Decreased Vessel Density Research Articles

Acute effects of high-intensity interval training on microvascular circulation: a case control study in uveal melanoma

Abstract Objectives The aim of this study was to explore the acute effects of high-intensity interval training (HIIT) on the microvascular circulation and vascular tumor microenvironment (TME) in a patient with uveal melanoma (UM). Additionally, the acceptance of the applied diagnostics and the exercise protocol in a clinical ophthalmic-oncology setting were evaluated. Methods This case-control study included a young adult male patient with UM previously treated with radiation and an age-matched healthy control. Participants underwent a baseline assessment of dynamic retinal vessel analysis (DRVA) and cardiopulmonary exercise testing (CPET) to determine endothelial function and intensity for HIIT. Optical coherences tomography angiography (OCTA) was performed before, immediately and 30 min after one session of HIIT. The primary outcome were changes in ocular vessel parameters and whole body oxygen uptake. Results The UM patient exhibited lower arterial dilation and constriction in the affected eye compared to his healthy eye and both eyes of the healthy control. OCTA revealed heterogeneous patterns of vascular response to HIIT in both participants. The tumor eye showed an increase followed by a significant decrease in vessel density post-exercise, while the healthy control exhibited minor increases. Conclusions The findings of this study highlighted the potential of UM combined with OCTA and DRVA as a model for examine exercise-induced vascular effects within the TME. However, a pre-treated UM as well as detailed image analyses and further research with longitudinal, randomized controlled designs are essential to validate these findings and address methodological limitations. Such investigations could refine integrative cancer treatment.

Comparison of Vessel Density and Retinal Sensitivity After Scleral Buckling and Phacovitrectomy in the Management of Macula-on Primary Rhegmatogenous Retinal Detachment.

The choice of surgical method for rhegmatogenous retinal detachment (RRD) may have a significant impact on the retina. In this study, we aimed to compare retinal function and structure after scleral buckling (SB) and phacovitrectomy (phaco-PPV) for macula-on RRD. This cross-sectional study included patients who underwent anatomically successful repair of macula-on RRD managed with SB (n=35) and phaco-PPV (n=35) between 2019-2023. All participants were examined within 6-20 months of surgery to evaluate the retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best-corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess the retinal function. Analysis of the microvascular network with OCTA between eyes after surgery and healthy eyes showed a decrease in VD. Significant changes in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) were observed only in eyes after SB surgery (p <0.001 and p=0.02, respectively). Analysis of retinal function assessed by MP showed a significant decrease (p<0.05) in retinal sensitivity after phaco-PPV (24.81±2.25 dB) and SB (24.18±2.14 dB) operations compared to the healthy control group (25.97 ± 1.51 dB), whereas postoperative BCVA showed no differences (p>0.05). Changes in retinal sensitivity were accompanied by impairment of the microvascular network in the eyes after SB and phaco-PPV surgeries due to macula-on RRD. Disorders were more pronounced in eyes following SB surgery, possibly secondary to mechanical stress.

Factors Associated with Retinal Microvasculature Dropout Induced by Elevation of Intraocular Pressure in Primary Open-Angle Glaucoma.

To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD). This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation. A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively. Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression. What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.

Evaluation of macular and optic nerve head changes by optical coherence tomography angiography in glaucomatous eyes

