Microvascular Vessel Density Research Articles

Quantitative microvascular analysis in different stages of retinitis pigmentosa using optical coherence tomography angiography

As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 μm; moderate, < 2500 μm; advanced, absence. Using optical coherence tomography angiography, quantitative microvascular parameters were analyzed. In total, 91 eyes from 49 patients were included. For the superficial capillary plexus (SCP) and deep capillary plexus (DCP), perfusion densities (PDs) in the early stage (SCP: 37.32 ± 8.11%; DCP: 21.19 ± 9.15%) were greater than those in moderate (SCP: 34.16 ± 6.65%, P = 0.011; DCP: 15.67 ± 8.85%, P = 0.031) and advanced stages (SCP: 33.71 ± 9.02%, P = 0.030; DCP: 12.83 ± 6.29%, P < 0.001). The choroidal vascularity index in the early stage (0.58 ± 0.03) was greater than those in the moderate (0.57 ± 0.02, P = 0.017) and advanced stage (0.56 ± 0.02, P = 0.033). The area and perimeter of foveal avascular zone (FAZ) in advanced stage (0.44 ± 0.26 mm2, 2.96 ± 0.86 mm, respectively) were larger than those in early (0.26 ± 0.11 mm2, P = 0.020; 2.19 ± 0.53 mm, P = 0.006, respectively) and moderate stage (0.28 ± 0.13 mm2, P = 0.043; 2.24 ± 0.67 mm, P = 0.013, respectively). During RP disease progression, retinal and choroidal microvascular vessel density decreases in the early stage, followed by FAZ enlargement in the advanced stage.

PO2_04. Retinal microvascular vessel density in women 3 years after hypertensive disorder of pregnancy

PO2_04. Retinal microvascular vessel density in women 3 years after hypertensive disorder of pregnancy

Evaluation of the Optic Nerve Head Using Optical Coherence Tomography Angiography in Systemic Sclerosis Patients.

To quantify microvascular vessel density in the optic disc using optical coherence tomography angiography (OCTA) in patients with systemic sclerosis (SS); to determine whether there is a difference in values between patients and controls; and to correlate the OCTA measurements with disease activity, damage risk, and drug usage. Patients aged 20 - 76 years who were followed up after a diagnosis of SS and age- and gender-matched controls. The patients underwent RTVue-XR AngioVue OCTA imaging in this cross-sectional observational study. A total of 61 eyes of 61 consecutive SS patients and 60 eyes of 60 controls were investigated. There was no statistically significant difference between the patients and control groups regarding the average RNFL (retinal fiber layer) and radial peripapillary capillary (RPC) vessel density (VD) measurements (p = 0.35, p = 0.25, respectively). As the antinuclear antibody (ANA) titer increased, RNFLsuperior (p = 0.01, r = - 0.327), RPCwhole (p = 0.029, r = 0.279), RPCperipapillary (p = 0.037, r = - 0.267), RPCsuperior (p = 0.003, r = - 0.371), and RPCinferior (p = 0.02, r = 0.297) values decreased with statistical significance. The RPCinside values were lower in anti-Scl-70-positive patients compared to patients negative for anti-Scl-70 (topoisomerase I) (p = 0.021). The RNFLnasal (p = 0.03, r = - 0.278) value decreased as the years of disease increased. The RPCinside value was higher in patients using hydroxychloroquine and calcium channel blockers than those who did not use them (p = 0.021 and p = 0.027, respectively). The RPCwhole, RPCperipapillary, and RPCnasal values were higher, with statistical significance in corticosteroid users than in those patients who did not use corticosteroids (p = 0.043, 0.030, and 0.033, respectively). There was no significant difference between the patients and control groups regarding the average RPC VD measurements. However, since this is the first study to analyze optic disc vessel density in SS patients, optic nerve blood flow changes in scleroderma with OCTA could be studied.

