Changes In Vascular Density Research Articles

Inflammatory cells proliferate in the choroid and retina without choroidal thickness change in early Type 1 diabetes

Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal inflammatory changes in diabetes have been reported and in vivo choroidal thickness (CT) has been searched as a marker of retinopathy with contradictory results. We aimed to investigate the early stages in the retina and choroid in an animal model of Type 1 diabetes. Type 1 diabetes was induced in male Wistar rats via a single i.p. streptozotocin injection. At 8 weeks after disease onset, CT, choroidal vascular density, VEGF and VEGFR2 expression, microglial cell and pericyte distribution were evaluated. Diabetic rats showed no significant change in CT and choroidal vascular density. A widened pericyte-free gap between the retinal pigment epithelium and the choroid was observed in diabetic rats. The immunoreactivity of VEGFR2 was decreased in the retina of diabetic rats, despite no statistically significant difference in the immunoreactivity of VEGF. The density of microglial cells significantly increased in the choroid and retina of diabetic rats. Reactive microglial cells were found to be more abundant in the choroid of diabetic rats. Evidences of the interconnection between the superficial, intermediate, and deep plexuses of the retina were also observed. At early stages, Type 1 diabetes does not affect choroidal thickness and choroidal vascular density. Proliferation and reactivity of microglial cells occurs in the choroidal stroma and the retina. The expression of VEGFR2 decreases in the retina.

Effect of panretinal photocoagulation on macular vasculature using optical coherence tomography angiography.

To evaluate the changes of macular vascular density in the superficial capillary (SCP) and the deep capillary plexus (DCP), foveal avascular area (FAZ), choroidal flow, and macular thickness after pan-retinal photocoagulation (PRP). In this prospective interventional non-comparative case series, patients with very severe nonproliferative (NPDR) and early proliferative diabetic retinopathy (PDR) and no significant macular edema who were candidates for pan-retinal photocoagulation underwent measurement of corrected distance visual acuity (CDVA), optical coherence tomography (OCT), Optical coherence tomography angiography (OCTA) at the baseline, 1, and 6 months following completion of PRP treatment. Thirty-nine eyes from 21 patients with diabetes were enrolled. Superficial and deep capillary plexus densities in the foveal and parafoveal area didn't change significantly 1 and 6 months post-PRP (p > 0.1 in all of them). The FAZ area constricted 6 months following PRP (p = 0.075). Based on the calculated circularity index, the FAZ became significantly more circular after 6 months of follow-up (p = 0.047). Although the choroidal flow area increased after PRP this increase wasn't statically significant neither at 1 month nor at 6 months post-PRP (p = 0.31 and 0.23, respectively). Although OCTA parameters were not significantly affected by PRP at both short-term (1 month) and long-term (6 months) follow-ups, the FAZ area became significantly circular after PRP may be due to redistribution of blood flow in hypoperfused foveal capillary plexus.

Optical coherence tomography angiography in myopic peripapillary intrachoroidal cavitation complicated by choroidal neovascularization.

To detect the vessel density (VD) of the radial peripapillary capillary (RPC) in eyes affected by pathological myopia with or without a peripapillary intrachoroidal cavitation (PICC) and in eyes with PICC complicated by choroidal neovascularization (CNV), using optical coherence tomography angiography (OCTA). We prospectively enrolled highly myopic patients from January 2016 to December 2019 at the Eye Clinic of the University of Naples "Federico II." We divided included patients into three groups: group 1 including patients with PICC complicated by CNV; group 2 including patients with PICC without complications; group 3 including patients with high myopia without PICC and CNV. One-way analysis of variance (ANOVA) followed by Bonferroni post hoc analysis was used to evaluate differences in VD of radial peripapillary capillary (RPC) in papillary whole, peripapillary regions and its sectors among the three groups. We enrolled 12 highly myopic eyes with PICC complicated by CNV, 21 highly myopic eyes with PICC without CNV and 23 highly myopic eyes without PICC. The myopic eyes with PICC revealed a statistically significant reduction in VD of the RPC comparing to the other groups (p < 0.001), especially in eyes affected by myopic PICC complicated by CNV (p < 0.001). These results were similar analyzing the VD in different sectors of the peripapillary region among the three groups (p < 0.001). OCTA detects the changes in peripapillary vascular density of highly myopic eyes. We demonstrated that the RPC vasculature is significantly influenced by the presence of PICC, especially in myopic eyes developing a CNV.

