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1.
Klin Monbl Augenheilkd ; 241(5): 619-625, 2024 May.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-38262426

RESUMO

In ocular graft-versus-host disease (GVHD), an inflammatory reaction occurs at the ocular surface after transplantation of allogeneic hematopoietic stem cells. Self-reactive T cells of the donor are particularly responsible for this. This can lead to a pronounced wetting disorder of the ocular surface, conjunctival hyperemia, and corneal ulceration up to perforation. The ocular GVHD is associated with a high degree of suffering, such as pain, photophobia, and reduction in visual acuity. This review provides an overview of typical ophthalmological findings, topical and systemic therapeutic approaches, and concomitant measures (e.g., scleral lenses, punctum plugs) and the appropriate management of complications.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Oftalmopatias/etiologia , Oftalmopatias/terapia , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia
2.
Front Med (Lausanne) ; 10: 1133381, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36891189

RESUMO

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

3.
Mol Biol Rep ; 49(7): 6093-6102, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35359237

RESUMO

PURPOSE: Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be observed clinically. METHODS: Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n = 30), acute anterior uveitis (AAU; n = 18), and primary open angle glaucoma (POAG; n = 20) were obtained during trabeculectomy or cataract surgery. Samples were analyzed by RNA-Seq, qRT-PCR, LC-IMS, Western-Blot, and LEGENDplex™ analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). RESULTS: RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG, p > 0.05). LC-IMS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which Angiopoetin, Lumican and Decorin were associated with angiogenesis and showed increased (p > 0.05) expression on Western-Blot analysis. LEGENDplex™ analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIA patients with treatment-refractory complicated course of uveitis. CONCLUSION: Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.


Assuntos
Artrite Juvenil , Glaucoma de Ângulo Aberto , Trabeculectomia , Uveíte Anterior , Uveíte , Artrite Juvenil/complicações , Artrite Juvenil/genética , Humanos , Neovascularização Patológica/genética , Trabeculectomia/efeitos adversos , Uveíte/complicações , Uveíte Anterior/complicações
4.
Ocul Immunol Inflamm ; 30(7-8): 1588-1594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33983102

RESUMO

PURPOSE: New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient's survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment. METHODS: In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here. RESULTS: Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases. CONCLUSIONS: Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient's vision without cessation of the tumor treatment.


Assuntos
Neoplasias , Transdução de Sinais , Humanos , Estudos Retrospectivos
7.
Ocul Immunol Inflamm ; 29(6): 1080-1089, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32160102

RESUMO

Purpose: To analyze circulating immune cells in patients with anterior uveitis (AU) associated to axial spondyloarthritis (SpA), or juvenile idiopathic arthritis (JIA).Methods: Venous blood samples were collected from healthy controls (n = 16), and either SpA (n = 19) or JIA (n = 23) patients with associated anterior uveitis (AU) during active flare, or after ≥3 months of inactivity. Frequencies of CD56+, MHC-I+, and S100A9+ monocytes, CCR7+ dendritic cells, CD56+dim natural killer (NK) cells and CD3+CD56bright T-cells were analyzed via flow cytometry. Serum S100A8/A9 levels were determined via ELISA.Results: SpA patients showed a reduced frequency of CD56+dim NK cells during uveitis activity, a constitutively activated monocyte phenotype, and elevated S100A8/A9 serum levels. In contrast, JIAU patients showed elevated frequencies of CD56+ monocytes and CCR7+ DC.Conclusion: Phenotype of peripheral immune cells differ between patients, probably contributing to different courses of acute onset AU in SpA and insidious onset AU in JIAU patients.Abbreviations: AU: anterior uveitis, AR: arthritis, JIA: juvenile idiopathic arthritis, SpA: axial spondyloarthritis.


