Retinal Venular 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.

#2851 Effects of dialysis on various microcirculatory beds in end-stage kidney disease (ESKD): a systematic review and meta-analysis

Abstract Background and Aims Microcirculatory dysfunction is common in ESKD-patients and may play a pivotal role in their cardiovascular burden. Besides traditional and chronic-kidney-disease (CKD)-specific risk factors, dialysis itself might contribute to the dysfunction of the microcirculation (MC). Although an intradialytic fall in systemic blood pressure (BP) may directly influence the microcirculatory perfusion, vascular beds in different organs may not react uniformly. This systematic review and meta-analysis evaluated the acute impact of hemodialysis (HD) and hemodiafiltration (HDF) on the MC in various vascular beds. Methods Pubmed and Embase databases were systematically explored until June 2023 by two independent researchers. All observational and interventional studies in ESKD patients that reported dialysis-induced alterations of the MC, measured at the cutaneous, sublingual, retinal, muscle or coronary beds were eligible. Dialysis-induced changes were extracted and pooled, using a fixed-effects meta-analysis when the studies were reasonably homogeneous in terms of outcomes and methodology. Results 17 Studies with 493 participants were included. Virtually all patients (99.8%) were treated with HD. No eligible studies on coronary or muscle MC were identified. Cutaneous MC was investigated in 7 studies, showing a mean reduction in transcutaneous oxygen pressure of −7.9 mmHg (95% CI −10.5 to –5.3, n = 4 studies) and a mean reduction in blood flow of −0.9 arbitrary units (95% CI −1.2 to −0.6, n = 3 studies). Cutaneous vasoreactivity was diminished in 2 out of 3 studies (reactive maximum microvascular hyperemia: −36% (p < 0.05); time to reach baseline skin temperature after standardized cooling: 65.6 seconds (p-value not reported); vs. no significant change in post-ischemic maximal flow (2.5, p = not significant (N.S.)). Sublingual MC was assessed in 3 studies, showing a mean decrease in microvascular flow index of −0.6 in small microvessels (vessel diameter (VD) <20-25 µm, 95% CI −1.0 to −0.2, n = 3 studies), but no significant change in proportion of perfused vessels (−0.5%, 95% CI −1.2 to 0.2, n = 2 studies). One study showed a significant reduction in sublingual perfused vessel density after treatment (VD <20 µm: −1.6 ± 3.1, p < 0.05; VD >20 µm: −0.6 ± 1.1, p < 0.05), whereas total vessel density was unaffected in another study (VD <20 µm: 0.5, p = N.S.). Retinal MC was investigated in 7 studies, showing that the perfused vessel density (PVD) remained unchanged in both the superficial and deep capillary plexus (PVD SCP −0.48, 95% CI (−0.99; 0.03); PVD DCP −0.48, 95% CI (−1.18; 0.23), n = 4 studies). One study reported a decreased PVD at the outer retina (−1.3 ± 5.7, p < 0.05), while conflicting results were observed in 2 studies (0.1, p = N.S.; vs. −2.9 ± 4.3, p < 0.001), reporting the PVD at the choriocapillaris level. One study found no change in retinal blood flow (0.4, p = N.S.). With regard to vessel diameter changes, an increase in retinal venular diameter was observed in 3 studies (retinal venular diameter: 11.2 µm, p = 0.002; central retinal vein equivalent: 12.7 µm, p < 0.001; retinal vessel diameter: 4.4, p < 0.01), and one study described impaired venular dilatation in response to flicker light (−4.0, p = 0.04). Conclusions Hemodialysis induces microvascular dysfunction in different organs, but its impact varies between vascular beds. Microvascular perfusion was most significantly impaired in the cutaneous and sublingual regions, whereas the retinal microcirculatory perfusion remained unaltered. Literature on the effect of hemodiafiltration on the MC is lacking.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std β = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std β = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std β = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

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.

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.

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.

