Central Retinal Venular Equivalent Research Articles

Impact of Shiftwork on Retinal Vasculature Diameters over a 5-Year Period: A Preliminary Investigation Using the BCOPS Study Data.

Our aim was to investigate the impact of shiftwork on changes in central retinal arteriolar equivalent (CRAE), a measure of arteriolar width, and central retinal venular equivalent (CRVE), a measure of venular width, over five years. The participants were 117 officers (72.7% men) examined at the first (2011-2014) and second (2015-2019) follow-up examinations in the Buffalo Cardio-Metabolic Occupational Police Stress study. Shiftwork data were obtained from the City of Buffalo, NY payroll records. Retinal diameters were measured using a standardized protocol. ANCOVA was used to compare mean change in CRAE and CRVE between the two examinations across shiftwork categories. Among men only, those who worked ≥70% hours on day shifts had a larger decrease in mean CRAE (-7.13 µm ± 2.51) compared to those who worked <70% day (-0.08 ± 0.96; p = 0.011). Among patrol officers, those who worked ≥70% day had a larger decrease in CRAE compared to those who worked <70% day (p = 0.015). Also, officers who worked ≥70% day had an increase in mean CRVE (µm) (4.56 ± 2.56) compared to those who worked <70% (-2.32 ± 1.32; p = 0.027). Over the five-year period, we observed adverse changes in arteriolar and venular diameters among officers who worked ≥70% on day shifts. The results should be interpreted with caution due to the small sample sizes.

Retinal changes and cardiac biomarker assessment in relation to chronic kidney disease: a single centre study

BackgroundThe prevalence of chronic kidney disease (CKD) is rising in Malaysia. Early detection is necessary to prevent disease progression, especially in terms of cardiovascular (CV) risk, the main cause of death in end-stage renal disease (ESRD). Retinal changes have proven to be a good predictor of CKD whereas cardiac biomarkers are useful in cardiovascular risk stratification. We aimed to demonstrate the correlation between retinal changes and cardiac biomarkers with CKD.MethodsThis single-centre cross-sectional study was conducted among patients with CKD stages 3, 4, and 5 (not on dialysis) from the Nephrology Clinic, Universiti Kebangsaan Malaysia Medical Centre. A total of 84 patients were recruited with an even distribution across all three stages. They underwent fundus photography where images were analysed for vessel calibre (central retinal venular equivalent (CRVE), central retinal arterial equivalent (CRAE), and tortuosity indices. Optical coherence tomography was used to measure macular volume. Blood samples were sent for laboratory measurement of high-sensitivity C-reactive protein (hs-CRP) and asymmetric dimethylarginine (ADMA). These parameters were analysed in relation to CKD.ResultsThe mean age was 58.8 ± 11.7 years, with 52.4% male and 47.6% female patients. Among them, 64.3% were diabetics. Retinal vessel tortuosity (r = -0.220, p-value = 0.044) had a negative correlation with the estimated glomerular filtration rate (eGFR). CRVE showed a positive correlation with proteinuria (r = 0.342, p = 0.001) but negative correlation with eGFR (r = -0.236, p = 0.031). Hs-CRP positively correlated with proteinuria (r = 0.313, p = 0.04) and negatively correlated with eGFR (r = -0.370, p = 0.001). Diabetic patients had a higher CRVE compared to non-diabetic patients (p = 0.02). History of ischaemic heart disease was associated with a smaller macula volume (p = 0.038). Male gender (r2 = 0.066, p = 0.031) and HbA1c had a positive influence (r2 = 0.066, p = 0.047) on retinal vessel tortuosity. There was a positive influence of age (r2 = 0.183, p = 0.012) and hs-CRP (r2 = 0.183, p = 0.045) on CRVE. As for macula volume, it negatively correlated with diabetes (r2 = 0.015, p = 0.040) and positively correlated with smoking (r2 = 0.015, p = 0.012).ConclusionOur study showed that eGFR value affects retinal vessel tortuosity, CRVE and hs-CRP. These parameters bear potential to be used as non-invasive tools in assessing CKD. However, only macula volume may be associated with CVD risk among the CKD population.

