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2.
Commun Biol ; 7(1): 1114, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256610

RESUMO

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).


Assuntos
Linfócitos B , Ativação Linfocitária , Sarcoidose , Humanos , Sarcoidose/imunologia , Sarcoidose/sangue , Sarcoidose/diagnóstico , Linfócitos B/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Países Baixos/epidemiologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico , Uveíte/imunologia , Uveíte/sangue , Uveíte/diagnóstico , Fator Ativador de Células B/sangue , Indonésia , Biomarcadores/sangue , Tuberculose/imunologia , Tuberculose/sangue , Tuberculose/diagnóstico
3.
Sci Rep ; 14(1): 20033, 2024 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198470

RESUMO

Uveitis is characterised by breakdown of the blood-retinal barrier (BRB), allowing infiltration of immune cells that mediate intraocular inflammation, which can lead to irreversible damage of the neuroretina and the loss of sight. Treatment of uveitis relies heavily on corticosteroids and systemic immunosuppression due to limited understanding of disease pathogenesis. We performed single-cell RNA-sequencing of retinas, as well as bulk RNA-sequencing of retinal pigment epithelial (RPE) cells from mice with experimental autoimmune uveitis (EAU) versus healthy control. This revealed that the Th1/Th17-driven disease induced strong gene expression changes in response to inflammation in rods, cones, Müller glia and RPE. In particular, Müller glia and RPE cells were found to upregulate expression of chemokines, complement factors, leukocyte adhesion molecules and MHC class II, thus highlighting their contributions to immune cell recruitment and antigen presentation at the inner and outer BRB, respectively. Additionally, ligand-receptor interaction analysis with CellPhoneDB revealed key interactions between Müller glia and T cell / natural killer cell subsets via chemokines, galectin-9 to P4HB/TIM-3, PD-L1 to PD-1, and nectin-2/3 to TIGIT signalling axes. Our findings elucidate mechanisms contributing to breakdown of retinal immune privilege during uveitis and identify novel targets for therapeutic interventions.


Assuntos
Doenças Autoimunes , Barreira Hematorretiniana , Análise de Célula Única , Uveíte , Animais , Uveíte/imunologia , Uveíte/genética , Uveíte/metabolismo , Uveíte/patologia , Barreira Hematorretiniana/metabolismo , Camundongos , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Modelos Animais de Doenças , Retina/metabolismo , Retina/imunologia , Retina/patologia , Epitélio Pigmentado da Retina/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Células Ependimogliais/metabolismo , Camundongos Endogâmicos C57BL
4.
Life Sci ; 355: 122996, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39173995

RESUMO

AIMS: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU). MAIN METHODS: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina. The transcriptome of activated retinal cells was determined by RNA-seq using RNA immunoprecipitated in complex with phosphorylated ribosomal protein S6. The retinal levels of protein products of relevant upregulated genes were quantified. The effect of BDNF on EAU was tested in unstimulated mice by its daily topical ocular administration (days 8-14 post-immunization). KEY FINDINGS: VS attenuated EAU development and decreased the expression of pro-inflammatory cytokines/chemokines and numbers of immune cells in the retina (n = 10-20 eyes/group for each analysis). In activated retinal cells of control mice (n = 30 eyes/group), VS upregulated genes encoding immunomodulatory neuropeptides, of which BDNF and vasoactive intestinal peptide (VIP) also showed increased mRNA and protein levels in the retina of VS-treated EAU mice (n = 6-10 eyes/group for each analysis). In unstimulated EAU mice, BDNF treatment mimicked the protective effects of VS by modulating the inflammatory and stem cell properties of Müller cells (n = 5 eyes/group for each analysis). SIGNIFICANCE: VS effectively suppresses EAU, at least through enhancing retinal levels of anti-inflammatory and neuroprotective factors, VIP and BDNF. Our findings also suggest BDNF as a promising therapeutic agent for uveitis treatment.


