Retinal Arteriolar Diameters Research Articles

Retinal blood vessel diameter changes with 60-day head-down bedrest are unaffected by antioxidant nutritional cocktail.

Long-term human spaceflight can lead to cardiovascular deconditioning, but little is known about how weightlessness affects microcirculation. In this study, we examined how the retinal microvessels and cerebrovascular regulation of 19 healthy male participants responded to long-term head-down bedrest (HDBR), an earth-based analog for weightlessness. In addition, we examined whether an anti-inflammatory/antioxidant cocktail could prevent the vascular changes caused by HDBR. In all study participants, we found a decrease in retinal arteriolar diameter by HDBR day 8 and an increase in retinal venular diameter by HDBR day 16. Concurrently, blood pressure at the level of the middle cerebral artery and the cerebrovascular resistance index were higher during HDBR, while cerebral blood flow velocity was lower. None of these changes were reversed in participants receiving the anti-inflammatory/antioxidant cocktail, indicating that this cocktail was insufficient to restore the microvascular and cerebral blood flow changes induced by HDBR.

Vascular function in patients with advanced heart failure and continuous-flow or pulsatile ventricular assist devices.

A significant proportion of patients with heart failure (HF) progress to an advanced stage, which is associated with a substantial increase in morbidity and mortality. These patients may be eligible for advanced treatment strategies such as mechanical circulatory support with ventricular assist devices (VAD). Vascular dysfunction is a hallmark of heart failure pathophysiology and prognosis. However, whether and to what degree the hemodynamic benefits of VADs influence vascular function remain unknown. In this study, we evaluated endothelial vascular function with flow-mediated vasodilatation (FMD) and with flicker-light induced retinal vasodilatation (FID). 34 patients with a VAD (age 58 ± 10years, 85% male, 74% ischemic heart disease, 26 continuous-flow (CF)-LVAD, and 8 pulsatile biventricular (bi)-VAD) were compared to 34 propensity-matched patients (mean age 62 ± 9years, 68% male, 59% ischemic heart disease) with advanced HF (AdvHF). Endothelial function of larger arteries (FMD) was significantly better in patients after VAD implantation compared to matched AdvHF patients (7.2 ± 4.6% vs. 5.0 ± 3.2%, p = 0.03), whereas microvascular arteriolar function (FIDart) did not differ (0.99 ± 1.43% vs. 1.1 ± 1.7%, p = 0.78). The arterio-venous ratio (AVR) was higher in the VAD group (0.90 ± 0.06 vs 0.85 ± 0.09, p = 0.01), reflecting wider retinal arteriolar and narrower venular diameters. There was no difference in vascular function between patients with CF-LVAD and pulsatile Bi-VAD. In patients with advanced heart failure, VAD implantation was associated with better endothelial function at the level of large arteries, but not in the microcirculation.

Remnant cholesterol is correlated with retinal vascular morphology and diabetic retinopathy in type 2 diabetes mellitus: a cross-sectional study

BackgroundThe association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR.MethodsThis cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (Df). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR.ResultsRC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] μm), CRVE (7.620 [5.298, 9.941] μm) and Df (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012–0.032).ConclusionsRC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher Df, and it may contribute to DR through the dilation of retinal venules.

Subcutaneous advanced glycation end products, cardiovascular risk factors and vascular health during childhood development in a Swiss population.

Skin-derived advanced glycation end products (sAGEs) have been associated with cardiovascular (CV) risk and mortality in adults. We hypothesize that cardiorespiratory fitness (CRF), body mass index (BMI) and vascular health are associated with development of sAGEs during childhood. In our prospective cohort study, 1171 children aged 6-8years were screened for sAGEs, BMI, retinal arteriolar diameters (CRAE) and pulse wave velocity (PWV), using standardized procedures. To determine CRF a 20m shuttle run was performed. After four 4years, all parameters were assessed in 675 children using the same protocols. Higher initial CRF levels were significantly associated with lower sAGEs (β [95 CI] -0.02 [-0.03 to -0.002] au, p = 0.022) levels at follow-up, although they showed a greater change from baseline to follow-up (β [95 CI] 0.02 [0.002 to 0.03] au, p = 0.027). Moreover, individuals with higher sAGEs at baseline showed narrower CRAE (β [95% CI] -5.42 [-8.76 to -2.08] μm, p = 0.001) at follow-up and showed a greater change in CRAE (β [95% CI] -3.99 [-7.03 to -0.96] μm, p = 0.010) from baseline to follow-up. Exercise and higher CRF may help mitigate the formation of AGEs during childhood, thereby reducing the risk for development of CV disease associated with AGEs-induced damage. Preventive strategies may need to target CRF early in life to achieve improvement of CV risk factors and may counteract the development of CV disease later in life.