Prevalence and Risk Factors of Fundus Pathology in Patients with Type 2 Diabetes in a Northeastern Chinese Cohort

ABSTRACT Purpose To assess the prevalence of and risk factors for fundus pathology in patients with type 2 diabetes mellitus (T2DM) in a cohort from northeastern China. Methods Patients were included from the Fushun Diabetic Retinopathy Cohort Study. Patients aged ≥ 30 years with T2DM were recruited between July 2012 and May 2013. Fundus pathology included retinal vascular occlusion (RVO), age-related macular degeneration (AMD), macular pathology, pathologic myopia (PM) and glaucomatous optic atrophy (GOA). Results A Total of 1998 patients with gradable fundus photographs were included in this study, of whom 388 (19.42%) had fundus pathology regardless of whether they had diabetic retinopathy (DR). There were 187 (9.36%) patients with AMD, 97 (4.85%) with GOA, 67 (3.35%) with macular pathology, 35 (1.75%) with PM and 23 (1.15%) with RVO. Advanced age was significantly associated with AMD (odds ratio (OR), 95% confidence interval (CI): 1.03, 1.01–1.05), macular pathology (OR, 95% CI: 1.06, 1.03–1.09) and GOA (OR, 95% CI: 1.06, 1.04–1.09). A wider central retinal arteriolar equivalent was protective against PM (OR, 95% CI: 0.78, 0.66–0.92). Wider central retinal venular equivalent was a protective factor for PM (OR, 95% CI: 0.75, 0.68–0.82) and GOA (OR, 95% CI: 0.93, 0.87–0.99). Conclusions One-fifth of these patients in northeast China with T2DM had fundus pathology regardless of whether they had DR, indicating the importance of early screening and long-term follow-up.

Effects of firsthand tobacco smoking on retinal vessel caliber: a systematic review and meta-analysis.

To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers. We performed a search on EMBASE and PubMed for studies up to 15th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed. Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases.

Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation

BackgroundPost-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.MethodsIn this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).Measurements and main resultsPCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.ConclusionOur results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.Trial registrationThis study was previously registered at ClinicalTrials (“All Eyes on PCS—Analysis of the Retinal Microvasculature in Patients with Post-COVID-19 Syndrome”. NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552).Graphical abstractPersistent endothelial dysfunction in post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis in patients. N = 41 PCS patients were recruited and retinal vessel analysis was performed to assess microvascular endothelial function. Images of SVA and DVA are illustrative for RVA data analysis. For each PCS patient and healthy cohort, venular vessel diameter of the three measurement cycles was calculated and plotted on a diameter-time curve. Patients exhibited reduced flicker-induced dilation in veins (vFID) measured by dynamic vessel analysis (DVA) and lower central retinal arteriolar equivalent (CRAE) and arteriolar-venular ratio (AVR) and a tendency towards higher central retinal venular equivalent (CRVE) when compared to SARS-CoV-2 infection naïve participants. Created with BioRender.com

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 Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.

Retinal blood vessel diameters in children and adults exposed to a simulated altitude of 3,000m.

