RESUMEN
PURPOSE: This study was performed to assess the prevalence of the vascularized foveal zone, including macular-foveal capillaries (MFC) and congenital retinal macrovessels (CRM), and to analyze the structural characteristics of the macular area in patients with MFC. MATERIAL AND METHODS: The first phase of the study evaluated the prevalence of MFC and CRM. Optical coherence tomography angiography (OCT-A) was performed, and OCT-A images of the foveal avascular zone were analyzed. In the second phase, two groups were formed: the MFC group (12 eyes, 9 patients, mean age 43.8±10.7 years) and the control group (18 eyes, 17 patients, mean age 43.0±11.8 years). A comparative analysis was performed assessing central retinal thickness (CRT), thickness of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and foveal pit depth. RESULTS: MFCs were detected in 45 eyes from a total sample of 1031 eyes of 536 patients. The presence of CRM was recorded in three eyes of three patients. RNFL thickness was significantly higher in the MFC group in the inferior parafoveal sector (26.50 [26.00; 29.50] and 24.50 [21.75; 26.50] µm; p=0.022) and in the foveal zone (15.50 [14.00; 16.00] and 12.00 [11.00; 14.00] µm; p=0.017). Additionally, patients with MFC had a higher thickness of GCL and IPL in the fovea, inferior, nasal, and temporal parafoveal sectors. The depth of the foveal pit was significantly lower in the MFC group compared to the control group (83.0 [77.4; 101.6] and 128.0 [107.5; 147.05] µm; p=0.001). CONCLUSION: The prevalence of MFC was 4.36% (calculated per number of eyes), while the prevalence of CRM - 0.29%. The macular area in patients with MFC had increased thickness of the inner retinal layers and decreased depth of the foveal pit, suggesting potential disruption in the natural process of ganglion cell migration and apoptosis during embryogenesis.
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Fóvea Central , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Fóvea Central/irrigación sanguínea , Fóvea Central/diagnóstico por imagen , Adulto , Femenino , Masculino , Tomografía de Coherencia Óptica/métodos , Prevalencia , Persona de Mediana Edad , Vasos Retinianos/diagnóstico por imagen , Capilares/diagnóstico por imagen , Capilares/patología , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Federación de Rusia/epidemiología , Agudeza Visual , Angiografía con Fluoresceína/métodosRESUMEN
Purpose: To assess the correspondence between interdigitation zone (IZ) reflectivity, ellipsoid zone (EZ) loss, inner retinal layer reflectivity, patterns of capillary dilation, and telangiectasia in eyes with early macular telangiectasia type 2 (MacTel). Patients and Methods: Twenty-eight eyes of 22 patients with grade 0-2 MacTel (according to the MacTel project classification) and 28 healthy control eyes were included in this study. Multimodal imaging, including optical coherence tomography (OCT) angiography, adaptive optics flood illumination ophthalmoscopy (AO-FIO) and blue light reflectance (BLR), was performed. The EZ, IZ, and outer plexiform layer (OPL) were analyzed on the structural OCT C-scans. The vascular density (VD) was measured on the binarized and skeletonized angiograms of the superficial vascular plexus and deep capillary complex. The vascular diameter index (VDI) was calculated by dividing the binarized VD by the skeletonized VD. Results: On AO-FIO, cone density in the MacTel zone was significantly lower in MacTel eyes than in controls, even in areas located outside the EZ loss (P < 0.001). A distinctive pattern of IZ reflectivity attenuation extended beyond the area of EZ attenuation. The shape and size of a strong OPL hyper-reflectivity corresponded to the MacTel white area (MacTel zone) seen on BLR. Capillary dilation and rarefaction were colocalized with this area, extending beyond visible telangiectasia. The VDI was higher in MacTel eyes than in controls (P < 0.001). Conclusions: These findings suggest that in early MacTel eyes, photoreceptor signal alteration, OPL hyper-reflectivity, and capillary dilation, potentially associated with Müller cell dysfunction, precede the EZ loss.
