Lower Vessel Density Research Articles

The protective role of gamma zone peripapillary atrophy in diabetic retinopathy: insights from deep learning and SS-OCT angiography.

To explore the relationship between peripapillary atrophy (PPA) and diabetic retinopathy (DR), and to uncover potential mechanisms using swept-source optical coherence tomography (SS-OCT) angiography. This cross-sectional study included 845 patients with type 2 diabetes (T2DM), who underwent detailed systemic and ophthalmic evaluations. A state-of-the-art deep learning method was employed to precisely identify the parapapillary beta and gamma zones. Based on PPA characteristics, eyes were categorized into four groups: without beta or gamma zone (Group A), isolated beta zone (Group B), isolated gamma zone (Group C), and with both beta and gamma zone (Group D). Digital fundus photography was utilized to diagnose and stage DR severity, while SS-OCT angiography quantified retinal and choroidal vasculature. Participants had a mean age of 66 ± 8.8years, with 437 (51.7%) male. Beta and gamma PPA zones were observed in 574 (67.9%) and 256 (30.3%) eyes, respectively. Beta zone PPA was associated with older age, whereas gamma zone PPA was correlated with longer axial length (AL), lower vessel density, and reduced choroidal thickness. Adjusted analyses revealed that eyes with isolated (Group C) or concurrent (Group D) gamma zone PPA conferred significantly lower DR grade, independent of known risk factors including systemic diabetes risk factors and AL. This study finds that gamma zone PPA is linked to a reduced risk of developing DR. These results imply that the gamma zone may reflect progressive myopia-associated thinning and microvascular depletion in posterior ocular tissues, potentially contributing to structural resilience against DR. This novel insight offers a promising avenue for understanding the interplay between PPA and DR.

Beyond the Surface: Investigating Silicone Oil's Impact on Macular Perfusion in Macula-off Rhegmatogenous Retinal Detachment via OCTA.

This study aims to compare macular vessel density (VD) in eyes with macula-off rhegmatogenous retinal detachment (RRD) after vitrectomy with gas or silicone oil (SO) tamponade. Patients with macula-off RRD who underwent vitrectomy with either gas or SO tamponade were included. Best-corrected visual acuity (BCVA) and VD in superficial and deep retinal capillary plexuses (SCP and DCP), choriocapillaris (CCP), and foveal avascular zone (FAZ) were assessed using optical coherence tomography angiography (OCTA). Comparisons were made with the unaffected fellow eye. Fifty patients (average age: 57.9±9.1 years) participated, with 26 eyes undergoing SO tamponade and 24 gas tamponade. No significant differences were found in baseline characteristics. Postoperative BCVA significantly improved in both groups. In the SO group, BCVA improved from 2.00±0.77 logMAR (20/2000 Snellen) to 0.95±0.52 logMAR (20/178 Snellen). In the gas tamponade group, BCVA improved from 2.12±0.70 logMAR (20/2636 Snellen) to 0.70±0.55 logMAR (20/100 Snellen) (p<0.001 for both groups). Moreover, the gas tamponade group achieved significantly better postoperative BCVA compared to the silicone oil group (p<0.05). SO tamponade group exhibited significantly lower VD in SCP, DCP, and CCP quadrants (p<0.05), while gas tamponade showed no significant differences. This study reveals a decrease in VD in SCP, DCP, and CCP induced by SO tamponade, suggesting potential toxic effects on macular perfusion. Gas tamponade resulted in superior BCVA outcomes and preserved VD. Further investigation into SO's underlying mechanisms and careful patient selection is warranted. Gas tamponade may offer better outcomes for macula-off RRD.