Retinal microvascular density analysis in patients with rheumatoid arthritis treated with hydroxychloroquine

PurposeRheumatoid arthritis (RA) is the most common inflammatory joint disease, and hydroxychloroquine (HCQ) is an established treatment. The extent to which HCQ impacts ocular microvascular vessel density (VD) in patients with RA without evidence of HCQ retinopathy has not yet been conclusively clarified. The main aim of this study was to evaluate VD measured by optical coherence tomography angiography (OCTA) in patients with RA treated with HCQ.MethodsThe VD data of the 3 × 3 mm OCT angiogram (RTVue XR Avanti, Optovue Inc., Fremont, California, USA) as well as the retinal thickness (RT) data of patients with RA (n = 30) and healthy controls (n = 30) were extracted and analyzed. The study group was further divided into patients undergoing HCQ treatment for > 5 years (high-risk-group) and < 5 years (low-risk group).ResultsPatients with RA showed no evidence of VD reduction compared to the control group in all obtained regions (p > 0.05). Correlation analysis revealed no dependency between VD, RT, and HCQ therapy duration or cumulative HCQ dose (p > 0.05). High-risk patients showed a decreased VD in the superficial quadrant of the superficial capillary plexus compared to low-risk-patients (p = 0.022). Whole-en-face RT was reduced in the high-risk group compared to the control group (p = 0.019).ConclusionOur study showed no evidence that HCQ diminishes VD in patients with RA without HCQ retinopathy measured by OCTA. However, RA patients with a long duration of therapy showed a significantly reduced RT. Our results suggest that quantitative VD analysis by OCTA may not be suitable for early detection of HCQ retinopathy and that the focus on detecting early HCQ retinopathy should be on intensive and sequential OCT diagnostics.

Variability of microcirculatory measurements in healthy volunteers

Reliable assessment of the microcirculation is important to investigate microcirculatory properties in various disease states. The GlycoCheck system automatically analyzes sublingual sidestream dark field images to determine the perfused boundary region (PBR; a measure of glycocalyx thickness), red blood cell filling percentage, and microvascular vessel density. Although GlycoCheck has been used to study the microcirculation in patients, little is known about the reproducibility of measurements in healthy volunteers. We assessed intra- and interobserver agreement by having two experienced observers perform three consecutive microcirculation measurements with the GlycoCheck system in 49 healthy volunteers. Intraobserver agreement of single measurements were poor (intraclass correlation coefficients (ICCs) < 0.4) for PBR, red blood cell filling percentage and microvascular vessel density. ICCs increased to values > 0.6 (indicating good reproducibility) for all parameters when performing and averaging three consecutive measurements. No systematic differences were observed between observers for any parameter. Interobserver variability was fair for PBR (ICC = 0.53) and red blood cell filling percentage (ICC = 0.58) and poor for perfused vessel density (ICC = 0.20). In conclusion, GlycoCheck software can be used with acceptable reliability and reproducibility for microcirculation measurements on a population level when averaging three consecutive measurements. Repeated measurements are preferably performed by the same observer.

Persistent reduction of retinal microvascular vessel density in patients with moderate and severe COVID-19 disease

ObjectiveThis study aims to analyse the possible recovery or worsening in retinal microvasculature after 8 months in a previously studied COVID-19 cohort.Methods and analysisA cross-sectional case–control study and a prospective...

Retinal Microvascular Vessel Density Differences between Adult Athletes and Nonathletes.

Regular physical activity may affect the neurovascular structures. Many studies have shown the positive effects of physical activity on ocular disorders such as glaucoma, retinopathy, and macular degeneration. Athletes were expected to have a better retinal vascular structure compared with the nonathletes. This study aimed to evaluate the effects of regular physical activity on the retinal microvascular structure. This observational and cross-sectional study was conducted between January and July 2020 with participants aged 20 to 35 years who had a visual acuity of ≥20/20, axial length of 22 to 24 mm, refractive defect spherical equivalent of ≤±1 D, and IOP of ≤21 mmHg. Updated AngioScan software (Navis version 1.8.0) of Nidek's RS-3000 Advance system was used to analyze the spectral-domain optical coherence tomography and optical coherence tomography angiography images. A total of 60 right eyes of 60 individuals were included in the study. Thirty subjects were in the athlete group, and 30 patients were in the nonathlete group. Sixteen of the individuals in the athlete group and 15 in the nonathlete group were women (P > .05). Retinal nerve fiber layer and ganglion cell complex thicknesses in all quadrants were thinner in nonathletes (P < .05). All of the Early Treatment Diabetic Retinopathy Study regions except central foveal subfield thickness were significantly higher in the athlete group (P < .05). In the nonathlete group, significantly reduced vessel densities of the superficial and deep capillary plexus and radial peripapillary capillary plexus, and the foveal avascular zone circularity index along with an increased foveal avascular zone perimeter and area were also detected (P < .05). Our study revealed that optical coherence tomography angiography measurements may be used in the determination of the effects of physical activity on retinal vascular structure changes.