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Angiografía con Fluoresceína , Oftalmoscopía , Telangiectasia Retiniana , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Femenino , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/fisiopatología , Telangiectasia Retiniana/diagnóstico por imagen , Masculino , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Angiografía con Fluoresceína/métodos , Persona de Mediana Edad , Anciano , Agudeza Visual/fisiología , Fondo de Ojo , Imagen Multimodal , Adulto , Capilares/patología , Capilares/diagnóstico por imagenRESUMEN
Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6 mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6 mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.
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Células Ganglionares de la Retina , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Estudios Transversales , Estudios Retrospectivos , Masculino , Células Ganglionares de la Retina/patología , Femenino , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Persona de Mediana Edad , Adulto , Miopía/patología , Miopía/diagnóstico por imagen , Miopía/fisiopatología , Microvasos/patología , Microvasos/diagnóstico por imagen , Longitud Axial del Ojo/patología , Longitud Axial del Ojo/diagnóstico por imagen , Fibras Nerviosas/patología , Angiografía con Fluoresceína/métodos , Adulto Joven , Anciano , Capilares/patología , Capilares/diagnóstico por imagenRESUMEN
Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p < 0.001) and in CTEPH (8.4 ± 1.5, p < 0.001) compared to asymptomatic controls (10.3 ± 1.0 capillaries/mm). Capillary density was similar in iPAH and hPAH and unrelated to hemodynamics in either PAH or CTEPH. A lower capillary density was predictive of clinical worsening in PAH (p 0.05). After normalization of pulmonary artery pressures by PEA or BPA, capillary density remained reduced in CTEPH patients. Capillary loop apex, capillary and venous- and arterial limb diameter were increased in patients with PAH and CTEPH compared to controls. Nailfold capillary density is reduced to a similar extent in iPAH, hPAH and CTEPH. Normalization of hemodynamics by PEA or BPA does not lead to a restoration of capillary density in CTEPH. Capillary dimensions were increased in both patients with PAH and CTEPH. Lower capillary density was predictive of clinical worsening in PAH. Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic microangiopathy and pulmonary vascular remodeling.
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Capilares , Hipertensión Pulmonar , Humanos , Femenino , Masculino , Persona de Mediana Edad , Capilares/patología , Capilares/fisiopatología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Anciano , Biomarcadores , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/complicaciones , Angioscopía Microscópica/métodos , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/cirugía , Endarterectomía/métodos , Densidad Microvascular , Enfermedad Crónica , Uñas/irrigación sanguínea , Estudios de Casos y ControlesRESUMEN
Age-related macular degeneration (AMD) is a multifactorial disease characterized by progressive alterations of different retinal structures ultimately leading to vision loss. Among these, the choriocapillaris (CC) has been found to be affected in different stages of AMD. In this review we provide a discussion on the different stages of AMD, focusing particularly on the alterations involving the CC. This has been possible thanks to the introduction of optical coherence tomography-angiography, a recently developed imaging technique which allows the detection of blood flow in choroidal vessels. Therefore, the aim of this review is to provide a description of the various alterations involving the CC in the different stages of AMD.