Background Optical coherence tomography angiography (OCTA) is introduced as a safe, noninvasive, and dye-free technology that provides an assessment of both large vessels and microvasculature of the retina and some parts of the choriocapillaris. Measuring vessel densities using OCTA at both the macula and optic nerve head (ONH) in glaucomatous eyes and comparing them with those of normal eyes will give us an idea about the effect of glaucoma on vessel densities and the role of OCTA in controlling and monitoring glaucoma progression, which remains despite the various medical and surgical treatment options, the second most common reason of blindness worldwide. Aims The current study aimed to assess vessel densities in glaucomatous patients at both the macula and ONH and compare them with vessel densities of normal participants and to assess if OCTA can be useful in the diagnosis and monitoring of the disease. Settings and design Case–control study. Patients and methods The study enrolled 60 patients who were divided into two groups. Group 1 included 30 patients with any type of glaucoma and group 2 included 30 normal participants. OCTA was performed on all of them to assess the macular and ONH vessel densities. Results Glaucomatous patients showed decreased vessel density at the macula and the ONH. The vessel densities at the foveal and all quadrants of parafoveal regions of the macula were decreased when compared with vessel densities of normal participants. Vessel densities at all quadrants of the peripapillary region also decreased when compared with those of normal participants with a strong positive correlation between average peripapillary vessel density and average peripapillary retinal nerve fiber layer thickness. Conclusions Both macular vessel density and ONH vessel density are affected in glaucoma and that may play a role in the diagnosis and follow-up of the disease.

Retinal vessel density and choroidal flow changes in oligoarticular juvenile idiopathic arthritis with and without uveitis.

This cross-sectional optical coherence tomography angiography (OCTA) study aimed to assess the macular and optic nerve head (ONH) vascular density, foveal avascular zone, and outer retina and choriocapillaris flow in oligoarticular juvenile idiopathic arthritis (oJIA). Prospective. Twenty-two eyes of 22 oJIA patients with uveitis (oJIA-U), 20 eyes of 20 oJIA patients without uveitis (isolated oJIA), and 26 healthy volunteers of similar ages and sexes were investigated. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, foveal avascular zone (FAZ) parameters, the flow area of the outer retina, and choriocapillaris were evaluated. Compared with the control group, both the oJIA-U group and isolated oJIA group showed significantly decreased vessel density of parafovea (p = 0.031 and p = 0.047, respectively) in DCP. Choriocapillaris flow area at 1mm radius was significantly lower in the oJIA-U group compared to the control group (p = 0.001). Choriocapillaris flow area at 2- and 3-mm radius were significantly lower in the oJIA-U group compared to the control group (p < 0.001, for both) and isolated oJIA-U group compared to the control group (p = 0.008 and p = 0.001, respectively). The VD and thickness parameters of SCP and ONH, FAZ, and outer retina flow area were similar between the groups. oJIA patients with and without uveitis revealed a decreased vessel density in the deep parafoveal region and choriocapillaris flow. Our findings suggest that retinal choroidal microvascular changes could be evident in oJIA-U patients without posterior segment involvement as well as oJIA patients without uveitis.

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs

BackgroundIntrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses.MethodsAt 119–120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3–4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit.ResultsLPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte “end feet” vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS.ConclusionLPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.

Macrophage scavenger receptor-A1 promotes skeletal muscle regeneration after hindlimb ischemia.

Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based therapeutic targets for ischemic disease. Here, we found mRNA level of SR-A1 was elevated in patients with critical limb ischemia by analysis of gene expression omnibus (GEO) database. Then we investigated the role and the underlined mechanisms of macrophage SR-A1 in a mouse HLI model. Compared with the SR-A1 fl/fl mice, the Lyz Cre/+/SR-A1 flox/flox (SR-A1 ΔMΦ) mice showed significantly lower laser doppler blood flow in the ischemic limb at day 7 after HLI. Consistently, histological analysis exhibited that ischemic limb of SR-A1 ΔMΦ mice displayed more sever and sustained necrotic morphology, inflammation and fibrosis, decreased vessel density and regeneration rate, compared with which of control SR-A1 fl/fl mice. Furthermore, restoration of wild-type myeloid cells to SR-A1 knock-out mice effectively relieved the doppler perfusion in the ischemic limb and restrained skeletal muscle damage 7 days post HLI. In line with in vivo findings, when co-cultivating macrophages with the mouse myoblast line C2C12, SR-A1 -/- bone marrow macrophage significantly inhibited myoblast differentiation in vitro. Mechanically, SR-A1 enhanced skeletal muscle regeneration response to HLI by inhibiting the oncostatin M (OSM) production via suppressed NF-κB signaling activation. These results indicates that SR-A1 is a promising candidate molecule to improve tissue repair and regeneration in peripheral ischemic arterial disease.