Comparative study of retinal nerve fibre layer thickness and retinal peripapillary capillary plexus microvascular vessel density: structure-function relationship analysis in glaucoma.

To investigate whether the retinal peripapillary capillary plexus vessel density (RPCP VD) or the retinal nerve fibre layer thickness (RNFLT) is better in showing the structure-function relationship in glaucoma. Sixty-seven patients with primary open-angle glaucoma (POAG) in one eye and no visual field loss in fellow eye were included in this study. The scans of RPCP VD and RNFLT, and the standard automated perimetry data [including mean deviation (MD), pattern standard deviation (PSD), sector-based pattern deviation (PD) values] were analysed and compared. The global RNFLT was associated with MD (P = 0.035). RNFLTs of the superotemporal, superonasal, inferotemporal and inferonasal quadrants were associated with the corresponding PD (P = 0.004, <0.001, 0.002 and 0.012). The global RPCP VD was found to be associated with MD and PSD (P = 0.030 and 0.049, respectively). RPCP VD of the superotemporal quadrant was associated with PD of the corresponding quadrant, as well as with PSD (P = 0.003 and 0.043, respectively). Remaining RPCP VD values were only associated with the PD values of the corresponding quadrants (P < 0.05). The associations of the RPCP VD with PD were stronger than those of the RNFLT with PD [RPCP VD vs RNFLT: R2 = 0.624 vs 0.558 (P < 0.001 for both) for the superotemporal, 0.649 vs 0.552 for the superonasal (P < 0.001 for both), 0.598 vs 0.427 for the inferotemporal (P < 0.001 for both), 0.581 vs 0.408 for the inferonasal (P < 0.001 for both), 0.594 vs 0.068 (P < 0.001 vs 0.098) for the temporal, and 0.338 vs 0.195 (P < 0.001 vs 0.004) for the nasal quadrants]. In conclusion, the VD of RPCP was more informative in terms of the structure-function relationship in POAG. Future prospective follow-up studies with larger sample sizes are required to confirm the findings.

Lipopolysaccharide-induced changes in the neurovascular unit in the preterm fetal sheep brain

BackgroundExposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep.MethodsChronically instrumented fetal sheep at 103–104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.9%, w/v). Ten days after the start of LPS exposure at 113–114 days of gestation, the sheep were killed, and the fetal brain perfused with formalin in situ. Vessel density, pericyte and astrocyte coverage of the blood vessels, and astrogliosis in the cerebral cortex and white matter were determined using immunohistochemistry.ResultsLPS exposure reduced (P < 0.05) microvascular vessel density and pericyte vascular coverage in the cerebral cortex and white matter of preterm fetal sheep, and increased the activation of perivascular astrocytes, but decreased astrocytic vessel coverage in the white matter.ConclusionsProlonged exposure to LPS in preterm fetal sheep resulted in decreased vessel density and neurovascular remodeling, suggesting that chronic inflammation adversely affects the neurovascular unit and, therefore, could contribute to long-term impairment of brain development.

Pregnancy at high altitude in the Andes leads to increased total vessel density in healthy newborns.

The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea-level controls. Pre- and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre- and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level (P < 0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P < 0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm(2); P ≤ 0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.

Neovascularization in Alkali-Burned Rabbit Cornea

Objective: To study the neovascularization in regenerating and proliferating corneal cells following a standard alkali injury in rabbit eye. Methods: Three and six weeks after the creation of an alkali burn in the center of the right cornea of six albino rabbits, the animals were killed and histological sections from the cornea of both eyes were stained, photographed and studied for a possible formation of a neovascularization. The photographs were examined using the Quantimet image analyzer (Leica) and statistical analysis of the data was performed. Results: Sections of the injured cornea showed the formation of neovessels in the epithelial and superficial stromal layers. The neovascularization is present after 3 weeks of the corneal injury. After 6 weeks from the corneal alkali burn, neovessels are increased. Conclusions: There is a growing body of evidence suggesting that vascular abnormalities may play a crucial role in several ocular diseases. To improve our knowledge of the vascular involvement in these conditions, there is a need for a non-invasive imaging modality capable of assessing microcirculation within ocular tissue beds both in vitro and in vivo. This study shows that ultra-high sensitive optical microangiography, associated with other experimental techniques, is an adequate technique to visualize the eye surface microcirculations and to quantify microvascular vessel density under both normal and physio-pathological conditions.