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Coroides , Angiografía con Fluoresceína , Degeneración Macular , Tomografía de Coherencia Óptica , Humanos , Coroides/irrigación sanguínea , Coroides/patología , Coroides/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Degeneración Macular/diagnóstico , Capilares/patología , Capilares/diagnóstico por imagen , Flujo Sanguíneo Regional/fisiologíaRESUMEN
Purpose: This study aimed to investigate the impact of distinctive capillary-large vessel (CLV) analysis in optical coherence tomography angiography (OCTA) on the classification performance of diabetic retinopathy (DR). Methods: This multicenter study analyzed 212 OCTA images from 146 patients, including 28 controls, 36 diabetic patients without DR (NoDR), 31 with mild non-proliferative DR (NPDR), 28 with moderate NPDR, and 23 with severe NPDR. Quantitative features were derived from the whole image as well as the parafovea and perifovea regions. A support vector machine classifier was employed for DR classification. The accuracy and area under the receiver operating characteristic curve were used to evaluate the classification performance, utilizing features derived from the whole image and specific regions, both before and after CLV analysis. Results: Differential CLV analysis significantly improved OCTA classification of DR. In binary classifications, accuracy improved by 11.81%, rising from 77.45% to 89.26%, when utilizing whole image features. For multiclass classifications, accuracy increased by 7.55%, from 78.68% to 86.23%. Incorporating features from the whole image, parafovea, and perifovea further improved binary classification accuracy from 83.07% to 93.80%, and multiclass accuracy from 82.64% to 87.92%. Conclusions: This study demonstrated that feature changes in capillaries are more sensitive during DR progression, and CLV analysis can significantly improve DR classification performance by extracting features that are specific to large vessels and capillaries in OCTA. Incorporating regional features further improves DR classification accuracy. Differential CLV analysis promises better disease screening, diagnosis, and treatment outcome assessment.
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Capilares , Retinopatía Diabética , Angiografía con Fluoresceína , Curva ROC , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/clasificación , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Femenino , Capilares/patología , Capilares/diagnóstico por imagen , Masculino , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Persona de Mediana Edad , Angiografía con Fluoresceína/métodos , Anciano , Estudios Retrospectivos , Fondo de Ojo , AdultoRESUMEN
A man in his 60s with hyperamylasemia underwent contrast-enhanced computed tomography, which revealed masses in his pelvic cavity on the right side and in the left axilla. Hence, a detailed examination was performed. Upon performing Sonazoid® (perfluorobutane) contrast-enhanced ultrasound, it was discovered that the right-sided pelvic cavity mass exhibited centripetal contrast-enhancement right from the early stage. Subsequently, the contrast material disappeared from the center and was washed out in the postvascular phase. The mass was suspected to be caused by vascular malformations. The right-sided pelvic cavity mass was excised, and upon histopathological examination, it was detected to be composed of capillary malformations. Thus, it was found that Sonazoid® contrast-enhanced ultrasound examination could aid in diagnosing retroperitoneal masses.
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Medios de Contraste , Compuestos Férricos , Hierro , Óxidos , Ultrasonografía , Humanos , Masculino , Fluorocarburos , Espacio Retroperitoneal/diagnóstico por imagen , Capilares/diagnóstico por imagen , Capilares/anomalías , Capilares/patología , Malformaciones Vasculares/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
A comparative study of the morphological and functional state of the microvasculature of the substantia nigra pars compacta of the brain (SNc) and bone marrow of rats was carried out using the rotenone model of Parkinson's disease (PD) and with subsequent administration of bacterial melanin (BM). The detection of microvasculature was carried out according to the histoangiological method of Chilingaryan. Animal behavior was studied using a cylinder test. An analysis of morphometric data showed that, in comparison with control animals, experimental animals with rotenone dysfunction showed an increase in capillary diameters and a general reduction in the capillary link in SNc. Behavioral tests have shown that the animals with rotenone intoxication exhibit a form of behavior inherent in PD (freezing, immobility, apathy). Under the influence of BM, the diameter of the capillaries in the SNc approaches the norm, and the capillary link is restored. Due to the protective effect of BM in rats with rotenone intoxication, the trophism of the brain tissue increases as a result of the approach of the lumen of the vessels to the norm and the opening of new branches in the capillary network, an increase in the density of capillaries, which ensures the safety of nerve cells. Animal behavior indicators are close to normal. A comprehensive analysis of cytogenetic data of rat bone marrow was also carried out. In animals with PD, compared to controls, there is a significant increase in the amount of polyploid cells (PC) and a decrease in the level of mitotic index (MI), which usually manifests itself in inflammatory processes and is accompanied by inhibition of bone marrow hematopoiesis. Under the influence of BM, a tendency towards normalization of MI was noted and a significant decrease in the percentage of PC was obtained, which possibly indicates its beneficial effect. The data obtained suggest that BM can be used as a therapeutic agent in the treatment of PD.
