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1.
J Med Case Rep ; 16(1): 167, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449024

RESUMO

BACKGROUND: Retinal arterial occlusive events in young patients are rare. However, because of physiological multifactorial adaptations during pregnancy, retinal vascular occlusive disease may occur spontaneously. In addition, a patent foramen ovale is a risk factor for an ischemic thromboembolic event. Since fluorescein angiography, a central tool in the evaluation of these occlusions, should be avoided during pregnancy, optical coherence tomography angiography, a novel technique, offers a good opportunity for visualizing vascular perfusion of retinal tissue. CASE PRESENTATION: Here we present a case series of three patients (Caucasian, nonsmoker) who visited our clinic owing to acute visual impairment and central scotoma. Using regular optical coherence tomography and optical coherence tomography angiography, retinal vascular occlusions were detected, thus initiating the evaluation of systemic risk factors. We report two patients (30 and 32 years old) who developed cilioretinal artery occlusion but whose etiology differed: one was of thromboembolic origin associated with patent foramen ovale, while the other was caused by hemodynamic blockade secondary to central retinal vein occlusion. In both cases, optical coherence tomography angiography revealed reperfusion of the cilioretinal artery occlusion. However, transient ischemia led to retinal atrophy after a few weeks. In the third patient (32 years old), 8 weeks after onset of scotoma, optical coherence tomography angiography revealed atrophy of the middle layers and impaired perfusion in the deep capillary plexus, and thus a paracentral acute middle maculopathy was diagnosed. All patients regained normal visual acuity and had otherwise uncomplicated pregnancies, and laboratory blood tests did not reveal any defects or alterations. CONCLUSIONS: As shown here, optical coherence tomography angiography enables risk-free imaging of retinal vessel perfusion during pregnancy. Together with regular optical coherence tomography, it allows one to predict functional outcome according to the existing retinal occlusion-related atrophy.


Assuntos
Forame Oval Patente , Oclusão da Artéria Retiniana , Doenças Retinianas , Adulto , Atrofia/complicações , Atrofia/patologia , Feminino , Angiofluoresceinografia/métodos , Forame Oval Patente/complicações , Humanos , Isquemia/diagnóstico , Gravidez , Oclusão da Artéria Retiniana/diagnóstico por imagem , Oclusão da Artéria Retiniana/etiologia , Doenças Retinianas/etiologia , Vasos Retinianos/patologia , Escotoma , Tomografia de Coerência Óptica/métodos
2.
Eur Rev Med Pharmacol Sci ; 26(6): 1906-1913, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35363339

RESUMO

OBJECTIVE: The aim of the study was to evaluate retinal and choroidal microvascular morphological changes in non-ocular sarcoidosis (NOS) patients using optical coherence tomography angiography (OCTA) and compare the results to age- and gender-matched healthy individuals. PATIENTS AND METHODS: This study included 37 NOS patients (group 1, 37 right eyes) referred to the Ophthalmology Department between 2019 and 2021, as well as 31 healthy individuals (group 2, 31 right eyes). Non-ocular sarcoidosis was defined as sarcoidosis confirmed by a positive lung X-ray and biopsy without ocular manifestation. All participants underwent a comprehensive ophthalmic examination. The SPECTRALIS® OCT was used for both fundus photography and macular analysis. All OCTA procedures were performed in the Angio Retina mode (6.0x6.0 mm) to assess retinal and choroidal microvascular morphology. RESULTS: Groups 1 and 2 had mean ages of 46.41±12.52 and 47.55±13.81 years, respectively (p=0.482). Group 1 had significantly increased superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities (VDs) in whole (p=0.059, 0.016), parafoveal (p=0.051, 0.015), and perifoveal (p=0.060, 0.010) regions relative to group 2. Group 1 was also associated with increased foveal avascular zone (FAZ) area (p=0.196), FAZ circumference (p=0.262), and foveal VD in 300 µm wide regions surrounding FAZ (p=0.003) relative to group 2. The outer retinal (p=0.712) and choriocapillaris (p=0.684) flows did not differ significantly between the two groups. CONCLUSIONS: Quantitative OCTA analysis revealed a higher tendency for retinal and choroidal microvascular morphological changes in NOS patients, demonstrating the potential of this novel, non-invasive imaging technology, which may provide sensitive and reliable results without using contrast materials.