Kefir peptides mitigate L-NAME-induced preeclampsia in rats through modulating hypertension and endothelial dysfunction

AimPreeclampsia is a complex and serious pregnancy disorder that leads to maternal and neonatal mortality worldwide. Kefir peptides (KPs), derived from various prebiotic fermentations in whole milk by kefir grains, were investigated for their potential therapeutic effects. In this study, we used the L-NAME in drinking water to induce a preeclampsia-like condition in spontaneous hypertension stroke-prone (SHRSP) pregnant rats. Main methodsThe rats were assigned to five groups: the normal group (WKY rats), the untreated group (SHRSP rat control pregnant), the L-NAME/Mock group (SHRSP rats fed with L-NAME water), the L-NAME/KPs-LD group (SHRSP rats fed with L-NAME water and low-dose KPs diets), and the L-NAME/KPs-HD group (SHRSP rats fed with L-NAME water and high-dose KPs diets) for a 20-day experiment. Chorioallantois membrane (CAM) assay was applied for ex vivo angiogenesis study of KPs treatment. Key findingsData showed that rats in the L-NAME group developed severe hypertension, proteinuria, placental damage, and embryo resorption. Pre-administration of KPs significantly reduced hypertension, proteinuria, improved generalized endothelial dysfunction, and decreased levels of anti-HIF-1α, sFLT1, anti-TNF-α, and IL-6 in the placenta of SHRSP rats. In ex vivo CAM study, L-NAME administration in chicken embryos resulted in lower vessel density and hemorrhage; however, angiogenesis was observed after KPs-HD treatment. SignificanceThe results indicate that kefir peptides improve renal lesions, prevent renal parenchyma damage, and balance endothelial and angiogenic dysfunction in both maternal and fetal sites in L-NAME-induced SHRSP pregnant rats.

Ultrasound Microvessel Imaging of the Human Placenta Demonstrates Altered Vessel Densities in Fetal Growth Restriction With Vascular and Immune Pathologies: A Pilot Case-Control Study.

Fetal growth restriction (FGR) is commonly associated with placental dysfunction, increasing perinatal morbidity and mortality. Visualizing placental vessels in utero would be advantageous for identifying functional FGR cause and determining proper management strategies. We aimed to utilize high-sensitivity ultrasound microvessel imaging (HUMI) for quantifying placental vessel density (VD) in pregnancies diagnosed with FGR. This pilot case-control study enrolled subjects in the third trimester with a diagnosis of FGR (n = 40) and gestational age-matched controls with normal fetal growth (n = 20) at a 2:1 ratio, respectively. The Verasonics Vantage ultrasound system was used to perform HUMI on each participant at one timepoint. Scanning involved randomized singular value decomposition-based clutter filtering to identify the villous tree, followed by step-by-step scanning to acquire 3-dimensional-like data. Mean VD was calculated from three ultrasound measurements per subject. Additional clinical and pathology data were also collected and compared. Sixteen participants were utilized to establish the scanning protocol and 2 met exclusion criteria at delivery. Thus, VD was successfully measured on 42 pregnancies scanned at 35 weeks 5 days on average. In FGR (n = 24), placental VD was significantly reduced compared to controls (P < .01). VD measures were as good at predicting FGR as systolic/diastolic (S/D) ratios (area under the curve 0.86 versus 0.80). In a smaller cohort, VD in placentas with a diagnosis of inflammatory villitis (n = 10) by histology showed an increase in VD compared to those without inflammation (P = .01). Low VD was correlated with increased S/D ratios (P = .03). HUMI is useful for identifying altered placental vascularization in utero for FGR. VD may be a valuable indicator for placental health and could lead to improved risk stratification methods considering underlying biology.

CORRIGENDUM: Optical coherence tomography angiography features in Waldenström macroglobulinemia patients without Hyperviscosity syndrome: A pilot prospective study

PurposeTo evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients. DesignProspective study. MethodsA total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. .Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA. ResultsThe two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17 % vs. 52.99 ± 2.52%; p < 0.001), as well as in the parafovea (53.01 ± 6.69 % vs. 55.30 ± 2.61%; p = 0.002), and fovea (21.38 ± 9.01 % vs. 30.31 ± 5.84 %; p < 0.001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07 % vs. 50.83 ± 5.46%; p = 0.005), as well as in the parafovea (56.76 ± 6.26 % vs. 52.59 ± 5.46%; p = 0.001), and fovea (38.75 ± 8.59 % vs. 33.43 ± 8.68 %; p < 0.001). ConclusionThe finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.