Assuntos
Doenças Autoimunes , Fator Neurotrófico Derivado do Encéfalo , Retinite , Uveíte , Animais , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Uveíte/metabolismo , Uveíte/tratamento farmacológico , Uveíte/imunologia , Retinite/tratamento farmacológico , Retinite/prevenção & controle , Retinite/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Feminino , Retina/metabolismo , Retina/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Peptídeo Intestinal Vasoativo/farmacologia , Modelos Animais de Doenças , Citocinas/metabolismo
5.
Retina ; 44(9): 1619-1632, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39167583

RESUMO

PURPOSE: To investigate changes to the vitreoretinal interface in uveitis with multimodal imaging including adaptive optics. METHODS: Four eyes (four patients) affected by fovea-attached (subtype 1A) or fovea-sparing epiretinal membranes (ERMs) on spectral-domain optical coherence tomography or visible internal limiting membrane (ILM) on infrared scanning laser ophthalmoscope (SLO) fundus imaging were recruited in this pilot study. The microstructure of the vitreoretinal interface was imaged using flood-illumination adaptive optics (FIAO), and the images were compared with the cross-sectional spectral-domain optical coherence tomography data. RESULTS: Adaptive optics images revealed multiple abnormalities of the vitreoretinal interface, such as deep linear striae in ERM, and hyperreflective microstructures at the location of ERMs and ILMs. The cone mosaic was imaged by FIAO and was found altered in the four eyes with ERMs or visible ILM. The same four eyes presented alteration of photopic 30 Hz flicker that was reduced in amplitude indicating cone inner retinal layer dysfunction. CONCLUSION: FIAO imaging can identify specific patterns associated with ERMs and ILMs. Correlating FIAO imaging of the vitreomacular interface with the structural alterations seen in FIAO at the level of the outer retinal structures can help understand the cause of significant macular dysfunction associated with ERM.


Assuntos
Membrana Epirretiniana , Imagem Multimodal , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Membrana Epirretiniana/diagnóstico , Projetos Piloto , Oftalmoscopia/métodos , Corpo Vítreo/patologia , Corpo Vítreo/diagnóstico por imagem , Uveíte/diagnóstico , Adulto , Acuidade Visual , Idoso , Estudos Transversais , Membrana Basal
6.
Ophthalmologie ; 121(9): 726-736, 2024 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-39145783

RESUMO

BACKGROUND: Uveitis leads to blindness in 10-15% of all cases in industrialized nations. The prevalence varies depending on the literature, ranging from 9 to 730 cases per 100,000 inhabitants. Local and systemic steroid applications, along with treatment involving immunomodulators, are the primary treatment options. In cases of chronic and refractory uveitis, especially with the manifestation of uveitic macular edema, intravitreal corticosteroids can contribute to reduce or completely replace systemic immunomodulatory therapy with disease-modifying antirheumatic drugs (DMARDs), biologics or corticosteroids. OBJECTIVE: This review article presents the currently available intravitreal corticosteroid implants used in the treatment of noninfectious uveitis. The indications, effectiveness, and side effect profiles are discussed within the context of the current literature. A total of 6 randomized controlled studies about FAc and DEX implants with more than 100 patients were included in this review. One subgroup analysis from a multicentric randomized study with 315 patients has been included as well. The outcome is discussed in this article. CONCLUSION: The efficacy and safety profile of intravitreal corticosteroids in uveitic macular edema have been evaluated in several studies in recent years. In some studies, they have been compared to systemic treatment options. With long-acting corticosteroid implants the number of relapses can be reduced and the time interval between relapses can be prolonged. Short-acting corticosteroid implants represent a treatment option during acute uveitic activity. The adverse effects of corticosteroids can be well-controlled in most cases. In phakic and/or young patients, however, adverse effects (such as cataract development) should be discussed in depth before treatment initiation as most corticosteroids are applied as long-term treatment.


Assuntos
Corticosteroides , Implantes de Medicamento , Injeções Intravítreas , Uveíte , Humanos , Uveíte/tratamento farmacológico , Doença Crônica , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Resultado do Tratamento , Edema Macular/tratamento farmacológico
7.
Front Immunol ; 15: 1356414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114654

RESUMO

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (ß: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.


Assuntos
Artrite Juvenil , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Uveíte , Humanos , Microbioma Gastrointestinal/genética , Artrite Juvenil/microbiologia , Artrite Juvenil/genética , Uveíte/microbiologia , Uveíte/etiologia , Uveíte/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único
8.
Int J Mol Sci ; 25(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39125957

RESUMO

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.


