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1.
Semin Immunopathol ; 41(4): 427-445, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175392

RESUMO

Mounting evidence suggests that immunological mechanisms play a fundamental role in the pathogenesis of diabetic retinopathy (DR) and diabetic macular edema (DME). Upregulation of cytokines and other proinflammatory mediators leading to persistent low-grade inflammation is believed to actively contribute to the DR-associated damage to the retinal vasculature, inducing breakdown of the blood-retinal barrier, subsequent macular edema formation, and promotion of retinal neovascularization. This review summarizes the current knowledge of the biological processes providing an inflammatory basis for DR and DME. In addition, emerging therapeutic approaches targeting inflammation are discussed, including blockade of angiopoietin 2 and other molecular targets such as interleukin (IL)-6, IL-1ß, plasma kallikrein, and integrins.

2.
Arthritis Rheumatol ; 71(12): 2081-2089, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31237427

RESUMO

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). METHODS: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. RESULTS: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). CONCLUSION: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up.

3.
PLoS One ; 14(1): e0210799, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30677041

RESUMO

AIMS: We aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis. MATERIAL AND METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of >300 µm as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm2 area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or <300 µm) within a 12 month period. RESULTS: Fifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis. CONCLUSION: Available treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.


Assuntos
Edema Macular/etiologia , Uveíte/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fóvea Central/diagnóstico por imagem , Fóvea Central/patologia , Humanos , Edema Macular/diagnóstico por imagem , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Prognóstico , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Adulto Jovem
4.
Am J Ophthalmol ; 200: 85-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30660771

RESUMO

PURPOSE: Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME. DESIGN: Retrospective case series. METHODS: Patients with CME secondary to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300 µm. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. RESULTS: A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n = 9), Behçet disease (n = 7), birdshot retinochoroidopathy (n = 4), idiopathic (n = 4), and sarcoidosis (n = 1). The ocular patterns were panuveitis (n = 9), anterior uveitis (n = 7), posterior uveitis (n = 5), and intermediate uveitis (n = 4). Most patients had CME in both eyes (n = 24). TCZ was used in monotherapy (n = 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5 µm; P = .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P = .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6 mg/day vs 3.1 ± 2.3 mg/day; P = .002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34 months. CONCLUSION: Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.

5.
Ocul Immunol Inflamm ; : 1-8, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30395738

RESUMO

PURPOSE: To study the risk factors for visual loss in presumed tuberculosis-related uveitis (TRU). METHODS: Retrospective observational cohort study of patients with TRU, either treated or not for tuberculosis, from January 2005 to January 2017. Clinical and demographic variables were recorded. Main outcome measure was a loss of visual acuity (VA) of ≥2 Snellen lines. A Generalized Estimation Equation was used to control between-eyes bias. A backward stepwise logistic regression multivariate analysis was conducted to elucidate independent risk factors. RESULTS: One hundred and thirty-eight eyes from 82 patients were included. There were 45 males, median age at onset of uveitis was 40 years (Interquartile range, IQR 24). The median follow-up was 36 months (IQR 49.75) and 51 patients completed antituberculous treatment (ATT) for a mean of 9.37 months. In the multivariate model, ATT was the only independent protective factor for loss of VA (OR 0.13, 95% CI 0.04-0.37, p < 0.001). CONCLUSION: ATT itself may prevent visual loss in TRU.