Assuntos
Artrite Juvenil/imunologia , Espondiloartrite Axial/imunologia , Imunidade Inata/fisiologia , Uveíte Anterior/imunologia , Adolescente , Adulto , Calgranulina A/sangue , Calgranulina B/sangue , Criança , Células Dendríticas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Fenótipo , Linfócitos T/imunologia
8.
Front Immunol ; 11: 573955, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154752

RESUMO

Patients with chronic anterior uveitis are at particularly high risk of developing secondary glaucoma when corticosteroids [e.g., dexamethasone (Dex)] are used or when inflammatory activity has regressed. Macrophage migration into the eye increases when secondary glaucoma develops and may play an important role in the development of secondary glaucoma. Our aim was to evaluate in vitro if increased hydrostatic pressure and corticosteroids could induce changes in macrophages phenotype. By using a pressure chamber cell culture system, we assessed the effect of increased hydrostatic pressure (HP), inflammation, and immunosuppression (Dex) on the M1/M2 phenotype of macrophages. Bone marrow-derived macrophages (BMDMs) were stimulated with medium, lipopolysaccharide (LPS, 100 ng/ml), Dex (200 ng/ml), or LPS + Dex and incubated with different HP (0, 20, or 60 mmHg) for 2 or 7 days. The numbers of CD86+/CD206- (M1 phenotype), CD86-/CD206+ (M2 phenotype), CD86+/CD206+ (intermediate phenotype), F4/80+/TNF-α+, and F4/80+/IL-10+ macrophages were determined by flow cytometry. TNF-α and IL-10 levels in cell culture supernatants were quantified by ELISA. TNF-α, IL-10, fibronectin, and collagen IV expression in BMDMs were detected by immunofluorescence microscopy. Higher HP polarizes macrophages primarily to an M1 phenotype (LPS, 60 vs. 0 mmHg, d2: p = 0.0034) with less extra cellular matrix (ECM) production and secondary to an M2 phenotype (medium, 60 vs. 0 mmHg, d7: p = 0.0089) (medium, 60 vs. 20 mmHg, d7: p = 0.0433) with enhanced ECM production. Dex induces an M2 phenotype (Dex, medium vs. Dex, d2: p < 0.0001; d7: p < 0.0001) with more ECM production. Higher HP further increased M2 polarization of Dex-treated macrophages (Dex, 60 vs. 0 mmHg, d2: p = 0.0417; d7: p = 0.0454). These changes in the M1/M2 phenotype by high HP or Dex treatment may play a role in the pathogenesis of secondary uveitic glaucoma- or glucocorticoid (GC)-induced glaucoma.


Assuntos
Pressão Hidrostática/efeitos adversos , Macrófagos/imunologia , Animais , Sobrevivência Celular , Células Cultivadas , Colágeno Tipo IV/metabolismo , Dexametasona/farmacologia , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Glaucoma/etiologia , Glaucoma/imunologia , Inflamação , Interleucina-10/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fenótipo , Fator de Necrose Tumoral alfa/metabolismo
9.
J Mol Neurosci ; 70(4): 600-609, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31907866