Assuntos
Vasos Retinianos , Sarcoidose , Adulto , Corioide/diagnóstico por imagem , Corioide/patologia , Angiofluoresceinografia/métodos , Humanos , Pessoa de Meia-Idade , Retina , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Sarcoidose/diagnóstico por imagem , Sarcoidose/patologia , Tomografia de Coerência Óptica/métodos
3.
PLoS One ; 17(4): e0267576, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35476813

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) remains the leading cause for blindness in children. Limited hyperoxia induced proliferative retinopathy (L-HIPR) was recently introduced as a potential animal model for ROP and persistent fetal vasculature; however, the detailed pathological changes remain unclear. METHODS: To model L-HIPR, we placed C57BL/6J mice in 65% oxygen from birth to post-natal day 7 (P7). We examined eyes at intervals between P12 and P30. Retinal morphometry, thickness, and preretinal fibrosis were quantified at different time points on histological sections stained with hematoxylin and eosin (H&E) and Masson Trichrome, respectively. Vascular development, angiogenesis, inflammation, and pericyte coverage were analyzed using immunohistochemistry staining in retinal flat mounts and cross sections. RESULTS: In L-HIPR, the hyaloidal vessels persisted until the latest time point in this study, P30 and began to invaginate the peripheral then central retina starting at P12. Central retinal distortion was noted beginning at P17, while the peripheral retina demonstrated a trend of thinning from P12 to P30. We found that L-HIPR was associated with delayed and abnormal retinal vascular development with subsequent retinal inflammation, pericyte loss and preretinal fibrosis. CONCLUSION: Our study presents a detailed analysis of the L-HIPR animal model demonstrating vitreoretinal pathologic changes, preretinal fibrosis and persistent hyaloidal vessels into adulthood. Based on our findings, we suggest that the persistence and peculiar stepwise migration of the hyaloidal vessels into the retina may provide a potential rescue mechanism for inner retinal development that deserves further study.


Assuntos
Membrana Epirretiniana , Hiperóxia , Neovascularização Retiniana , Retinopatia da Prematuridade , Vitreorretinopatia Proliferativa , Adulto , Animais , Modelos Animais de Doenças , Membrana Epirretiniana/patologia , Fibrose , Humanos , Hiperóxia/complicações , Hiperóxia/patologia , Recém-Nascido , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Retina/patologia , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/patologia , Vasos Retinianos/patologia , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/patologia , Vitreorretinopatia Proliferativa/patologia
4.
Sci Rep ; 12(1): 3660, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256658

RESUMO

Cerebral small vessel disease (CSVD) is associated with changes in the retinal vasculature which can be assessed non-invasively with much higher resolution than the cerebral vasculature. To detect changes at a microvascular level, we used optical coherence tomography angiography which resolves retinal and choroidal vasculature. Participants with CSVD and controls were included. White matter lesions were determined on magnetic resonance imaging (MRI). The retinal and choroidal vasculature were quantified using swept-source optical coherence tomography angiography. Data were analysed using linear regression. We included 30 participants (18 females; patients, n = 20; controls, n = 10) with a mean age of 61 ± 10 years. Patients had a higher mean white matter lesion index and number of lesions than controls (p ≤ 0.002). The intraindividual deviation of choriocapillaris reflectivity differed significantly between age-matched patients (0.234 ± 0.012) and controls (0.247 ± 0.011; p = 0.029). Skeleton density of the deep retinal capillaries was significantly associated with the number of lesions on MRI (ß = - 5.3 × 108, 95%-confidence interval [- 10.3 × 108; - 0.2 × 108]) when controlling for age. The choroidal microvasculature and the deep retinal vascular plexus, as quantified by optical coherence tomography angiography, are significantly altered in CSVD. The value of these findings in diagnosing or monitoring CSVD need to be assessed in future studies.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Corioide , Idoso , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Feminino , Angiofluoresceinografia/métodos , Humanos , Pessoa de Meia-Idade , Retina , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos
5.
J Am Heart Assoc ; 11(6): e024226, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35253475

