mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.

Nail fold capillaroscopy in leprosy: Unveiling the microvascular changes.

BACKGROUND: Leprosy, a chronic infectious disease, is associated with various nail changes. Its etiopathogenesis is multifaceted, with microvascular damage being crucial. Nail fold capillaroscopy (NFC) emerges as a novel tool for detecting early vascular deficits in leprosy. The study aimed to assess and provide a complete clinical characterization of NFC changes in leprosy patients. METHODS: It is an observational cross-sectional study, done over a period of 1.5 year (January 2021 to august 2022) in a tertiary care hospital, encompassing 60 patients diagnosed with leprosy (18-60 years). After obtaining informed consent; detailed history, complete cutaneous and neurological examinations were conducted. All fingernails and toenails were examined for clinical changes. Subsequently, onychoscopy was performed using USB type of video-dermatoscope (Model AM7115MZT Dino-lite), a non-invasive tool. This was followed by NFC which was done for all fingernails and images were recorded by single operator, which were then assessed for quantitative and qualitive changes and statistical analysis was conducted using SPSS v20, with mean capillary density compared using Student's t-test, morphological change frequencies assessed by proportions, and group comparisons made using Chi-square or Fischer exact tests, with a significance threshold of p < 0.05. RESULTS: Among the 60 patients, 39 were in the lepromatous group, which included both borderline lepromatous (BL) and lepromatous leprosy (LL) patients, and 17 were in the tuberculoid group, which included borderline tuberculoid (BT) leprosy patients; 23.3 % had Type 1 reactions, and 18.3 % had Type 2 reactions. Nail fold capillaroscopy (NFC) showed microvasculature changes in 93.3 % of patients. The average capillary density was 6.8 ± 1.5 capillaries per mm, with the lepromatous group having a lower density (6.5 ± 1.09) compared to the tuberculoid group (7.0 ± 0.86). The most common NFC changes in the tuberculoid group were tortuous capillaries (70 %), capillary dropouts, and dilated capillaries (both 64.7 %). In the lepromatous group, capillary dropouts (82 %) were most frequent, followed by tortuous (69 %), receding (69 %), and dilated capillaries (66 %). A dilated and prominent subpapillary plexus was more common in the lepromatous group (35 %, p = 0.04). Patients with trophic changes in the lepromatous group had more capillary dropouts and bizarre capillaries. Capillary dropouts, dilated capillaries, and visible subpapillary venous plexus were more prevalent in patients with Type 2 reactions. CONCLUSION: NFC changes are prevalent in both tuberculoid and lepromatous leprosy, which may be an indicator of peripheral vascular compromise and trophic changes, especially in lepromatous leprosy. NFC can be an auxiliary tool for detecting microvascular abnormalities in leprosy patients.

Type II Muscle Fiber Capillarization Is an Important Determinant of Post-Exercise Microvascular Perfusion in Older Adults.

INTRODUCTION: Microvascular perfusion is essential for post-exercise skeletal muscle recovery to ensure adequate delivery of nutrients and growth factors. This study assessed the relationship between various indices of muscle fiber capillarization and microvascular perfusion assessed by contrast-enhanced ultrasound (CEUS) at rest and during recovery from a bout of resistance exercise in older adults. METHODS: Sixteen older adults (72 ± 6 y, 5/11 male/female) participated in an experimental test day during which a muscle biopsy was collected from the vastus lateralis and microvascular perfusion was determined by CEUS at rest and at 10 and 40 min following a bout of resistance exercise. Immunohistochemistry was performed on muscle tissue samples to determine various indices of both mixed and fiber-type-specific muscle fiber capillarization. RESULTS: Microvascular blood volume at t = 10 min was higher compared with rest and t = 40 min (27.2 ± 4.7 vs. 3.9 ± 4.0 and 7.0 ± 4.9 AU, respectively, both p < 0.001). Microvascular blood volume at t = 40 min was higher compared with rest (p < 0.001). No associations were observed between different indices of mixed muscle fiber capillarization and microvascular blood volume at rest and following exercise. A moderate (r = 0.59, p < 0.05) and strong (r = 0.81, p < 0.001) correlation was observed between type II muscle fiber capillary-to-fiber ratio and the microvascular blood volume increase from rest to t = 10 and t = 40 min, respectively. In addition, type II muscle fiber capillary contacts and capillary-to-fiber perimeter exchange index were strongly correlated with the microvascular blood volume increase from rest to t = 40 min (r = 0.66, p < 0.01 and r = 0.64, p < 0.01, respectively). CONCLUSION: Resistance exercise strongly increases microvascular blood volume for at least 40 min after exercise cessation in older adults. This resistance exercise-induced increase in microvascular blood volume is strongly associated with type II muscle fiber capillarization in older adults.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study.