7.
Ophthalmology ; 125(9): 1444-1451, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29602570

RESUMO

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

8.
Med Clin (Barc) ; 151(8): 336-337, 2018 Oct 23.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29525112
9.
Clin Exp Rheumatol ; 36(4): 652-657, 2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29303704

RESUMO

OBJECTIVES: To assess the efficacy of golimumab (GLM), a fully humanised anti-TNF-α monoclonal antibody, in refractory juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: This was a multicentre study of JIA-associated uveitis refractory to standard synthetic immunosuppressive drugs and in most cases to other anti-TNF-α agents. Results were expressed as mean±standard deviation or as median (range or interquartile range). The Wilcoxon signed-rank test was used to compare continuous variables. A literature review of the efficacy of GLM in uveitis related to JIA was also conducted. RESULTS: We studied 7 patients (5 females; mean age 21.7±7.5 years; 13 affected eyes). Uveitis was bilateral in 6. Cystoid macular oedema (CME) occurred in 3 patients (5 eyes). Besides corticosteroids and synthetic immunosuppressive drugs, patients had received before GLM a median of 2 biologic agents (range 0-3) including adalimumab (n=6), etanercept (n=2), infliximab (n=3) and abatacept (n=2). GLM dose was 50 mg/sc every 4 weeks. After 6 months of therapy the number of anterior chamber cells decreased from 1 [0.25-1.5] to 0 [0-0.5] (p=0.02) and optical coherence tomography (in patients with CME) from 313.6±77.05 to 261.4±75.1 µm (p=0.03). The best-corrected visual acuity increased from 0.5 to 0.62 (p=0.018). Complete remission of uveitis was achieved in 4 of 7 patients after 16.8±11.4 months of follow-up. However, 2 of the seven patients had to be switched to tocilizumab due to inefficacy. Local erythema at the injection site was observed in 2. CONCLUSIONS: GLM may be considered in the management of refractory JIA-related uveitis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Juvenil/complicações , Uveíte/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Tomografia de Coerência Óptica , Uveíte/fisiopatologia , Acuidade Visual
10.
Ocul Immunol Inflamm ; 26(5): 786-792, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28010156

RESUMO

PURPOSE: To investigate bacillus Calmette-Guérin (BCG) infective capability and cytotoxicity in ARPE-19 cells. METHODS: BCG inoculum was dispensed at a MOI 100:1 for 3 h in 90% confluent ARPE-19 cells. Infection rates at different time points were determined by colony forming units (CFU) count and, in parallel, by the number of microscopically infected cells. WST-1 reagent was used for cytotoxicity assays. RESULTS: A 67-year-old man previously treated with intravesical BCG for bladder carcinoma presented with chronic, refractory, bilateral uveitis with macular edema. Quiescence was achieved only after commencing antituberculous treatment. BCG infection rate by two methods peaked at 48 h (16 ± 5.7% by CFU count and 40 ± 7.7% by microscopy; p = 0.058). BCG adhesion, phagocytosis, intracellular proliferation and cytolysis was observed. Cytotoxicity was minimal and did not differ from uninfected cells. CONCLUSIONS: BCG can infect at low rates and proliferate in ARPE-19 cells without toxicity in the surrounding monolayer.


Assuntos
Vacina BCG/uso terapêutico , Epitélio Pigmentado da Retina/patologia , Neoplasias da Bexiga Urinária/complicações , Uveíte Intermediária/complicações , Idoso , Células Cultivadas , Humanos , Masculino , Mycobacterium bovis/imunologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Uveíte Intermediária/tratamento farmacológico
11.
Retina ; 38(7): 1361-1370, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28520640

RESUMO

BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). METHODS: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24. RESULTS: Sixteen eyes from 12 patients (10 women) were included. Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients achieved 24 months of follow-up and that is the census date for data collection. Before TCZ was commenced, ME was present, and all patients had been previously treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia (n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%; confidence interval) was 516 ± 55 µm at baseline, improving to 274 ± 13 at Month 12 (P = 0.0004), and sustained at 274 ± 14 at Month 24 of follow-up (P = 0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.78 ± 0.18 (Snellen 20/120 ± 20/30) at baseline to 0.42 ± 0.17 (20/52 ± 20/30) at Month 12 (P = 0.0001) and 0.40 ± 0.17 (20/50 ± 20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn in 5 patients with sustained remission at Month 12 but in all, ME relapsed between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions led to recovery of uveitis control and ME resolution. Two adverse events were reported during two 4-month follow-ups: one Grade 1 neutropenia and one community-acquired pneumonia. CONCLUSION: In this long-term study, TCZ was effective and had a comparable safety profile to published data for TCZ use in other indications, when used for the treatment of refractory uveitis-related ME.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Angiofluoresceinografia/métodos , Fóvea Central/patologia , Edema Macular/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Uveíte/complicações , Acuidade Visual , Adolescente , Adulto , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Fóvea Central/efeitos dos fármacos , Fundo de Olho , Humanos , Injeções Intravenosas , Interleucina-6/antagonistas & inibidores , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Adulto Jovem
12.
Med. clín (Ed. impr.) ; 149(6): 261-266, sept. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-166555

