal arterioles, but not to retinal venules. Sex and other confounding CV or ocular factors had no effect on the relationship of SBP and retinal vessel calibre.

Retinal Vascular Caliber in Coronary Heart Disease and Its Risk Factors

Background: Many clinical and experimental articles have suggested that the retinal vascular diameter can be used as a predictor of coronary heart disease (CHD). However, the results and reliability of the prediction are still controversial. Objective: A meta-analysis of observational study was conducted to clarify the relationships of retinal vessel caliber with CHD and CHD risk factors. Method: PubMed and Embase were searched for all observational studies on the relationship of retinal vessel caliber with CHD and CHD risk factors from 2001 to 2021. The meta-analysis has been registered in PROSPERO (registration number is CRD42021267154). Result: A total of 14 articles were selected for the inclusion in this meta-analysis. In the primary outcome, smaller retinal arteriolar caliber was related to CHD, and the results achieved statistical significance (MD: −5.55, 95% CI: −8.07 to −3.02, p < 0.0001), while there was no significant difference in vein caliber between CHD and healthy people (MD: 1.10, 95% CI: −3.55 to 5.76, p = 0.64 > 0.05). Smaller retinal arteriolar caliber was related to increasing age, male sex, bigger BMI, and hypertension. Bigger retinal arteriolar caliber was related to current smoking. Smaller retinal venule caliber was related to increasing age and hypertension. Bigger retinal venule caliber was related to current smoking, bigger BMI, and diabetes. Conclusion: Smaller retinal arteriolar caliber was related to CHD, while there was no significant difference in venule caliber between CHD and healthy people. Retinal vascular caliber also independently related to CHD risk factors (e.g., age, gender, smoke, BMI, hypertension, and diabetes).

Retinal vascular measures from diabetes retinal screening photographs and risk of incident dementia in type 2 diabetes: A GoDARTS study.

ObjectivePatients with diabetes have an increased risk of dementia. Improved prediction of dementia is an important goal in developing future prevention strategies. Diabetic retinopathy screening (DRS) photographs may be a convenient source of imaging biomarkers of brain health. We therefore investigated the association of retinal vascular measures (RVMs) from DRS photographs in patients with type 2 diabetes with dementia risk.Research Design and MethodsRVMs were obtained from 6,111 patients in the GoDARTS bioresource (635 incident cases) using VAMPIRE software. Their association, independent of Apo E4 genotype and clinical parameters, was determined for incident all cause dementia (ACD) and separately Alzheimer's disease (AD) and vascular dementia (VD). We used Cox’s proportional hazards with competing risk of death without dementia. The potential value of RVMs to increase the accuracy of risk prediction was evaluated.ResultsIncreased retinal arteriolar fractal dimension associated with increased risk of ACD (csHR 1.17; 1.08–1.26) and AD (HR 1.33; 1.16–1.52), whereas increased venular fractal dimension (FDV) was associated with reduced risk of AD (csHR 0.85; 0.74–0.96). Conversely, FDV was associated with increased risk of VD (csHR 1.22; 1.07–1.40). Wider arteriolar calibre was associated with a reduced risk of ACD (csHR 0.9; 0.83–0.98) and wider venular calibre was associated with a reduced risk of AD (csHR 0.87; 0.78–0.97). Accounting for competing risk did not substantially alter these findings. RVMs significantly increased the accuracy of prediction.ConclusionsConventional DRS photographs could enhance stratifying patients with diabetes at increased risk of dementia facilitating the development of future prevention strategies.

Retinal microvasculature and risk of spontaneous abortion in multiethnic Southeast Asian women