Retinal and optic nerve microvasculature assessment in nephritic and nonnephritic systemic lupus erythematosus: a comparative analysis

Background Lupus nephritis is considered one of the most common complications of systemic lupus erythematosus (SLE) that greatly affects the overall prognosis. Retinopathy, as one of the disease complications, is an indicator of disease severity, frequent renal impairment, and poor prognosis. Therefore, screening of subclinical retinopathy is of great importance as retinopathy and nephropathy are somehow associated in SLE patients. Aim The aim of this study was to assess the changes in retinal and optic nerve microcirculation in nephritic and nonnephritic SLE patients without clinical evidence of retinopathy or optic neuropathy. Patients and methods This is a prospective observational study that included 66 SLE patients. They were divided into two groups: group A that included 34 patients with nephritis and group B that included 32 patients without nephritis. In addition, 33 healthy participants (group C) were included as a control group. The participants were assessed with optical coherence tomography angiography of the macula and optic nerve. Assessment of vessel densities (VD), foveal avascular zone, retinal nerve fiber layer thickness, and optic nerve head and peripapillary VD were done. Results Group B patients were found to have significantly lower VDs in whole superficial VD (P=0.014) and all sectors of perifovea (P=0.005, 0.006, and 0.013 for whole, superior hemiretina, and inferior hemiretina, respectively). In addition, there was a significantly lower VD of the deep capillary plexus (DCP) in the parafovea (P=0.003, 0.004, and 0.01 for whole, superior, and inferior hemiretina, respectively) and in the perifovea (P=0.007, 0.002, and 0.014 for whole, superior hemiretina, and inferior hemiretina, respectively). Group A showed specific reduction of VD of the DCP of whole and perifoveal superior hemiretina (P=0.04) and choriocapillaris flow parameters (P=0.003). They also showed increase of inferior retinal nerve fiber layer thickness and whole image capillary density (P=0.036 and 0.001, respectively). Concerning the peripapillary capillary density, the whole image peripapillary capillary density and inferior peripapillary VD of group A was increased in comparison to group B (P=0.023 and 0.009, respectively) with no statistically significant difference with group C. Conclusion Nephritic SLE patients showed reduction in VD of the DCP of the perifoveal superior hemiretina and choriocapillaris, while nonnephritic SLE patients showed reduction of VD of the SCP of the perifovea and DCP of parafovea and perifovea.

Quantitative eco-anatomical analysis reveals distinctive stem traits of six Cannabis sativa cultivars in Rif Mountains (Northern Morocco)

Cannabis sativa stands out as an important crop with significant socioeconomic importance in the Rif Mountains of North Morocco. Recently the number of new cultivars developed in this region has gradually increased for different purposes. In this current study, we delve into the eco-anatomical characteristics of stems across six of the most prevalent Cannabis sativa cultivars in Morocco: ‘Avocat’, ‘Beldiya’, ‘Critical Plus’, ‘Industriel’, ‘Khardala’, and ‘Mexicana’. The investigation encompasses the measurement and analysis of six key eco-anatomical traits: plant height, stem diameter, vessel size, vessel density, number of vessels joined in radial files, and coefficient of hydraulic conductivity. Our aim is to elucidate the variations among these cultivars and underscore their agricultural and ecological relevance. Through anatomical examinations of stem cross-sections, our findings reveal notable disparities and distinctive features among the cultivars. The ‘Khardala’ cultivar exhibits the highest values across most measured eco-anatomical traits, while ‘Beldiya’ and ‘Mexicana’ show similar trait values, particularly with low stem diameter and vessel density. In contrast, ‘Industriel’ stands out with the lowest vessel size and highest vessel density. ‘Critical Plus’ and ‘Avocat’ closely resemble ‘Khardala’ in vessel size and stem diameter. Regarding hydraulic conductivity, ‘Khardala’ ranks highest, followed by ‘Avocat’ and ‘Critical Plus’, while ‘Industriel’ registers the lowest. Our findings underscore increased water demand and uptake potential in ‘Khardala’, ‘Critical Plus’, and ‘Avocat’, contrasting with ‘Industriel’, ‘Beldiya’, and ‘Mexicana’. Anatomical diversity among Cannabis cultivars in our study likely stems from genetic lineage and ecological adaptation.

