Search Results (254)

Background and Clinical Significance: Hepatic sarcoidosis is a benign lesion of unknown etiology. The gold standard for diagnosing hepatic sarcoidosis is histopathological examination. The symptoms and imaging findings of patients with hepatic sarcoidosis are often atypical, leading to misdiagnosis as hepatocellular carcinoma (HCC). Ultrasound resolution microscopy (URM) can overcome the diffraction limit, enabling fine visualization and quantitative analysis of the microvascular networks. This study aimed to provide new evidence for the differential diagnosis of these two diseases by comparing the URM parameters of hepatic sarcoidosis initially misdiagnosed as HCC with those of HCC. Case Presentation: A 67-year-old woman was admitted to the hospital due to upper abdominal pain for two weeks. Ultrasonography revealed a liver mass. The lesion was located in segment IV of the left hepatic lobe, was approximately 18 × 10 mm in size, and appeared hypoechoic. Contrast-enhanced ultrasound and enhanced magnetic resonance imaging both showed a “fast-in, fast-out” pattern, strongly suggesting HCC. The tumor markers were within the normal range. The patient underwent a laparoscopic left hepatic lobectomy. The histopathological diagnosis of the resected specimen was “hepatic sarcoidosis”. URM examination was performed during the preoperative diagnostic process. Subsequently, the URM parameters of the patient’s lesion were analyzed and compared with those of HCC. The results showed differences in multiple URM parameters, including microvascular flow velocity, diameter, microvascular density ratio, and vascular distribution, between this case of hepatic sarcoidosis and HCC. Conclusions: URM can quantitatively and multidimensionally evaluate the microvasculature of liver lesions, providing new reference data for the diagnosis and differential diagnosis of hepatic sarcoidosis. Full article

Vitamin D deficiency is increasingly recognized as a systemic factor influencing retinal health through inflammatory, neuroprotective, and vasculotropic pathways. Evidence regarding early retinal alterations in otherwise healthy adults remains limited. This cross-sectional study evaluated 120 eyes from 60 healthy adults stratified by serum 25(OH)D levels into <30 ng/mL (n = 60) and ≥30 ng/mL (n = 60). All subjects underwent optical coherence tomography (OCT), OCT angiography (OCTA), visual field testing, and contrast sensitivity assessment. Central macular thickness (CMT), ganglion cell complex (GCC) thickness, and perfusion density in the superficial and deep capillary plexuses (SCP, DCP) were compared between groups. Vitamin-D-insufficient eyes showed significantly reduced CMT (267.66 ± 13.31 µm vs. 274.69 ± 14.96 µm; p = 0.035). GCC thinning was significant only in the inner inferior nasal sector (70.7 ± 13.14 µm vs. 76.45 ± 12.12 µm; p = 0.030), whereas other GCC sectors were comparable between groups. Perfusion density was lower in the DCP across whole, inner, and outer regions (all p < 0.001) and in the SCP inner (p = 0.027) and outer (p = 0.009) regions, while whole SCP did not differ (p = 0.065). FAZ area was numerically larger in vitamin-D-insufficient eyes but was not statistically different (p = 0.168). Functionally, retinal sensitivity decline was greater in vitamin-D-insufficient eyes (−2.89 ± 1.29 dB vs. −2.16 ± 1.04 dB; p = 0.003), and mean central sensitivity was lower (p = 0.010), whereas contrast sensitivity did not differ between groups. Serum vitamin D levels < 30 ng/mL are associated with early, subclinical, structural and microvascular retinal alterations in healthy adults, supporting a potential role of hypovitaminosis D as a modifier of retinal integrity. Full article

Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods: This cross-sectional study included 38 patients (76 eyes) with TED. Each patient underwent a comprehensive ophthalmological evaluation, CAS assessment, and a detailed medical history. Optical coherence tomography angiography (OCTA) was performed to quantify vessel density (VD) in the superficial and deep capillary plexus (SCP and DCP). Exophthalmos, extraocular muscle thickness and orbital fat thickness were measured on MRI scans to evaluate structural changes. Laboratory analyses included thyroid hormone levels, thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase antibodies (anti-TPO), and lipid profile. Results: Active TED patients (CAS ≥ 3) had significantly higher TRAb levels (p < 0.001), while anti-TPO did not differ between groups. Active eyes showed significantly higher DCP VD in the whole image (p = 0.013), parafovea (p = 0.012), and perifovea (p = 0.009) across all quadrants, with no difference in SCP or the foveal avascular zone (FAZ). In linear mixed model regression analyses, after adjusting for previous glucocorticosteroid therapy, higher triglycerides, greater medial rectus thickness, and whole-image DCP VD independently predicted higher CAS values (R² = 42, p < 0.001). After adjusting for age and sex, CAS remained significantly positive predictor of DCP VD in the parafovea (R² = 0.22, p < 0.001). Conclusions: Changes in DCP VD reflect TED activity and structural orbital involvement. Full article