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Conducta Animal , Modelos Animales de Enfermedad , Melaninas , Rotenona , Animales , Melaninas/metabolismo , Ratas , Conducta Animal/efectos de los fármacos , Masculino , Médula Ósea/efectos de los fármacos , Enfermedad de Parkinson/patología , Porción Compacta de la Sustancia Negra/efectos de los fármacos , Porción Compacta de la Sustancia Negra/patología , Porción Compacta de la Sustancia Negra/metabolismo , Ratas Wistar , Capilares/efectos de los fármacos , Capilares/patologíaAsunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Células Endoteliales , Hipertensión Pulmonar , Receptor Notch4 , Transducción de Señal , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Animales , Humanos , Receptor Notch4/metabolismo , Receptor Notch4/genética , Reprogramación Celular , Capilares/metabolismo , Capilares/patología , Ratones , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Arteria Pulmonar/citologíaRESUMEN
OBJECTIVES: Connective tissue-associated interstitial lung diseases (CTD-ILD) are believed to be caused by microvascular damage. The objective of this study was to assess the nailfold capillaroscopy (NFC) pattern in patients diagnosed with both CTD-ILD and non-CTD-ILD to identify microvascular changes and determine the relation between capillaroscopic parameters, clinical variables, and disease-related measurements. PATIENTS AND METHODS: This cross-sectional study included 95 patients with interstitial lung disease who applied to our Rheumatology and Chest Clinics between September 2021 and July 2023. The patients were divided into two groups based on their diagnosis: non-CTD-ILD (group 1) and CTD-ILD (group 2). Nailfold capillaroscopy was performed. RESULTS: Ninety-five patients, 49 (51% female, mean age 62.31 ± 11.027 years) in group 1 and 46 (69.6% female, mean age 62.09 ± 10.887 years) in group 2, were included in the study. Abnormal capillary morphologies were both detected in the CTD-ILD group and the non-CTD-ILD groups. In patients with a usual interstitial pneumonia (UIP) pattern on chest computed tomography (CT), tortuosity was higher than in patients with non-specific interstitial pneumonia (NSIP) (P = 0.041), and the proportion of tortuosity increased significantly as the duration of the disease increased (P = 0.016). CONCLUSION: Our study highlights capillaroscopic abnormalities alone may not be sufficient to differentiate CTD-ILD (other than systemic sclerosis) from non-CTD-ILD. The presence of NFC abnormalities in non-CTD-ILD may suggest that fibrotic lung disease could potentially play a role in the deterioration of the microvascular structure or abnormal angiogenesis. Our study demonstrated that a multidisciplinary approach, incorporating clinical, morphological, pathological, and serological evaluations, is necessary for interpreting ILD. Key Points ⢠Capillaroscopic abnormalities can also be seen in non-CTD-ILD. ⢠Capillaroscopy findings do not distinguish the non-Ssc etiology of ILD. ⢠Nailfold capillaroscopy may have the potential to serve as a useful tool in predicting prognosis and monitoring the disease progression in patients with idiopathic pulmonary fibrosis (IPF).