Association of Intravitreal Aflibercept With Optical Coherence Tomography Angiography Vessel Density in Patients With Proliferative Diabetic Retinopathy

Although previous studies have evaluated the association between anti-vascular endothelial growth factor therapy and macular vessel density, they were confounded by the presence of macular edema, which may be associated with artifacts and segmentation errors in optical coherence tomography angiography (OCTA). To evaluate the association of intravitreal aflibercept with changes in macular vascular density using OCTA in patients with proliferative diabetic retinopathy without diabetic macular edema. This post hoc analysis of a randomized clinical trial used data on 40 eyes of 40 patients with proliferative diabetic retinopathy without diabetic macular edema who were enrolled in the Intravitreal Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy (RECOVERY) clinical trial from August 1, 2016, to June 31, 2017. Three patients were lost to follow-up at month 12, and 5 patients were excluded from analysis because of poor OCTA image quality, leaving 16 patients in each cohort in the final analysis. Data analysis was performed from March 1, 2018, to January 15, 2019. In the RECOVERY trial, patients were randomized into cohorts receiving 2 mg of aflibercept injections monthly (n = 20) or quarterly (n = 20) and treated for 12 months. The percentage of vascular density (in total scan and foveal and parafoveal regions) was compared before and after 12 months of therapy. The sample for this OCTA analysis included 32 eyes from 32 patients (mean [SD] age, 48.37 [12.30] years; 17 [53.1%] male). The mean (SD) total scan vascular density for the superficial vascular complex was 42.28% (4.03%; 95% CI, 40.63%-43.93%) at baseline and 39.64% (4.01%; 95% CI, 37.91%-41.37%) at month 12 (P = .69). For the deep vascular complex, the mean (SD) vascular density was 48.42% (4.99%; 95% CI, 46.36%-50.47%) at baseline and 45.69% (4.63%; 95% CI, 43.69%-47.70%) at month 12 (P = .40). For the choriocapillaris, the mean (SD) vascular density was 64.42% (3.36%; 95% CI, 63.04%-65.81%) at baseline and 62.55% (4.79%; 95% CI, 60.48%-64.62%) at month 12 (P = .16). There was no difference in vascular density parameters between monthly and quarterly injection arms at month 12. In this study, macular vascular density did not change after 12 months of intravitreal aflibercept therapy. Because nonperfusion is expected to progress in diabetic retinopathy, this finding may represent a beneficial association between anti-vascular endothelial growth factor therapy and macular vascular density. ClinicalTrials.gov Identifier: NCT02863354.

Quantitative analysis of retinal microvascular changes in macular telangiectasia type 2 using optical coherence tomography angiography.

PurposeTo evaluate retinal vascular changes on optical coherence tomography angiography (OCTA) in patients with macular telangiectasia type 2 (MacTel 2) and to assess their correlation with visual acuity.MethodsTwenty-six patients (52 eyes) with MacTel 2 and 20 age-matched controls (40 eyes) were included. Fundus examinations, including fundus autofluorescence, swept-source optical coherence tomography, and OCTA, were performed. Differences in the vascular density in the fovea and parafovea, the area of the foveal avascular zone, and the diameter of the ellipsoid zone defect of the two groups were analyzed.ResultsThe foveal vascular density of the superficial capillary plexus was significantly lower in the MacTel 2 group than in the control group (p = 0.027). The vascular density in the entire deep capillary plexus was also significantly less in the MacTel 2 group than in the control group (all p < 0.05). The mean diameter of ellipsoid-zone disruption on OCT in the MacTel 2 group was 634.6 ± 104.3 𝜇m. The foveal avascular zone areas of the superficial and deep capillary plexuses were significantly enlarged in the MacTel 2 group compared to those in the control group (0.45 ± 0.12 mm2 vs. 0.27 ± 0.08 mm2, p < 0.001; 0.56 ± 0.15 mm2 vs. 0.40 ± 0.14 mm2, p = 0.001). In addition, the enlarged foveal avascular zone of the superficial and deep plexus was negatively correlated with best corrected visual acuity (logMAR) in MacTel 2 patients (p = 0.013, r = -0.642 and p = 0.042, and r = -0.511, respectively).ConclusionsRetinal vascular density changes occur in the superficial fovea and in the entire deep capillary plexus of patients with MacTel 2. The enlarged foveal avascular zone areas of the superficial and deep plexuses were prominent in the MacTel 2 group, and this enlargement correlates with worsened visual acuity.