Background/Objectives: Astrocytoma IDH-mutant CNS WHO grade 4 is a malignant tumor of the central nervous system characterized by tumor necrosis, microvascular proliferation, and/or homozygous CDKN2A/B deletion. This study aims to investigate the prognostic role of the consequences of hypoxic events leading to necrosis and microvascular density, observing their associations with clinical-imaging parameters and morphogenetics. Methods: We performed a retrospective analysis over a 10-year period. Clinical and imaging data were collected from observation sheets and electronic databases. Six immunohistochemical markers and FISH testing were used to evaluate the prognosis and neoformation of blood vessels. Based on the whole slide image, the necrotic percentage was assessed, and the microvascular density was quantified. All data were statistically analyzed. Results: We identified 44 cases, with a mean age of 57.86 years. From a clinical perspective, advanced age, arterial hypertension, diabetes mellitus, and acute onset of clinical manifestations represent negative prognostic factors. In imaging, the increased rate of resectability is a protective factor, while the presence of residual volume and an increased residual volume have a negative impact on survival. The consequences of hypoxic events (tumor necrosis and microvascular density) are negative risk factors for survival. Added to these are p53 overexpression, loss of PTEN, deletion, and amplification of the CDKN2A gene. Conclusions: We observed that necrosis and increased microvascular density resulting from microvascular proliferation are both defining features of the tumor and impact patient prognosis and survival. In addition, they induce or are associated with other essential changes (p53, PTEN, CDKN2A) that promote tumor aggressiveness. Full article

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus, driven by oxidative stress, inflammation, and microvascular dysfunction. Dapagliflozin, a selective inhibitor of sodium–glucose cotransporter type 2 (SGLT2), is used in the treatment of type 2 diabetes and has pleiotropic antioxidant and anti-inflammatory effects. The aim of this study was to evaluate the neuroprotective effects of dapagliflozin in an experimental model of streptozotocin (STZ)-induced diabetic peripheral neuropathy in mice. C57BL/6 mice were divided into three groups: control (DM–), STZ-induced diabetes (DM+), and diabetes + dapagliflozin (DM + DAPA, 10 mg/kg/day, oral administration for 12 weeks). Clinical (glycemia, weight, diuresis), electrophysiological, and histopathological parameters were evaluated, and behavioral tests (Open Field, Von Frey, Hot Tail) were performed. Dapagliflozin significantly reduced hyperglycemia, limited weight loss and polyuria, and improved locomotor behavior and nociceptive sensitivity. Electrodiagnostically, the treatment increased the amplitude and reduced the duration of motor potentials, indicating improved nerve conduction. Histological analyses showed decreased hydroxynonenal (HNE) immunoreactivity, suggesting attenuation of oxidative stress, reduced perineural fibrogenesis, and maintained intraepidermal nerve fiber density. Dapagliflozin exerts significant neuroprotective effects in experimental diabetic peripheral neuropathy by reducing oxidative stress, inflammation, and fibrosis and maintaining the structural and functional integrity of peripheral nerves. Full article

Background: Trabeculectomy remains gold-standard surgical approach for intraocular pressure (IOP) control in glaucoma, yet its impact on optic nerve head (ONH) morphology and retinal microvasculature has not been fully clarified. This study aimed to investigate structural and vascular changes of the ONH and macula after trabeculectomy using spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). Methods: In this retrospective study, data from 22 patients with primary open-angle glaucoma who underwent uncomplicated trabeculectomy were reviewed. The fellow eye served as control. Structural parameters, including Bruch’s membrane opening (BMO), maximum cup depth (MCD), and cup area, were measured with SD-OCT. Vessel density (VD) of the optic disc, peripapillary retina, and macular superficial (SCP) and deep (DCP) capillary plexuses were analyzed with OCTA. Preoperative and two-month postoperative data were compared using paired statistical tests. Results: Mean IOP decreased from 23.1 ± 3.9 mmHg to 13.2 ± 3.2 mmHg (p < 0.001). Significant postoperative reductions were observed in BMO (−5 ± 6%, p = 0.004), MCD (−31 ± 8%, p < 0.001), and cup area (−44 ± 18%, p < 0.001). RNFL thickness and ONH vascular parameters remained stable. In contrast, DCP vessel density increased in the foveal (p = 0.002) and parafoveal (p = 0.023) regions, while SCP density showed no significant change. Conclusions: Trabeculectomy was associated with measurable reversal of optic disc cupping, indicating partial structural recovery of the ONH following IOP reduction. The selective improvement in deep retinal vessel density suggests a layer-specific microvascular response. These findings provide further insight into the interplay between mechanical and vascular mechanisms in glaucoma and may inform postoperative monitoring strategies. Full article