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Enfermedades Pulmonares Intersticiales , Angioscopía Microscópica , Humanos , Femenino , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Transversales , Anciano , Pronóstico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Uñas/irrigación sanguínea , Uñas/diagnóstico por imagen , Capilares/diagnóstico por imagen , Capilares/patología , Tomografía Computarizada por Rayos XRESUMEN
Stroke is not only associated with muscle weakness, but also associated with reduced muscle fatigue resistance and reduced desaturation during exercise that may be caused by a reduced oxidative capacity and/or microvasculature. Therefore, the objective of the present study was to determine the effects of stroke on muscle mass, fiber size and shape, capillarization and oxidative capacity of the rat m. extensor carpi radialis (ECR) and m. flexor carpi ulnaris (FCU) after a photothrombotic stroke in the forelimb region of the primary sensorimotor cortex. The main observation of the present study was that 4 weeks after induction of stroke there were no significant changes in muscle fiber size and shape. Although there was no significant capillary rarefaction, there was some evidence for remodeling of the capillary bed as reflected by a reduced heterogeneity of capillary spacing (p = 0.006) that may result in improved muscle oxygenation. In the ECR, but not in the FCU, this was accompanied by reduction in muscle fiber oxidative capacity as reflected by reduced optical density of sections stained for succinate dehydrogenase (p = 0.013). The reduced oxidative capacity and absence of significant capillary rarefaction resulted in a capillary to fiber ratio per unit of oxidative capacity that was higher after stroke in the ECR (p = 0.01), but not in the FCU. This suggests that at least during the early stages, stroke is not necessarily accompanied by muscle fiber atrophy, and that stroke-induced reductions in oxidative capacity resulting in relative excess of capillarization are muscle specific.
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Capilares , Músculo Esquelético , Animales , Masculino , Ratas , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/irrigación sanguínea , Capilares/metabolismo , Capilares/patología , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Oxidación-Reducción , Ratas Wistar , Ratas Sprague-DawleyRESUMEN
The peribiliary capillary plexus (PCP) regularly and densely lines the basal side of the lining epithelia of normal bile ducts. To determine the pathology of the PCP in high-grade biliary intraepithelial neoplasms (BilINs) and intraductal papillary neoplasms of the bile duct (IPNBs), a precursor of cholangiocarcinoma (CCA), and CCA. Seventy-six cases of surgically resected high-grade BilIN and 83 cases of IPNB were histopathologically examined using endothelial immunostaining of PCP; all cases of high-grade BilIN and 40 cases of IPNB were associated with invasive CCA. Invasive and preinvasive neoplasms were pathologically examined referring to a two-layer pattern composed of biliary lining epithelia and underlying PCP unique to the bile duct. All high-grade BilIIN cases had an underlying single layer of capillaries, similar to PCP (PCP-like capillaries). In 43% of the 83 cases of IPNB, these capillaries were regularly distributed in almost all stalks and intervening stroma of intraluminal neoplastic components, while in the remaining 57% of IPNB, capillaries were sparsely or irregularly distributed in intraluminal components showing cribriform or solid growth patterns composed of striking atypical neoplastic epithelia. Invasive carcinomas associated with high-grade BilIN and IPNB were not lined with capillaries. The loss of PCP-like capillaries underlying high-grade BilIN and in stalks or stroma of IPNB may be involved in the malignant progression of these precursors. Immunostaining of PCP could be a new pathological tool for the evaluation of malignant progression and vascular supply in CCA and its precursors.