Introduction: Technological advances have made high-altitude ski slopes easily accessible to skiers of all ages. However, research on the effects of hypoxia experienced during excursions to such altitudes on physiological systems, including the ocular system, in children is scarce. Retinal vessels are embryologically of the same origin as vessels in the brain, and have similar anatomical and physiological characteristics. Thus, any hypoxia-related changes in the morphology of the former may reflect the status of the latter. Objective: To compare the effect of one-day hypoxic exposure, equivalent to the elevation of high-altitude ski resorts in North America and Europe (∼3,000m), on retinal vessel diameter between adults and children. Methods: 11 adults (age: 40.1 ± 4.1years) and 8 children (age: 9.3 ± 1.3years) took part in the study. They spent 3days at the Olympic Sports Centre Planica (Slovenia; altitude: 940m). During days 1 and 2 they were exposed to normoxia (FiO2 = 0.209), and day 3 to normobaric hypoxia (FiO2 = 0.162 ± 0.03). Digital high-resolution retinal fundus photographs were obtained in normoxia (Day 2) and hypoxia (Day 3). Central retinal arteriolar equivalent (CRAE) and venular equivalents (CRVE) were determined using an Automated Retinal Image Analyser. Results: Central retinal arteriolar and venular equivalents increased with hypoxia in children (central retinal arteriolar equivalent: 105.32 ± 7.72µm, hypoxia: 110.13 ± 7.16µm, central retinal venular equivalent: normoxia: 123.39 ± 8.34µm, hypoxia: 130.11 ± 8.54µm) and adults (central retinal arteriolar equivalent: normoxia: 105.35 ± 10.67µm, hypoxia: 110.77 ± 8.36µm; central retinal venular equivalent: normoxia: 126.89 ± 7.24µm, hypoxia: 132.03 ± 9.72µm), with no main effect of group or group*condition interaction. A main effect of condition on central retinal arteriolar and venular equivalents was observed (central retinal arteriolar equivalent:normoxia: 105.34 ± 9.30µm, hypoxia: 110.50 ± 7.67µm, p < 0.001; central retinal venular equivalent: normoxia: 125.41 ± 7.70µm, hypoxia: 131.22 ± 9.05µm, p < 0.001). Conclusion: A 20-hour hypoxic exposure significantly increased central retinal arteriolar and venular equivalents in adults and children. These hypoxia-induced increases were not significantly different between the age groups, confirming that vasomotor sensitivity of the retinal vessels to acute hypoxia is comparable between adults and prepubertal children.

Alterations in Retinal Vessel Diameters in Patients with Retinal Vein Occlusion before and after Treatment with Intravitreal Ranibizumab

Purpose: To investigate the alterations of retinal vessel diameters in patients with macular edema secondary to retinal vein occlusion (RVO), before and after treatment with intravitreal ranibizumab. Methods: Digital retinal images were obtained from 16 patients and retinal vessel diameters were measured before and three months after treatment with intravitreal ranibizumab with validated software to determine central retinal arteriolar and venular equivalents, as well as arteriolar to venular ratio. Results: In 17 eyes of 16 patients with macular edema secondary to RVO (10 with branch RVO and 6 with central RVO) aged 67 ± 10.2 years, we found that diameters of both retinal arterioles and venules were significantly decreased after intravitreal ranibizumab treatment. Specifically, the central retinal arteriolar equivalent was 215.2 ± 11.2 μm at baseline and 201.2 ± 11.1 μm at month 3 after treatment (p < 0.001), while the central retinal venular equivalent was 233.8 ± 29.6 μm before treatment versus 207.6 ± 21.7 μm at month 3 after treatment (p < 0.001). Conclusions: A significant vasoconstriction in both retinal arterioles and venules in patients with RVO was found at month 3 after intravitreal ranibizumab treatment compared to baseline. This could be of clinical importance, since the degree of vasoconstriction might be an early marker of treatment efficacy, compatible with the idea that hypoxia is the major trigger of VEGF in RVO. Further studies should be conducted to confirm our findings.

Retinal Microvascular Abnormalities Predict Clinical Outcomes in Patients with Heart Failure.