The Early Pathogenesis of Diabetic Retinopathy and Its Attenuation by Sodium-Glucose Transporter 2 Inhibitors.

The early pathogenetic mechanism of diabetic retinopathy (DR) and its treatment remain unclear. Therefore, we investigated the early pathogenic alterations in DR using streptozotocin-induced diabetic mice and the protective effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors against these alterations. Retinal vascular leakage was assessed by dextran fluorescence angiography. Retinal thickness and vascular leakage were increased 2 and 4 weeks after onset of diabetes, respectively. Immunostaining showed that morphological change of microglia (amoeboid form) was observed at 2 weeks. Subsequently, increased angiopoietin-2 expression, simultaneous loss of pericytes and endothelial cells, decreased vessel density, retinal hypoxia, and increased vascular endothelial growth factor (VEGF)-A/VEGF receptor system occurred at 4 weeks. SGLT2 inhibitors (luseogliflozin and ipragliflozin) had a significant protective effect on retinal vascular leakage and retinal thickness at a low dose that did not show glucose-lowering effects. Furthermore, both inhibitors at this dose attenuated microglia morphological changes and these early pathogenic alterations in DR. In vitro study, both inhibitors attenuated the lipopolysaccharide-induced activation of primary microglia, along with morphological changes toward an inactive form, suggesting the direct inhibitory effect of SGLT2 inhibitors on microglia. In summary, SGLT2i may directly prevent early pathogenic mechanisms, thereby potentially playing a role in preventing DR.

Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease.

Hypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD.The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six months following the 2k2c operation.Systolic blood pressure was significantly greater in the RHRSP group than in the sham-operated group at week 4 post-surgery and continued to increase over time, leading to cognitive decline by week 20. Arterial spin labeling revealed cerebral hypoperfusion in the RHRSP group at 8 weeks, accompanied by vascular remodeling and decreased vessel density. Diffusion tensor imaging and Luxol fast blue staining indicated that white matter disintegration and demyelination gradually progressed in the corpus callosum and that myelin basic protein levels decreased. Eight weeks after surgery, blood-brain barrier (BBB) leakage into the corpus callosum was observed. The albumin leakage area was negatively correlated with the myelin sheath area (r=-0.88, p<0.001). RNA-seq analysis revealed downregulation of most angiogenic genes and upregulation of antiangiogenic genes in the corpus callosum of RHRSPs 24 weeks after surgery.RHRSPs developed cerebral hypoperfusion, BBB disruption, spontaneous white matter damage, and cognitive impairment as the duration of hypertension increased. RHRSPs share behavioral and neuropathological characteristics with CSVD patients, making them suitable animal models for preclinical trials related to CSVD.

Root topological order drives variation of fine root vessel traits and hydraulic strategies in tropical trees.

Vessel traits contribute to plant water transport from roots to leaves and thereby influence how plants respond to soil water availability, but the sources of variation in fine root anatomical traits remain poorly understood. Here, we explore the variations of fine root vessel traits along topological orders within and across tropical tree species. Anatomical traits were measured along five root topological orders in 80 individual trees of 20 species from a tropical forest in southwestern China. We found large variations for most root anatomical traits across topological orders, and strong co-variations between vessel traits. Within species, theoretical specific xylem hydraulic conductivity (Kth) increased with topological order due to increased mean vessel diameter, size heterogeneity, and decreased vessel density. Across species, Kth was associated with vessel fraction in low-order roots and correlated with mean vessel diameter and vessel density in high-order roots, suggesting a shift in relative anatomical contributors to Kth from the second- to fifth-order roots. We found no clear relationship between Kth and stele: root diameter ratios. Our study shows strong variations in root vessel traits across topological orders and species, and highlights shifts in the anatomical underpinnings by varying vessel-related anatomical structures for an optimized water supply.