BACKGROUND: Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. METHODS: The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. RESULTS: This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all). CONCLUSIONS: In this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Automated nailfold capillary density measurement method based on improved YOLOv5.

Nailfold capillary density is an essential physiological parameter for analyzing nailfold health; however, clinical images of the nailfold are taken in many situations, and most clinicians subjectively analyze nailfold images. Therefore, based on the improved "you only look once v5" (YOLOv5) algorithm, this study proposes an automated method for measuring nailfold capillary density. The improved technique can effectively and rapidly detect distal capillaries by incorporating methods or structures such as 9mosaic, spatial pyramid pooling cross-stage partial construction, bilinear interpolation, and efficient intersection over union. First, the modified YOLOv5 algorithm was used to detect nailfold capillaries. Subsequently, the number of distal capillaries was filtered using the 90° method. Finally, the capillary density was calculated. The results showed that the Average Precision (AP)@0.5 value of the proposed approach reached 85.2 %, which was an improvement of 4.93 %, 5.24 %, and 107 % compared with the original YOLOv5, YOLOv6, and simple-faster rapid-region convolutional network (R-CNN), respectively. For different nailfold images, using the density calculated by nailfold experts as a benchmark, the calculated results of the proposed method were consistent with the manually calculated results and superior to those of the original YOLOv5.

Age-related alterations in retinal capillary function.

PURPOSE: To determine age-related alterations in the retinal capillary function (RCF, the ability to transport blood flow) in healthy subjects. METHODS: A total of 148 healthy subjects (aged 18 to 83 years) were enrolled, and one eye of each subject was imaged. Retinal blood flow (RBF) was measured using a Retinal Function Imager, and retinal capillary density (RCD, expressed as fractal dimension Dbox) was measured using optical coherence tomography angiography. RCF was defined as the ratio of RBF to RCD, representing the ability to transport blood flow. The relationship between RCF and age was analyzed. In addition, the cohort was divided into four groups (G1, <35 years, G2, 35-49 years, G3, 50-64 years, and G4, ≥65 years) for further analysis. RESULTS: With all data, the relation between the RCF and age had a trend of a quadratic model (G1-4: r = 0.16, P = 0.14). After 35 years (i.e., G2-4), the relation had a trend between the RCF and age fitted into a negative linear model (r = -0.23, P = 0.05). Moreover, after 50 years (i.e., G3-4), the negative linear model became stronger (r = -0.37, P = 0.03). The average RCF was 2.24 ± 0.22 µl/s/Dbox in G4, significantly lower than that in G2 (2.65 ± 0.56 µl/s/Dbox, P = 0.018) and G3 (2.64 ± 0.70 µl/s/Dbox, P = 0.034), but did not reach a significant level compared to that in G1 (2.55 + 0.51 µl/s/Dbox, P = 0.056). CONCLUSIONS: This is the first study to determine age-related alterations in the RCF in a healthy population. Decreased RCF in the older group may represent a characteristic pattern of normal aging.

Peripapillary microvasculature changes after vitrectomy in epiretinal membrane via swept-source OCT angiography.