Retinal venular vessel diameters are smaller during ten days of bed rest

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m–2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

Effects of high-intensity interval training on retinal vessel diameters and oxygen saturation in patients with hypertension: A cross-sectional and randomized controlled trial

IntroductionArterial hypertension is a global healthcare burden that affects macrovascular and microvascular structure and function and can promote vascular end-organ damage. This study aimed 1) to evaluate differences in microvascular health between normotensive individuals and patients with arterial hypertension and 2) to assess the effects of short-term high-intensity interval training (HIIT) on microvascular health in the subgroup with arterial hypertension as add-on treatment to antihypertensive medication. MethodsIn the cross-sectional part, central retinal arteriolar (CRAE) and venular diameter equivalent (CRVE), arteriolar-to-venular diameter ratio (AVR), and retinal oxygen saturation (O2-saturation) were investigated in 19 normotensive healthy controls (mean age 56 ± 7 years) and 41 patients with arterial hypertension (mean age 59 ± 7 years). In the subsequent randomized controlled trial (RCT), patients with arterial hypertension were randomized to an intervention group (HIIT 3×/week) or a control group that received standard physical activity recommendations after baseline assessment. Assessments of retinal vessel biomarkers and patients` characteristics were repeated after the intervention period of 8 weeks. ResultsIn the cross-sectional part, individuals with normal blood pressure (BP) showed lower body mass index (BMI), body fat, 24 h systolic and diastolic BP, higher peak oxygen uptake, wider CRAE (174 ± 17 μm vs. 161 ± 17 μm, p = 0.009), and higher AVR (0.84 ± 0.05 vs. 0.79 ± 0.05, p = 0.003) compared to patients with hypertension. In the RCT, patients with arterial hypertension showed reduced BMI and fasting glucose levels after HIIT and control condition. In addition, the intervention group reduced body fat percentage (27.0 ± 5.5 vs. 25.8 ± 6.1, p = 0.023) and increased peak oxygen uptake (33.3 ± 5.7 vs. 36.7 ± 5.1, p < 0.001). No changes in BP were found in either group. The intervention group showed narrower CRVE (β −4.8 [95 % CI, −8.85, −0.81] p = 0.020) and higher AVR (0.03 [0.01, 0.04] p < 0.001) after eight weeks of HIIT compared to the control group. No statistically significant changes in retinal O2-saturation were found in either group. ConclusionShort-term HIIT proved to be an effective treatment to ameliorate hypertension-induced retinal microvascular abnormalities in patients with hypertension. Retinal vessel diameters may prove to be a sensitive biomarker to quantify treatment efficacy at the microvascular level, at the earliest possible stage in patients with hypertension.

Abstract 120: Greater 24-hour Blood Pressure Variability Is Associated With Higher Retinal Microvascular Resistance And Smaller Lumen Diameter In Healthy Normotensive Adults