Impact of systemic hypertension on inner retinal layer thickness and macular microvasculature in patients with diabetic retinopathy.

To investigate the effects of hypertension (HTN) on inner retinal thickness and macular microvasculature in patients with diabetic retinopathy (DR). Subjects were classified into three groups: patients with type 2 diabetes mellitus (T2DM) (T2DM group), patients with DR (DR-HTN group), and patients with DR and HTN (DR + HTN group). The ganglion cell complex (GCC) thicknesses and the macular vessel density (VD) were compared. Linear regression analyses were performed to identify factors associated with the VD in the DR + HTN group. The mean GCC thicknesses were 112.2 ± 12.3, 109.2 ± 13.7, and 106.2 ± 11.2μm in the T2DM, DR-HTN, and DR + HTN groups, respectively (P = 0.045). The mean VDs were 25.4 ± 5.0, 24.3 ± 8.9, and 21.2 ± 7.1% (P = 0.014) for the superficial capillary plexus (SCP) and 25.9 ± 4.3, 22.9 ± 8.5, and 20.2 ± 6.6% (P < 0.001) for the deep capillary plexus (DCP) in the T2DM, DR-HTN, and DR + HTN groups, respectively. In multivariate analyses, the duration of HTN was a significant factor associated with the VD of both SCP (B = -0.24, P = 0.010) and DCP (B = -0.21, P = 0.016). Patients with both DR and HTN had a thinner GCC and lower VDs of SCP and DCP than those with DR alone. These outcomes could be associated with the synergistic ischemic effects in DR patients with HTN. Moreover, the duration of HTN in DR patients was significantly associated with macular VD in both SCP and DCP.

Optical Coherence Tomography Angiography Assessment of Optic Nerve Head and Macula Across the Primary Angle Closure Disease Spectrum.

The microvasculature of the optic disc and macula in eyes with acute primary angle closure and primary angle closure glaucoma was lower across the disease spectrum, but the significant difference was only observed in primary angle closure glaucoma. To assess the microvasculature in the optic nerve head (ONH) and macula across the primary angle closure disease (PACD) spectrum using optical coherence tomography angiography (OCTA). OCTA (AngioVue, Fremont, CA) imaging was performed on 122 PACD subjects. Flow area (FA) and vessel density (VD) in the ONH, radial peripapillary capillary (RPC) network, and superficial and deep capillary plexuses of the macula were calculated and compared across the PACD spectrum using linear regression models with generalized estimating equations adjusted for inter-eye correlation. A total of 234 eyes including 44 primary angle closure suspects (PACS), 93 primary angle closure (PAC), 79 primary angle closure glaucoma (PACG), and 18 PAC with a history of previous acute primary angle closure (APAC) were included in the analysis. Compared with other groups, PACG eyes showed smaller FA in the ONH (1.35±0.02mm 2 ), RPC (0.78±0.03mm 2 ), and the superficial retinal layer (1.08±0.03mm 2 ) (all P <0.05). Lower VD was also observed in the "whole image," "inside disc," and "peripapillary" regions of the ONH and RPC, and the "whole image" and "parafoveal" regions of the retinal layer in the PACG group when compared with other groups (all P <0.05). No significant differences were found for the other groups (all P >0.05). Lower VD in the ONH, RPC, and superficial retinal layer significantly correlated with worse visual field loss in PACG eyes (all P <0.05). Significant reduction in the microvasculature of the optic disc and macula in PACG suggests that glaucoma development may contribute to lower VD in these regions.