Background: Narrower retinal arterioles and wider retinal venules have been associated with the incidence of heart failure (HF). However, whether they are predictive of the prognosis of heart failure (HF) is unclear. We aimed to explore the role of retinal vessel calibers in predicting long-term clinical outcomes of HF. Methods: This is a prospective, single-center, observational study that surveyed patients in a tertiary referral hospital for the treatment of HF. Retinal vessel caliber was graded using retinal photography. The primary endpoint was the composite endpoint of HF rehospitalization and mortality at 12 months. Results: There were 55 patients with chronic HF included in the final analysis. At 12 months, the cumulative incidence of the primary endpoint, HF rehospitalization, and mortality tended to be higher with the widening of the central retinal venular equivalent (CRVE) (p for non-linearity = 0.059) and was significantly increased when CRVE reached a cut-off value (283 μm) (p = 0.011) following adjustment for age, sex, etiology of HF, and diabetes. No association between the central retinal arteriolar equivalent (CRAE) and arteriolar-to-venular caliber ratio (AVR) was found with the clinical outcome in both univariable and multivariable Cox regression. CRAE, CRVE, and AVR had no relationship with the concentration of the N-terminal pro-B-type natriuretic peptide. In addition, CRVE was not associated with cardiac diastolic and systolic function. Conclusions: When the retinal venular caliber widens to a certain point, the composite incidence of HF rehospitalization and mortality significantly increase, suggesting retinal vessel caliber imaging may provide insight into the development of HF.

Mid- to Late-Life Time-Averaged Cumulative Blood Pressure and Late-Life Retinal Microvasculature: The ARIC Study.

BackgroundThe associations of time‐averaged cumulative blood pressure (BP) from midlife to late life with microvasculature expressed as retinal vessel diameters is not well studied. The aim of this study was to evaluate the association of cumulative systolic BP and diastolic BP (DBP) with retinal vessel calibers, focusing on race differences.Methods and ResultsThe analysis included 1818 adults from the ARIC (Atherosclerosis Risk in Communities) study attending the fifth visit (2011–2013; age 77±5 years, 17.1% Black participants). Time‐averaged cumulative BPs were calculated as the sum of averaged BPs from adjacent consecutive visits (visits 1–5) indexed to total observation time (24±1 years). Summarized estimates for central retinal arteriolar equivalent and central retinal venular equivalent at the fifth visit represent average retinal vessel diameters. The arteriole:venule ratio was calculated. We tested for effect modification by race. Results from multiple linear regression models suggested that higher time‐averaged cumulative DBP (β [95% CI] per 1‐SD increase: −1.78 [−2.53, −1.02], P<0.001 and −0.005 [−0.009, −0.002], P=0.004, respectively) but not systolic BP (−0.52 [−1.30, 0.26], P=0.189 and 0.001 [−0.002, 0.005], P=0.485, respectively) was associated with smaller central retinal arteriolar equivalent and arteriole:venule ratio. The association between time‐averaged cumulative DBP and arteriole:venule ratio was strongest in White participants (interaction P=0.007). The association of cumulative systolic BP and DBP with central retinal venular equivalent was strongest in Black participants (interaction P=0.015 and 0.011, respectively).ConclusionsExposure to higher BP levels, particularly DBP, from midlife to late life is associated with narrower retinal vessel diameters in late life. Furthermore, race moderated the association of cumulative BP exposure with retinal microvasculature.

Incidence, progression and regression of diabetic retinopathy in a northeastern Chinese population

AimTo determine the incidence, progression and regression of diabetic retinopathy (DR), with corresponding risk factors, in a northeastern Chinese population of patients with type 2 diabetes.MethodsAmong 2006 patients who completed...

Association Between the Metabolic Syndrome and Retinal Microvascular Diameters Among Police Officers.

We examined the associations of the metabolic syndrome severity score (MSSS) and the metabolic syndrome (MetSyn) components with central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Participants in this cross-sectional study were 253 officers from the Buffalo Cardio-Metabolic Occupational Police Stress study (2011-2014). The MSSS is a z -score that represents the severity of MetSyn and was estimated using a sex/race-specific equation and the five MetSyn components. Associations of MSSS and the MetSyn with CRAE/CRVE were obtained using linear regression models or analysis of covariance. For every 1-standard deviation of MSSS, CRAE decreased by 2.3 μm (SE = 1.2, P = 0.0262) and CRVE increased by 3.4 μm (SE = 1.6, P = 0.0308) after adjusting for confounders. Officers with higher MSSS had narrower (ie, worse) arteriolar diameters and wider (ie, worse) venular diameters.

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 > 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.