Introduction: Elevated blood pressure (BP) is associated with damage to high flow, low resistance target organs such as the retina. Recent evidence suggests that 24-hour BP variability (BPV) is a novel risk factor for cardiovascular disease, independent of 24-hour average BP. However, whether 24-hour BPV is related to concentric retinal arteriole remodeling in healthy adults is unknown. Thus, the purpose of our study was to determine the degree to which 24-hour BPV is associated with retinal lumen diameter and vascular resistance in healthy young/middle-aged adults, independent of 24-hour average BP. Methods: Healthy, normotensive adults aged 25 to 60 years (n=40; 50% female) underwent measurements of retinal arteriole diameter and flow using laser speckle flowgraphy. 24-hour brachial BP was determined using ambulatory BP monitoring. BPV was calculated as the standard deviation of all BP recordings for systolic and diastolic BP. Retinal vascular resistance was calculated as ocular perfusion pressure divided by mean retinal flow across 4 arterioles. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). Results: Higher 24-hour systolic and diastolic average BP were associated with smaller retinal lumen diameter and elevated vascular resistance (P&lt;0.05). Although both systolic BPV (r=0.391, P=0.012) and diastolic BPV (r=0.315, P=0.048) were associated with higher retinal vascular resistance, only diastolic BPV was associated with smaller retinal arteriole lumen diameter (r=-0.393, P=0.012). The association of greater diastolic BPV with smaller retinal arteriole lumen diameter (β=-0.363, P=0.01) and higher retinal vascular resistance (β=0.395, P=0.007) remained after adjusting for age, body mass index, cfPWV, and 24-hour average diastolic BP. Conclusion: Higher diastolic BPV may contribute to adverse remodeling of retinal arterioles in healthy normotensive adults independent of arterial stiffness and traditional cardiovascular disease risk factors. Future studies could utilize local metabolic vasodilation via diffuse luminance flicker to examine whether retinal arteriole autoregulatory mechanisms are impaired in individuals with higher BPV.

Cardiorespiratory fitness and development of childhood cardiovascular risk: The EXAMIN YOUTH follow-up study.

Background: Obesity- and hypertension-related cardiovascular (CV) risk has been shown to originate in childhood. Higher body mass index (BMI) and blood pressure (BP) have been associated with increased large artery stiffness and a lower microvascular arteriolar-to-venular diameter ratio (AVR) in children. This study aimed to investigate the association of cardiorespiratory fitness (CRF) with development of BMI, BP and vascular health during childhood. Methods: In our prospective cohort study, 1,171 children aged 6-8years were screened for CRF, BMI, BP, retinal vessel diameters and pulse wave velocity using standardized protocols. Endurance capacity was assessed by 20m shuttle run test. After 4years, all parameters were assessed in 664 children using the same protocols. Results: Children with a higher CRF at baseline developed a significantly lower BMI (β [95% CI] -0.09 [-0.11 to -0.06] kg/m2, p < 0.001), a lower systolic BP (β [95% CI] -0.09 [-0.15 to -0.03]mmHg, p = 0.004) and a higher AVR (β [95% CI] 0.0004 [0.00004 to 0.0007] units, p = 0.027) after 4years. The indirect association of CRF with development of retinal arteriolar diameters was mediated by changes in BMI. Conclusion: Our results identify CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in children. Obesity-related CV risk has been shown to track into adulthood, and achieving higher CRF levels in children may help counteract the development of CV risk and disease not only in pediatric populations, but may also help reduce the burden of CVD in adulthood. Registration: http://www.clinicaltrials.gov/ (NCT02853747).

Effects of Gold Nanoparticles Phytoreduced with Rutin in an Early Rat Model of Diabetic Retinopathy and Cataracts.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycaemia. Plant-based therapies are characterised by low tissue bioavailability. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Eye fundus of retinal arterioles, transmission electron microscopy (TEM) of lenses, and histopathology of retinas were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fibre disorganisation. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately oedematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA and increased antioxidant capacity. Retinal edema and disorganisation in lens fibres were still present.

Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events: a prospective observational study.

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations. However, the ability of retinal vasculature changes, specifically focusing on retinal vessel diameter, to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively. While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events, they have not incorporated this information into a predictive model. Therefore, this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke. Additionally, we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors. We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University. All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years. We found that, after adjusting for related risk factors, patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin (MAD0.5-1.0DD) of ≥ 74.14 μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin (MVD0.5-1.0DD) of ≥ 83.91 μm tended to experience recurrent cerebrovascular events. We established three multivariate Cox proportional hazard regression models: model 1 included traditional risk factors, model 2 added MAD0.5-1.0DD to model 1, and model 3 added MVD0.5-1.0DD to model 1. Model 3 had the greatest potential to predict subsequent cerebrovascular events, followed by model 2, and finally model 1. These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke, and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