RESUMO

El término vasculitis retinianas (VR) engloba un grupo de entidades potencialmente graves que forman parte de las enfermedades inflamatorias intraoculares que afectan al segmento posterior del ojo. Según la naturaleza del proceso inflamatorio, las VR se clasifican en predominantemente inflamatorias o isquemizantes (VR oclusivas). Su diagnóstico es clínico y su etiología puede ser infecciosa o inmunomediada. Pueden constituir cuadros oculares aislados o bien formar parte de una enfermedad sistémica potencialmente grave, de la que pueden ser la manifestación inicial. Las nuevas técnicas de imagen retiniana, como la angiografía fluoresceínica de campo amplio o la tomografía de coherencia óptica-angiografía, nos ayudarán a clasificar la VR y guiarán la sospecha diagnóstica. Las VR pueden representar un reto diagnóstico y requerir un abordaje multidisciplinar. Por ello, el conocimiento de las VR es importante para que se pueda establecer un diagnóstico temprano e instaurar el tratamiento adecuado (AU)


The term retinal vasculitis (RV) encompasses a heterogeneous group of sight-threatening conditions that are included in the intraocular inflammatory diseases that affect the posterior segment of the eye. Based on the nature of the inflammatory process, RV are classified into predominantly inflammatory or ischaemic (occlusive RV). The diagnosis is clinical and the aetiology can be infectious or non-infectious (immune-mediated). RV can be an isolated ocular syndrome or be associated with a systemic disease, of which they can represent the first manifestation. New retinal imaging techniques such as ultra-wide field fluorescein angiography and optical coherence tomography angiography will help us classify the RV and aid the diagnostic process, which can be challenging and require a multidisciplinary approach. Therefore, clinical knowledge of RV is essential for prompt diagnosis and to establish the appropriate treatment (AU)


Assuntos
Humanos , Vasculite Retiniana/diagnóstico , Uveíte/diagnóstico , Diagnóstico por Imagem/métodos , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Diagnóstico Diferencial , Flebite/diagnóstico
13.
Autoimmun Rev ; 16(10): 1079-1089, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28778705

RESUMO

Interleukin-6 (IL-6) is a key cytokine that is strongly up-regulated during infection and inflammation. Featuring pleiotropic activity, IL-6 is responsible for the induction of hepatic acute-phase proteins, trafficking of acute and chronic inflammatory cells, differentiation of adaptive T cell responses, homeostatic regulation, and tissue regeneration. Dysregulated IL-6 production has been associated with the development of a wide variety of systemic immune-mediated, chronic diseases, and even certain types of cancer. From the ocular perspective, significant elevation of IL-6 has been found in ocular fluids derived from diabetic macular edema, retinal vein occlusion, and refractory/chronic uveitis patients. During the last decade, tocilizumab, a neutralizing monoclonal antibody (mAb) that targets the IL-6 receptor (IL-6R), has been approved for the treatment of rheumatoid arthritis in >100 countries worldwide. Furthermore, it has been reported to be effective for the treatment of a number of autoimmune diseases including uveitis and its associated macular edema. Currently numerous candidate molecular strategies targeting the IL-6 signaling pathways are in progress through clinical trials in various disorders. Herein we discuss the basic biology of IL-6 and its pathological role in the development of immune-mediated conditions, particularly focusing on inflammatory eye diseases. It also provides an overview of the on-going clinical trials with the new anti-IL-6 mAbs and their potential use in the clinical practice.