RESUMO

The purpose of the study was studying the influence of different NOD agonists on the morphological phenotype of primary murine microglia and to examine their influence on characteristic cytokines. Primary CD11b-positive cells were isolated from the brain of neonatal mice. The microglial phenotype of the cells was examined by ionized calcium-binding adapter molecule (Iba)1 staining. After14 days in culture, these cells were stimulated by iE-DAP, L18-MDP, or M-TriDAP as NOD1, NOD2, and NOD1/2 agonists, respectively. The cellular morphology was recorded and compared to the phenotype of cells cultured in medium alone or after LPS stimulation. The cells developed a specific phenotype only after treatment with the NOD2 agonist L18-MDP. These cells were characterized by straight extensions carrying tiny spikes and had a high ramification index. This was in sharp contrast to all other treatments, which always resulted in an amoeboid phenotype typically shown by activated microglia in vivo and by cultured microglia in vitro. The staining intensity of IL-6 and TNF-α did not reveal any clear difference independent of the NOD agonist treatment. In contrast, an increased staining intensity was observed for IL-10 after L18-MDP treatment. The NOD2 agonist L18-MDP induced a morphologically distinct phenotype characterized by microspike-decorated dendritiform extensions and a high degree of ramification in primary murine microglia. Increased ramification index and elevated staining intensity of anti-inflammatory IL-10 as hallmarks suggest that a M2-like phenotype of microglia was induced.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/farmacologia , Adjuvantes Imunológicos/farmacologia , Ácido Diaminopimélico/análogos & derivados , Microglia/efeitos dos fármacos , Proteína Adaptadora de Sinalização NOD1/agonistas , Proteína Adaptadora de Sinalização NOD2/agonistas , Fenótipo , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Forma Celular , Extensões da Superfície Celular/efeitos dos fármacos , Células Cultivadas , Ácido Diaminopimélico/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Microglia/citologia , Microglia/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Exp Eye Res ; 185: 107676, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31128101

RESUMO

Evidence of an age-related increase of ß-synuclein (SNCB) in several parts of the visual system including the retina has been reported. SNCB is thought to function as an antagonist of α-synuclein in neurodegenerative diseases, but the exact role of SNCB remains unclear. The presented work studies two different aspects of the onset and role of SNCB in the retinal pigment epithelium (RPE). First, the topographical and intracellular distributions of SNCB in the RPE of non-human marmoset monkey (Callithrix jacchus) were evaluated in paraffin-embedded eyes and RPE whole mounts from different developmental stages (neonatal, adolescent, and adult). Thus, revealed distinct lifetime-related alterations of the topographical and intracellular distributions of SNCB in the primate macula compared to the retinal periphery. Furthermore, the function and influences of SNCB on ARPE-19 cells and primary porcine RPE (ppRPE) cells were characterized by exposing these cells with recombinant SNCB (rSNCB) at different concentrations. Moreover, apoptosis, protein- and mRNA-expression levels of factors of the p53/MDM2 signaling cascade and inflammation- and oxidation-related genes were investigated. The observed dose-depended decreased apoptosis rates together with the PLD2 mediated activation of the p53 pathway promotes senescence-related processes in SNCB exposed common ARPE-19 cells from human origin. Further, increased HMOX1 and NOX4 levels indicate increased oxidative stress and inflammatory responses triggered by SNCB. The obtained differences in the distribution of SNCB in primate RPE together with alterations of cellular functions in rSNCB-exposed RPE cells (e.g., ARPE-19, ppRPE) support SNCB-related effects like inflammatory response and stress-related properties on RPE over lifetime. The possible functional relevance of SNCB in physiological aging converting into a pathophysiological condition should be investigated in further studies.


Assuntos
Envelhecimento/fisiologia , Retina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , beta-Sinucleína/metabolismo , Animais , Apoptose , Callithrix , Linhagem Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/fisiologia , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Masculino , NADPH Oxidase 4/metabolismo , Estresse Oxidativo , Inclusão em Parafina , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Retina/efeitos dos fármacos , Retina/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais , Sus scrofa , Proteína Supressora de Tumor p53/genética , beta-Sinucleína/farmacologia
11.
Br J Ophthalmol ; 103(10): 1413-1417, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30563912