Bivariate relation of vascular health and blood pressure progression during childhood

Background and aimsHypertension is a major risk factor for the development of cardiovascular disease (CVD) in adulthood. High blood pressure (BP) is associated with subclinical vascular impairments as early as childhood. We aimed to assess the association of retinal microvascular diameters and large artery pulse wave velocity (PWV) with progression of childhood BP. MethodsIn our prospective Basel cohort study, 1171 children aged 6–8 years were screened for BP, body mass index, retinal vessel diameters and PWV using standardized protocols. After 4 years, all parameters were assessed in 749 children using the same protocols. ResultsChildren with narrower central retinal arteriolar diameters (CRAE) and higher PWV at baseline developed higher systolic BP after 4 years (β [95% CI] 0.6 [0.072 to 1.164] mmHg per 10 μm decrease, p = 0.026 and β [95% CI] 0.6 [0.331 to 0.838] mmHg per 0.1 m/s increase, p < 0.001, respectively). Children with increased systolic BP at baseline developed narrower CRAE and higher PWV at follow-up (β [95% CI] −3.3 [-4.43 to −2.09] μm per 10 mmHg increase, p < 0.001 and β [95% CI] 0.13 [0.10 to 0.16] m/s per 10 mmHg increase, p < 0.001, respectively). ConclusionsRetinal arteriolar diameter and PWV independently predict progression of childhood BP, while initial BP is linked to development of micro- and macrovascular impairments, describing a bivariate temporal relationship between vascular health and BP. Childhood may present a window of opportunity for initiation of primary prevention strategies for the treatment of high BP to help prevent manifestation of CVD later in life.

Prevalence and Associations of Nonglaucomatous Optic Nerve Atrophy in High Myopia: The Ural Eye and Medical Study

To assess the prevalence of non-glaucomatous optic nerve atrophy (NGOA) and its associations in highly myopic individuals. Population-based study. The Ural Eye and Medical Study included 5899 (80.5%) out of 7328 eligible individuals. The participants underwent an ophthalmological and general examination. NGOA, graded into five arbitrary stages, was characterized by decreased visibility of the retinal nerve fiber layer (RNFL) on fundus photographs and on red-free fundus photographs, neuroretinal rim pallor, abnormally thin retinal arteriole diameter, and abnormally thin peripapillary RNFL as measured by optical coherence tomography. NGOA prevalence and degree. Out of 5709 (96.9%) participants with axial length measurements, 130 (2.3%) individuals were highly myopic, of which 116 (89.2%) participants (age:57.8±11.1 years; range:41.0-84.2 years; axial length:27.0±1.2mm; range:26.01-32.87mm) had available fundus photographs and OCT images and were included into the present study. NGOA prevalence was 34/116 (29.3%;95%CI:21.0,38.0), and mean NGOA degree in eyes with NGOA was 1.7±1.0 arbitrary units. Higher NGOA degree correlated (multivariable analysis; regression coefficient r2:0.59) with longer axial length (beta:0.22; B:0.18; 95%CI:0.05,0.31; P=0.007), wider temporal parapapillary gamma zone width (beta:0.50; B:0.45; 95%CI:0.30,0.59; P<0.001), higher prevalence of diabetes (beta:0.20; B:0.63; 95%CI:0.20,1.06; P=0.005), and higher systolic blood pressure (beta:0.15; B:0.01; 95%CI:0.001,0.02; P=0.03). Higher NGOA prevalence was associated with longer axial length (odds ratio (OR):7.45; 95%CI:2.15,25.7; P=0.002), wider temporal parapapillary gamma zone (OR:6.98; 95%CI:2.61,18.7; P<0.001), and higher systolic blood pressure (OR:1.05; 95%CI:1.01,1.10; P=0.02). In this ethnically mixed population from Russia with an age of 40+ years, high axial myopia showed a relatively high prevalence of NGOA, increasing with longer axial length and wider temporal parapapillary gamma zone. For each millimeter of axial elongation and widening of gamma zone, the odds for NGOA increased 7.45-fold and 6.98-fold, respectively. The axial elongation-associated and gamma zone-related increase in the distance between the retinal ganglion cells and the optic disc may lead to a lengthening and stretching of the retinal ganglion cell axons and may pathogenetically be of importance. In highly myopic eyes, NGOA may be a reason for visual field and central visual acuity loss, unexplainable by myopic macular pathologies.