RESUMO

Background This study examined the associations between quantitative optical coherence tomography angiography (OCTA) parameters and myocardial abnormalities as documented on cardiovascular magnetic resonance imaging in patients with systemic hypertension. Methods and Results We conducted a cross-sectional study of 118 adults with hypertension (197 eyes). Patients underwent cardiovascular magnetic resonance imaging and OCTA (PLEX Elite 9000, Carl Zeiss Meditec). Associations between OCTA parameters (superficial and deep retinal capillary density) and adverse cardiac remodeling (left ventricular mass, remodeling index, interstitial fibrosis, global longitudinal strain, and presence of left ventricular hypertrophy) were studied using multivariable linear regression analysis with generalized estimating equations. Of the 118 patients with hypertension enrolled (65% men; median [interquartile range] age, 59 [13] years), 29% had left ventricular hypertrophy. After adjusting for age, sex, systolic blood pressure, diabetes, and signal strength of OCTA scans, patients with lower superficial capillary density had significantly higher left ventricular mass (ß=-0.150; 95% CI, -0.290 to -0.010), higher interstitial volume (ß=-0.270; 95% CI, -0.535 to -0.0015), and worse global longitudinal strain (ß=-0.109; 95% CI, -0.187 to -0.032). Lower superficial capillary density was found in patients with hypertension with replacement fibrosis versus no replacement fibrosis (16.53±0.64 mm-1 versus 16.96±0.64 mm-1; P=0.003). Conclusions We showed significant correlations between retinal capillary density and adverse cardiac remodeling markers in patients with hypertension, supporting the notion that the OCTA could provide a non-invasive index of microcirculation alteration for vascular risk stratification in people with hypertension.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Adulto , Estudos Transversais , Feminino , Fibrose , Angiofluoresceinografia/métodos , Humanos , Hipertensão/complicações , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Remodelação Ventricular
6.
Lupus ; 31(5): 541-554, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35282713

RESUMO

OBJECTIVE: This study aimed to investigate subclinical retinal microvascular changes with optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE) and healthy controls (HCs), and to evaluate the relationship between OCTA findings and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). MATERIALS AND METHODS: In this study, 47 eyes of SLE and 41 eyes of healthy control (HC) were evaluated. The SLE patients were divided into two subgroups: low disease activity (LDA) (SLEDAI≤5) and high disease activity (HDA) (SLEDAI>6). The results of OCTA were compared between SLE patients and HCs as well as the SLE subgroups. The relationship between OCTA results and SLEDAI-2K was evaluated. RESULTS: There were no differences in foveal avascular zone (FAZ) areas between the SLE patients and HCs. Central foveal thickness (CFT) was lower in SLE patients (p = .046). Superficial capillary plexus (SCP) vessel density (VD) in SLE patients was significantly lower only in the foveal area compared to that in HCs (p = .006). Deep capillary plexus (DCP) VD in SLE patients was significantly lower in all areas except the temporal parafoveal area compared to that in the HCs. There was no statistically significant difference between SLE groups with LDA and HDA in FAZ or any of the other areas, including SCP and DCP. When the correlation between OCTA findings and SLEDAI-2K was examined, both SCP and DCP VD were found to be negatively correlated. CONCLUSIONS: It was observed that DCP VDs were affected in SLE patients with LDA, and SCP VDs were also affected in addition to DCP with HDA. This suggests that DCP may be the first capillary plexus to be comprised in SLE. VDs were negatively correlated with disease activity. It was concluded that OCTA can be a useful tool in assessing subclinical retinal microvascular pathology and disease activity in patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Tomografia de Coerência Óptica , Angiofluoresceinografia/métodos , Fóvea Central/irrigação sanguínea , Fóvea Central/diagnóstico por imagem , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos
7.
Vestn Oftalmol ; 138(1): 44-51, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35234420