Assuntos
Artrite , Biomarcadores , Proteômica , Sarcoidose , Sinovite , Lágrimas , Uveíte , Humanos , Lágrimas/metabolismo , Biomarcadores/metabolismo , Uveíte/metabolismo , Uveíte/genética , Uveíte/diagnóstico , Feminino , Masculino , Artrite/genética , Artrite/metabolismo , Sinovite/metabolismo , Sinovite/genética , Sarcoidose/genética , Sarcoidose/metabolismo , Adulto , Proteômica/métodos , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Pessoa de Meia-Idade , Mutação , Proteoma/metabolismo , Doenças Hereditárias Autoinflamatórias
10.
J Extracell Vesicles ; 13(8): e12497, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39140452

RESUMO

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been recognized as promising cytotherapeutics due to their demonstrated immunomodulatory effects in various preclinical models. The immunomodulatory capabilities of EVs stem from the proteins and genetic materials they carry from parent cells, but the cargo contents of EVs are significantly influenced by MSC tissues and donors, cellular age and culture conditions, resulting in functional variations. However, there are no surrogate assays available to validate the immunomodulatory potency of MSC-EVs before in vivo administration. In previous work, we discovered that microcarrier culture conditions enhance the immunomodulatory function of MSC-EVs, as well as the levels of immunosuppressive molecules such as TGF-ß1 and let-7b in MSC-EVs. Building on these findings, we investigated whether TGF-ß1 levels in MSC-EVs could serve as a surrogate biomarker for predicting their potency in vivo. Our studies revealed a strong correlation between TGF-ß1 and let-7b levels in MSC-EVs, as well as their capacity to suppress IFN-γ secretion in stimulated splenocytes, establishing biopotency and surrogate assays for MSC-EVs. Subsequently, we validated MSC-EVs generated from monolayer cultures (ML-EVs) or microcarrier cultures (MC-EVs) using murine models of experimental autoimmune uveoretinitis (EAU) and additional in vitro assays reflecting the Mode of Action of MSC-EVs in vivo. Our findings demonstrated that MC-EVs carrying high levels of TGF-ß1 exhibited greater efficacy than ML-EVs in halting disease progression in mice with EAU as well as inducing apoptosis and inhibiting the chemotaxis of retina-reactive T cells. Additionally, MSC-EVs suppressed the MAPK/ERK pathway in activated T cells, with treatment using TGF-ß1 or let-7b showing similar effects on the MAPK/ERK pathway. Collectively, our data suggest that MSC-EVs directly inhibit the infiltration of retina-reactive T cells toward the eyes, thereby halting the disease progression in EAU mice, and their immunomodulatory potency in vivo can be predicted by their TGF-ß1 levels.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Fator de Crescimento Transformador beta1 , Uveíte , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Camundongos , Uveíte/terapia , Uveíte/imunologia , Uveíte/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , MicroRNAs/metabolismo , Doenças Autoimunes/terapia , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Imunomodulação , Camundongos Endogâmicos C57BL , Humanos , Feminino
11.
Turk J Ophthalmol ; 54(4): 198-204, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39205423

RESUMO

Objectives: Behçet uveitis (BU) is a potentially blinding disorder. The main determinant of visual prognosis is early and appropriate treatment that provides rapid suppression of inflammatory attacks, control of subclinical inflammation, and prevention of new attacks. Our study aimed to determine the Turkish uveitis specialists' approach regarding the treatment choices and management of special situations such as pregnancy, vaccination, and surgical planning in BU patients, and to increase information sharing and raise awareness of issues where knowledge is lacking. Materials and Methods: A web-based survey including 16 questions about the treatment approach in ocular involvement of Behçet's disease was sent via e-mail to uveitis specialists in Türkiye. Based on the answers of 49 ophthalmologists who responded to the survey, we evaluated the approaches of uveitis specialists in our country to initiating treatment, selecting therapeutic agents, monitoring, switching and stopping treatment, and special situations such as surgical planning, vaccination, and pregnancy in BU patients. Results: Uveitis specialists in our country mostly act in accordance with the guidelines in the decision to start treatment, selection of therapeutic agents, and monitoring the safety of treatment in BU. However, there is a lack of information about the therapeutic approach in pregnancy and vaccination practices. It was also observed that there is no consensus on the precautions to be taken before cataract surgery. Conclusion: Our study has shown that there is a need for more detailed and widespread information sharing on treatment in preparation for ocular surgery, safety monitoring, drug use during pregnancy, and vaccination in BU patients.