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.

Analysis of retinal arteriolar and venular parameters in primary open angle glaucoma.

To measure the retinal vessels of primary open angle glaucoma (POAG) patients on spectral domain optical coherence tomography (SD-OCT) with a full-width at half-maximum (FWHM) algorithm to better explore their structural changes in the pathogenesis of POAG. In this retrospective case-control study, the right eyes of 32 patients with POAG and 30 healthy individuals were routinely selected. Images of the supratemporal and infratemporal retinal vessels in the B zones were obtained by SD-OCT, and the edges of the vessels were identified by the FWHM method. The internal and external diameters, wall thickness (WT), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR) of the blood vessels were studied. Compared with the healthy control group, the POAG group showed a significantly reduced retinal arteriolar outer diameter (RAOD), retinal arteriolar lumen diameter (RALD) and WSCA in the supratemporal (124.22±12.42 vs 138.32±10.73 µm, 96.09±11.09 vs 108.53±9.89 µm, and 4762.02±913.51 vs 5785.75±1148.28 µm2, respectively, all P<0.05) and infratemporal regions (125.01±15.55 vs 141.57±10.77 µm, 96.27±13.29 vs 110.83±10.99 µm, and 4925.56±1302.88 vs 6087.78±1061.55 µm2, all P<0.05). The arteriolar WT and WLR were not significantly different between the POAG and control groups, nor were the retinal venular outer diameter (RVOD), retinal venular lumen diameter (RVLD) or venular WT in the supratemporal or infratemporal region. There was a positive correlation between the arteriolar parameters and visual function. In POAG, narrowing of the supratemporal and infratemporal arterioles and a significant reduction in the WSCA is observed, while the arteriolar WT and WLR do not change. Among the venular parameters, the external diameter, internal diameter, WT, WLR, and WSCA of the venules are not affected.

Microvascular constriction via fatty acid-mediated oxidative stress in humans

Purpose: Excess plasma lipids promote oxidative stress and impair vascular function. Herein, we examined microcirculatory blood flow and tested the hypothesis that a co-infusion of a water-soluble antioxidant (ascorbic acid, AA) would attenuate reductions in retinal arteriole lumen diameter and increase resistance resulting from acutely elevated plasma lipids in healthy adults. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 8 healthy, middle-aged adults (2 men/6 women) with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Co-infusion of AA was administered at 0.06g/kg fat free mass in 100 ml saline at 5 mL/min over 20 min (bolus) followed by a drip infusion at 0.02 g/kg fat-free mass in 30 ml saline at 0.33 mL/min over 90 min. Retinal arteriole lumen diameter and resistance were assessed via Laser Speckle Flowgraphy at baseline and after infusion. Results: Lipid infusion significantly increase plasma fatty acid concentrations (lipid w/o AA: +36 ± 18 vs. lipid with AA: +41 ± 13 vs. μmol/L, P=0.84). AA infusion significantly increased plasma ascorbic acid concentrations (lipid w/o AA: -1 ± 7 vs. lipid with AA: +26 ± 11 μmol/L, P=0.04). A significant increase in retinal arteriole resistance was observed following lipid infusion (lipid w/o AA: +20 ± 8 %, vs. lipid with AA: +17 ± 8 %, P=0.40). In accordance, lipid infusion significantly reduced retinal arteriole lumen diameter; however, co-infusion of AA reversed the lipid-mediated decrease in retinal arteriole diameter (lipid w/o AA: -3 ± 1 % vs. lipid with AA: +3 ± 2 %, P=0.01). Conclusions: Although microvascular resistance was increased, co-infusion of the antioxidant (ascorbic acid) reversed the fatty acid-mediated reduction in arteriole lumen diameter. Therefore, these preliminary findings suggest that acute elevations in plasma fatty acids induce microvascular constriction via an oxidative stress pathway. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CTSA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Retinal vessel caliber and tortuosity and prediction of 5-year incidence of hypertension.