PURPOSE: To evaluate the peripapillary microvasculature changes in patients with epiretinal membrane (ERM) following pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling using swept-source optical coherence tomography angiography (SS-OCTA). METHOD: Medical records and multimodal imaging data of 33 eyes after PPV for ERM were retrospectively reviewed. Peripapillary SS-OCTA images of 6×6 mm2 were recorded at at pre- and post-operatively every 6 months for 1 year. A semi-automated method was used to analyzed SS-OCTA images, excluding the optic disc area, using the MATLAB software. The peripapillary vessel density (pVD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) was quantified in four quadrants (superior, inferior, nasal and temporal). RESULT: The mean pVD in SCP and DCP decreased at 6- and 12-months follow-up. In sectoral analysis, superior, inferior, and temporal quadrants pVD in SCP and DCP were significantly reduced at 1 year after vitrectomy (all p < 0.05). Meanwhile, inferior quadrants pVD in SCP and DCP showed the earliest significant reduction at 6-months (p = 0.022 and 0.048, respectively). A reduction of post-operative mean pVD in DCP was significantly greater in patients with diabetic retinopathy (p = 0.043). CONCLUSION: Peripapillary capillary density significantly decreased after surgical removal of ERM. Vitrectomy with ILM peeling can cause peripapillary microvascular damage starting in inferior sector.

Depletion of vascular adaptive mechanisms in hypertension-induced injury of the heart and kidney.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a signalling protein of critical importance for angiogenesis. In an effort to better understand its significance in hypertension-induced injury of the heart and kidney we aimed at studying the changes in its expression in an experimental model and correlated it with capillary density in the myocardium and the renal parenchyma. METHODS: We used two age groups of spontaneously hypertensive rats (6- and 12-month-old), indicative of early and advanced hypertension. VEGF expression was assessed and a semi-quantitative analysis of its immunoreactivity was conducted. Changes in capillary density in the myocardium and kidney were assessed for statistical significance and correlations with VEGF expression were established. RESULTS: We reported stronger VEGF expression in animals with early compared to advanced hypertension in all examined structures. Capillary density decreased significantly at age 12 months compared to 6 months and was significant in all examined structures. A positive correlation was established between capillary density and the expression of VEGF. CONCLUSION: These findings underscore the key significance of VEGF for compensatory angiogenesis and suggest that a statistically significant depletion of these vascular adaptive mechanisms is a major aspect in the cascade of hypertension-induced injury of the heart and kidney (Tab. 3, Fig. 26, Ref. 47).

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans.

The final steps of the O2 cascade during exercise depend on the product of the microvascular-to-intramyocyte P O 2 ${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non-invasive methods to determine D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW ), and hypothesized that: (i) k in well oxygenated muscle (kHIGH ) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH  - kLOW ) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s-1  mg-1 (∼5.8 ml min-1  100 g-1 ). CD ranged 348 to 586 mm-2 . kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min-1 , P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = -0.10, P = 0.755). Δk ranged -0.26 to -2.55 min-1 , and correlated with CD (r = -0.68, P = 0.015). m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity. KEY POINTS: We determined post-exercise recovery kinetics of quadriceps muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) measured by near-infrared spectroscopy (NIRS) in humans under conditions of both non-limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables. The m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH ) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = -0.68) of biopsy samples. NIRS provides non-invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.

Evaluation of subclinical retinal microvascular changes in systemic lupus erythematosus patients using optical coherence tomography angiography and its relationship with disease activity.