To better understand the underlying pathogenesis of spontaneous abortion that affects 10%-20% of recognized pregnancies. We used retinal imaging to study the role of systemic microvasculature and the risk of spontaneous abortion. A prospective multiethnic preconception cohort study conducted in Singapore. Hospital-based. A total of 1,032 Southeast Asian women who intended to conceive naturally were screened at study entry, among which 480 women spontaneously conceived within the 12-month observation period. After excluding 24 women who were lost to follow-up, we calculated the spontaneous abortion rate among 456 women. Further, we included 379 women for the final association analysis because 63 women did not undergo preconception retinal imaging examination and 14 had other types of pregnancy loss instead of spontaneous abortion. Trained photographers performed retinal examination using a 45-degree nonmydriatic retinal camera at study entry during the preconception screening. Using a semiautomated, computer-based program, we assessed quantitative retinal microvascular measurements, including caliber, fractal dimension, curvature tortuosity, and branching angle. Clinical research coordinators collected information on sociodemographic status, menstrual characteristics, and lifestyle, and assessed blood pressure and anthropometry at study entry. We performed a modified Poisson regression model to estimate the relative risk (RR) and 95% confidence interval (CI) for each retinal microvascular feature and its association with spontaneous abortion after adjusting for major confounders such as maternal prepregnancy, body mass index, and previous pregnancy loss history. We reported a spontaneous abortion rate of 13.4% (61 out of 456). Among all retinal microvascular features, retinal arteriolar caliber, retinal arteriolar, and venular curvature tortuosity were associated with a high risk of incident spontaneous abortion. In the regression model, per SD increase in retinal curvature tortuosity was associated with a 25%-34% increased risk of incident spontaneous abortion (arteriolar: unadjusted RR, 1.29 [95% CI, 1.06-1.56] and adjusted RR, 1.26 [1.04-1.53]; venule: unadjusted RR, 1.30 [1.08-1.55] and adjusted RR, 1.34 [1.09-1.64]). Our prospective cohort observed an increased risk of spontaneous abortion among Asian women with more tortuous retinal vessels assessed during the preconception phase. Our results indicate a role of vascular inflammatory and oxidative stress in the pathogenesis of spontaneous abortion. ClinicalTrials.gov, NCT03531658.

Ocular changes in nephrotic syndrome patients with preserved renal functions

BackgroundOptical coherence tomography (OCT) measurements of central choroidal thickness (CCT) and retinal thickness have been proposed as inflammatory indicators for a variety of systemic disorders, particularly those with a vascular component. The relationship between nephrotic syndrome (NS) and visual impairment is not clear. The aim of this study was to evaluate the ocular changes in primary NS patients with preserved renal functions. MethodsA total of 60 participants (30 NS patients, 30 healthy control subjects) was recruited in this cross-sectional and comparative study. Retinal and choroidal examinations were performed via the spectral domain OCT. Enhanced depth imaging (EDI) mode of the OCT was used for choroidal analysis. ResultsAlthough not statistically significant, CCT was found to be higher in the NS group compared to the control group (p = 0.07). Central foveal thickness (CFT) and retinal arteriolar caliber (RAC) values were statistically significantly lower in the patients with nephrotic syndrome, whereas retinal venular caliber (RVC) and choroidal vascularity index (CVI) values were similar in both groups. RAC and RVC were not statistically significantly correlated with CCT or CFT in both groups (p > 0.05). ConclusionThe results of the current study showed a significant difference between the NS group and the control group in terms of some ocular changes (i.e., CFT and RAC). As a result, CCT, CFT and RAC measurements with OCT may be used as a marker of inflammation in NS patients.

Deep-learning retinal vessel calibre measurements and risk of cognitive decline and dementia.

Previous studies have explored the associations of retinal vessel calibre, measured from retinal photographs or fundus images using semi-automated computer programs, with cognitive impairment and dementia, supporting the concept that retinal blood vessels reflect microvascular changes in the brain. Recently, artificial intelligence deep-learning algorithms have been developed for the fully automated assessment of retinal vessel calibres. Therefore, we aimed to determine whether deep-learning-based retinal vessel calibre measurements are predictive of risk of cognitive decline and dementia. We conducted a prospective study recruiting participants from memory clinics at the National University Hospital and St. Luke's Hospital in Singapore; all participants had comprehensive clinical and neuropsychological examinations at baseline and annually for up to 5 years. Fully automated measurements of retinal arteriolar and venular calibres from retinal fundus images were estimated using a deep-learning system. Cox regression models were then used to assess the relationship between baseline retinal vessel calibre and the risk of cognitive decline and developing dementia, adjusting for age, gender, ethnicity, education, cerebrovascular disease status, hypertension, hyperlipidemia, diabetes, and smoking. A total of 491 participants were included in this study, of whom 254 developed cognitive decline over 5 years. In multivariable models, narrower retinal arteriolar calibre (hazard ratio per standard deviation decrease = 1.258, P = 0.008) and wider retinal venular calibre (hazard ratio per standard deviation increase = 1.204, P = 0.037) were associated with increased risk of cognitive decline. Among participants with cognitive impairment but no dementia at baseline (n = 212), 44 progressed to have incident dementia; narrower retinal arteriolar calibre was also associated with incident dementia (hazard ratio per standard deviation decrease = 1.624, P = 0.021). In summary, deep-learning-based measurement of retinal vessel calibre was associated with risk of cognitive decline and dementia.

Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes.

To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes. Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP-vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status-was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI). Among 1770 individuals with diabetes, incidences were 6.3% (n=79/1259) for CVD, 48.7% (n=166/341) for HTN, 14.6% (n=175/1199) for DKD, and 59.4% (n=336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (p=.027) and better reclassification of 11.4% of the cases and 4.6% of the controls (p=.008). We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.