The reduction of LEDD leads to visual dysfunction in patients with PD after STN-DBS: a randomized clinical trial

Background: Medication adjustment after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson’s disease (PD) may influence visual function. However, no clinical trials have been designed specifically to investigate this effect. Objectives: To compare the effects of levodopa equivalent daily dose (LEDD) reduction and non-reduction on visual function in patients with Parkinson’s disease (PD) following STN-DBS. Methods: This was a multi-center, prospective, randomized, double-blinded clinical trial. A total of 208 patients with Parkinson’s disease were referred for DBS between June 2019 and July 2021 and analyzed between June 2023 and July 2023. STN-DBS was performed, and the LEDD was reduced in one study arm but not in the other. The primary outcome measure was visual impairment in Parkinson’s disease questionnaire (VIPD-Q) with or without LEDD reduction 12 months postoperatively, and the secondary outcomes included retinal nerve fiber layer (RNFL) thickness, vessel density, eye-tracking system results, contrast sensitivity and visual field. Results: During the short-term follow-up, DBS implantation and stimulation did not significantly affect visual function (VIPD-Q, baseline vs. 1 month, 9.269±8.385 vs. 8.938±7.666, Mann–Whitney U tests; P=0.6746). In the long-term follow-up, the reduction group demonstrated a significant decline in visual function, RNFL thickness, and vessel density after STN-DBS compared with the control group without STN-DBS (P&lt;0.001). Conclusions: Visual dysfunction, particularly a thinner RNFL and lower vessel density, is related to LEDD reduction after STN-DBS. Prolonged administration of dopamine-mimetic drugs prevents visual symptoms. Thus, physicians should consider LEDD adjustment when patients report visual dysfunction before surgery or severe visual symptoms after STN-DBS.

Quantifying ocular microcirculation in hypertension patients with carotid artery stenosis.

Carotid artery stenosis (CAS) is one of the most common macrovascular complications of hypertension. The ophthalmic artery springs from the internal carotid artery; however, the effect of CAS on ocular microcirculation has not been quantified in hypertension patients. This study aimed to quantify ocular microcirculation metrics in hypertension with CAS (HCAS) patients and to explore the relationship between micro- and macroangiopathy in hypertension. All participants (community-based) underwent detailed assessments, including carotid ultrasonography, optical coherence tomography angiography (OCTA), and enhanced depth imaging (EDI)-OCT. CAS was diagnosed using carotid ultrasonography. Retinal microcirculation metrics, including vessel density (VD), skeleton density (SD), fractal dimension (FD), and foveal avascular zone (FAZ), were quantified using OCTA and ImageJ software. Choroidal microcirculation metrics, including subfoveal choroidal thickness (SFCT), luminal area (LA), and choroidal vascularity index (CVI), were quantified using EDI-OCT and ImageJ. Retinal vessel caliber metrics, including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery/vein ratio (AVR), were calculated using revised formulas. The above metrics were compared among the HCAS group, hypertension with no CAS (HNCAS) group, and healthy control group. The mutual effects between ocular metrics and CAS were evaluated using regression analyses. In a comparison of the HCAS vs. HNCAS groups, retinal metrics including VD, SD, FD, and choroidal metrics including CVI and LA were significantly decreased in the HCAS group (all p < 0.05); however, FAZ, SFCT, and retinal vessel caliber metrics including CRAE, CRVE, and AVR were comparable between groups (all p > 0.05). In a comparison of HNCAS and the healthy control group, VD, SD, and CRAE showed that AVR was significantly decreased in the HNCAS group (all p < 0.05); meanwhile, choroidal metrics were comparable between groups (all p > 0.05). Linear regression analyses showed that intima-media thickness (IMT) (p = 0.01) and peak systolic velocity (PSV) (p = 0.002) were negatively related to retinal VD in hypertension patients. Logistic regression analyses disclosed that older age (p < 0.001), smoking history (p = 0.002), lower VD (p = 0.04), SD (p = 0.02), and CVI (p < 0.001) were related to the presence of CAS in hypertension patients. CAS in hypertension-induced hypoperfusion in retinal and choroidal microcirculation and the decreased retinal VD and choroidal CVI were significantly associated with the presence of CAS in patients with hypertension, suggesting that hypertension macro- and microangiopathy were mutually affected and share the common pathophysiology. Furthermore, OCT could be a useful tool to assess hypertension patient's CAS risk profiles in a non-invasive way.

Diagnostic ability of the combination of retinal microvasculature evaluation and static automated perimetry for early primary open-angle glaucoma.