OBJECTIVE: This study aimed to investigate subclinical retinal microvascular changes with optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE) and healthy controls (HCs), and to evaluate the relationship between OCTA findings and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). MATERIALS AND METHODS: In this study, 47 eyes of SLE and 41 eyes of healthy control (HC) were evaluated. The SLE patients were divided into two subgroups: low disease activity (LDA) (SLEDAI≤5) and high disease activity (HDA) (SLEDAI>6). The results of OCTA were compared between SLE patients and HCs as well as the SLE subgroups. The relationship between OCTA results and SLEDAI-2K was evaluated. RESULTS: There were no differences in foveal avascular zone (FAZ) areas between the SLE patients and HCs. Central foveal thickness (CFT) was lower in SLE patients (p = .046). Superficial capillary plexus (SCP) vessel density (VD) in SLE patients was significantly lower only in the foveal area compared to that in HCs (p = .006). Deep capillary plexus (DCP) VD in SLE patients was significantly lower in all areas except the temporal parafoveal area compared to that in the HCs. There was no statistically significant difference between SLE groups with LDA and HDA in FAZ or any of the other areas, including SCP and DCP. When the correlation between OCTA findings and SLEDAI-2K was examined, both SCP and DCP VD were found to be negatively correlated. CONCLUSIONS: It was observed that DCP VDs were affected in SLE patients with LDA, and SCP VDs were also affected in addition to DCP with HDA. This suggests that DCP may be the first capillary plexus to be comprised in SLE. VDs were negatively correlated with disease activity. It was concluded that OCTA can be a useful tool in assessing subclinical retinal microvascular pathology and disease activity in patients with SLE.

Ocular surface microcirculation is better preserved with pulsatile versus continuous flow during cardiopulmonary bypass-An experimental pilot.

BACKGROUND: Non-pulsatile cardiopulmonary bypass (CPB) may induce microvascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass. METHODS: Ocular surface microcirculation in small tissue volumes (~0.1 mm3 ) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was examined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified. RESULTS: At limbus, velocities improved with pulsatility (p < 0.01) and deteriorated with CF (p < 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p < 0.01), accompanied by an increase in capillary density (p < 0.01). Microvascular oxygen saturation decreased in both groups. CONCLUSION: Ocular surface capillary densities and flow patterns are better preserved with pulsatile versus CF during 6 h of CPB in sleeping piglets.

The Value of Optical Coherence Tomography Angiography in Pituitary Adenomas.

OBJECTIVE: This study aims to explore the value of retinal vessel density (VD) in diagnosing optic nerve injuries in patients with pituitary adenomas using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional retrospective study, 100 patients with pituitary adenomas and 71 participants for normal controls, who visited the Beijing Tiantan Hospital from January 2019 to May 2021, were enrolled. The OCTA was used to measure retinal thickness and VD, and the correlation of these parameters with visual field (VF) factors was analyzed. Receiver operating characteristic curves were used to compare the value of the above parameters in diagnosing VF abnormalities in the patients with pituitary adenomas; the differences in retinal VD between 41 patients with pituitary adenomas who had normal retinal thicknesses and 41 patients in the normal control group with no statistical differences in gender and age were compared. RESULTS: The radial peripapillary capillary (RPC) density, superficial retinal capillary plexus (SRCP) density, retinal nerve fiber layer thickness, and ganglion cell layer complex thickness correlated with VF parameters (p < 0.05). The RPC density in the temporal quadrant had the highest capability in diagnosing VF abnormalities, with an area under the curve = 0.821, p < 0.001, with 72.3% sensitivity and 82.7% specificity. The mean RPC density and RPC density in the nasal and temporal quadrants in the 41 patients with pituitary adenomas who had normal retinal thicknesses were reduced compared with the normal control group (49.95% ± 1.86% vs. 51.30% ± 1.87%, p = 0.002; 49.09% ± 3.13% vs. 50.41% ± 3.90%, p = 0.034; 54.33% ± 3.14% vs. 55.89% ± 3.08%, p = 0.020) and other parameters had no statistical differences compared with the normal control group. CONCLUSIONS: The density of the RPC and SRCP may also be sensitive and specific indicators of VF damage in patients with pituitary adenomas. Measuring retinal VD in patients with pituitary adenomas may be a supplement to help identify VF impairments. In addition, abnormal retinal vascular density may indicate VF impairment in patients who are unable to cooperate with VF examinations.

Effects of a single aerobic exercise on perfused boundary region and microvascular perfusion: a field study.