Objectives: To assess retinal microvascular changes in patients with Grade II and III obesity before and after bariatric surgery using Optical Coherence Tomography Angiography (OCTA), and to compare these metrics with age- and sex-matched healthy controls. Methods: Prospective, consecutive, longitudinal cohort study with a 12-month follow-up. Grade II and III obese patients scheduled for bariatric surgery underwent comprehensive ophthalmic examinations, including OCTA imaging, prior to the surgery and postoperatively at 1 month, 6 months, and 12 months post-surgery. Results: A total of 43 eyes from 43 patients with obesity (one eye per patient) were included at baseline. At 12 months post-surgery, there was a significant increase in vessel density (VD) (16.70 vs. 17.68; p < 0.01) and perfusion density (PD) (0.406 vs. 0.433; p < 0.01), reaching values comparable to those of the control group (17.73 and 0.434, respectively). Significant reductions were also observed in body mass index (BMI) (43.74 vs. 29.53; p < 0.01), body weight (122.44 kg vs. 81.90 kg; p < 0.01), and intraocular pressure (IOP) (15.72 mmHg vs. 14.16 mmHg; p < 0.01). Conclusions: This study demonstrates a compelling association between obesity and retinal microvascular impairment, highlighting the efficacy of bariatric surgery not only in achieving substantial weight loss but also in improving the retinal perfusion of these patients, achieving metrics at 12 months comparable to age- and sex-matched healthy controls at baseline. These findings raise the hypothesis of the potential utility of OCTA as a monitoring tool for tracking the microvascular status in patients with obesity undergoing bariatric surgery in a longitudinal manner. Full article

Background: Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten exposure in genetically predisposed individuals. Beyond gastrointestinal symptoms, CD is increasingly recognized to affect extraintestinal organs, including the eye. Methods: A PubMed, Cochrane, Web of Science, and Scopus databases search up to April 2025 was conducted to identify studies on ocular involvement in CD. Results: Large population-based cohorts have demonstrated an increased risk of cataract and uveitis in individuals with CD. Cross-sectional and case–control studies further report reduced tear break-up time and decreased Schirmer test values, indicating tear film instability and associated ocular surface abnormalities. Additional findings include reduced anterior chamber depth and volume, alterations in subfoveal and peripapillary choroidal thickness, thinning of the retinal nerve fiber layer, and microvascular changes such as reduced superficial and deep capillary plexus densities. Furthermore, deficiencies of vitamins A, D, B12, and iron have been consistently associated with structural and functional ocular alterations, underscoring the contribution of impaired nutrient absorption. Conclusions: Ocular involvement in CD likely reflects the interplay of immune dysregulation, nutritional deficiencies, and microvascular alterations. Ophthalmic referrals should be considered in CD patients presenting with ocular symptoms. Early recognition and regular monitoring may facilitate timely diagnosis, improve visual outcomes, and support normal ocular development. Full article

Diabetic retinopathy (DR) is a microvascular disorder of the retina due to diabetes mellitus (DM). Natural products are widely used to prevent and treat various diseases caused by DM. This study aims to evaluate the effect of buah merah (Pandanus conoideus Lamk.) extract on retinal density and apoptosis in a diabetic rat model. A total of 30 male rats (Rattus norvegicus) weighing 120–150 g were induced with diabetes using alloxan and divided into five groups: group 1 (normal control), 2 (diabetic control), 3 (diabetes + 1 mL buah merah extract), 4 (1.5 mL), and 5 (2 mL). Buah merah extract, equivalent to 12 mg total carotenoids, 10 mg total tocopherols, 1.348 mg alpha-tocopherol, and 3.4 mg beta-carotene, was administered for 14 days. Retina was examined using hematoxylin and eosin (HE) staining for photoreceptor and retinal ganglion cell density, and immunohistochemistry (IHC) of Caspase-3 for apoptosis. The results showed that group 3 had photoreceptor and retinal ganglion cell densities close to normal, with photoreceptor density values of 722.52 ± 147.56 and ganglion 18.73 ± 5.61. The post hoc test confirmed a significant protective effect of buah merah extract in group 3 (p-value 0.014). However, buah merah extract was found to maintain photoreceptor and retinal ganglion cell density, but no significant inhibitory effect was observed on photoreceptor or retinal ganglion cell apoptosis. Further studies are needed to better understand the mechanism and potential therapeutic effect of buah merah extract. Full article