To investigate the diagnostic ability of retinal superficial vasculature evaluation by optic coherence tomography angiography (OCTA) combined with visual field (VF) testing for early primary open-angle glaucoma (POAG). In this cross-sectional study, 84 participants were included, including 11 in the ocular hypertension (OHT) group, 11 in the preperimetric POAG (pre-POAG) group, 29 in the early POAG group and 33 in the control group. All participants underwent 6 × 6 mm2 scans of macula and optic nerved head by optic coherence tomography (OCT) and OCTA, along with white-on-white and blue-on-yellow VF testing by static automated perimetry. The ability of diagnosing early glaucoma by either various examinations separately or combination of examinations in both terms of function and structure was studied using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The superficial retinal vessel densities (VD) in peri-nasal, para-temporal, peri-temporal and peri-inferior regions around the macula, as well as vessel area densities (VAD) in all peripapillary regions, were significantly different among the four groups, with lower VD or VAD in the early POAG patients compared to the normal individuals. The diagnostic ability of peripapillary superficial retinal VAD alone or VF testing alone was limited for early POAG only. However, the combination of these two was more effective in distinguishing normal individuals from OHT subjects or pre-POAG patients without VF defects, with better performance than the combination of peripapillary retinal nerve fiber layer (RNFL) thickness and VF indicators. Peripapillary retinal vessel densities were generally lower in early POAG patients compared to normal individuals. The combination of peripapillary superficial retinal VAD by OCTA with white-on-white VF testing improved the ability to distinguish POAG patients at early stage without function impairment, which may help in providing reference and guidance for the following-up and treatment of suspected POAG patients.

Intereye Microvascular Differences in Patients With Same-Stage Diabetic Retinopathy Revealed by OCTA.

To evaluate microvascular intereye differences in diabetic patients with same-stage diabetic retinopathy (DR) in both eyes as assessed using optical coherence tomography angiography (OCTA). In this cross-sectional study, fovea-centered swept-source 6 × 6 mm OCTA scans were acquired using a 200 kHz OCTA device. Vessel density (VD) and fractal dimension were calculated on binarized, vessel-segmented images in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Foveal avascular zone (FAZ) area (FAZA) and perimeter (FAZP) was measured and FAZ circularity (FAZC) calculated. Absolute difference (δabs) and asymmetry index between eyes was assessed and compared across DR stages. Differences of VD, FD, and FAZ parameters between left and right eye were evaluated using linear mixed models. A total of 336 eyes of 168 diabetic patients without DR and with DR stages ranging from mild nonproliferative to proliferative DR were included for analysis. The intereye comparison revealed significantly lower VD in the SCP (estimate [95% CI] = -0.009 [-0.01; -0.006], P < 0.01), as well as a significantly lower FD in the SCP (-0.007 [-0.009; -0.005], P < 0.01) of the left compared to the right eye. FAZC of the left compared to the right eye was lower in eyes without DR, moderate DR, and PDR (P < 0.05). FAZ δabs and asymmetry index were higher in more advanced disease stages (P < 0.05). OCTA metrics provide important information on the retinal microvasculature in systemic diseases such as DR. Our results reveal a significant intereye difference with lower VD and FD in the SCP as well as higher FAZ impairment of the left compared to the right eye.

Comparison of macular and optic disc vessel density in thyroid orbitopathy: a comparative octa study.