RESUMO

PURPOSE: To compare microcirculatory changes in patients with early stages of primary angle closure disease (PACD) and primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study retrospectively analyzed the clinical data of 60 eyes with PACD, 30 with initial POAG, and 30 eyes without any ophthalmic pathologies. Vessel density (VD) in the optic nerve head and peripapillary retina (wiVD Disc), as well as in the inner layers of fovea and parafovea (wiVD Macula) and their different sectors were determined in all patients by optical coherence tomography angiography (OCTA). The correlation of VD with axial length (AL), anterior chamber depth (ACD), lens thickness (TL), and corneal-compensated intraocular pressure (IOPcc) was assessed. RESULTS: The wiVD Disc in PACD (42.47±4.23%) was lower than in POAG eyes (47.46±2.10%), p<0.001, but the difference for wiVD Macula was not significant: 41.71±4.55% and 39.29±2.46%, respectively (p=0.47). In both PACD and POAG, all OCTA parameters were lower than in normal eyes: p=0.000 for both wiVD Disc and wiVD Macula. WiVD Disc correlated with ACD both in PACD (r=0.724, p=0.012) and in POAG (r= 0.685, p=0.012), but a correlation with IOPcc was found only in PACD (r= -0.670, p=0.033). The largest number of inverse correlations was found between TL and VD both for wiVD Disc (r= -0.714, p=0.006) and the parameters of macular area (in para- and perifovea). CONCLUSION: OCTA parameters differ significantly from the norm even in the early stages of both PACD and POAG. In PACD, there was a significant decrease in microcirculation in the peripapillary retina compared to POAG, which had an inverse correlation with IOPcc; there was also an inverse correlation of OCTA parameters in the optic nerve head and macula with lens thickness.


Assuntos
Glaucoma de Ângulo Aberto , Angiofluoresceinografia/métodos , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular , Microcirculação , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
8.
Retina ; 42(3): 485-493, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35188490

RESUMO

PURPOSE: To explore the condition of fellow eyes of patients with macular neovascularization Type 3 (MNV3) and to verify whether the retinal-choroidal anastomosis (RCA) develops equally in all MNV types. METHODS: The contralateral eyes of 94 patients with MNV3, 96 patients with MNV1, and 96 patients with MNV2 were included. Multimodal imaging was performed. The MNV3 stage including the development of fibrosis and RCA over 24 months was determined. RESULTS: In the contralateral eyes of patients of the solitary (one lesion) MNV3 group, 32 eyes (42.1%) showed early/intermediate age-related macular degeneration, 25 eyes (33%) showed MNV3, and 11 eyes (14.5%) experienced fibrosis, of which 4 eyes (5.2%) had a RCA, 7 eyes (9.2%) had atrophy after resolved MNV3, and 1 eye (1.3%) developed MNV1. In the multifocal (more than one lesion) MNV3 group, 2 eyes (11.1%) showed early/intermediate age-related macular degeneration, 9 eyes (50%) showed 15 MNV3 lesions, and 4 eyes (22.2%) showed fibrosis, of which 2 eyes (11.1%) manifested with a RCA and 3 eyes (16.7%) showed atrophy after resolved MNV3. The number of eyes with a RCA accounted for 40% of all eyes with fibrosis. The count of simultaneous bilateral multifocal MNV3 was 5 (55.6%). In the MNV1 and MNV2 groups, no eye developed a RCA. The incidence of RCAs in the scarred eyes in MNV3 was significantly higher (P < 0.0001). CONCLUSION: Retinal-choroidal anastomosis is an exclusive clinical feature of MNV3. The development of the multifocal MNV3 is usually bilateral and simultaneous. The occurrence of fibrosis in MNV3 has decreased dramatically after the introduction of the antiangiogenic therapy.


Assuntos
Fístula Artério-Arterial/diagnóstico por imagem , Corioide/irrigação sanguínea , Artérias Ciliares/patologia , Neovascularização Retiniana/diagnóstico por imagem , Vasos Retinianos/patologia , Idoso , Idoso de 80 Anos ou mais , Artérias Ciliares/diagnóstico por imagem , Corantes/administração & dosagem , Estudos Transversais , Feminino , Fibrose/diagnóstico , Angiofluoresceinografia , Seguimentos , Atrofia Geográfica/diagnóstico , Humanos , Verde de Indocianina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica
9.
Sci Rep ; 12(1): 3089, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35197526

RESUMO

Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces, i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR.


Assuntos
Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/patologia , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Curva ROC , Vasos Retinianos/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença
11.
Invest Ophthalmol Vis Sci ; 63(2): 18, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35138346