Vessel density on optical coherence tomography angiography is prognostic for future disease course in intermediate uveitis.

As most rare diseases, intermediate uveitis lacks reliable endpoints necessary for randomized clinical trials. Therefore, we investigated longitudinal changes of retinal and choriocapillaris perfusion on optical coherence tomography angiography (OCT-A) in intermediate uveitis and their prognostic value for future best corrected visual acuity (BCVA) and central retinal thickness (CRT). In this retrospective, longitudinal cohort study eyes of patients with intermediate uveitis were imaged by swept-source OCT-A (macula-centered 3 × 3mm; PLEX Elite 9000, Zeiss) and stratified into clinically stable, worsened and improved based on changes in clinical parameters. Superficial (SRL) and deep retinal layers (DRL) were automatically analyzed for vessel density (VD) and choriocapillaris layer for non-perfused area (CCNPA) using ImageJ. Mixed-effects regression analysis controlling for age, sex, and OCT-A signal strength index (SSI) was used to evaluate the prognostic value of OCT-A parameters. 91 eyes (62 stable, 12 worsened, and 17 improved) were included in the analysis and mean follow-up time was 296 days. Longitudinal changes of VD were different between all three groups (p = 0.002 for SRL and p = 0.017 for DRL). Clinically worsened eyes showed a decrease in VD (- 0.032 ± 0.055 for SRL and - 0.027 ± 0.025 for DRL), whereas clinically improved eyes showed an increase in VD (0.037 ± 0.039 for SRL and 0.001 ± 0.023 for DRL). No difference was found for CCNPA. When controlling for age, sex, and SSI, observed differences held true in clinically worsened eyes for DRL (p = 0.011) and in clinically improved eyes for SRL (p = 0.002). An increase of CCNPA in clinically worsened eyes (p = 0.03) compared to clinically stable and improved eyes was evident. Predictive analysis revealed an association of VD in SRL and DRL at baseline with BCVA at follow-up (p = 0.039 and p = 0.047, respectively) and of VD in SRL at baseline with CRT at follow-up (p = 0.046). Alterations in retinal perfusion on OCT-A in intermediate uveitis are partly reversible and OCT-A VD may serve to predict future BCVA and CRT. Thus, perfusion parameters on OCT-A might aid monitoring and serve as prognostic imaging-biomarker.

Decreased retinal capillary density as a beneficial response to 24-week high-speed circuit resistant training in healthy older adults

PurposeTo determine the changes in retinal microvascular density after a 24-week high-speed circuit resistance training program (HSCT) in healthy older adults. MethodsThirty healthy older adults were recruited and randomly assigned to either a training group (HSCT) or a non-training (CON) group. Fifteen subjects (age 73.3 ± 7.76 yrs) in the HSCT group exercised three times per week on non-consecutive days for 24 weeks. Fifteen subjects in the CON group (age 72.2 ± 6.04 yrs) did not have formal physical training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at the 24-week follow-up. The vessel densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured. ResultsThere were no demographic differences between the study groups. There were significant decreases in the retinal vessel densities of RVN, SVP and DVP in the HSCT group (P < 0.05). However, there were no significant changes in all three vascular measurements in the CON group (P > 0.05), although the changes showed a decreasing trend. The decreased vessel densities were doubled in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05). ConclusionsThis is the first study to reveal the decreased retinal vessel densities as a possible imaging marker for the beneficial effects of the 24-week HSCT program in older adults.