Evaluation of Changes in Macular Perfusion Detected by Optical Coherence Tomography Angiography following 3 Intravitreal Monthly Bevacizumab Injections for Diabetic Macular Edema in the IMPACT Study

Objective To evaluate macular perfusion changes following intravitreal bevacizumab injections for diabetic macular edema (DME) using spectral domain optical coherence tomography angiography (SD-OCTA). Methods This study was a prospective noncomparative interventional case series. Treatment naïve patients with DME underwent full ophthalmological examination and SD-OCTA scanning at baseline and after 3 intravitreal bevacizumab injections. Both the 6 × 6 and 3 × 3 mm macular scan protocols were used. Pretreatment and posttreatment OCTA images were automatically aligned using a commercially available retina alignment software (i2k Align Retina software); then the fractal dimension (FD), vascular density (VD), and skeleton VD changes were obtained at the full retinal thickness (Full) and superficial (SCP) and deep (DCP) capillary plexuses after processing images using a semiautomated program. The foveal avascular zone (FAZ) was manually measured and FD was calculated using the FracLac plugin of ImageJ. Results Forty eyes of 26 patients were included. Following injections, there were an 8.1% increase in FAZ, 1.3% decrease in FD-Full and FD-SCP, 1.9% decrease in FD-DCP, 8% decrease in VD-Full, 9.1% decrease in VD-SCP, 10.6% decrease in VD-DCP, 13.3% decrease in skeleton VD-Full, 12.5% decrease in skeleton VD-SCP, and 16.3% decrease in skeleton VD-DCP in the 6 × 6 mm macular area and a 2.6% decrease in FD-Full, 3.4% decrease in FD-SCP, 11.5% decrease in VD-Full, 14.3% decrease in VD-SCP, and 25.1% decrease in skeleton VD-SCP in the 3 × 3 mm macular area which were all statistically significant (p < 0.05). Using univariate and multivariate analysis, the pretreatment FD, VD, and skeleton VD at each capillary layer significantly negatively correlated with the change in FD, VD, and skeleton VD at the corresponding capillary layer, respectively (p < 0.05). Conclusion OCTA is a useful noninvasive tool for quantitative evaluation of macular perfusion changes following DME treatment. This trial is registered with NCT03246152.

REDUCED VASCULAR DENSITY IN THE CHOROID AFTER TREATMENT WITH PHOTODYNAMIC THERAPY COMBINED WITH AFLIBERCEPT IN PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

To investigate changes of vascular density in the choroid of patients with polypoidal choroidal vasculopathy treated with photodynamic therapy (PDT) combined with intravitreal aflibercept. This study examined 12 eyes of 12 patients, who were diagnosed as polypoidal choroidal vasculopathy. All patents underwent optical coherence tomography before and at 3 months after PDT combined with intravitreal aflibercept treatment. Using en face optical coherence tomography images, we analyzed vascular density of the area outside the polypoidal choroidal vasculopathy lesion and within the PDT exposure area at the level of the choriocapillaris and middle layer of the choroid. In the outer layer of the choroid, the thickest vessel was selected in the area exposed to PDT, with the diameter of the vessel analyzed. The vascular density in the choriocapillaris and middle layer of the choroid significantly decreased from 0.54 ± 0.09 before treatment to 0.44 ± 0.07 after PDT treatment in the choriocapillaris and from 0.53 ± 0.10 to 0.47 ± 0.08 in the middle layer of the choroid, respectively. There was also a significant reduction in the diameter of the largest vessel from 309 ± 85 µm at baseline to 220 ± 52 µm. Photodynamic therapy may cause occlusion of the choriocapillaris and middle vessels in the choroid, as well as stenosis of the large vessels.