Retinal vessel diameters: Can they predict future risk of infertility in patients with varicocele?

The objective of this study was to assess the relationship between retinal vessel diameters, such as retinal arteriolar diameter, retinal venular diameter, and arteriolar/venular ratio (AVR), as clinical parameters of fertility in varicocele patients. Sixty-eight (68) infertile varicocele men with abnormal semen parameters and sixty-one (61) varicocele normozoospermic men were included in the study. Moreover, fifty-eight (58) healthy normozoospermic men without varicocele were enrolled as a control group. For each participant, retinal vascular diameters were measured from the digital retinal photographs as a central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and AVR. In addition, hormones (total testosterone and FSH), and semen parameters were assessed and correlated with retinal vessel diameters. The mean CRAE, CRVE, and AVR values were 147.8 ± 15.8 μm, 198.3 ± 39.3 μm, and 0.61 ± 0.01 in infertile varicocele patients, respectively. Significant difference of CRAE, CRVE, and AVR were found when comparing infertile varicocele patients with both varicocele and control normozoospermic male groups (p = 0.01, p = 0.006, and p = 0.007; respectively). Larger retinal venular caliber and smaller AVR ratio showed a significant inverse correlation with both sperm parameters and hormones (total testosterone and FSH) (p < 0.05). No significant correlations were found between CRAE with both sperm parameters and hormonal values (total testosterone and FSH) (p > 0.05). Infertile patients with varicocele showed a significant relationship with the retinal vascular diameter (CRVE and AVR ratio). This finding supports recommendation for regular eye examinations in the varicocele population.

Association of Central Retinal Arteriolar and Venular Equivalents with Brain-aging and Macular Ganglion Cell-inner Plexiform Layer Thickness

ABSTRACT Introduction Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration. Methods Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005–2008) age 21–84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010–2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015–2017, were also investigated. Results Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively. Discussion The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.

Habitual intake of dietary advanced glycation end products is not associated with generalized microvascular function—the Maastricht Study

ABSTRACTBackgroundEndogenously formed advanced glycation end products (AGEs) may be important drivers of microvascular dysfunction and the microvascular complications of diabetes. AGEs are also formed in food products, especially during preparation methods involving dry heat.ObjectivesWe aimed to assess cross-sectional associations between dietary AGE intake and generalized microvascular function in a population-based cohort.MethodsIn 3144 participants of the Maastricht Study (mean ± SD age: 60 ± 8 y, 51% men) the dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of our ultra-performance LC–tandem MS dietary AGE database and an FFQ. Microvascular function was determined in the retina as flicker light–induced arteriolar and venular dilation and as central retinal arteriolar and venular equivalents, in plasma as a z score of endothelial dysfunction biomarkers (soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1, soluble E-selectin, and von Willebrand factor), in skin as the heat-induced skin hyperemic response, and in urine as 24-h albuminuria. Associations were evaluated using multiple linear regression adjusting for demographic, cardiovascular, lifestyle, and dietary factors.ResultsOverall, intakes of CML, CEL, and MG-H1 were not associated with the microvascular outcomes. Although higher intake of CEL was associated with higher flicker light–induced venular dilation (β percentage change over baseline: 0.14; 95% CI: 0.02, 0.26) and lower plasma biomarker z score (β: −0.04 SD; 95% CI: −0.08, −0.00 SD), the effect sizes were small and their biological relevance can be questioned.ConclusionsWe did not show any strong association between habitual intake of dietary AGEs and generalized microvascular function. The contribution of dietary AGEs to generalized microvascular function should be further assessed in randomized controlled trials using specifically designed dietary interventions.