To determine the microvascular and structural changes in the peripapillary and macular areas observed in patients with active thyroid orbitopathy(TO) before and after steroid treatment and compare with inactive TO and the control group by optical coherence tomography angiography (OCTA). This cross-sectional study included 34 eyes of 17 active TO patients, 108 eyes of 54 inactive TO patients, and 60 eyes of 30 healthy controls. Central macular thickness (CMT), ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, central choroidal thickness (CCT), retinal nerve fiber layer (RNFL) thickness, choroidal thickness in the peripapillary region, superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris vessel densities were determined by OCTA in before and after 12-week steroid treatment of active TO cases, inactive TO and control groups. Between the three groups in macula OCTA, a statistically significant difference was observed in the inferior and nasal quadrants in SCP (all p = 0.01) and only in the temporal quadrant choriocapillaris (p = 0.005). In peripapillary OCTA, a statistically significant difference was found only in the central choriocapillaris (p = 0.03). In the comparison of the active group before and after treatment, there was a statistically significant decrease in CMT and CCT; a statistically significant increase was observed in GCL-IPL (all p < 0.01). There was a statistically significant decrease in SCP and DCP only in the central (all p < 0.01). There was a statistically significant increase was found in the lower quadrant macular SCP vessel density and mean macular DCP in post-treatment measurements (p = 0.01 and p = 0.03, respectively). Peripapillary SCP and DCP vessel density was increased after treatment (p < 0.01). Active TO group had lower vessel density than inactive group and after treatment, vessel density was increased. Non-invasive quantitative analysis of retinal and optic disc perfusion using OCTA could be useful in early treatment before complications occur and monitoring patients with TO.

Reduced Aqueous Humor Outflow Pathway Arborization in Childhood Glaucoma Eyes.

To compare aqueous humor outflow (AHO) pathway patterns between eyes of childhood glaucoma patients and non-glaucomatous patients receiving cataract surgery. Aqueous angiography was performed in childhood glaucoma eyes (n = 5) receiving glaucoma surgery and in pediatric (n = 1) and healthy adult (n = 5) eyes receiving cataract surgery. Indocyanine green (0.4%) was introduced into the anterior chamber, and AHO was imaged using an angiographic camera (SPECTRALIS HRA+OCT with Flex Module). Images were acquired and analyzed (ImageJ with Analyze Skeleton 2D/3D plugin) from the nasal sides of the eyes, the usual site of glaucoma angle procedures. Image analysis endpoints included AHO vessel length, maximum vessel length, number of branches, number of branch junctions, and vessel density. Qualitatively, childhood glaucoma eyes demonstrated lesser AHO pathway arborization compared to pediatric and adult eyes without glaucoma. Quantitatively, childhood glaucoma and healthy adult cataract eyes showed similar AHO pathway average branch lengths and maximum branch lengths (P = 0.49-0.99). However, childhood glaucoma eyes demonstrated fewer branches (childhood glaucoma, 198.2 ± 35.3; adult cataract, 506 ± 59.5; P = 0.002), fewer branch junctions (childhood glaucoma, 74.6 ± 13.9; adult cataract, 202 ± 41.2; P = 0.019), and lower vessel densities (childhood glaucoma, 8% ± 1.4%; adult cataract, 17% ± 2.5%; P = 0.01). Childhood glaucoma patients demonstrated fewer distal AHO pathways and lesser AHO pathway arborization. These anatomical alternations may result in a new source of trabecular meshwork-independent AHO resistance in this disease cohort. Elevated distal outflow pathway resistance due to decreased AHO pathway arborization may explain some cases of failed trabecular bypass surgery in childhood glaucoma.

Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy.

To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups. OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

Amyloid β oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction

BackgroundAlthough abnormal accumulation of amyloid beta (Aβ) protein is thought to be the main cause of Alzheimer’s disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid β induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aβ deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding.MethodsTwo-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aβ oligomer stereotactic injection model was established to explain the relationship between Aβ and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms.ResultsVasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aβ-injected model, suggesting a direct relationship between Aβ and vascular dysfunction. Pericytes showed impaired features including low PDGFRβ expression and increased pro-inflammatory chemokines secretion under the administration of Aβ in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency.ConclusionsOur results provide new insights into the pathogenic mechanism underlying Aβ-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.

Maternal Supplementation with Ornithine Promotes Placental Angiogenesis and Improves Intestinal Development of Suckling Piglets.