Современные инструменты и методики эпигенетической защиты здорового старения и долголетия Homo sapiens

The human brain is the main tool and the most valuable resource on our planet. New epigenetics Homo sapiens and H. sapiens brain manage the interaction of genetic and epigenetic programs of aging and healthy longevity. Epigenetic clocks are mathematical models and artificial intelligence that predict the biological age of a person using DNA methylation data and are the most accurate biomarkers of the aging process. Genetic and epigenetic factors that limit a person’s life expectancy are relevant in biogerontological, biophysical and neurophysiological studies, especially from the point of view of the medical economy. Cerebrovascular aging can be considered from several points of view, including changes in vascular density (number of capillaries and arterioles), vascular plasticity (dynamic regulation of vascular density or structure) and vascular reactivity (adaptation of vessels to acute metabolic changes in tissues). The main control mechanisms in the cerebral circulation are unique in comparison with other vascular channels and include, but are not limited to such features as the blood-brain barrier, perivascular innervation, intracellular communication between neurons, perivascular glial cells and smooth muscle cells, high tissue metabolism, lack of anoxic tolerance and the presence of collateral arteries. Multidisciplinary and multimodal interaction in the triad brain-eyes-vessels makes it possible to identify early biomarkers of both general accelerated and pathological aging, and to diagnose neurodegeneration in a timely manner, and to carry out effective neurorehabilitation of cognitive impairment. Biochipping, neural and brain chips, the next (new) generation sequencing technology will allow the study of the expression of thousands of genes that will be used as biomarkers. Combined and hybrid methods of neuroimaging in collaboration with artificial intelligence technologies are modern tools for the diagnosis and prevention of cognitive impairment and healthy aging of the H. sapiens brain.

Retinal Vascular Changes in Patients with Chronic Obstructive Pulmonary Disease: An Optical Coherence Tomography Angiography Study.

Objectives:In the current study, we aimed to investigate retinal vascular density and blood flow changes in patients with chronic obstructive pulmonary disease (COPD) using optical coherence tomography angiography (OCTA) (AngioVue Avanti, Optovue).Methods:Thirty eyes of 30 patients with COPD and 30 eyes of 30 healthy controls were evaluated with OCTA. Foveal and parafoveal vessel density, inner retinal and choriocapillary flow area, and foveal avascular zone (FAZ) area were measured and compared between the groups.Results:No statistically significant differences were observed in the outer retinal flow area and choriocapillary flow area measurements between the groups (p=0.609 and p=0.162, respectively). There was no statistically significant difference in FAZ and FAZ perimeter values between the groups (p=0.725 and p=0.820, respectively). Vascular density measurements in the superficial foveal and parafoveal areas were not statistically significantly different between the groups (p>0.05, for all). Deep parafoveal vascular density values of the COPD group were statistically significantly lower than the control group in all investigated areas except the superior and inferior quadrants.Conclusion:The results of our study demonstrated for the first time that vascular density decreased in the parafoveal area due to COPD-related hypoxemia and endothelial dysfunction.

Changes in vascular calcification and bone mineral density in calcium supplement users from the Canadian Multi-center Osteoporosis Study (CaMOS)

Background and aimsCalcium supplements have been associated with increased cardiovascular events. This study investigates the relationship between calcium supplement use and the 5 year progression of abdominal aorta calcification (AAC) in participants from one center of the Canadian Multi-Centre Osteoporosis Study (CaMOS). MethodsParticipants (n = 296; 217 women and 79 men) had lateral spine X-rays and DEXA bone mineral density (BMD) scans (femoral neck, lumbar spine and total hip) taken at two time points within a 5 year interval. AAC was assessed using the Framingham Method. Calcium supplement use was assessed by a facilitated health history questionnaire and medication inventory. ResultsAAC significantly increased over 5 years, AAC progression was significantly greater in calcium supplement users, as compared to non-users, overall and in females. The amount of calcium was positively correlated to AAC progression. A multi-variable linear regression model was generated for women only, as there were not enough men for multivariable modelling. Calcium supplement use and amount remained significantly associated with AAC progression after adjustment for age, hypertension, diabetes and smoking history. Change in AAC score was not associated with change in BMD T-Score. In univariate analyses of males, calcium supplement use was associated with a significantly greater BMD loss at the lumbar spine, hip, and femoral neck. ConclusionsOlder female calcium supplement users had significantly higher AAC progression over 5 years, but did not have any significant BMD preservation. These results suggest that vascular calcification may contribute to the cardiovascular events observed in calcium supplement users.