RESUMO

Purpose: To characterize the early structural and functional changes in the retinal microvasculature in response to hyperglycemia in the Ins2Akita mouse. Methods: A custom phase-contrast adaptive optics scanning light ophthalmoscope was used to image retinal capillaries of 9 Ins2Akita positive (hyperglycemic) and 9 Ins2Akita negative (euglycemic) mice from postnatal weeks 5 to 18. A 15 kHz point scan was used to image capillaries and measure red blood cell flux at biweekly intervals; measurements were performed manually. Retinal thickness and fundus photos were captured monthly using a commercial scanning laser ophthalmoscope/optical coherence tomography. Retinal thickness was calculated using a custom algorithm. Blood glucose and weight were tracked throughout the duration of the study. Results: Elevated blood glucose (>250 mg/dL) was observed at 4 to 5 weeks of age in Ins2Akita mice and remained elevated throughout the study, whereas euglycemic littermates maintained normal glucose levels. There was no significant difference in red blood cell flux, capillary anatomy, lumen diameter, or occurrence of stalled capillaries between hyperglycemic and euglycemic mice between postnatal weeks 5 and 18. Hyperglycemic mice had a thinner retina than euglycemic littermates (p < 0.001), but retinal thickness did not change with duration of hyperglycemia despite glucose levels that were more than twice times normal. Conclusions: In early stages of hyperglycemia, retinal microvasculature structure (lumen diameter, capillary anatomy) and function (red blood cell flux, capillary perfusion) were not impaired despite 3 months of chronically elevated blood glucose. These findings suggest that hyperglycemia alone for 3 months does not alter capillary structure or function in profoundly hyperglycemic mice.


Assuntos
Capilares/patologia , Retinopatia Diabética/fisiopatologia , Eritrócitos/fisiologia , Hiperglicemia/fisiopatologia , Vasos Retinianos/patologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Glicemia/metabolismo , Capilares/diagnóstico por imagem , Retinopatia Diabética/diagnóstico por imagem , Modelos Animais de Doenças , Contagem de Eritrócitos , Masculino , Camundongos , Oftalmoscópios , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica
12.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35135877

RESUMO

Reduced blood flow and impaired neurovascular coupling are recognized features of glaucoma, the leading cause of irreversible blindness worldwide, but the mechanisms underlying these defects are unknown. Retinal pericytes regulate microcirculatory blood flow and coordinate neurovascular coupling through interpericyte tunneling nanotubes (IP-TNTs). Using two-photon microscope live imaging of the mouse retina, we found reduced capillary diameter and impaired blood flow at pericyte locations in eyes with high intraocular pressure, the most important risk factor to develop glaucoma. We show that IP-TNTs are structurally and functionally damaged by ocular hypertension, a response that disrupted light-evoked neurovascular coupling. Pericyte-specific inhibition of excessive Ca2+ influx rescued hemodynamic responses, protected IP-TNTs and neurovascular coupling, and enhanced retinal neuronal function as well as survival in glaucomatous retinas. Our study identifies pericytes and IP-TNTs as potential therapeutic targets to counter ocular pressure-related microvascular deficits, and provides preclinical proof of concept that strategies aimed to restore intrapericyte calcium homeostasis rescue autoregulatory blood flow and prevent neuronal dysfunction.


Assuntos
Estruturas da Membrana Celular/fisiologia , Glaucoma/patologia , Pericitos/fisiologia , Retina/citologia , Retina/patologia , Animais , Antígenos , Cálcio/metabolismo , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Glaucoma/etiologia , Fenômenos Magnéticos , Masculino , Camundongos , Microesferas , Nanotubos , Regiões Promotoras Genéticas , Proteoglicanas , Vasos Retinianos/patologia , Técnicas de Cultura de Tecidos
13.
Hypertension ; 79(5): 874-886, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35114816

RESUMO

The structural and functional alterations of microvessels are detected because of physiological aging and in several cardiometabolic diseases, including hypertension, diabetes, and obesity. The small resistance arteries of these patients show an increase in the media or total wall thickness to internal lumen diameter ratio (MLR or WLR), often accompanied by endothelial dysfunction. For decades, micromyography has been considered as a gold standard method for evaluating microvascular structural alterations through the measurement of MLR or WLR of subcutaneous small vessels dissected from tissue biopsies. Micromyography is the most common and reliable method for assessing microcirculatory endothelial function ex vivo, while strain-gauge venous plethysmography is considered the reference technique for in vivo studies. Recently, several noninvasive methods have been proposed to extend the microvasculature evaluation to a broader range of patients and clinical settings. Scanning laser Doppler flowmetry and adaptive optics are increasingly used to estimate the WLR of retinal arterioles. Microvascular endothelial function may be evaluated in the retina by flicker light stimulus, in the finger by tonometric approaches, or in the cutaneous or sublingual tissues by laser Doppler flowmetry or intravital microscopy. The main limitation of these techniques is the lack of robust evidence on their prognostic value, which currently reduces their widespread use in daily clinical practice. Ongoing and future studies will overcome this issue, hopefully moving the noninvasive assessment of the microvascular function and structure from bench to bedside.