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Neoplasias de los Conductos Biliares , Capilares , Colangiocarcinoma , Humanos , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Masculino , Femenino , Capilares/patología , Persona de Mediana Edad , Conductos Biliares Intrahepáticos/patología , Anciano , Carcinoma in Situ/patología , Lesiones Precancerosas/patología , Adulto , Anciano de 80 o más Años , InmunohistoquímicaRESUMEN
BACKGROUND: Leprosy, a chronic infectious disease, is associated with various nail changes. Its etiopathogenesis is multifaceted, with microvascular damage being crucial. Nail fold capillaroscopy (NFC) emerges as a novel tool for detecting early vascular deficits in leprosy. The study aimed to assess and provide a complete clinical characterization of NFC changes in leprosy patients. METHODS: It is an observational cross-sectional study, done over a period of 1.5 year (January 2021 to august 2022) in a tertiary care hospital, encompassing 60 patients diagnosed with leprosy (18-60 years). After obtaining informed consent; detailed history, complete cutaneous and neurological examinations were conducted. All fingernails and toenails were examined for clinical changes. Subsequently, onychoscopy was performed using USB type of video-dermatoscope (Model AM7115MZT Dino-lite), a non-invasive tool. This was followed by NFC which was done for all fingernails and images were recorded by single operator, which were then assessed for quantitative and qualitive changes and statistical analysis was conducted using SPSS v20, with mean capillary density compared using Student's t-test, morphological change frequencies assessed by proportions, and group comparisons made using Chi-square or Fischer exact tests, with a significance threshold of p < 0.05. RESULTS: Among the 60 patients, 39 were in the lepromatous group, which included both borderline lepromatous (BL) and lepromatous leprosy (LL) patients, and 17 were in the tuberculoid group, which included borderline tuberculoid (BT) leprosy patients; 23.3 % had Type 1 reactions, and 18.3 % had Type 2 reactions. Nail fold capillaroscopy (NFC) showed microvasculature changes in 93.3 % of patients. The average capillary density was 6.8 ± 1.5 capillaries per mm, with the lepromatous group having a lower density (6.5 ± 1.09) compared to the tuberculoid group (7.0 ± 0.86). The most common NFC changes in the tuberculoid group were tortuous capillaries (70 %), capillary dropouts, and dilated capillaries (both 64.7 %). In the lepromatous group, capillary dropouts (82 %) were most frequent, followed by tortuous (69 %), receding (69 %), and dilated capillaries (66 %). A dilated and prominent subpapillary plexus was more common in the lepromatous group (35 %, p = 0.04). Patients with trophic changes in the lepromatous group had more capillary dropouts and bizarre capillaries. Capillary dropouts, dilated capillaries, and visible subpapillary venous plexus were more prevalent in patients with Type 2 reactions. CONCLUSION: NFC changes are prevalent in both tuberculoid and lepromatous leprosy, which may be an indicator of peripheral vascular compromise and trophic changes, especially in lepromatous leprosy. NFC can be an auxiliary tool for detecting microvascular abnormalities in leprosy patients.
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Capilares , Angioscopía Microscópica , Uñas , Valor Predictivo de las Pruebas , Humanos , Adulto , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Uñas/irrigación sanguínea , Adulto Joven , Adolescente , Capilares/diagnóstico por imagen , Capilares/patología , Capilares/fisiopatología , Microcirculación , Enfermedades de la Uña/microbiología , Enfermedades de la Uña/diagnóstico por imagen , Enfermedades de la Uña/patología , Densidad Microvascular , Lepra/diagnóstico por imagen , Lepra/patología , Lepra/microbiología , Lepra/diagnósticoRESUMEN
Capillaries are the smallest blood vessels (<10 µm in diameter) in the body and their walls are lined by endothelial cells. These microvessels play a crucial role in nutrient and gas exchange between blood and tissues. Capillary endothelial cells also produce vasoactive molecules and initiate the electrical signals that underlie functional hyperemia and neurovascular coupling. Accordingly, capillary function and density are critical for all cell types to match blood flow to cellular activity. This begins with the process of angiogenesis, when new capillary blood vessels emerge from pre-existing vessels, and ends with rarefaction, the loss of these microvascular structures. This review explores the mechanisms behind these processes, emphasizing their roles in various microvascular diseases and their impact on surrounding cells in health and disease. We discuss recent work on the mechanisms controlling endothelial cell proliferation, migration, and tube formation that underlie angiogenesis under physiological and pathological conditions. The mechanisms underlying functional and anatomical rarefaction and the role of pericytes in this process are also discussed. Based on this work, a model is proposed in which the balance of angiogenic and rarefaction signaling pathways in a particular tissue match microvascular density to the metabolic demands of the surrounding cells. This negative feedback loop becomes disrupted during microvascular rarefaction: angiogenic mechanisms are blunted, reactive oxygen species accumulate, capillary function declines and eventually, capillaries disappear. This, we propose, forms the foundation of the reciprocal relationship between vascular density, blood flow, and metabolic needs and functionality of nearby cells.