Background: Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, unrefreshed sleep, and cognitive disturbances. Despite extensive research, its pathophysiology remains incompletely understood, and there are no validated biomarkers for diagnosis. Videocapillaroscopy is a non-invasive imaging technique that enables detailed visualization of microvascular structures and may provide insights into microcirculatory alterations associated with FM. Methods: Thirty patients with FM and 30 healthy controls underwent oral videocapillaroscopy at four sites: right and left buccal mucosa and upper and lower labial mucosa. Quantitative parameters, including capillary caliber, density, and length, were extracted using a validated neural-network-based software, while qualitative parameters, including visibility, orientation, and the presence of microhemorrhages, were assessed by the operator. Results: Capillary length was significantly reduced in fibromyalgia patients (297.49 ± 26.82 µm) compared to healthy controls (324.43 ± 37.59 µm; p = 0.002), and capillary orientation differed significantly between groups (p < 0.05). Capillary caliber, density, and visibility did not show statistically significant differences. Conclusions: These findings indicate subtle microvascular alterations in the oral mucosa of patients with fibromyalgia. Although the observed changes are not sufficient for diagnostic purposes or early detection, they provide preliminary evidence that videocapillaroscopy can detect microvascular features associated with FM in the oral mucosa. Further studies with larger cohorts and longitudinal designs are warranted to clarify the clinical relevance of these observations and to explore their potential association with symptom severity or disease progression. Full article

Exposure to stress during early developmental stages correlates with persistent alterations in multiple physiological systems, including the renal system. In rodents, maternal separation (MS) is a widely used experimental model to simulate postnatal adversity. Although this condition affects various renal parameters, a gap persists in knowledge regarding its impact on the functional unit of the kidney and the organization of the parenchyma. Thus, the objective of this systematic review was to analyze the effects of MS on the morphofunctional characteristics of the kidney in rodent models. We developed a protocol a priori following the SYRCLE and PRISMA guidelines and registered it in PROSPERO (CRD420251004703). We searched Web of Science, Scopus, Medline, Embase, BIREME-BVS, and SciELO without language or date restrictions, targeting experimental studies in rodents subjected to MS that evaluated structural, functional, or molecular alterations. Three independent reviewers performed data selection and extraction, and they assessed the risk of bias using the SYRCLE’s RoB tool. We included seven studies that met the eligibility criteria. At the structural level, studies reported cellular infiltrates positive for MPO, CD44, and TLR4, along with increased cortical and medullary microvascular density. Regarding renal function, the included studies described changes in ACE1 and ACE2 activity, oxidative stress, and enzymatic imbalance accompanied by a compensatory antioxidant response. At the molecular level, the studies reported variations in the expression of adrenergic receptors and the renin-angiotensin system. These findings suggest that MS may compromise the organization and functional integrity of the developing kidney, underscoring the need for studies that integrate structural and functional analyses in greater depth. Full article

In the current study, we focus on analyzing the relationship between changes in micro- and macrocirculation and different stages of metabolic memory. We hypothesized that early poor glycemic control induces lasting endothelial changes detectable in pediatric type 1 diabetes (T1D) microcirculation. We assessed microcirculation structure and function using capillaroscopy, transcutaneous oxygen pressure (TcPO₂), and optical coherence tomography (OCT). We evaluated macrovascular circulation using pulsatility index (PI), ankle-brachial index (ABI) and pulse pressure (PP). We also examined the relationship between circulation parameters, the age at onset, and diabetes duration. The study included 67 patients with uncomplicated type 1. We divided all patients into four groups based on their HbA_1c levels at T1D onset and their average HbA_1c after one and two years. We assessed the concentrations of TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, serum angiogenin, VEGF, sVCAM-1, ICAM-1, sP-Selectin, AGEs, and sRAGE. We compared subgroups with different levels of metabolic memory but comparable T1D duration and age at diagnosis. Micro- and macrovascular parameters were similar between the groups. Our comparison of subgroups with identical metabolic memory but different durations and ages at diagnosis revealed clear differences. The subgroup with a shorter T1D duration showed higher capillary density and a smaller inter-capillary distance compared to those with a longer diabetes duration. This subgroup with shorter duration had significantly lower AGE levels and a reduced TNF-α/IL-35 ratio, along with higher levels of IL-35, IL-4, and IL-12, compared to the longer-duration group. Our findings indicate that in youths with uncomplicated T1D, disease duration—not metabolic memory—plays a dominant role in early microvascular alterations. Full article