Assuntos
Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/terapia , Turquia/epidemiologia , Feminino , Uveíte/diagnóstico , Uveíte/terapia , Uveíte/etiologia , Imunossupressores/uso terapêutico , Masculino , Gravidez , Inquéritos e Questionários , Adulto
12.
Int J Pharm ; 663: 124563, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39111353

RESUMO

The modulation of inflammation is effective to treat many ocular surface diseases. Thus the low bioavailability of common anti-inflammatory eye-drops urges the development of ocular drug delivery systems to extend the ocular retention and enhance the cellular uptake for improving anti-inflammatory effect of eye-drops. Here we covalently conjugate two molecules of clinically anti-inflammatory drug (i.e., dexamethasone) with a small peptide (i.e., Tyr-Glu-Asn-Pro-Thr-Tyr) to generate an anti-inflammatory hydrogel eye-drop. With a self-assembled ability, the designed supramolecular hydrogel achieves gel-sol-gel transition by varying shearing forces which increases the pre-corneal retention of drug. The fluorescent imaging reveals the efficient cellular uptake of designed conjugate via clathrin-mediated endocytosis. A rodent model of endotoxin-induced uveitis verifies that the supramolecular hydrogel eye-drop suppresses inflammation responses without ocular irritation. As a rational approach to design anti-inflammatory drugs as eye-drops, this work overcomes the frequent instillation of clinical eye-drops and further improves the bioavailability of anti-inflammatory drugs, which may provide an effective and household way to fight ocular surface inflammation.


Assuntos
Anti-Inflamatórios , Clatrina , Dexametasona , Endocitose , Hidrogéis , Soluções Oftálmicas , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Endocitose/efeitos dos fármacos , Hidrogéis/administração & dosagem , Dexametasona/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Clatrina/metabolismo , Camundongos , Inflamação/tratamento farmacológico , Uveíte/tratamento farmacológico , Masculino , Humanos , Sistemas de Liberação de Medicamentos
13.
Dermatol Online J ; 30(3)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-39090042

RESUMO

Blau syndrome is an autosomal dominant chronic inflammatory disease, which may begin with skin manifestations in the first months of life, alerting physicians to the diagnosis. This case reports a patient diagnosed jointly by pediatric dermatology and rheumatology consultants at two years of age.


Assuntos
Artrite , Sarcoidose , Sinovite , Uveíte , Humanos , Sinovite/genética , Sinovite/diagnóstico , Uveíte/diagnóstico , Sarcoidose/diagnóstico , Sarcoidose/patologia , Artrite/diagnóstico , Pré-Escolar , Masculino , Feminino , Artrite Infecciosa/diagnóstico , Doenças Hereditárias Autoinflamatórias
14.
Asia Pac J Ophthalmol (Phila) ; 13(4): 100082, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39019261

RESUMO

The integration of artificial intelligence (AI) with healthcare has opened new avenues for diagnosing, treating, and managing medical conditions with remarkable precision. Uveitis, a diverse group of rare eye conditions characterized by inflammation of the uveal tract, exemplifies the complexities in ophthalmology due to its varied causes, clinical presentations, and responses to treatments. Uveitis, if not managed promptly and effectively, can lead to significant visual impairment. However, its management requires specialized knowledge, which is often lacking, particularly in regions with limited access to health services. AI's capabilities in pattern recognition, data analysis, and predictive modelling offer significant potential to revolutionize uveitis management. AI can classify disease etiologies, analyze multimodal imaging data, predict outcomes, and identify new therapeutic targets. However, transforming these AI models into clinical applications and meeting patient expectations involves overcoming challenges like acquiring extensive, annotated datasets, ensuring algorithmic transparency, and validating these models in real-world settings. This review delves into the complexities of uveitis and the current AI landscape, discussing the development, opportunities, and challenges of AI from theoretical models to bedside application. It also examines the epidemiology of uveitis, the global shortage of uveitis specialists, and the disease's socioeconomic impacts, underlining the critical need for AI-driven approaches. Furthermore, it explores the integration of AI in diagnostic imaging and future directions in ophthalmology, aiming to highlight emerging trends that could transform management of a patient with uveitis and suggesting collaborative efforts to enhance AI applications in clinical practice.