RESUMO

BACKGROUND/AIMS: To assess the impact of papillary leakage and active inflammation on optical coherence tomography (OCT)-based retinal nerve fibre layer thickness (RNFLT) and Bruch's membrane opening minimum rim width (BMO-MRW) measurements in uveitic eyes with and without secondary glaucoma. METHODS: Prospective, single-centre analysis of patients with uveitis. All patients included received a fluorescein angiography examination and an OCT scan measuring the BMO-MRW and the RNFLT in three concentric peripapillary ring scans. RESULTS: Overall, 95 eyes of 56 patients were enrolled. Papillary leakage and active inflammation were present in 39 (41%) and 57 (60%) eyes, respectively. Twenty-one eyes were classified as glaucomatous; 10 of those glaucomatous eyes showed papillary leakage. Both BMO-MRW and RNFLT measurements were significantly increased in eyes with papillary leakage (BMO-MRW: p=0.0001; RNFLT: first to third ring (p<0.0001)). Active inflammation led to a significantly thickened RNFLT (first ring: p=0.0026; second ring: p=0.0009; third ring: p=0.0002) while only a trend towards increased values could be observed in the BMO-MRW measurements (p=0.3063). Glaucomatous eyes with papillary leakage demonstrated significantly higher values on both BMO-MRW and RNFLT measurements than glaucomatous eyes without leakage (BMO-MRW: p=0.0159; RNFLT: first ring: p=0.0062; second ring: p=0.0037; third ring: p=0.0197). No significant difference could be observed between glaucomatous eyes with leakage and non-glaucomatous eyes without leakage (BMO-MRW: p=0.4132; RNFLT: first ring: p=0.5412; second ring: p=0.3208; third ring: p=0.1164). CONCLUSIONS: The OCT scanning parameters BMO-MRW and RNFLT were significantly influenced by papillary leakage in uveitic eyes with and without glaucoma. RNFLT values were also significantly increased while active inflammation was present. In patients with uveitis, these OCT-based imaging tools should be interpreted with caution, especially in those with papillary leakage or active inflammation.


Assuntos
Lâmina Basilar da Corioide/patologia , Glaucoma de Ângulo Aberto/diagnóstico , Edema Macular/diagnóstico , Fibras Nervosas/patologia , Disco Óptico/irrigação sanguínea , Células Ganglionares da Retina/patologia , Uveíte/complicações , Adulto , Idoso , Permeabilidade Capilar , Feminino , Angiofluoresceinografia , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Curva ROC , Tomografia de Coerência Óptica , Campos Visuais
12.
Front Immunol ; 9: 1773, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105034

RESUMO

HLA-B27 is the allele most frequently associated with human anterior uveitis. The majority of HLA-B27-positive [acute anterior uveitis (AAU)] patients develop clinically distinct symptoms with acute symptomatic onset of flare and a recurrent disease course characterized by a massive cellular ocular infiltrate during uveitis relapse. By contrast, uveitis in HLA-B27-negative [idiopathic anterior uveitis (IAU)] patients tends to develop a clinically less fulminant, more chronic, and typically asymptomatic disease course. To analyze systemic immune responses in the different uveitis entities, we analyzed peripheral blood cells by flow cytometry. In addition, as a pro-inflammatory biomarker serum, S100A8/A9 levels were quantified by ELISA from patients with AAU (n = 27) and IAU (n = 21), and in healthy controls (n = 30). Data were obtained either during active uveitis flare or after 3 months of inactivity. IAU patients showed a transiently increased frequency of CD56- and CD163-positive monocytes and of both granulocytic myeloid-derived suppressor cells and Th17 cells during active uveitis. By contrast, AAU patients showed an elevated frequency of monocytes, activated T cells, and elevated S100A8/A9 serum levels during clinically quiescent disease. The differentially regulated response of both innate and adaptive immune cells in the blood may be related to the clinically distinct characteristics of the two different uveitis entities.


Assuntos
Antígeno HLA-B27/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Uveíte Anterior/etiologia , Uveíte Anterior/metabolismo , Adulto , Autoimunidade , Biomarcadores , Calgranulina A/sangue , Calgranulina B/sangue , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Uveíte Anterior/diagnóstico , Adulto Jovem
13.
Klin Monbl Augenheilkd ; 235(5): 568-575, 2018 May.
Artigo em Alemão | MEDLINE | ID: mdl-29739026