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Capilares , Células Endoteliales , Rarefacción Microvascular , Neovascularización Patológica , Neovascularización Fisiológica , Transducción de Señal , Humanos , Animales , Capilares/metabolismo , Capilares/fisiopatología , Capilares/patología , Neovascularización Patológica/fisiopatología , Neovascularización Patológica/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Rarefacción Microvascular/fisiopatología , Rarefacción Microvascular/metabolismo , Pericitos/metabolismo , Pericitos/patología , Proliferación Celular , Movimiento Celular , Densidad Microvascular , AngiogénesisRESUMEN
This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.
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Capilares , Retinopatía Diabética , Oftalmoscopía , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/patología , Femenino , Masculino , Oftalmoscopía/métodos , Persona de Mediana Edad , Capilares/diagnóstico por imagen , Capilares/patología , Adulto , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Anciano , Angiografía con Fluoresceína/métodosRESUMEN
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK, an endothelial transmembrane receptor signaling through PIK3CA. Venous malformations are associated with pain, bleedings, thrombosis, pulmonary embolism, esthetic deformities and, in severe cases, life-threatening situations. No authorized medical treatment exists for patients with venous malformations. Here, we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes. We showed that these malformations only partially signal through AKT proteins. We compared the efficacy of different drugs, including rapamycin, a mTORC1 inhibitor, miransertib, an AKT inhibitor and alpelisib, a PI3Kα inhibitor at improving the lesions seen in the mouse model. We demonstrated the effectiveness of alpelisib in preventing vascular malformations' occurrence, improving the already established ones, and prolonging survival. Considering these findings, we were authorized to treat 25 patients with alpelisib, including 7 children displaying PIK3CA (n = 16) or TEK (n = 9)-related capillary venous malformations resistant to usual therapies including sirolimus, debulking surgical procedures or percutaneous sclerotherapies. We assessed the volume of vascular malformations using magnetic resonance imaging (MRI) for each patient. Alpelisib demonstrated improvement in all 25 patients. Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated. MRI showed a decrease of 33.4% and 27.8% in the median volume of PIK3CA and TEK malformations respectively, over 6 months on alpelisib. In conclusion, this study supports PI3Kα inhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.
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Capilares , Fosfatidilinositol 3-Quinasa Clase I , Malformaciones Vasculares , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Animales , Ratones , Humanos , Malformaciones Vasculares/genética , Malformaciones Vasculares/tratamiento farmacológico , Malformaciones Vasculares/patología , Capilares/efectos de los fármacos , Capilares/patología , Femenino , Masculino , Sirolimus/farmacología , Sirolimus/uso terapéutico , Niño , Modelos Animales de Enfermedad , Terapia Molecular Dirigida , TiazolesRESUMEN
Purpose: 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). Methods: 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. Results: 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). Conclusions: 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.
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Retinopatía Diabética , Angiografía con Fluoresceína , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/diagnóstico por imagen , Estudios Transversales , Tomografía de Coherencia Óptica/métodos , Masculino , Femenino , Persona de Mediana Edad , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Angiografía con Fluoresceína/métodos , Anciano , Densidad Microvascular , Fóvea Central/irrigación sanguínea , Fóvea Central/diagnóstico por imagen , Fóvea Central/patología , Adulto , Fondo de Ojo , Capilares/patología , Capilares/diagnóstico por imagen , Microvasos/patología , Microvasos/diagnóstico por imagen , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by NOTCH3 mutation. Nailfold capillaroscopy is a non-invasive technique typically used for rheumatic diseases. It has potential in other conditions linked to vascular pathology. However, capillaroscopy in CADASIL has not been explored. This study aims to investigate whether capillaroscopy measurements can correlate with brain vascular changes in preclinical CADASIL patients, specifically those with NOTCH3 mutation. METHODS: This study included 69 participants from the Taiwan Precision Medicine Initiative (TPMI) dataset who visited Taichung Veterans General Hospital from January to December 2022. All individuals underwent genetic studies, brain imaging and nailfold capillaroscopy. The Mann-Whitney U test was used to compare results of brain imaging between carriers and controls. It was also used to compare measurements in nailfold capillaroscopy within each group. Spearman Rank Correlation Analysis was used to explore the relationship between capillary measurements and brain MRI results. RESULTS: White matter hyperintensities (WMH) expression was positively correlated with capillary dimension and negatively correlated with density. Our results presented that R544C carriers exhibited a diffuse increase in WMH (p < 0.001) and a global reduction in gray matter volume but preserved in specific areas. The white matter lesion scores in all brain regions were higher in the mutation carriers than the controls. (p < 0.001). CONCLUSION: This research highlights the association of nailfold capillaroscopy findings with white matter lesions in preclinical CADASIL patients. Capillaroscopy guides an effective screening strategy in individuals with NOTCH3 mutations.