Assuntos
Inteligência Artificial , Uveíte , Humanos , Inteligência Artificial/tendências , Uveíte/diagnóstico , Gerenciamento Clínico
15.
Tuberculosis (Edinb) ; 148: 102547, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39084001

RESUMO

PURPOSE: To determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection. METHODS: Concentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection. RESULTS: One-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&-II, IP-10, MIP-1ß, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+. CONCLUSION: Decreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.


Assuntos
Biomarcadores , Infecções por HIV , Tuberculose Ocular , Uveíte , Humanos , Masculino , Biomarcadores/urina , Feminino , Adulto , Pessoa de Meia-Idade , Uveíte/urina , Uveíte/microbiologia , Uveíte/diagnóstico , Tuberculose Ocular/urina , Tuberculose Ocular/diagnóstico , Infecções por HIV/urina , Infecções por HIV/complicações , Coinfecção/urina , Diagnóstico Diferencial , Soropositividade para HIV/urina , Soropositividade para HIV/complicações , Soronegatividade para HIV , Adulto Jovem , Valor Preditivo dos Testes , Urinálise/métodos
16.
Int J Pharm ; 662: 124516, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39067549

RESUMO

Uveitis is a group of inflammatory ocular pathologies. Endotoxin-Induced Uveitis (EIU) model represent a well-known model induced by administration of Lipopolysaccharide (LPS). The aim is to characterize two models of EIU through two routes of administration with novel noninvasive imaging techniques. 29 rats underwent Intraocular Pressure (IOP) measurements, Optical Coherence Tomography (OCT), proteomic analysis, and Positron Emission Tomography and Computed Tomography (PET/CT). Groups included healthy controls (C), BSS administered controls (Ci), systemically induced EIU with LPS (LPSs), and intravitreally induced EIU with LPS (LPSi) for IOP, OCT, and proteomic studies. For 18F-FDG PET/CT study, animals were divided into FDG-C, FDG-LPSs and FDG-LPSi groups and scanned using a preclinical PET/CT system. LPSi animals exhibited higher IOP post-induction compared to C and LPSs groups. LPSi showed increased cellular infiltrate, fibrotic membranes, and iris inflammation. Proinflammatory proteins were more expressed in EIU models, especially LPSi. PET/CT indicated higher eye uptake in induced models compared to FDG-C. FDG-LPSi showed higher eye uptake than FDG-LPSs but systemic uptake was higher in FDG-LPSs due to generalized inflammation. OCT is valuable for anterior segment assessment in experimental models. 18F-FDG PET/CT shows promise as a noninvasive biomarker for ocular inflammatory diseases. Intravitreal induction leads to higher ocular inflammation. These findings offer insights for future inflammatory disease research and drug studies.


Assuntos
Modelos Animais de Doenças , Pressão Intraocular , Lipopolissacarídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteômica , Tomografia de Coerência Óptica , Uveíte , Animais , Uveíte/induzido quimicamente , Uveíte/diagnóstico por imagem , Uveíte/metabolismo , Tomografia de Coerência Óptica/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Proteômica/métodos , Lipopolissacarídeos/toxicidade , Pressão Intraocular/efeitos dos fármacos , Ratos , Masculino , Fluordesoxiglucose F18/administração & dosagem , Endotoxinas/toxicidade , Ratos Sprague-Dawley
17.
Indian J Ophthalmol ; 72(8): 1156-1161, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39078959

RESUMO

CONTEXT: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. PURPOSE: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. SETTINGS AND DESIGN: Retrospective multicentric, survey-based study. METHODS: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. RESULTS: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. CONCLUSIONS: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.