With arterial hypertension as a global risk factor for cerebrovascular and cardiovascular diseases, we examined whether retinal blood vessel caliber and tortuosity assessed by a vessel-constraint network model can predict the incidence of hypertension. The community-based prospective study included 9230 individuals who were followed for 5 years. Ocular fundus photographs taken at baseline were analyzed by a vessel-constraint network model. Within the 5-year follow-up, 1279 (18.8%) and 474 (7.0%) participants out of 6813 individuals free of hypertension at baseline developed hypertension and severe hypertension, respectively. In multivariable analysis, a higher incidence of hypertension was related to a narrower retinal arteriolar diameter ( P < 0.001), wider venular diameter ( P = 0.005), and a smaller arteriole-to-venule diameter ratio ( P < 0.001) at baseline. Individuals with the 5% narrowest arteriole or the 5% widest venule diameter had a 17.1-fold [95% confidence interval (CI):7.9, 37.2] or 2.3-fold (95% CI: 1.4, 3.7) increased risk for developing hypertension, as compared with those with the 5% widest arteriole or the 5% narrowest venule. The area under the receiver operator characteristic curve for predicting the 5-year incidence of hypertension and severe hypertension was 0.791 (95% CI: 0.778, 0.804) and 0.839 (95% CI: 0.821, 0.856), respectively. Although the venular tortuosity was positively associated with the presence of hypertension at baseline ( P = 0.01), neither arteriolar tortuosity nor venular tortuosity was associated with incident hypertension (both P ≥ 0.10). Narrower retinal arterioles and wider venules indicate an increased risk for incident hypertension within 5 years, while tortuous retinal venules are associated with the presence rather than the incidence of hypertension. The automatic assessment of retinal vessel features performed well in identifying individuals at risk of developing hypertension.

PS-BPC03-8: MORNING BLOOD PRESSURE SURGE AND THE VASCULATURE: A COMPARISON BETWEEN YOUNG DIPPERS AND NON-DIPPERS FROM THE AFRICAN-PREDICT STUDY

Background and aim: Adverse changes in large arteries and retinal microvascular calibres are predictors for hypertension and stroke. These adverse changes were reported in response to the suppressed night-time dipping as well as in hypertensive individuals with exaggerated morning surge. However, it is unknown whether young healthy individuals with normal morning surge, but with non-dipping night-time blood pressure profile, will already present with early onset of micro and macrovascular changes. We investigated the relationship of morning surge with retinal vessel calibres and large artery stiffness in healthy young dippers and non-dippers. Methods: We included black and white participants (N = 323), aged 20–30 years, determined sleep-trough surge. We determined central retinal artery and vein equivalents from fundus images, as well as carotid-femoral pulse wave velocity. Results: Dippers had a greater morning surge (within normal range) (p &lt; 0.001) and a greater proportion of individuals with exaggerated morning surge (p &lt; 0.001). In dippers only, we found a positive relationship between central retinal artery equivalent and morning surge (p = 0.040). In sensitivity analysis, the association between central retinal artery equivalent and morning surge in dippers lost significance (p = 0.09) when 24-hour diastolic blood pressure was replaced with night-time diastolic blood pressure. However, an independent negative association between central retinal artery equivalent and night-time diastolic blood pressure (p &lt; 0.001) emerged. Normal morning surge of dippers was positively associated with central retinal artery equivalent (dependent on night-time dipping). Conclusion: Normal night-time dipping may therefore be involved in preserving retinal arteriolar diameter of dippers, which may reflect a lower vascular resistance.

Vasomotion in Retinal Arterioles Is Modified by Exercise and Flicker Stimulation.