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CADASIL , Capilares , Angioscopía Microscópica , Mutación , Receptor Notch3 , Humanos , CADASIL/genética , CADASIL/diagnóstico por imagen , Receptor Notch3/genética , Masculino , Femenino , Persona de Mediana Edad , Adulto , Capilares/patología , Capilares/diagnóstico por imagen , Angioscopía Microscópica/métodos , Imagen por Resonancia Magnética , Uñas/irrigación sanguínea , Uñas/diagnóstico por imagen , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
During metastatic dissemination, circulating tumour cells (CTCs) enter capillary beds, where they experience mechanical constriction forces. The transient and persistent effects of these forces on CTCs behaviour remain poorly understood. Here, we developed a high-throughput microfluidic platform mimicking human capillaries to investigate the impact of mechanical constriction forces on malignant and normal breast cell lines. We observed that capillary constrictions induced nuclear envelope rupture in both cancer and normal cells, leading to transient changes in nuclear and cytoplasmic area. Constriction forces transiently activated cGAS/STING and pathways involved in inflammation (NF-κB, STAT and IRF3), especially in the non-malignant cell line. Furthermore, the non-malignant cell line experienced transcriptional changes, particularly downregulation of epithelial markers, while the metastatic cell lines showed minimal alterations. These findings suggest that mechanical constriction forces within capillaries may promote differential effects in malignant and normal cell lines.
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Neoplasias de la Mama , Células Neoplásicas Circulantes , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Línea Celular Tumoral , Capilares/patología , Núcleo Celular/metabolismo , Metástasis de la Neoplasia , Membrana Nuclear/metabolismoRESUMEN
OBJECTIVE: This study aimed to clarify the effect of Type I diabetes (DIA) on transcapillary PO2 gradients, which are oxygen-driving factors between the blood and the interstitium, in the contracting muscle of rats. METHODS: Wistar male rats were divided into the diabetic (streptozocin i.p.) and sham groups. Microvascular and interstitial PO2 were measured in the extensor digitorum longus muscle during electrical stimulation-induced muscle contraction, using the phosphorescence quenching method. Transcapillary PO2 gradient, ΔPO2, was calculated as microvascular minus interstitial PO2. RESULTS: Resting microvascular PO2 was higher in the diabetic group than in the sham group (6.3 ± 1.7 vs. 4.7 ± 0.9 mmHg, p < 0.05) and remained for 180 s. Interstitial PO2 from rest to muscle contraction did not differ between the groups. The ΔPO2 was higher in the diabetic group than in the sham group at rest and during muscle contraction (4.03 ± 1.42 vs. 2.46 ± 0.90 mmHg at rest; 3.67 ± 1.51 vs. 2.22 ± 0.65 mmHg during muscle contraction, p < 0.05). Marked muscle atrophy was observed in the diabetic group. CONCLUSION: DIA increased microvascular and transcapillary PO2 gradients in the skeletal muscle. The enhanced PO2 gradients were maintained from rest to muscle contraction in diabetic muscle.