Changes in vascular density in resected tissue of 97 patients with mild malformation of cortical development, focal cortical dysplasia or TSC-related cortical tubers

Recent studies suggested a possible association between malformations of cortical development and microvascular density. In this study we aimed to further elucidate the relation between microvascular density and cortical developmental abnormalities in a cohort of 97 patients with epilepsy and histologically proven mild malformation of cortical development (mMCD), focal cortical dysplasia (FCD) or tuberous sclerosis complex (TSC). Surgical tissue samples were analyzed with quantitative measures of vessel density, T-cell response, microglial activation and myelin content. Subsequently, the results were compared to an age- and localization matched control group. We observed an increase in microvasculature in white matter of TSC cortical tubers, which is linked to inflammatory response. No increase was seen in mMCD or FCD subtypes compared to controls. In mMCD/FCD and tubers, lesional cortex and white matter showed increased vascular density compared to perilesional tissues. Moreover, cortical vessel density increased with longer epilepsy duration and older age at surgery while in controls it decreased with age. Our findings suggest for that the increase in white matter vascular density might be pathology-specific rather than a consequence of ongoing epileptic activity. Increased cortical vessel density with age and with longer epilepsy duration in mMCD/FCD’s and tubers, however, could be a consequence of seizures.

Association between choroidal vascular density, age and sex: A prospective study.

To evaluate choroidal vascular density changes in regards to age and sex. This was a prospective, cross-sectional study. We studied 78 volunteers. All participants underwent a complete ophthalmologic examination and assessment of the choroidal vascular density (CVD) using swept-source optical coherence tomography (SS-OCT). CVD obtained by automated software of the SS-OCT. We evaluated the CVD correlation with age and compared female to male. The study included 78 right eyes of 78 individuals: 40 females and 38 males. The participants' age and the CVD were significantly correlated (r= -0.39, p < 0.001). The mean CVD of the females and males were 0.26 ± 0.08 and 0.23 ± 0.05, respectively (p = 0.03). CVD was found to be associated with age and sex.

Responses of Types 1 and 2 Neovascularization in Age-Related Macular Degeneration to Anti-Vascular Endothelial Growth Factor Treatment: Optical Coherence Tomography Angiography Analysis

ABSTRACTPurpose: To compare the responses of types 1 (sub-pigment epithelial) and 2 (subretinal) neovascularization in neovascular age-related macular degeneration (AMD) to anti-vascular endothelial growth factor (VEGF) treatment.Methods: Fifty-five treatment-naïve neovascular AMD eyes (53 patients) were retrospectively included for analysis. All patients were treated with three loading injections of anti-VEGF agent, followed by further injections as required. The lesion size and vascular density of type 1 and 2 lesions before and after treatment for 12 months were analyzed using optical coherence tomography angiography (OCTA).Results: The mean lesion size of the type 1 neovascularization group (42 eyes) showed no significant change from 2.12 ± 1.01 mm2 at baseline to 2.08 ± 0.91 mm2 at 12 months (P = .682). However, the mean lesion size of type 2 neovascularization significantly decreased from 1.23 ± 0.93 mm2 at baseline to 0.79 ± 0.61 mm2 at 12 months (P = .022). The proportion of eyes with lesion sizes that decreased by more than 40% from baseline was also significantly higher for the type 2 compared to the type 1 neovascularization group (46.2% versus 11.9%, P = .007). Vascular density showed no significant changes for both groups after treatment and showed no association with the change in lesion size. There was no significant difference between the groups in terms of visual acuity improvement.Conclusion: OCTA analysis revealed different responses to anti-VEGF treatment depending on the location of neovascularization in neovascular AMD. Type 2 neovascularization was significantly regressed compared to type 1 neovascularization after anti-VEGF treatment. However, the changes in vascular density and visual outcome showed no significant differences between groups after 12 months of treatment.

Ultrastructural and histological changes in tibial remnant of ruptured anterior cruciate ligament stumps: a transmission electron microscopy and immunochemistry-based observational study.