Retinal Vascular Caliber Changes in Early Type 2 Diabetic Patients without Retinopathy

Purpose: To evaluate the retinal vascular caliber in early type 2 diabetic patients without retinopathy.Methods: This retrospective study reviewed the medical records of 85 patients who were diagnosed with type 2 diabetes (age, 10-48 years) and sex-matched healthy controls. Dilated fundus examinations were performed to confirm the absence of diabetic retinopathy. Fundus photographs were acquired and analyzed using software that semi-automatically measured retinal vascular caliber. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were determined using the revised Parr-Hubbard formula. Healthy controls were examined using the same approach.Results: There were no significant differences between patients and controls in terms of CRAE (149.92 ± 21.29 µm and 144.85 ± 17.14 µm, respectively; p = 0.137) or CRVE (195.85 ± 22.94 µm and 196.69 ± 18.43 µm, respectively; p = 0.829). However, AVR was significantly higher in the patient group (0.768 ± 0.088 vs. 0.737 ± 0.061; p = 0.031). In the patient group, AVR was significantly correlated with hemoglobin A1c (r = 0.325, p = 0.006), but not with body mass index (p = 0.478).Conclusions: An increase in peripapillary AVR may be an early feature of retinal vessels observed in patients with type 2 diabetes, which is closely related to elevated blood sugar.

Analysis of retinal blood vessel diameters in patients with COPD undergoing a pulmonary rehabilitation program.

Regular exercise positively affects cardiovascular physiology, translating into the adequate capacity of microvascular blood vessels to dilate in response to acute bouts of exercise. However, this remains unstudied in patients with chronic obstructive pulmonary disease (COPD), who often suffer from cardiovascular comorbidity. Therefore, we studied acute changes in retinal blood vessel diameters in response to high-intensity exercise in patients with COPD. The effect of an exercise-based 8-week pulmonary rehabilitation (PR) program was evaluated. We consider changes in these retinal metrics as an indicator of microvascular reactivity. Demographics and clinical characteristics of 41 patients were collected at the start and end of the PR program. Patients performed a high-intensity exercise test on a cycle ergometer at the start and end of the PR program, during which we collected retinal images. Fundus images were taken immediately before and 0, 5, 10, 15, and 30min after the ergometer test. Widths of retinal blood vessels, represented as Central Retinal Arteriolar and Venular Equivalents (CRAE and CRVE), were calculated. Thirty patients with COPD completed the study protocol (57% males; mean age: 64±7years; mean FEV1: 45±17%pred). We did not observe a change in retinal vessel widths following the ergometer test at the start of the PR program. This null result remained at the end of the 8-week PR program. Our observations did not alter when considering responders and non-responders to PR. Retinal blood vessel diameters of patients with COPD did not change following an exercise test on an ergometer. The exercise-based PR program of eight weeks did not counteract the blunted retinal microvascular response.

Cross-Talk Between Large Artery Stiffness and Retinal Microvasculature in Children: The ExAMIN Youth SA Study.

Background: Cross-talk between the macro-and microvasculature is considered an important contributor to target organ damage. Previous findings were predominantly in adult populations and investigation into this mechanism in children may provide insight into the development of early adverse vascular changes. Whether any ethnic differences in cross-talk is evident, also remains to be determined.Objective: To determine whether retinal microvascular diameters are associated with large artery stiffness in young children and whether ethnic differences are evident.Materials and Methods: In this cross-sectional study, 730 black (n = 437) and white (n = 293) school children aged 5-9 years were included. Pulse wave velocity (PWV) was measured and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters were calculated from fundus images. The arterio-venous ratio (AVR) was subsequently calculated.Results: Pulse wave velocity was lower (p ≤ 0.001) in the black group when compared to the white group. The black group had a narrower CRAE, wider CRVE and lower AVR (all p < 0.001). Pulse wave velocity associated negatively with CRAE (r = –0.141, p = 0.003) and AVR (r = –0.185, p ≤ 0.001) in the black group only. A positive association between PWV and CRVE was seen in the black (r = 0.174, p ≤ 0.001) and white (r = 0.119, p = 0.043) group.Conclusion: Large artery stiffness is associated with retinal arterial narrowing and venular widening in children, suggesting cross-talk between the macro-and microvasculature. Ethnic differences in these associations are also evident. Our findings warrant further investigation into environmental and sociocultural risk factors contributing to premature cardiovascular disease development.