Association between functional parameter and structural, and vascular parameters in advanced glaucoma

Aims/Purpose: We aimed to evaluate the function‐vasculature, and function–structure relationships in advanced glaucoma patients.Methods: This cross‐sectional study included 29 eyes of 24 advanced glaucoma patients. Advanced glaucoma was classified as visual fields (VFs) with a mean deviation (MD) below ‐12 dB according to Hodapp‐Parrish‐Anderson classification system. The structural parameters, cup/disc area ratio, cup/disc vertical ratio, cup/disc horizontal ratio, rim area, disc area, cup volume, retinal nerve fibre layer thickness, macular ganglion cell complex (GCC) thickness, were measured using optical coherence tomography (OCT, Optovue, Fremont, CA). The vessel density of superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), outer retina (OR), and choriocapillaris (CC) were analysed by optical coherence tomography angiography (OCTA, DRI OCT Triton Plus, Topcon, Tokyo, Japan). For all layers, the average vessel density of the area between 1 mm and 3 mm diameter circles was calculated, assuming the 1 mm diameter area centered on the fovea as the central region. Relationships between 10–2 VF MD values, and structural and vascular parameters were assessed by Pearson's correlation coefficients. p &lt; 0.05 was considered statistically significant.Results: The mean ± SD age of all patients was 61.9 ± 15.8 years and 75% were male. For structural parameters, there was a positive correlation between the MD and GCC thickness values (p = 0.001, r = 0.617), while none of the parameters of the optic disc were related to the MD value. There were significant positive correlations with the vessel densities of the SRCP and CC layers (p = 0.001, r = 0.593 and p = 0.002, r = 0.541, respectively).Conclusions: Decreased vessel densities of the SRCP and CC were significantly associated with severity of visual field damage. This study showed that OCTA can be a promising method in daily use for monitoring advanced glaucoma.

Investigation of Blood Supply to the Macular Region of the Retina in Chronic Myeloproliferative Diseases

Chronic myeloproliferative diseases (CMPD) are tumor diseases of hematopoietic tissue with increased proliferation of one or more lines of myelopoiesis. Quite often with this pathology there are find references to damage to the organ of vision. With CMPD changes in the composition of peripheral blood are observed, leading to changes in the rheology of blood and contributing to the deterioration of microcirculation of eye tissues. In addition, abnormal proliferation of hematopoietic cells and prolonged specific therapy weaken the body’s immune system, contributing to the development of systemic inflammation. These processes can lead to deterioration of blood supply to eye tissues, in particular in the macular region. Purpose. To evaluate vessel density (VD) in the superficial and deep vascular plexuses of retina and the area of foveolar avascular zone (FAZ) using optical coherence tomography with angiography function (OCTA) in patients with CMPD. Patients and methods. The study included 25 patients with CMPD (50 eyes) and 20 volunteers (40 eyes), comparable in gender and age, without a history of hemoblastosis. All the examined patients underwent comprehensive ophthalmological diagnostics, including OCTA. Results. According to the results, patients with CMPD revealed a significant decrease in VD in all sectors (except the foveolar zone) in both studied vascular plexuses, as well as a significant increase in area of FAZ compared to the control group. Conclusion. A decrease in VD in the vascular plexuses of the retina, as well as an increase in area of FAZ, are signs of deterioration of retinal blood supply and retinal ischemia. It is possible that these changes may lead to violations of blood rheology, as well as chronic systemic inflammation observed in patients with CMPD. Deterioration of blood flow and prolonged retinal hypoxia can contribute to serious visual impairment of patients. In this regard, patients with CMPD require more detailed monitoring, possibly with correction of the main treatment.

Non-Invasive Evaluation of Retinal Vascular Alterations in a Mouse Model of Optic Neuritis Using Laser Speckle Flowgraphy and Optical Coherence Tomography Angiography.

Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs). Although previous studies suggest that retinal blood flow alterations occur during optic neuritis, the precise location, the degree of impairment, and the underlying mechanisms remain unclear. In this study, we utilized two emerging non-invasive imaging techniques, laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA), to investigate retinal vascular changes in a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE). We associated these changes with leukostasis, RGC injury, and the overall progression of EAE. LSFG imaging revealed a progressive reduction in retinal blood flow velocity and increased vascular resistance near the optic nerve head in the EAE model, indicating impaired ocular blood flow. OCTA imaging demonstrated significant decreases in vessel density, number of junctions, and total vessel length in the intermediate and deep capillary plexus of the EAE mice. Furthermore, our analysis of leukostasis revealed a significant increase in adherent leukocytes in the retinal vasculature of the EAE mice, suggesting the occurrence of vascular inflammation in the early development of EAE pathology. The abovechanges preceded or were accompanied by the characteristic hallmarks of optic neuritis, such as RGC loss and reduced visual acuity. Overall, our study sheds light on the intricate relationship between retinal vascular alterations and the progression of optic neuritis as well as MS clinical score. It also highlights the potential for the development of image-based biomarkers for the diagnosis and monitoring of optic neuritis as well as MS, particularly in response to emerging treatments.

Neurodegeneration with Brain Iron Accumulation Disorders and Retinal Neurovascular Structure.

The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. To investigate NBIA's neurological and ophthalmological manifestations. This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations. Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome. Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society.

TMIC-23. UNRAVELLING THE HETEROGENEITY OF GLIOBLASTOMA'S VASCULAR LANDSCAPE

Abstract BACKGROUND Glioblastoma tumours are highly vascular and angiogenic. However, they are also heterogeneous, comprising many different macro- and microenvironments. Reflecting this, tumour-associated blood vessels are variable in their distribution, structure, and function. Despite the significance of vasculature in the development and progression of glioblastoma, its complexity remains poorly defined. Therefore, characterising vascular diversity across the glioblastoma landscape is a crucial step in the development of targeted therapies. METHODS 40 glioblastoma and 5 epilepsy cases were immunohistochemically labelled with a vascular antibody panel (PDGFRβ, ColIV, αSMA, UEA-1 and GFAP) to identify and subtype vessels. Single-vessel image analysis was performed to analyse vascular coverage and to classify vascular subtypes based on marker co-expression. Labelling with haemoglobin, ZO-1, and claudin-5 allowed for the evaluation of vascular leakage and blood-brain barrier integrity. Tissue segmentation was performed to analyse vascular coverage, vascular subtypes, and vascular integrity across the tumour macro-environment. RESULTS No significant difference in gross vascular coverage was found between tumour and epilepsy tissue. However, vascular coverage within glioblastoma varied significantly depending on the tumour macro-environment. Whilst vascular coverage in the tumour periphery was comparable to epilepsy tissue, increased vessel density was observed in the intermediate tumour zone, followed by decreased vessel density towards the tumour core. Reflecting this variation, multiple vessel subtypes, including previously described glomerular microvascular proliferation, mother vessels, vascular malformations and hyperplastic vessels, were identified. These tumour vessels display highly irregular shapes, sizes, and cellular compositions. Finally, glioblastoma tissue displayed a significant increase in haemoglobin leakage and a decrease in vascular integrity compared to epilepsy tissue. CONCLUSION Characterising this vascular landscape provides valuable insights for treatment strategies related to hypoxia and angiogenesis, two key factors driving tumour growth. Indeed, targeting specific vessel subtypes to address compromised vascular function and aberrant vascularisation may improve outcomes for glioblastoma patients.

Subclinical macular vessel density alterations in patients with juvenile systemic lupus erythematosus.