The endothelium and the glycocalyx play a pivotal role in regulating microvascular function and perfusion in health and critical illness. It is unknown today, whether aerobic exercise immediately affects dimensions of the endothelial surface layer (ESL) in relation to microvascular perfusion as a physiologic adaption to increased nutritional demands. This monocentric observational study was designed to determine real-time ESL and perfusion measurements of the sublingual microcirculation using sidestream dark field imaging performed in 14 healthy subjects before and after completing a 10 km trial running distance. A novel image acquisition and analysis software automatically analysed the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration of the ESL, in vessels between 5 and 25 µm diameter. Microvascular perfusion was assessed by calculating RBC filling percentage. There was no significant immediate effect of exercise on PBR and RBC filling percentage. Linear regression analysis revealed a distinct association between change of PBR and change of RBC filling percentage (regression coefficient ß: - 0.026; 95% confidence interval - 0.043 to - 0.009; p = 0.006). A single aerobic exercise did not induce a change of PBR or RBC filling percentage. The endothelium of the microvasculature facilitates efficient perfusion in vessels reacting with an increased endothelial surface layer.

Comparison of Choroidal Thickness, Foveal Avascular Zone, and Macular Capillary Density in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Ranibizumab or Aflibercept-A Prospective Study.

This prospective comparative case series aims to compare best-corrected visual acuity (BCVA), retinal microvasculature, and retinal structural changes in patients treated with either ranibizumab or aflibercept for macular edema (ME) secondary to treatment-naïve branch retinal vein occlusion (BRVO) by optical coherence tomography angiography (OCTA). Ten patients were enrolled with macular capillary density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and foveal avascular zone (FAZ) measured in both eyes before and after treatment. Final central retinal thickness and BCVA improved significantly (p < 0.05), and densities of SCP and DCP of BRVO sectors were significantly lower at baseline than fellow eye counterparts and remained persistently lower during treatment, particularly in the aflibercept group (p < 0.05). SCP density, DCP density of both BRVO sectors (p = 0.0001, p < 0.0001), and non-BRVO sectors (p < 0.0001, p < 0.0001) were significantly correlated with final BCVA for diseased eyes. Using multivariate general linear model analysis, and including OCTA parameters only, but not all of the available clinical data, DCP density of BRVO sectors in both eyes was the most predictive factor for final visual outcome (probability p < 0.0001). OCTA offered further qualitative and quantitative evaluation of treatment-naïve BRVO. Judging by OCTA parameters, not only in the diseased eye but also in the fellow eye, DCP density of BRVO sectors was the most predictive factor of final visual outcome.

Evaluation of retinal microvascular structures by optical coherence tomography angiography in primary Sjögren's syndrome.

OBJECTIVES: There are insufficient data in the literature on how retinal capillaries are affected in primary Sjögren's syndrome (PSS). The aim of this study was to evaluate the retinal capillary density (CD) in PSS using optical coherence tomography angiography (OCTA). METHODS: In this case-control study, 26 eyes from 13 PSS patients and 39 eyes from 20 healthy controls (HCs) were included. The CD in the regions of the superior capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillaries (RPC) as well as assessment parameters of the foveal avascular zone (FAZ) were examined by OCTA. RESULTS: The mean CD (%) was 50.2 ± 4.2 and 50.5 ± 3.4 in the SCP (p = 0.904), 49.2 ± 7.5 and 53.9 ± 5.7 in the DCP (p = 0.006) and 50.8 ± 2.1 and 49.8 ± 2.2 in the RPC (p = 0.088) regions in patients with PSS and HCs, respectively. In patients with PSS and HCs, the mean sizes of the FAZ were 0.243 ± 0.07 mm2 and 0.283 ± 0.13 mm2 (p = 0.142), and the mean sizes of the non-flow area were 0.480 ± 0.11 mm2 and 0.509 ± 0.13 mm2, respectively (p = 0.359). The correlation coefficients (Rho) of retinal CD in the SCP, DCP and RPC regions with disease duration were - 0.545 (p = 0.004), - 0.389 (p = 0.050) and - 0.795 (p < 0.001), respectively. CONCLUSION: The retinal CD in PSS is lower than that in the healthy population in deep retinal capillaries, and retinal CD shows a negative correlation with disease duration in PSS. CLINICAL TRIALS REGISTRATION: This study was not registered to clinicaltrials.gov.