Influence of physical fitness and retinal microcirculation on the development of cognitive abilities from childhood to preadolescence

The retinal microcirculation serves a proxy of cerebrovascular function and has been linked with both physical fitness and cognitive function. We investigated the role of physical fitness for the development of executive function in children as well as its mediation by microvascular health. Using a cross-lagged panel design, 365 children aged six to eight years completed a baseline assessment, which was followed up after four years. Retinal vessel analysis was performed on digital retinal images obtained with a fundus camera. Additionally, a computerized Flanker task was administered to assess the inhibitory aspect of executive function. With regard to physical fitness tests, participants completed a shuttle run and 20-m sprints. Path-analyses showed that higher performance on the shuttle run and 20-m sprint at baseline were both associated with lower reaction times on the Flanker task at follow-up, when autoregressive effects were accounted for. Stages achieved on the shuttle run at baseline were further related to narrowing of retinal venular diameters, which in turn predicted performance on the Flanker task. However, the direct relation of physical fitness components to reaction time was higher compared to the indirect relation via retinal venular diameters. High physical fitness contributes to the development of cognitive abilities from childhood to preadolescence. This association is not mediated by retinal vessel diameters, while the microvascular phenotype of narrower retinal venules is independently related to a better development of information processing and inhibitory control.

Relationships between quantitative retinal microvascular characteristics and cognitive function based on automated artificial intelligence measurements.

Introduction: The purpose of this study is to assess the relationship between retinal vascular characteristics and cognitive function using artificial intelligence techniques to obtain fully automated quantitative measurements of retinal vascular morphological parameters. Methods: A deep learning-based semantic segmentation network ResNet101-UNet was used to construct a vascular segmentation model for fully automated quantitative measurement of retinal vascular parameters on fundus photographs. Retinal photographs centered on the optic disc of 3107 participants (aged 50-93years) from the Beijing Eye Study 2011, a population-based cross-sectional study, were analyzed. The main parameters included the retinal vascular branching angle, vascular fractal dimension, vascular diameter, vascular tortuosity, and vascular density. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Results: The results showed that the mean MMSE score was 26.34 ± 3.64 (median: 27; range: 2-30). Among the participants, 414 (13.3%) were classified as having cognitive impairment (MMSE score < 24), 296 (9.5%) were classified as mild cognitive impairment (MMSE: 19-23), 98 (3.2%) were classified as moderate cognitive impairment (MMSE: 10-18), and 20 (0.6%) were classified as severe cognitive impairment (MMSE < 10). Compared with the normal cognitive function group, the retinal venular average diameter was significantly larger (p = 0.013), and the retinal vascular fractal dimension and vascular density were significantly smaller (both p < 0.001) in the mild cognitive impairment group. The retinal arteriole-to-venular ratio (p = 0.003) and vascular fractal dimension (p = 0.033) were significantly decreased in the severe cognitive impairment group compared to the mild cognitive impairment group. In the multivariate analysis, better cognition (i.e., higher MMSE score) was significantly associated with higher retinal vascular fractal dimension (b = 0.134, p = 0.043) and higher retinal vascular density (b = 0.152, p = 0.023) after adjustment for age, best corrected visual acuity (BCVA) (logMAR) and education level. Discussion: In conclusion, our findings derived from an artificial intelligence-based fully automated retinal vascular parameter measurement method showed that several retinal vascular morphological parameters were correlated with cognitive impairment. The decrease in retinal vascular fractal dimension and decreased vascular density may serve as candidate biomarkers for early identification of cognitive impairment. The observed reduction in the retinal arteriole-to-venular ratio occurs in the late stages of cognitive impairment.

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.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

Application of the Full-Width-at-Half-Maximum Image Segmentation Method to Analyse Retinal Vascular Changes in Patients with Diabetic Retinopathy.