Assuntos
Doenças Autoimunes/imunologia , Interleucina-6/imunologia , Uveíte/imunologia , Humanos
14.
Med Clin (Barc) ; 149(6): 261-266, 2017 Sep 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28687121

RESUMO

The term retinal vasculitis (RV) encompasses a heterogeneous group of sight-threatening conditions that are included in the intraocular inflammatory diseases that affect the posterior segment of the eye. Based on the nature of the inflammatory process, RV are classified into predominantly inflammatory or ischaemic (occlusive RV). The diagnosis is clinical and the aetiology can be infectious or non-infectious (immune-mediated). RV can be an isolated ocular syndrome or be associated with a systemic disease, of which they can represent the first manifestation. New retinal imaging techniques such as ultra-wide field fluorescein angiography and optical coherence tomography angiography will help us classify the RV and aid the diagnostic process, which can be challenging and require a multidisciplinary approach. Therefore, clinical knowledge of RV is essential for prompt diagnosis and to establish the appropriate treatment.


Assuntos
Vasculite Retiniana/diagnóstico por imagem , Angiofluoresceinografia , Humanos , Oftalmoscopia , Vasculite Retiniana/classificação , Vasculite Retiniana/etiologia , Tomografia de Coerência Óptica
16.
Arthritis Rheumatol ; 69(3): 668-675, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27696756

RESUMO

OBJECTIVE: To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. RESULTS: We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 µm to 259.1 ± 39.5 µm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. CONCLUSION: TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Juvenil/complicações , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Uveíte/etiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
17.
Am J Physiol Cell Physiol ; 312(3): C244-C253, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28003224

RESUMO

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Barreira Hematorretiniana/fisiologia , Proteína C-Reativa/metabolismo , Permeabilidade Capilar/fisiologia , Células Epiteliais/fisiologia , Epitélio Pigmentado da Retina/fisiologia , Barreira Hematorretiniana/efeitos dos fármacos , Proteína C-Reativa/química , Permeabilidade Capilar/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Humanos , Isoformas de Proteínas/química , Isoformas de Proteínas/efeitos da radiação , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos
18.
J Rheumatol ; 43(12): 2183-2188, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27633821

RESUMO

OBJECTIVE: To report on experience using the anti-interleukin 6 receptor antibody tocilizumab (TCZ) to treat severe and therapy-refractory uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Retrospective data were gathered from patients with JIA receiving TCZ treatment for uveitis. JIA and related uveitis data (disease onset, activity, structural complications, and topical and systemic antiinflammatory treatment) were evaluated at the start of TCZ (baseline) and every 3 months during TCZ therapy. RESULTS: A total of 17 patients (14 women) with active uveitis were included (mean age 15.3 ± 6.9 yrs, mean followup time 8.5 mos). In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, methotrexate (MTX), and other synthetic and biological disease-modifying antirheumatic drugs, including ≥ 1 tumor necrosis factor-α (TNF-α) inhibitor. Uveitis inactivity was achieved in 10 patients after a mean of 5.7 months of TCZ treatment (in 3 of them, it recurred during followup) and persisted in the remaining 7 patients. By using TCZ, systemic corticosteroids or immunosuppressives could be spared in 7 patients. Macular edema was present in 5 patients at baseline and improved in all of them under TCZ treatment. Arthritis was active in 11 patients at the initial and in 6 at the final followup visit. CONCLUSION: TCZ appears to represent a therapeutic option for severe JIA-associated uveitis that has been refractory to MTX and TNF-α inhibitors in selected patients. The present data indicate that inflammatory macular edema responds well to TCZ in patients with JIA-associated uveitis.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Imunossupressores/uso terapêutico , Uveíte/tratamento farmacológico , Adolescente , Artrite Juvenil/complicações , Criança , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Uveíte/complicações , Adulto Jovem
19.
Clin Exp Rheumatol ; 34(6 Suppl 102): S34-S40, 2016 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27054359