Anterior cruciate ligament (ACL) rupture is a common injury and has a non-union rate of 40-100%. Important cellular events, such as fibroblast proliferation, angiogenesis and change in collagen fibril thickness in the ACL remnant, as described in other dense connective tissue, might have an implication in graft recovery following ACL reconstruction. Thus we conducted a study with an aim to characterize the ultrastructural and histological features of ruptured ACL tibial stump and correlate the same with the duration of injury. This was a prospective observational study in which 60 ruptured human ACLs were evaluated for collagen fibril thickness, blood vessel density (per mm2) and fibroblast density (per mm2) with the help of transmission electron microscopy, immunohistochemistry via CD34 antibody staining and light microscopy (H&E staining). The findings were correlated with duration of injury. Fifty-four male and six female patients with a mean duration of the injury of 23.01weeks (SD = 26.09; range 2-108weeks) were included for the study and were divided on the basis of duration of injury as follows: Group I (≤6weeks; N = 16), Group II (7-12weeks; N = 18), Group III (13-20weeks; N = 7), Group IV (21-50weeks; N = 12), Group V (> 50weeks; N = 7). A significant correlation was seen with blood vessel density (r = 0.303, p = 0.01) and fibroblast density (r = - 0.503, p = 0.001). Thickness of collagen fibril did not correlate with the duration of injury (r = 0.15, p = 0.23). The thickness of the collagen reached its peak after 50weeks following injury, whereas highest density of blood vessel and fibroblast was seen at 12-20weeks. Matched pair analysis revealed a significant decrease in collagen fibril thickness and an increase in fibroblast density at 7-12weeks. Following injury to ACL, the ruptured tibial stump undergoes a series of changes at the cellular level vis-à-vis changes in collagen fibril thickness, vascular density and fibroblast density that possibly suggest an intrinsic healing response. This further may have implications on the functional outcome following ACL reconstruction with remnant preservation. III.

Correlating Changes in the Macular Microvasculature and Capillary Network to Peripheral Vascular Pathologic Features in Familial Exudative Vitreoretinopathy

To evaluate the macular microvasculature in patients with familial exudative vitreoretinopathy (FEVR) using OCT angiography (OCTA) and to assess for peripheral vascular changes using widefield fluorescein angiography (WFA). Multicenter, retrospective, comparative, observational case series. We identified 411 patients with FEVR, examined between September 2014 and June 2018. Fifty-seven patients with FEVR and 60 healthy controls had OCTA images of sufficient quality for analysis. Custom software was used to assess for layer-specific, quantitative changes in vascular density and morphologic features on OCTA by way of vessel density (VD), skeletal density (SD), fractal dimension (FD), vessel diameter index (VDI), and foveal avascular zone (FAZ). Widefield fluorescein angiography images were reviewed for peripheral vascular changes including capillary dropout, late-phase angiographic posterior and peripheral vascular leakage (LAPPEL), vascular dragging, venous-venous shunts, and arteriovenous shunts. Macular microvascular parameters on OCTA and peripheral angiographic findings on WFA. OCT angiography analysis of 117 patients (187 eyes; 92 FEVR patients and 95 control participants) demonstrated significantly reduced VD, SD, and FD and greater VDI in patients with FEVR compared with controls in the nonsegmented retina, superficial retinal layer (SRL), and deep retinal layer (DRL). The FAZ was larger compared with that in control eyes in the DRL (P < 0.0001), but not the SRL (P= 0.52). Subanalysis by FEVR stage showed the same microvascular changes compared with controls for all parameters. Widefield fluorescein angiography analysis of 95 eyes (53 patients) with FEVR demonstrated capillary nonperfusion in all eyes: 47 eyes (49.5%) showed LAPPEL, 32 eyes (33.7%) showed vascular dragging, 30 eyes (31.6%) had venous-venous shunts, and 33 eyes (34.7%) had arteriovenous shunts. Decreasing macular VD on OCTA correlated with increasing peripheral capillary nonperfusion on WFA. Decreasing fractal dimension on OCTA correlated with increasing LAPPEL severity on WFA. Patients with FEVR demonstrated abnormalities in the macular microvasculature and capillary network, in addition to the peripheral retina. The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA.