This study used spectral domain optical coherence tomography (SD-OCT) and full-width-at-half-maximum image segmentation to investigate the morphological changes of retinal blood vessels in patients with diabetic retinopathy (DR). Seventy-five patients with type 2 diabetes mellitus (T2DM) without DR and 65 patients with DR were studied. Vascular images of superior temporal region B of the retina were obtained by SD-OCT. The edges of retinal vessels were identified by the full-width-at-half-maximum image segmentation method. The lumen diameter, wall thickness (WT), wall cross-sectional area (WCSA), and wall-to-lumen ratio (WLR) were investigated. We found that, compared with the no diabetic retinopathy (NDR) group, patients in the DR group had an increased retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), and WT (128.80 μm versus 104.88 μm; 147.01 μm versus 135.60 μm; 18.29 μm versus 15.26 μm, P < 0.05, respectively). The retinal venular lumen diameter (RVLD), retinal venular outer diameter (RVOD), and venular WT in the DR group were also increased (146.17 μm versus 133.66 μm; 180.20 μm versus 156.43 μm; 17.01 μm versus 11.38 μm, P < 0.05, respectively). The morphological changes in retinal vessels were significantly correlated with DR stage. In conclusion, in diabetic patients with DR, both retinal arteries and veins are widened and exhibit increased vascular thickness.

Lipoprotein Subclasses Independently Contribute to Subclinical Variance of Microvascular and Macrovascular Health.

Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.

In-vivo assessment of retinal vessel diameters and observer variability in mice: A methodological approach.

BackgroundCentral retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents are predictive for cardiovascular and all-cause mortality in humans. The aim of this study was to investigate the inter- and intraobserver variability for the assessment of CRAE and CRVE in mice using fluorescein contrast enhancement as compared to crude analysis.MethodsThree high quality images with (F) and without fluorescein (NF) of eight mice (type C57BL) were recorded and analysed by two independent experienced investigators to investigate interobserver variability. In addition, one investigator analysed 20 F and 20 NF images twice to investigate intraobserver variability. The time course of CRAE and CRVE vessel responses after fluorescein injection were recorded in one mouse every 30 seconds for 15 minutes.ResultsThe interobserver variability was lower in F images compared to NF images for CRAE (r = 0.99, p < 0.001 vs. r = 0.65, p = 0.083) and CRVE (r = 0.99, p < 0.001 vs. r = 0.79, p = 0.019). Intraobserver variability for CRAE (r = 0.99, p < 0.001 vs. r = 0.48, p = 0.032) and CRVE (r = 0.98, p < 0.001 vs. r = 0.86, p < 0.001) were lower in F compared to NF images. Fluorescein injection induced vascular staining mimicking vessel dilation (+14%) followed by a long-lasting stable staining phase well suited for precise measurements.ConclusionsMeasurement variability can be optimized by use of fluorescein as contrast enhancement in mice. Standardization for time of image acquisition after fluorescein injection is advisable. Translation of static retinal vessel analysis into a rodent model has the potential to bridge the research gap between proof of concept studies in animals and clinical studies in humans.

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis

PurposeThe study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis.MethodsThis was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG).ResultsPatients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis.ConclusionsThere was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

NEURODEGENERATION, MICROVASCULAR DYSFUNCTION AND THEIR INTERACTION: ASSOCIATIONS WITH COGNITIVE PERFORMANCE – THE MAASTRICHT STUDY

Objective: The main objective was to investigate whether there was an interaction between retinal nerve fibre layer (RNFL) thickness, an index of neurodegeneration, and retinal venular diameter, an index of microvascular dysfunction, in the associations of RNFL thickness and retinal venular diameter with global cognitive performance, an index of cognitive function. Design and method: We used cross-sectional data from The Maastricht Study (n = 1,785 participants, 47.8% men, mean age 59 years, and 24.5% with type 2 diabetes [oversampled by design]) and tested for an interaction between RNFL thickness and retinal venular diameter in the non-linear associations of RNFL thickness and retinal venular diameter with global cognitive performance. RNFL thickness was defined as low (lowest quartile) and high (highest three quartiles combined). Retinal venular diameter was defined as wide (highest quartile) and narrow (lowest three quartiles combined). All associations were adjusted for potential confounders (demographic variables and cardiovascular risk factors). In addition, we tested for interaction by hypertension. Results: The association of RNFL thickness with global cognitive performance was modified by retinal venular diameter (Pinteraction = 0.02) and the association of retinal venular diameter with global cognitive performance was modified by RNFL thickness (Pinteraction = 0.02). After full adjustment, low versus high RNFL thickness was associated with lower global cognitive performance in individuals with, but not in individuals without, a wide retinal venular diameter (beta, [95% confidence interval] low versus high RNFL thickness, -0.26 [-0.43; -0.08] versus -0.03 [-0.14; 0.08], respectively); and wide versus narrow retinal venular diameter was associated with lower global cognitive performance in individuals with, but not in individuals without, a low RNFL thickness (-0.27 [-0.47; -0.06] versus 0.01 [-0.11; 0.12], respectively). Hypertension modified the above associations. In stratified analyses, the above associations were stronger in individuals with, versus without, hypertension. Conclusions: In summary, the present population-based study found an interaction between neurodegeneration, estimated from RNFL thickness, and microvascular dysfunction, estimated from retinal venular diameter, in the associations of RNFL thickness and retinal venular diameter with global cognitive performance. Hence, the interaction between neurodegeneration and microvascular dysfunction may contribute to the pathobiology of cognitive dysfunction.