Assuntos
Hipertensão , Arteríolas , Humanos , Fluxometria por Laser-Doppler/métodos , Microcirculação , Vasos Retinianos/patologia
14.
Diabetes ; 71(4): 733-746, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35043147

RESUMO

Microaneurysms are biomarkers of microvascular injury in diabetic retinopathy (DR). Impaired retinal capillary perfusion is a critical pathogenic mechanism in the development of microvascular abnormalities. Targeting fundamental molecular disturbances resulting from capillary nonperfusion, such as increased vascular endothelial growth factor expression, does not always reverse the anatomic complications of DR, suggesting that other pathogenic mechanisms independent of perfusion also play a role. We stratify the effects of capillary nonperfusion, inflammation, and pericyte loss on microaneurysm size and leakage in DR through three-dimensional analysis of 636 microaneurysms using high-resolution confocal scanning laser microscopy. Capillary nonperfusion, pericyte loss, and inflammatory cells were found to be independent predictors of microaneurysm size. Nonperfusion alone without pericyte loss or inflammation was not a significant predictor of microaneurysm leakage. Microaneurysms found in regions without nonperfusion were significantly smaller than those found in regions with nonperfusion, and their size was not associated with pericyte loss or inflammation. In addition, microaneurysm size was a significant predictor of leakage in regions with nonperfusion only. This report refines our understanding of the disparate pathophysiologic mechanisms in DR and provides a histologic rationale for understanding treatment failure for microvascular complications in DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Microaneurisma , Diabetes Mellitus/patologia , Retinopatia Diabética/patologia , Humanos , Inflamação/patologia , Microaneurisma/patologia , Pericitos/patologia , Vasos Retinianos/patologia , Fator A de Crescimento do Endotélio Vascular
15.
Med Sci Monit ; 28: e932996, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35001073

RESUMO

BACKGROUND The aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME). MATERIAL AND METHODS Optical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro. RESULTS Patients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated. CONCLUSIONS SNHG5 correlates with the development of DME and is a potential target for therapy.


Assuntos
Humor Aquoso/metabolismo , Retinopatia Diabética , Células Endoteliais/metabolismo , Edema Macular/metabolismo , RNA Longo não Codificante , Fator A de Crescimento do Endotélio Vascular/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Retinopatia Diabética/sangue , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/sangue , RNA Longo não Codificante/metabolismo , Retina/diagnóstico por imagem , Retina/patologia , Neovascularização Retiniana/diagnóstico por imagem , Neovascularização Retiniana/etiologia , Vasos Retinianos/patologia , Vasos Retinianos/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual
16.
Sci Rep ; 12(1): 752, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031636

RESUMO

This meta-analysis aimed to analyze retinal microvasculature features in eyes with Behçet's disease (BD) using optical coherence tomography angiography (OCTA). Electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched for published studies comparing retinal microvasculature characteristics between eyes with BD and controls. Continuous variables were calculated using the mean difference (MD) with 95% confidence interval (CI). Review Manager software (version 5.30) was used to conduct statistical analysis. A total of 13 eligible studies involving 599 eyes with BD and 622 control eyes were included in the meta-analysis. The pooled results showed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in eyes with BD than in control eyes (superficial VD: MD = - 3.05, P < 0.00001; deep VD: MD = - 4.05, P = 0.0004). The foveal superficial and deep VD values were also significantly lower in the BD group than in the control group (superficial VD: MD = - 1.50, P = 0.009; deep VD: MD = - 4.25, - = 0.03). Similarly, the analysis revealed a significant reduction in the parafoveal superficial and deep VD in eyes with BD than in control eyes (superficial VD: MD = - 3.68, P < 0.00001; deep VD: MD = - 4.95, P = 0.0007). In addition, the superficial and deep foveal avascular zones (FAZs) were significantly larger in patients with BD than in controls (superficial FAZ: MD = 0.06, P = 0.02; deep FAZ: MD = 0.12, P = 0.03). The present meta-analysis found that macular whole enface VD, foveal VD, and parafoveal VD were lower in eyes with BD, and the FAZ was larger in patients with BD. The findings suggest that OCTA can assist clinicians in diagnosing and monitoring the status of patients with BD.