The blood vessels of the placenta are crucial for fetal growth. Here, lower vessel density and ornithine (Orn) content were observed in placentae for low-birth-weight fetuses versus normal-birth-weight fetuses at day 75 of gestation. Furthermore, the Orn content in placentae decreased from day 75 to 110 of gestation. To investigate the role of Orn in placental angiogenesis, 48 gilts (Bama pig) were allocated into four groups. The gilts in the control group were fed a basal diet (CON group), while those in the experimental groups were fed a basal diet supplemented with 0.05% Orn (0.05% Orn group), 0.10% Orn (0.10% Orn group), and 0.15% Orn (0.15% Orn group), respectively. The results showed that 0.15% Orn and 0.10% Orn groups exhibited increased birth weight of piglets compared with the CON group. Moreover, the 0.15% Orn group was higher than the CON group in the blood vessel densities of placenta. Mechanistically, Orn facilitated placental angiogenesis by regulating vascular endothelial growth factor-A (VEGF-A). Furthermore, maternal supplementation with 0.15% Orn during gestation increased the jejunal and ileal villi height and the concentrations of colonic propionate and butyrate in suckling piglets. Collectively, these results showed that maternal supplementation with Orn promotes placental angiogenesis and improves intestinal development of suckling piglets.

Blocking TGF-β- and Epithelial-to-Mesenchymal Transition (EMT)-mediated activation of vessel-associated mural cells in glioblastoma impacts tumor angiogenesis.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. GBM displays excessive and unfunctional vascularization which may, among others, be a reason for its devastating prognosis. Pericytes have been identified as the major component of the irregular vessel structure in GBM. In vitro data suggest an epithelial-to-mesenchymal transition (EMT)-like activation of glioma-associated pericytes, stimulated by GBM-secreted TGF-β, to be involved in the formation of a chaotic and dysfunctional tumor vasculature. This study investigated whether TGF-β impacts the function of vessel associated mural cells (VAMCs) in vivo via the induction of the EMT transcription factor SLUG and whether this is associated with the development of GBM-associated vascular abnormalities. Upon preventing the TGF-β-/SLUG-mediated EMT induction in VAMCs, the number of PDGFRβ and αSMA positive cells was significantly reduced, regardless of whether TGF-β secretion by GBM cells was blocked or whether SLUG was specifically knocked out in VAMCs. The reduced amount of PDGFRβ+ or αSMA+ cells observed under those conditions correlated with a lower vessel density and fewer vascular abnormalities. Our data provide evidence that the SLUG-mediated modulation of VAMC activity is induced by GBM-secreted TGF-β¬ and that activated VAMCs are key contributors in neo-angiogenic processes. We suggest that a pathologically altered activation of GA-Peris in the tumor microenvironment is responsible for the unstructured tumor vasculature. There is emerging evidence that vessel normalization alleviates tumor hypoxia, reduces tumor-associated edema and improves drug delivery. Therefore, avoiding the generation of an unstructured and non-functional tumor vasculature during tumor recurrence might be a promising treatment approach for GBM and identifies pericytes as a potential novel therapeutic target.

Optical coherence tomography angiography to assess for retinal vascular changes in Neuro-Sjögren.

Sjögren's syndrome is an autoimmune disease characterized by sicca symptoms and various extraglandular manifestations including vasculitis. Neurological involvement occurs frequently (Neuro-Sjögren) and often mimics immune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP). We aim to assess relevant differences in vessel density (VD) in Optical Coherence Tomography Angiography (OCTA) in those diseases to use it as an easily available diagnostic tool. Prospective, monocentric pilot-study. OCTA (Heidelberg Engineering OCT SPECTRALIS) of the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus (DCP) of the retina was prospectively performed in Neuro-Sjögren, age-matched CIDP patients (n = 31, each), and healthy controls (n = 30). Vessel density (VD) and foveal avascular zone (FAZ) was measured with Erlangen Angio Tool. Significantly lower VD were found for the DCP and ICP in Neuro-Sjögren and CIDP patients compared to healthy controls (p = 0.0002 and <0.0001). When group comparison was age-adjusted, these differences were not found anymore. Different frequencies of "low" retinal blood flow in each layer comparing Neuro-Sjögren and CIDP patients were not found. FAZ revealed no significant differences between patients with Neuro-Sjögren, CIDP and healthy controls. This study found no significant differences in VD or the foveal avascular zone between Neuro-Sjögren and CIDP patients using OCTA, suggesting that inflammatory vascular changes in the retina are uncommon in Neuro-Sjögren patients.