The aim is to evaluate subclinical alterations of macular microvasculature in patients with juvenile systemic lupus erythematosus (JSLE). This is a cross-sectional study of 29 eyes of 29 patients diagnosed with JSLE and 29 eyes of 29 healthy controls. The vessel density (VD) of the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), choriocapillaris (CC), and area of foveal avascular zone (FAZ) was measured using optical coherence tomography angiography (OCTA). A multiple linear regression analysis was performed to evaluate the effects of disease duration and activity on OCTA parameters. The VD of total (p = .007) and the superior (p = .014) and inferior (p = .004) quadrants in SCP was significantly lower in children with JSLE. The VD of total and all quadrants in ICP decreased (p = .015, p = .0045, p = .015, p = .033), except that of the temporal quadrant (p = .366). The total (p = .011) and superior quadrant (p<.01) DCP-VD showed a significant decrease in children with JSLE. The decrease in VD in the total (p = .003) and nasal quadrant (p = .017) of CC was also remarkable. No significant difference in the FAZ area was found between the two groups (p = .774). Multiple linear regression analyses adjusted for age, spherical equivalent, and intraocular pressure were conducted. No contributing factor to OCTA parameters was found. We demonstrated decreased VD in all layers of the retina and CC in patients with JSLE without ocular involvement. Early screening and close follow-up were recommended.

Effects of obstructive sleep apnea on retinal microvasculature.

To detect retinal microvascular variations in obstructive sleep apnea syndrome patients. This prospective, observational case-control study included healthy controls and patients with mild, moderate, and severe obstructive sleep apnea syndrome. Vascular parameters, foveal avascular area, and flow areas in macula-centered, 6.00×6.00 mm2 scan size optical coherence tomography angiography images were compared. The control group had the highest whole image, parafoveal, and perifoveal vessel density among the groups in both superficial and the deep capillary plexus (all P<0.05). Rapid eye movement sleep apnoea-hypopnoea index was reversely correlated with whole (Rho=-0.195, P=0.034), parafoveal (Rho=-0.242, P=0.008), perifoveal (Rho=-0.187, P=0.045) vessel density in the superficial capillary plexus, and whole (Rho=-0.186, P=0.046), parafoveal (Rho=-0.260, P=0.004), perifoveal (Rho=-0.189, P=0.043) vessel density in the deep capillary plexus, though the mean and non-rapid eye movement sleep apnoea-hypopnoea index related with only parafoveal vessel density in the superficial capillary plexus (Rho=-0.213, P=0.020; Rho=-0.191, P=0.038) and the deep capillary plexus (Rho=-0.254, P=0.005; Rho=-0.194, P=0.035). This study shows decreased vessel density and its reverse correlation with the apnoea-hypopnoea index in patients with obstructive sleep apnea syndrome.

Retinal microvascular changes in unilateral functional amblyopia detected by oct-angiography and follow-up during treatment.

To evaluate the macular microvascular changes using optical coherence tomographic angiography (OCT-A) in children with unilateral amblyopia and their reversibility during treatment. Patients with unilateral strabismic or anisometropic amblyopia or residual amblyopia from early congenital cataract surgery, examined between October 2019 and March 2021, were included. Vessel density and perfusion density in the superficial capillary plexus and area, perimeter and circularity of the foveal avascular zone (FAZ) were analysed using OCT-A in amblyopic eyes, contralateral eyes and control group healthy eyes. Correlation analyses between the microvascular parameters and the visual acuity were performed. In a pilot study on a few patients from the amblyopic cohort, longitudinal follow-up during treatment was also performed. A total of 128 eyes of 64 patients were included: 32 amblyopic eyes compared with 32 contralateral eyes and 64 control eyes. Vessel density and perfusion density in the superficial capillary plexus were significantly lower in amblyopic eyes compared to control eyes in 6 × 6 mm (p < 0.02) and 3 × 3 mm (p < 0.01) scans. Correlation analyses showed a linear decrease in vessel density and perfusion density with decreasing visual acuity. The microvascular changes observed were reversible with the occlusion treatment of amblyopia (p < 0.001). The study found a decrease in vessel density and perfusion density in the macula of children with unilateral functional amblyopia. These microvascular changes were correlated with visual acuity and appeared to be reversible with treatment of amblyopia. On the whole, OCT-A appears to be a relevant complementary examination when it comes to diagnosing and monitoring functional amblyopia.