RESUMO

Cataracts are a frequent complication of uveitis, and their management can be challenging. Operation planning requires knowledge of the cause (e.g., infectious versus noninfectious) and course of uveitis, including any intraocular comorbidities (e.g., macular edema). Preoperative patient selection is particularly important in uveitis patients to achieve good surgical results. Steroid-sparing disease-modifying antirheumatic drugs (DMARDs) can reduce the rate of postoperative complications and can improve visual acuity. Before the operation, a stable inactivity of intraocular inflammation must be achieved. The surgical approach should be minimally invasive. Intraocular lens implantation should only be performed under stable inflammatory control. By using intraocular corticosteroids (e.g., dexamethasone acetonide implant, triamcinolone acetonide) the complication rate can be reduced. Postoperatively, the additional anti-inflammatory medication should be intensified and continued for up to 3 months. With careful patient selection, planning and execution of cataract surgery and postoperative care, satisfactory anatomical and functional outcomes can be achieved in uveitis patients.


Assuntos
Extração de Catarata , Catarata , Uveíte , Catarata/complicações , Glucocorticoides , Humanos , Triancinolona Acetonida , Uveíte/complicações , Uveíte/tratamento farmacológico
14.
Front Immunol ; 9: 708, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29675026

RESUMO

Patients with juvenile idiopathic arthritis often develop chronic anterior uveitis (JIAU). JIAU patients possess a particularly high risk for developing secondary glaucoma when inflammatory inactivity has been achieved. By using multiplex bead assay analysis, we assessed levels of pro- and anti-inflammatory cytokines, chemokines, or metalloproteinases in the aqueous humor (AH) of patients with clinically inactive JIAU with (JIAUwG) or without secondary glaucoma (JIAUwoG), or from patients with senile cataract as controls. Laser-flare photometry analysis prior to surgery showed no significant differences between JIAUwG or JIAUwoG. Compared with the control group, levels of interleukin-8, matrix metalloproteinase-2, -3, -9, serum amyloid A (SAA), transforming growth factor beta-1, -2, -3 (TGFß-1, -2, -3), and tumor necrosis factor-alpha in the AH were significantly higher in patients with clinically inactive JIAUwG or JIAUwoG. Samples from JIAwoG patients displayed significantly higher levels of SAA (P < 0.0116) than JIAUwG patients. JIAUwG patients showed an increased level of TGFß-2 in AH samples compared with JIAUwoG (P < 0.0009). These molecules may contribute to the clinical development of glaucoma in patients with JIAU.


Assuntos
Humor Aquoso/metabolismo , Artrite Juvenil/complicações , Citocinas/metabolismo , Glaucoma/etiologia , Glaucoma/metabolismo , Uveíte Anterior/etiologia , Uveíte Anterior/metabolismo , Adolescente , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/metabolismo , Biomarcadores , Criança , Pré-Escolar , Humanos , Mediadores da Inflamação , Fatores de Risco , Uveíte Anterior/complicações , Uveíte Anterior/tratamento farmacológico
15.
Ann Rheum Dis ; 77(8): 1107-1117, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29592918

RESUMO

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. OBJECTIVES: To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). RESULTS: In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe.


Assuntos
Artrite Juvenil/complicações , Uveíte/etiologia , Uveíte/terapia , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Gerenciamento Clínico , Medicina Baseada em Evidências/métodos , Glucocorticoides/uso terapêutico , Humanos , Programas de Rastreamento/métodos , Metotrexato/uso terapêutico , Índice de Gravidade de Doença , Uveíte/diagnóstico
16.
Klin Monbl Augenheilkd ; 235(9): 1035-1042, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-28599333

RESUMO

Macular edema in uveitis patients is certainly the most frequent complication leading to a permanent and irreversible reduction in vision during the course of the disease. Thanks to optical coherence tomography (OCT) technology and fluorescein angiography (FAG), significantly more macular edemas are detected. Macular edema can be found in various uveitis varieties and can show different clinical patterns. All macular edema should be treated. Macular edema with active inflammation usually reacts very well to general uveitis treatment. In the case of eyes without visible inflammation, however, the response to such therapy is usually less effective. According to the latest treatment recommendations, dexamethasone implants should be used as the first intravitreal therapy. Vascular endothelial growth factor inhibitors (VEGF inhibitors) are second-line treatment regimens. The choice of therapy is, therefore, primarily based on the degree of inflammation and the individual complications, such as glaucoma, lens situation or previous increase in IOP after steroid administration. These individual complications may allow using VEGF inhibitors as first line treatment. An improvement in the macular edema can be achieved with both groups of active substances.