Assuntos
Síndrome de Behçet/patologia , Microvasos/patologia , Vasos Retinianos/patologia , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico por imagem , Feminino , Fóvea Central/irrigação sanguínea , Humanos , Macula Lutea/irrigação sanguínea , Edema Macular/diagnóstico por imagem , Edema Macular/etiologia , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Vasculite Retiniana/diagnóstico por imagem , Vasculite Retiniana/etiologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica
18.
Invest Ophthalmol Vis Sci ; 63(1): 14, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-35006270

RESUMO

Purpose: To determine whether protein kinase a (PKA) and exchange protein for cAMP 1 (Epac1) inhibit NIMA-related kinase 7 (Nek7) to block the NOD-like receptor family pyrin domain-containing family member 3 (NLRP3) signaling pathway. Methods: Retinal endothelial cells (RECs) were grown in normal (5 mM) or high (25 mM) glucose. Some cells were treated with a Nek7 cDNA plasmid, Nek7 siRNA; an Epac1 agonist, forskolin; a PKA agonist; or an empty vector. Epac1 floxed and Cdh5-cre Epac1 mice and Nek7 floxed and Cdh5-cre Nek7 mice were also used. Western blot analyses were done on cell culture or whole retinal lysates for NLRP3, cleaved caspase 1, interleukin-1-beta (IL-1ß). A PKA activity assay was also done. Results: Nek7 cDNA increased NLRP3 signaling proteins, but Nek7 siRNA inhibited high-glucose induction of these proteins in retinal endothelial cells. Epac1 and forskolin both reduced Nek7 and NLRP3 pathway proteins, even when given in combination with Nek7 cDNA. Elimination of Nek7 in endothelial cells reduced NLRP3 signaling proteins in whole retinal lysates from mice. Conclusions: Nek7 regulated NLRP3 inflammasome protein levels both in vitro and in vivo. Both Epac1 and PKA lie upstream of Nek7 and NLRP3 and can overcome excessive Nek7 levels. These studies establish that cAMP proteins can inhibit Nek7 and block activation of the NLRP3 inflammasome proteins.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Endotélio Vascular/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Inflamassomos/metabolismo , Quinases Relacionadas a NIMA/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Vasos Retinianos/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Camundongos , Camundongos Knockout , Quinases Relacionadas a NIMA/metabolismo , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Vasos Retinianos/patologia , Transdução de Sinais
19.
Eye (Lond) ; 36(5): 930-940, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34650219

RESUMO

Fluorescein and indocyanine green angiography have been the traditional ways to image the vasculature of the iris in the last few decades. Because of the invasive nature of these procedures, they are performed in rare situations, and thus, our understanding about iris vasculature is very limited. Optical coherence tomography angiography (OCTA) is a noninvasive imaging method that enables the detailed visualization of the retinal and choroidal vascular networks. More recently, it has been also used for the examination of the iris vasculature in healthy and disease eyes. However, there is a lack of uniformity in the image acquisition protocols and interpretations in both healthy and pathological conditions. Artifacts of iris OCTA include shadowing, motion, segmentations errors, mirror effects. OCTA devices have an eye-tracking system designed for the posterior segment and the applications of these systems on the anterior segment can determine motion lines, vessel duplication, and vessel discontinuity. OCTA of the iris should always be performed under ambient room lighting to create miosis and reduce iris vasculature changes during the examination. In the near future, eye-tracking systems specifically designed for the iris vessels could permit the follow-up function, and the development of new OCTA metrics could reveal interesting applications of this new imaging technique.


Assuntos
Iris , Tomografia de Coerência Óptica , Corioide , Angiofluoresceinografia/métodos , Humanos , Iris/diagnóstico por imagem , Iris/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos
20.
Schizophr Bull ; 48(1): 80-89, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34554256

RESUMO

BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.


Assuntos
Microvasos/patologia , Transtornos Psicóticos/patologia , Vasos Retinianos/patologia , Esquizofrenia/patologia , Tomografia de Coerência Óptica , Adulto , Angiografia , Feminino , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia , Vasos Retinianos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Adulto Jovem
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