RESUMO

OBJECTIVES: To assess the efficacy of other biologic therapies, different from infliximab (IFX) and adalimumab (ADA), in patients with Behçet's disease uveitis (BU). METHODS: Multicenter study of 124 patients with BU refractory to at least one standard immunosuppressive agent that required IFX or ADA therapy. Patients who had to be switched to another biologic agent due to inefficacy or intolerance to IFX or ADA or patient's decision were assessed. The main outcome measures were the degree of anterior and posterior chamber inflammation and macular thickness. RESULTS: Seven (5.6%) of 124 cases (4 women/3 men; mean age, 43 (range 28- 67) years; 12 affected eyes) were studied. Five of them had been initially treated with ADA and 2 with IFX. The other biologic agents used were golimumab (n=4), tocilizumab (n=2) and rituximab (n=1). The ocular pattern was panuveitis (n=4) or posterior uveitis (n=3). Uveitis was bilateral in 5 patients (71.4%). At baseline, anterior chamber and vitreous inflammation were present in 6 (50%) and 7 (58.3%) of the eyes. All the patients (12 eyes) had macular thickening (OCT>250µm) and 4 of them (7 eyes), cystoid macular edema (OCT>300 µm). Besides reduction anterior chamber and vitreous inflammation, we observed a reduction of OCT values, from 330.4±58.5 µm at the onset of the biological agent to 273±50 µm at month 12 (p=0.06). Six patients achieved a complete remission of uveitis. CONCLUSIONS: The vast majority of patients with BU refractory to standard immunosuppressive drugs are successfully controlled with ADA and/or IFX. Other biologic agents appear to be also useful.


Assuntos
Adalimumab/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Substituição de Medicamentos , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/efeitos adversos , Adulto , Idoso , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Produtos Biológicos/efeitos adversos , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/efeitos adversos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Espanha , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/imunologia
20.
Acta Ophthalmol ; 94(6): e395-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27009382

RESUMO

PURPOSE: To evaluate serum cytokine profile from patients with active scleritis in a two-centre prospective case-control study. METHODS: The serum of 20 active scleritis patients not treated with any local, periocular, or systemic immunomodulatory therapy (IMT) was analysed with multiplex assay to determine the levels of 11 cytokines interleukin (IL)-1ß, IL-6, IL-2, IFN-γ, IL-10, IL-12p40, IL-13, IL-17A, IL-5, TNF-α, and TNF-ß, and with ELISA to determine the levels of TGF-ß1, IL-22, and IL-23. Twenty-five age-matched healthy volunteers were used as controls. In a subgroup of 13 patients with active disease, a second serum sample was obtained when the disease was inactive and levels of IL-22 were determined. Serum IL-22 levels from patients with active scleritis were correlated with type of scleritis (non-necrotizing and necrotizing), degree of inflammation (0-4+ :≤2+ and >2+), and associated systemic disease. RESULTS: Serum levels of IL-22 were elevated in active scleritis patients compared to controls (6.41 ± 1.52 pg/ml versus 1.93 ± 0.39 pg/ml, p = 0.012) and significantly decreased after scleritis remission with the use of IMT (p = 0.005). There was no statistical association with scleritis type, degree of inflammation, or associated systemic disease. The serum levels of other cytokines were not significantly different from controls. CONCLUSION: In our study cohort, IL-22 serum levels were significantly elevated in active scleritis patients compared to controls and decreased significantly after remission. Our results suggest that IL-22, a T helper (Th) 17- and Th22- derived cytokine, may play a critical role in the physiopathology of scleritis.


Assuntos
Interleucinas/sangue , Esclerite/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Esclerite/diagnóstico
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