Vasomotion is spontaneous oscillations in the diameter of resistance vessels with derived effects on blood flow, and it has been proposed that disturbances in vasomotion may be involved in retinal vascular disease. The purpose of this study was to investigate whether retinal vasomotion shows regional variation and is modified by activated autoregulation. Video recordings of the diameter of retinal arterioles previously obtained from 55 normal persons were subjected to Fourier analysis to characterize the frequencies and propagation of spontaneous diameter changes in retinal arterioles. The analyses were performed on peripapillary temporal retinal arterioles, on arteriolar branches toward the macular area and the retinal periphery, and were performed during rest, during an increase in the arterial blood pressure induced by isometric exercise, and during increased retinal metabolism induced by flickering light. There was no propagation of diameter changes along the studied vascular segments. Isometric exercise constricted the arterioles significantly by (mean ± SD) 1.76% ± 3.56% (P = 0.02) and increased the power of diameter oscillations at very low frequencies (0.1-1.4 c/min). Flicker stimulation dilated the arterioles significantly by (mean ± SD) 5.10% ± 2.91% (P < 0.0001) and reduced the power of diameter oscillations at all but the very low frequencies (P < 0.006 for all comparisons). Flicker-induced dilation and changes in hydraulic conductance were lower in peripheral than in macular arterioles. Retinal vasomotion in normal persons increases during increased arterial blood pressure and decreases during flicker stimulation. The findings may act as a basis for the study of vasomotion in retinal vascular disease.

Role of Prostaglandins in Nitric Oxide-Induced Glial Cell-Mediated Vasodilation in Rat Retina.

We previously identified that NO derived from neuronal cells acts on glial cells and causes vasodilation in the healthy rat retina via the release of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) by activation of the arachidonic acid cascade. However, it is not clear which PG types are involved in these responses. The aim of the present study was to identify prostanoid receptors involved in glial cell-derived vasodilation induced by NO in rat retina. Male Wistar rats were used to examine the effects of intravitreal pretreatment with indomethacin, a cyclooxygenase inhibitor; PF-04418948, a prostanoid EP2 receptor antagonist; and CAY10441, a prostanoid IP receptor antagonist, on the changes in the retinal arteriolar diameter induced by intravitreal administration of NOR3, an NO donor. Retinal arteriolar diameters were measured using ocular fundus images captured with a high-resolution digital camera in vivo. The increase in the retinal arteriolar diameter induced by intravitreal injection of NOR3 was significantly suppressed by intravitreal pretreatment with indomethacin and PF-04418948, but not by CAY10441. The dose of PF-04418948 and CAY10441 injected intravitreally in the present study significantly reduced the increase in the retinal arteriolar diameter induced by prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), respectively. These results suggest that activation of the arachidonic acid cascade and subsequent stimulation of prostanoid EP2 receptors are involved in rat retinal vasodilatory responses evoked by NO-induced glial cell stimulation. Therefore, glial cell-derived PGE2, similar to EETs, may play an important role in retinal vasodilatory mechanisms.

Non-Invasive Metabolic and Structural Retinal Markers in Patients with Giant Cell Arteritis and Polymyalgia Rheumatica: A Cross-Sectional Study.

Giant cell arteritis (GCA) is a potential sight-threatening disease. Although it is associated with polymyalgia rheumatica (PMR), visual loss is not common in PMR. A retinal oximeter can be used to conduct a direct, non-invasive, in vivo assessment of the vascular system. In a cross-sectional study, we measured the retinal oxygen saturation and retinal vessel calibers in GCA patients, PMR patients, and control participants. Twenty GCA patients (38 eyes), 19 PMR patients (33 eyes), and 12 controls (20 eyes) were investigated. Images were analyzed using Oxymap Analyzer software 2.5.0 (Oxymap ehf., Reykjavik, Iceland). Groups were compared using an age- and sex-adjusted linear mixed model regression. The median (IQR) age for GCA patients was 69.0 (66.5–76.5) years, for PMR 69.0 (67.0–72.0) years, and for the controls 75.5 (71.5–81.0) years, respectively. As compared to the controls (115.3 µm), the retinal arterioles were significantly wider in patients with GCA (124.4 µm; p = 0.023) and PMR (124.8 µm; p = 0.049). No difference was found in the retinal venular caliber or vascular oxygen saturation. These results indicate that GCA and PMR patients differ similarly in the retinal arteriolar diameter compared to controls. Further studies are needed in order to clarify the underlying inflammatory mechanisms in retinal arteriolar vessels and if these parameters can be used to predict clinical outcomes.