In vivo volumetric imaging of microcirculation within human skin under psoriatic conditions using optical microangiography.

There is a growing body of evidence suggesting that vascular abnormalities may play crucial role in several dermatologic diseases, such as psoriasis, port wine stain, and skin cancer. To improve our understanding of vascular involvement in these skin conditions, there is a need for a non-invasive imaging modality capable of assessing 3D microcirculations within skin tissue beds in vivo. This study aims to demonstrate whether ultra-high sensitive optical microangiography (UHS-OMAG) is feasible to visualize skin microcirculations in 3D and to quantify microvascular vessel density under normal and psoriatic conditions in vivo. An UHS-OMAG system operating at 1,310 nm wavelength was used for in vivo imaging of microcirculation in human skin. The system has a spatial resolution of ∼10 µm × 20 µm (axial × lateral), running at 280 fps to acquire 3D imaging dataset to represent morphology and capillary level microvascular blood perfusion within the scanned skin tissue volume. The sensitivity of the system to the blood flow is as low as ∼4 µm/second. With this system, we performed the imaging experiments on the skin of a volunteer with stable plaque-type psoriasis. The microcirculation and structural information of normal and diseased skins were compared both qualitatively and quantitatively. The UHS-OMAG is capable of differentiating the microcirculation within the normal skins from that in the psoriatic skins. The 3D optical images show that the blood vessel elongation and the dense network in the psoriatic lesion skin, the appearance of which is not observed within the normal skin. Based on the results obtained from one subject, the statistical analyses show that higher blood vessel density presented within the psoriasis lesion skin than that of the normal skin. UHS-OMAG can be a valuable tool for imaging skin microcirculations non-invasively with high-speed and high-sensitivity, and therefore may have a useful role in future clinical diagnosis and treatment of dermatologic diseases such as psoriasis in human subjects.

Healing of a free tracheal autograft is enhanced by topical vascular endothelial growth factor in an experimental rabbit model

Objective: In 1996, we introduced the free tracheal autograft technique for repair of congenital tracheal stenosis from complete tracheal rings in infants and children. Sources of possible concern with this procedure include the potential for autograft ischemia, patch dehiscence, and recurrent stenosis. Vascular endothelial growth factor is a potent angiogenic inducer (particularly in the setting of ischemia, hypoxia, or both) and is postulated to promote tissue healing. The purpose of this study was to test the hypothesis that pretreatment of tracheal autografts with topical vascular endothelial growth factor would enhance tracheal healing. Methods: In a rabbit model of tracheal reconstruction (n = 32), an elliptically shaped portion of the anterior tracheal wall was excised. The excised portion of trachea was one third of the tracheal circumference and 2 cm in length (6 tracheal rings). This portion of trachea (the autograft) was soaked in either vascular endothelial growth factor (5 μg/mL, n = 16) or normal saline solution (n = 16) for 15 minutes before being reimplanted in the resultant tracheal opening. Animals were killed and autografts were examined at 2 weeks, 1 month, and 2 months postoperatively for gross and microscopic characteristics. Results: By 2 weeks, and progressing through 1 and 2 months, autografts treated with vascular endothelial growth factor, as compared with control autografts, had reduced luminal stenosis, submucosal fibrosis, and inflammatory infiltrate ( P < .05). The autografts tended to become malaligned in control animals, whereas the tracheal architecture was preserved in rabbits treated with vascular endothelial growth factor. Microvascular vessel density was significantly greater in all vascular endothelial growth factor groups ( P < .05) at all time intervals. Conclusions: Topical treatment of free tracheal autografts with vascular endothelial growth factor in a rabbit tracheal reconstruction model enhanced healing, as evidenced by accelerated autograft revascularization, reduced submucosal fibrosis and inflammation, and preservation of the normal tracheal architecture. Topical vascular endothelial growth factor may improve future results of tracheal reconstruction.