Background: Retinal microvascular changes may serve as biomarkers for disease activity in multiple sclerosis (MS). This study evaluated macular and peripapillary vascular plexus densities using optical coherence tomography angiography (OCTA) in patients with relapsing MS (RMS) and healthy controls (HCs), exploring their association with disease activity based on the NEDA-3 concept. Methods: In a cross-sectional study, 117 RMS patients and 37 HCs underwent OCTA imaging. Parameters analyzed included superficial vascular plexus (SVP), deep vascular plexus (DVP), foveal avascular zone (FAZ), and radial peripapillary capillary (RPC) density. Images with artifacts were excluded. Associations between OCTA metrics and demographic, clinical, and MRI volumetrics, as well as NEDA-3 status, were evaluated using multivariate generalized estimating equations. Receiver operating characteristic (ROC) curves assessed predictive capacity. Results: Compared to HCs, MS eyes with prior optic neuritis showed significantly lower SVP density (p < 0.05). DVP and FAZ parameters did not differ between groups. SVP and DVP densities correlated with age, disease duration, relapse history, and MRI volumetrics, including gray matter and whole brain volume. SVP density predicted NEDA-3 status (AUC = 0.82), while DVP also showed predictive value (AUC = 0.64). FAZ FD (Foveal density) was associated with gray matter and whole brain atrophy (AUC = 0.62–0.61). Conclusions: Retinal vascular alterations correlate with clinical and MRI measures in MS. Reduced SVP and DVP densities may serve as markers of recent disease activity, and FAZ metrics reflect neurodegeneration. OCTA may be a valuable non-invasive tool for monitoring MS progression. Full article

Post-COVID-19 syndrome (PCS) is a multifactorial disorder comprising different subgroups. Our study aimed to investigate the longitudinal changes in retinal microcirculation in PCS patients. Eighty PCS patients were recruited at the Department of Ophthalmology at the Friedrich-Alexander University of Erlangen-Nürnberg. Retinal microcirculation was measured twice using optical coherence tomography angiography (OCT-A) within the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and peripapillary region. Vessel density (VD) was calculated using the Erlangen Angio Tool with an APSified and Bruch’s membrane opening-based analyses. The least-squares means (LS-Means) of VD were 30.4 (SE = 0.168) vs. 30.3 (SE = 0.166) (SVP), 22.4 (SE = 0.143) vs. 22.2 (SE = 0.141) (ICP), 23.9 (SE = 0.186) vs. 23.8 (SE = 0.185) (DCP), and 27.4 (SE = 0.226) vs. 27.0 (SE = 0.224) (peripapillary) in patients with PCS at visits 1 and 2, respectively. The study cohort showed physically stable PCS symptoms with PEM/fatigue and concentration disorders as major symptoms and only a slight, clinically irrelevant improvement of the Bell Score. The multivariate longitudinal model confirmed the clinical observations by showing that VD did not change significantly during follow-up (p = 0.46). Strong interdependencies between the macular layers (p < 0.001) were observed. The data of the present study suggests that while overall APSified macular VD and BMO-based APSified peripapillary VD were stable within a PCS cohort of physically stable PCS symptoms, individual patients may experience coordinated microvascular changes, particularly within the macular plexuses. Together, the results support a model of heterogeneous yet biologically consistent microvascular response in PCS pathophysiology. Full article

Animal models are essential for studying tumor pathophysiology; however, most lack the capacity for repeated in vivo observation of tumor growth and vascularization over extended periods. This study aimed to establish a novel in vivo model using the mouse dorsal skinfold chamber. Tumor induction was performed using different membrane types (two polytetrafluoroethylene meshes and a polydioxanone plate), followed by monitoring of tumor vascularization via intravital fluorescence microscopy (IVM). Tumors developed successfully over six weeks, demonstrating sustained vascular supply and enabling, for the first time, the investigation of vascular networks in advanced tumors. Among the membranes tested, the polydioxanone membrane facilitated easier chamber preparation but may negatively affect angiogenesis and promote inflammation. IVM revealed persistent microcirculation in manifested tumors over six consecutive days, allowing detailed assessment of microvascular parameters, leukocyte–endothelial interactions, and functional capillary density. This model enables repetitive, high-resolution visualization of tumor microcirculation dynamics in vivo. In conclusion, this improved mouse dorsal skinfold chamber combined with IVM provides a powerful tool for investigating tumor angiogenesis and evaluating therapeutic interventions in advanced tumors. Full article