Carotid disease and retinal optical coherence tomography angiography parameters in patients with non-arteritic anterior ischemic optic neuropathy.

PURPOSE: In order to analyze the data and retinal microvasculature for non-arteritic anterior ischemic optic neuropathy (NAION), patients were referred to have carotid Doppler ultrasound (CDU) from 2016 to 2020. METHODS: In this case-control observational study, 30 NAION patients were evaluated with CDU. Twenty-two NAION patients (at least 3 months after the onset of symptoms) and 9 normal subjects underwent a complete ophthalmic examination including optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). NAION eyes and fellow eyes were further divided into two groups based on the presence of carotid stenosis (CS). NAION patients with CS were termed "CS-NAION"; and those without CS were termed "NCS-NAION." Measurements of radial peripapillary capillary vessel density (RPC VD), ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses were compared among groups. RESULTS: Fourteen of 30 NAION patients referred to have carotid Doppler were positive for CS with each one of such referrals having less than 50% stenosis. RNLF, GCC and RPC VDs were reduced in NAION patients' eyes, when compared to controls and the fellow eyes. RPC VD was significantly lower in the temporal-superior (P = 0.037) and the superior-temporal (P = 0.012) sectors of the NCS-NAION patients than in the CS-NAION patients. No significant differences were found between CS-fellow eyes and NCS-fellow eyes in terms of RPC VDs, RNLF or GCC. CONCLUSION: Results of the study highlight the effect of the carotid artery stenosis on ocular perfusion pressure in the pathogenesis of NAION. More extensive studies are necessary.

Passive muscle heating attenuates the decline in vascular function caused by limb disuse.

Limb disuse has profound negative consequences on both vascular and skeletal muscle health. The purpose of this investigation was to determine whether repeated application of passive heat, applied to the knee extensor muscles, could mitigate the detrimental effects of limb disuse on vascular function. This was a randomized, single-blinded placebo controlled trial. Twenty-one healthy volunteers (10 women, 11 men) underwent 10 days of unilateral lower limb immobilization and were randomized to receive either a daily 2 h sham (Imm) or heat treatment (Imm+H) using pulsed shortwave diathermy. Vascular function was assessed with Doppler ultrasound of the femoral artery and the passive leg movement technique. Biopsies of the vastus lateralis were also collected before and after the intervention. In Imm, femoral artery diameter (FAD) and PLM-induced hyperaemia (HYP) were reduced by 7.3% and 34.3%, respectively. Changes in both FAD (4% decrease; P = 0.0006) and HYP (7.8% increase; P = 0.003) were significantly attenuated in Imm+H. Vastus lateralis capillary density was not altered in either group. Immobilization significantly decreased expression of vascular endothelial growth factor (P = 0.006) and Akt (P = 0.001), and increased expression of angiopoietin 2 (P = 0.0004) over time, with no differences found between groups. Immobilization also upregulated elements associated with remodelling of the extracellular matrix, including matrix metalloproteinase 2 (P = 0.0046) and fibronectin (P = 0.0163), with no differences found between groups. In conclusion, limb immobilization impairs vascular endothelial function, but daily muscle heating via diathermy is sufficient to counteract this adverse effect. These are the first data to indicate that passive muscle heating mitigates disuse-induced vascular dysfunction. KEY POINTS: Limb disuse can be unavoidable for many of reasons (i.e. injury, bed rest, post-surgery), and can have significant adverse consequences for muscular and vascular health. We tested the hypothesis that declines in vascular function that result from lower limb immobilization could be mitigated by application of passive heat therapy. This report shows that 10 days of limb immobilization significantly decreases resistance artery diameter and vascular function, and that application of passive heat to the knee extensor muscle group each day for 2 h per day is sufficient to attenuate these declines. Additionally, muscle biopsy analyses showed that 10 days of heat therapy does not alter capillary density of the muscle, but upregulates multiple factors indicative of a vascular remodelling response. Our data demonstrate the utility of passive heat as a therapeutic tool to mitigate losses in lower limb vascular function that occur from disuse.

Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography.

Age-related blood-brain barrier (BBB) disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microcirculation for prevention of VCID and AD. To facilitate this research, there is an urgent need for sensitive and easy-to-adapt imaging methods that enable longitudinal assessment of changes in BBB permeability and brain capillarization in aged mice and that could be used in vivo to evaluate treatment efficiency. To enable longitudinal assessment of changes in BBB permeability in aged mice equipped with a chronic cranial window, we adapted and optimized two different intravital two-photon imaging approaches. By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that, in 24-mo-old C57BL/6J mice, cumulative permeability of the microvessels to fluorescent tracers of different molecular masses (0.3 to 40 kDa) is significantly increased compared with that of 5-mo-old mice. Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice. Cortical capillary density, assessed both by intravital two-photon microscopy and optical coherence tomography was also decreased in aged mice vs. young mice. The presented methods have been optimized for longitudinal (over the period of 36 wk) in vivo assessment of cerebromicrovascular health in preclinical geroscience research.NEW & NOTEWORTHY Methods are presented for longitudinal detection of age-related increase in blood-brain barrier permeability and microvascular rarefaction in the mouse cerebral cortex by intravital two-photon microscopy and optical coherence tomography.

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging.

AIM: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology. METHODS: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI). RESULTS: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm2 (95% CI 28.2-38.2 cpll/mm2). In the image sequences with vascular networks, mean TVD was 12.5 mm/mm2 (95% CI 11.2-13.77 mm/mm2), mean PVD was 12.2 (95% CI 11.0-13.5 mm/mm2), MFI was 3 and PPV was 100%. CONCLUSIONS: Incident dark field imaging allows for noninvasive, real time visualization and objective evaluation and quantification of the microcirculation of the uterine cervix. The organized vascular patterns and optimal perfusion observed in healthy subjects allow for comparison with cervical pathology, for example in patients with cervical dysplasia or cervical cancer.

Nailfold capillary changes in newly diagnosed hypertensive patients: An observational analytical study.

INTRODUCTION: Nail Fold capillaroscopy (NFC) is used to evaluate microvascular changes in the horizontally lying capillaries in the proximal nail fold. Arterial hypertension affects the microvascular beds producing structural changes. Our objective was to evaluate qualitative and quantitative NFC changes in newly diagnosed hypertensives as compared to age and sex matched normotensive controls and to determine association, if any, with microvascular changes visualized on fundoscopy. MATERIALS AND METHODS: This observational, analytical study involved 41 newly diagnosed hypertensives (18-60 years) with 41 normotensive age and sex matched normotensive controls. The mean capillary density (MCD) and morphological changes were assessed for all, while fundoscopy was done for study group participants. The collected data was statistically analyzed. RESULTS: The MCD in newly diagnosed hypertensives (5.21 ± 0.90 capillaries/mm) was significantly lower than normotensive controls (6.50 ± 0.65 capillaries/mm) (p < 0.001) in our study. Qualitative morphologic changes were more common in hypertensive patients including meandering capillaries, capillary dilation, avascular areas, bushy capillaries, and microhemorrhages (p value <0.001). Capillary disarray (73.17%) was a unique morphologic change seen significantly more commonly in study group (p < 0.001). Among hypertensives, MCD was lesser in patients with retinopathy (p = 0.125) and with microalbuminuria, while avascular areas and dilated capillaries were significantly more common. CONCLUSION: Our study supports the role of NFC with USB dermatoscope in detecting unique microvascular morphological alterations in hypertensives, which were more frequent as well as distinctive, as compared to healthy controls. A good correlation with fundoscopic features and microalbuminuria suggests that it could be useful in predicting/detecting cardiovascular, or renal complications early, with an advantage of easy accessibility and repeatability.