Assuntos
Inibidores da Angiogênese , Anticorpos Monoclonais Humanizados , Injeções Intravítreas , Humanos , Índia/epidemiologia , Estudos Retrospectivos , Masculino , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Feminino , Incidência , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Acuidade Visual , Endoftalmite/epidemiologia , Endoftalmite/diagnóstico , Seguimentos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/epidemiologia
18.
J Med Case Rep ; 18(1): 309, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961469

RESUMO

BACKGROUND: Hodgkin's lymphoma (HL) is an extremely rare cause of ocular inflammation that is usually not considered in the typical workup of uveitis and other eye diseases. A few cases of ocular inflammation were reported previously showcasing HL with absence of typical symptoms of HL at presentation. Acknowledging the potential ocular inflammation associated with HL can prompt ophthalmologists to broaden their diagnostic approach and collaborate with internal medicine departments to investigate this rare yet significant etiology. CASE PRESENTATION: A 17-year-old Caucasian woman presenting unilateral panuveitis was later diagnosed with HL. The ocular findings were non-necrotizing scleritis, anterior uveitis, vitritis, white/yellowish chorioretinal lesions, papillitis and vasculitis. A left supra-clavicular lymph node biopsy confirmed the diagnosis of nodular sclerosing Hodgkin's lymphoma stage IIB. Other causes of uveitis were excluded. Chemotherapy led to remission of the disease and the ocular lesions became quiescent with persistent pigmented chorioretinal scars. CONCLUSIONS: Hodgkin's lymphoma should be considered in the differential diagnosis of diseases that can occasionally be revealed by unilateral ocular inflammation. A comprehensive, multidisciplinary approach is key to properly assessing such cases.


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/diagnóstico , Feminino , Adolescente , Diagnóstico Diferencial , Esclerite/diagnóstico , Esclerite/etiologia , Esclerite/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pan-Uveíte/diagnóstico , Pan-Uveíte/tratamento farmacológico , Pan-Uveíte/etiologia
19.
Clin Rheumatol ; 43(9): 2933-2942, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39066867

RESUMO

OBJECTIVES: We aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment. METHOD: Patients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease. RESULTS: The study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795-0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439-6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet's disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765-72.231, p = 0.001). CONCLUSION: We suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease. Key Points • Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease. • Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease. • Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet's disease.


Assuntos
Uveíte , Humanos , Feminino , Masculino , Uveíte/epidemiologia , Uveíte/complicações , Criança , Fatores de Risco , Adolescente , Estudos Retrospectivos , Índice de Gravidade de Doença , Idade de Início , Pré-Escolar , Fatores Sexuais
20.
Ophthalmic Surg Lasers Imaging Retina ; 55(8): 443-447, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38976508

RESUMO

OBJECTIVE: This study examined the long-term outcomes of scleral-sutured fixated intraocular lenses (SSIOLs) in patients with uveitis. PATIENTS AND METHODS: Retrospective, consecutive review of uveitis patients with SSIOL fixation from January 2017 to December 2020. SSIOL techniques included four-point fixation with the Akreos A060 or enVista MX60 (Bausch + Lomb) lens, or Hoffman's pockets rescue. RESULTS: Thirteen eyes of 13 patients received an SSIOL (9 AO60, 2 MX60, 2 Hoffman's pockets). Diagnoses included pan- (9), anterior (2), and posterior uveitis (2). Average LogMAR best-corrected visual acuity pre- and postoperatively was 1.01 (Snellen ∼20/200) and 0.50 (Snellen ∼20/60), respectively (P = 0.003). No patients had postoperative SSIOL dislocation or conjunctival suture erosion. Six patients (46%) had uveitis flares postoperatively. Average follow-up was 50.2 months (range = 36.8 to 67.5). CONCLUSION: This series demonstrates a 0% dislocation and suture exposure rate. Risks of uveitis flares postoperatively are high despite aggressive perioperative control but are manageable with current treatments; therefore, patients must be continually monitored. [Ophthalmic Surg Lasers Imaging Retina 2024;55:443-447.].


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Esclera , Técnicas de Sutura , Uveíte , Acuidade Visual , Humanos , Estudos Retrospectivos , Feminino , Masculino , Esclera/cirurgia , Pessoa de Meia-Idade , Adulto , Uveíte/complicações , Uveíte/cirurgia , Uveíte/diagnóstico , Seguimentos , Implante de Lente Intraocular/métodos , Idoso , Resultado do Tratamento , Adulto Jovem , Fatores de Tempo , Suturas , Desenho de Prótese
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