Assuntos
Edema Macular , Esteroides/uso terapêutico , Uveíte , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Tomografia de Coerência Óptica , Uveíte/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual
18.
Klin Monbl Augenheilkd ; 234(5): 652-656, 2017 May.
Artigo em Alemão | MEDLINE | ID: mdl-28505673

RESUMO

Background HLA-B27 positive acute anterior uveitis is the most common type of uveitis, and it is an autoimmune disease that can be triggered by infections. The precise mechanism of the interaction between involved microbes (mostly gram negative bacteria) and the host immune system is not clear. The disease probably results from an imbalance between pro- and anti-inflammatory components. Project description This article gives a compact overview about the current knowledge of the clinic and the etiopathogenesis of acute anterior uveitis as a basis for future research approaches. The goal of the current research is to classify the cellular and molecular pathogenetic factors in acute anterior uveitis. In this regard, a project on uveitis within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye", examines the hypothesis that dysregulation of regulatory cell populations and anti-inflammatory cytokines, such as interleukin-10 (IL-10), might contribute to the development of ocular autoimmunity following infections. The goal is to establish new markers for individual susceptibility in the risk group of the HLA-B27 positive population, because only about 1% of the HLA-B27 positive population will eventually develop acute anterior uveitis. Conclusions Translational research approaches to identify predisposed risk groups from the HLA-B27 population could improve patient care both on a prophylactic and a therapeutic level.


Assuntos
Corpo Ciliar/imunologia , Citocinas/imunologia , Antígeno HLA-B27/imunologia , Mediadores da Inflamação/imunologia , Iris/imunologia , Modelos Imunológicos , Uveíte Anterior/imunologia , Animais , Medicina Baseada em Evidências , Humanos , Fatores Imunológicos/imunologia , Pesquisa Translacional Biomédica/tendências , Uveíte Anterior/tratamento farmacológico
19.
Klin Monbl Augenheilkd ; 234(5): 679-685, 2017 May.
Artigo em Alemão | MEDLINE | ID: mdl-28505676

RESUMO

Background Ophthalmology, principally, is a very successful subdiscipline in medicine. Nonetheless, there are still unmet medical needs which necessitate translational research. Methods The funding instrument of a Research Unit (RU) of the German Research Foundation (DFG) is presented as exemplified by the RU 2240 at the Department of Ophthalmology at the University of Cologne. Results The Research Unit integrates different research groups working on pathologic ocular inflammation, macrophages/microglia and (lymph)angiogenesis to collaborate in a synergistic way. Rotation positions allow young clinicians to rotate into research labs for a defined period of time. A Research Unit is also a powerful strategic tool to strengthen clinical and experimental ophthalmology at individual medical faculties. Conclusions The funding instrument of a Research Unit is highly suitable for fostering translational research in a medical subdiscipline such as ophthalmology, supporting the next generation of (clinician) scientists in ophthalmology and finding new cures for our patients.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Endoftalmite/tratamento farmacológico , Endoftalmite/imunologia , Imunidade Celular/efeitos dos fármacos , Linfangiogênese/efeitos dos fármacos , Linfangiogênese/imunologia , Pesquisa Translacional Biomédica/tendências , Animais , Modelos Animais de Doenças , Imunidade Celular/imunologia , Imunoterapia/métodos , Resultado do Tratamento
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