Histologic assessment of ligament vascularity and synovitis in dogs with cranial cruciate ligament disease.

To assess the relationship between histologic degeneration of cranial cruciate ligaments (CCLs) and severity of synovitis and ligament vascularity. CCL and synovium from 59 stifle joints (53 dogs). CCL and synovium specimens were obtained from stifle joints of juvenile (15 joints; 12 dogs) and adult (25 joints; 22 dogs) dogs with intact CCLs and dogs with CCL rupture (rCCL; 19 joints; 19 dogs). Vascular density and degenerative changes of the CCL core region and severity of synovitis were semiquantitatively evaluated. Relationships were analyzed by use of a random effects model to account for correlated specimens. Mean ± SD modified Bonar scores (scale, 0 to 9) of adults (4.85 ± 0.44) and dogs with rCCL (5.69 ± 0.49) were significantly higher than scores of juveniles (1.13 ± 0.55). Vascularity scores (scale, 0 to 3) were significantly higher for juveniles (3.00 ± 0.24) than for adults (1.53 ± 0.27) and dogs with rCCL (0.78 ± 0.23). Synovitis scores were not significantly different among groups. There was a significant negative relationship between modified Bonar scores and vascularity scores for juveniles and adults and for adults and dogs with rCCL when controlling for age, but there was not a significant relationship between modified Bonar scores and synovitis scores. There was a significant relationship between modified Bonar scores and body weight of adults. Poor blood supply to the core region could be an important underlying condition for spontaneous degeneration of the CCL in at-risk dogs.

Retinal vascular density evaluated by optical coherence tomography angiography in macular telangiectasia type 2.

To evaluate the retinal and choroidal vascular changes through optical coherence tomography angiography (OCTA) in patients with macular telangiectasia type 2 (MacTel 2). Our study included 20 patients (40 eyes) with MacTel 2, and age-matched and sex-matched 18 subjects (36 eyes) in the control group. Fundus color photographs, fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography and OCTA were performed. Foveal vascular density and parafoveal vascular density (PFVD), and foveal retinal thickness and parafoveal retinal thickness, choroidal thickness (CT) and retinal ganglion cell-inner plexiform layer (GCIPL) were compared between MacTel 2 patients and normal age-matched controls. The retinal whole vascular density and PFVD of the deep plexus were significantly lower in patients with MacTel 2 than that of the control group (56.93% vs. 58.54%, p = 0.003; and 60.38% vs. 61.66%, p = 0.045). The foveal avascular zone (FAZ) of the deep plexus was significantly enlarged in patients with MacTel 2 than that of the control group (0.44 vs. 0.36, p = 0.009). There was a positive and statistically significant correlation between the FAZ of the superficial and deep plexus and CT in patients with MacTel 2. There was a positive and statistically significant correlation between retinal whole, parafoveal temporal quadrant vascular density of the superficial and deep plexus and GCIPL thickness in patients with MacTel 2. Our study demonstrated that important retinal vascular density and FAZ changes in MacTel 2 occur in the deep capillary plexus of the retina.

Optical Coherence Tomography Angiography Study for Evaluation of Microvascular Changes in the Subclinical Diabetic Retinopathy

Background: diabetic retinopathy is the specific microvascular complication of diabetes mellitus and affects 1 of 3 with DM. DR remains a leading cause of vision loss in working adult population. Patients with severe levels of DR were reported to have poor quality of life and reduced physical, emotional and social well-being, and they utilize more health care resources. Objective: this study aimed to evaluate the vascular density, perfusion density and foveal avascular parameters changes in subjects with diabetes mellitus showing no manifestations of diabetic retinopathy using optical coherence tomography angiography. Methods: 40 subjects were categorized into two groups, group A for healthy subjects and group B for the diabetic subjects. HbA1c, renal functions, liver functions and lipid profile were obtained from each individual. Best corrected visual acuity were obtained from each individual and each were subjected to full ophthalmic examination, IOP measurement, fundus fluorescein angiography FFA, Optical Coherence Tomography OCT and Optical Coherence Tomography Angiography OCTA. Results: statisticallysignificantdifferenceswerefoundbetweenthehealthygroupand the diabeticgroupin OCTA parameters. Full vascular density VD significantly decreases in the diabetic patients even in those showed BCVA ≥ 0.7 and totally intact FFA and OCT (P>0.001). Perfusion density PD also was significantly decreased in the diabetic patients (P>0.001). Foveal avascular zone showed significant changes in area value and perimeter, however the circularity changes were statisticallyinsignificant.Conclusion: using OCTA was proven to be clinically significant in differentiating healthy eyes from diabetic eyes that showed no clinically acceptable hallmarks. So, that the term “Subclinical diabetic retinopathy” was suggestible to refer to a clinical state where the FAZ metrics, vascular density and perfusion density showed a particular deviation from the normal healthy parameters.