Exploring Retinal Blood Vessel Diameters as Biomarkers in Multiple Sclerosis.

We aimed to determine whether retinal vessel diameters and retinal oxygen saturation in newly diagnosed patients with multiple sclerosis (pwMS) are different from those of a healthy population. Retinal blood vessel diameters were measured using imaging with a spectrophotometric non-invasive retinal oximeter. Twenty-three newly diagnosed untreated relapsing-remitting MS (RRMS) patients (mean age: 32.2 ± 7.5 years, age range = 18–50 years, 56.5% female) were measured and compared to 23 age- and sex-matched healthy controls (HCs) (mean age: 34.8 ± 8.1 years). Patients with Optic Neuritis were excluded. Retinal venular diameter (143.8 µm versus 157.8 µm: mean; p = 0.0013) and retinal arteriolar diameter (112.6 µm versus 120.6 µm: mean; p = 0.0089) were smaller in pwMS when compared with HCs, respectively. There was no significant difference in the oxygen saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively. There was a significant difference in the median low contrast visual acuity (2.5% contrast) between the pwMS and the HC groups (p = 0.0143) Retinal arteriolar and venular diameter may have potential as objective biomarkers for MS.

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.

Mouse microphthalmia-associated transcription factor (Mitf) mutations affect the structure of the retinal vasculature.

Mice carrying pathogenic variants in the microphthalmia transcription factor (Mitf) gene show structural and functional changes in the retina and retinal pigment epithelium. The purpose of this study was to assess the vascular changes in Mitf mice carrying pathogenic variants by determining their retinal vessel diameter. Mice examined in this study were: B6-Mitfmi-vga9/+ (n = 6), B6-Mitfmi-enu22(398) /Mitfmi-enu22(398) (n = 6) and C57BL/6J wild type mice (n = 6), all 3 months old. Fundus images were taken with a Micron IV camera after intraperitoneal injection of fluorescein salt. Images were adjusted to enhance contrast and a custom written MATLAB program used to extract the mean vascular diameter at a pre-defined distance from the optic disc. The number of vessels, mean diameter and mean total diameter were examined. The mean diameter of retinal veins in Mitfmi-enu22(398) /Mitfmi-enu22(398) mice was 18.8% larger than in wild type (p = 0.026). No differences in the meandiameter of the retinal arteries were found between the genotypes. Mitfmi-enu22(398) /Mitfmi-enu22(398) mice have 17.2% more retinal arteries (p = 0.026), and 15.6% more retinal veins (p = 0.041) than wild type. A 24.8% increase was observed in the mean combined arterial diameter in mice with the Mitfmi-enu22(398)/ Mitfmi-enu22(398) compared to wild type mice (p = 0.024). A 38.6% increase was found in the mean combined venular diameter in mice with the Mitfmi-enu22(398) /Mitfmi-enu22(398) pathogenic variation as compared to wild type (p = 0.004). The mean combined retinal venular diameter in the Mitfmi-vga9/+ mice was 17.8% larger than in wild type (p = 0.03). An increase in vascularization of the retina in Mitfmi-enu22(398) /Mitfmi-enu22(398) mice was found, indicating an increased demand for blood flow to the retina.