Inter-relationship between retinal and choroidal vasculatures using optical coherence tomography angiography in normal eyes.

To quantify vascular and structural macular variables in healthy eyes and to investigate correlations between these variables and age using optical coherence tomography angiography. A total of 261 eyes of 261 subjects with normal fundus were included. Central macular thickness, ganglion cell layer to inner plexiform layer thickness, outer retina layer thickness, subfoveal choroidal thickness, and choroidal vascularity index were measured using optical coherence tomography. Foveal avascular zone area, vascular density, and flow void area were measured using optical coherence tomography angiography. Vascular density in the superficial capillary plexus was correlated with central macular thickness, ganglion cell layer to inner plexiform layer thickness, and outer retina layer thickness (P < 0.001, P = 0.004, and P < 0.001, respectively). Vascular density in the deep capillary plexus was correlated with central macular thickness and outer retina layer thickness (P = 0.003 and P = 0.001, respectively). Vascular density of choriocapillaris was correlated with vascular density of superficial capillary plexus and deep capillary plexus (P < 0.001 and P = 0.001, respectively). Vascular density of choriocapillaris varies with retinal vascular density rather than the structure of choroid using optical coherence tomography angiography. In contrast, retinal vascular density changes as the retinal structure. Our results provide more information about the relationship between retina and choroid.

Microvascular networks in the area of the auditory peripheral nervous system

Using transgenic fluorescent reporter mice in combination with an established tissue clearing method, we detail heretofore optically opaque regions of the spiral lamina and spiral limbus where the auditory peripheral nervous system is located and provide insight into changes in cochlear vascular density with ageing. We found a relatively dense and branched vascular network in young adults, but a less dense and thinned network in aged adults. Significant reduction in vascular density starts early at the age of 180 days in the region of the spiral limbus (SL) and continues into old age at 540 days. Loss of vascular volume in the region of spiral ganglion neurons (SGN) is delayed until the age of 540 days. In addition, we observed that two vascular accessory cells are closely associated with the microvascular system: perivascular resident macrophages and pericytes. Morphologically, perivascular resident macrophages undergo drastic changes from postnatal P7 to young adult (P30). In postnatal animals, most perivascular resident macrophages exhibit a spherical or nodular shape. In young adult mice, the majority of perivascular resident macrophages are elongated and display an orientation parallel to the vessels. In our imaging, some of the perivascular resident macrophages are caught in the act of transmigrating from the blood circulation. Pericytes also display morphological heterogeneity. In the P7 mice, pericytes are prominent on the capillary walls, relatively large and punctate, and less uniform. In contrast, pericytes in the P30 mice are relatively flat and uniform, and less densely distributed on the vascular network. With triple fluorescence labeling, we did not find obvious physical connection between the two systems, unlike neuronal-vascular coupling found in brain. However, using a fluorescent (FITC-conjugated dextran) tracer and the enzymatic tracer horseradish peroxidase (HRP), we observed robust neurovascular exchange, likely through transcytotic transport, evidenced by multiple vesicles present in the endothelial cells. Taken together, our data demonstrate the effectiveness of tissue-clearing methods as an aid in imaging the vascular architecture of the SL and SGNs in whole mounted mouse cochlear preparations. Structure is indicative of function. The finding of differences in vascular structure in postnatal and young adult mice may correspond with variation in hearing refinement after birth and indicate the status of functional activity. The decrease in capillary network density in the older animals may reflect the decreased energy demand from peripheral neural activity. The finding of active transcytotic transport from blood to neurons opens a potential therapeutic avenue for delivery of various growth factors and gene vectors into the inner ear to target SGNs.