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1.
Can J Ophthalmol ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31712042

RESUMO

OBJECTIVE: Discontinuation of interventional clinical trials and nonpublication of completed trials represent a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in ophthalmology patients. METHODS: A retrospective, cross-sectional study of ophthalmology-based interventional clinical trials in ClinicalTrials.gov dating back to 1972 was conducted. χ2 tests were used to determine any potential associations between trial characteristics and trial completion. The Mann-Whitney U test was used to compare median time to publication between academic and industry-sponsored trials. RESULTS: Of 2926 included trials, 413 (14%) were discontinued early with only 19 of these studies being published. A total of 2027 (81%) of the 2513 completed trials were not published. A total of 277 419 participants were enrolled in unpublished, completed trials, whereas an estimated 20 843 participants were enrolled in trials that were never completed and never to led to publication. The odds of study discontinuation among industry-sponsored trials were 27% greater than government/academia-sponsored (National Institutes of Health, National Eye Institute, National Institutes of Health Clinical Center, U.S. and foreign university-based teaching hospitals) trials (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.03-1.57, p = 0.03). Furthermore, the odds of nonpublication among industry-sponsored trials were 55% more than those funded by government/academia (OR = 1.55, 95% CI 1.27-1.89, p < 0.0001). CONCLUSIONS: The nonpublication of many completed trials and of preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Greater transparency through the publication of the entire spectrum of clinical trials' results as well as those that are terminated early could minimize publication bias and thus lead to a more robust medical literature.

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.
Hum Mol Genet ; 27(24): 4333-4343, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30215709

RESUMO

Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered a prototypic member of the recently proposed 'MHC-I (major histocompatibility complex class I)-opathy' family. Genetic studies have pinpointed the endoplasmic reticulum aminopeptidase (ERAP1) and (ERAP2) genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2 haplotypes in 84 Dutch cases and 890 controls. We identified association at variant rs10044354, which mediated a marked increase in ERAP2 expression. We also identified and cloned an independently associated ERAP1 haplotype (tagged by rs2287987) present in more than half of the cases; this ERAP1 haplotype is also the primary risk and protective haplotype for other MHC-I-opathies. We show that the risk ERAP1 haplotype conferred significantly altered expression of ERAP1 isoforms in transcriptomic data (n = 360), resulting in lowered protein expression and distinct enzymatic activity. Both the association for rs10044354 (meta-analysis: odds ratio (OR) [95% CI]=2.07[1.58-2.71], P = 1.24 × 10(-7)) and rs2287987 (OR[95% CI]: =2.01[1.51-2.67], P = 1.41 × 10(-6)) replicated and showed consistent direction of effect in an independent Spanish cohort of 46 cases and 2103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype associated with Birdshot more strongly than either variant alone [meta-analysis: P=3.9 × 10(-9)]. Finally, we observed that ERAP2 protein expression is dependent on the ERAP1 background across three European populations (n = 3353). In conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark of Birdshot and provide rationale for strategies designed to correct ERAP function for treatment of Birdshot and MHC-I-opathies more broadly.

4.
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.

5.
Rheumatology (Oxford) ; 57(5): 856-864, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29471416

RESUMO

Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Behçet/complicações , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adolescente , Adulto , Idoso , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/etiologia , Adulto Jovem
6.
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
7.
Med. clín (Ed. impr.) ; 149(12): 552.e1-552.e12, dic. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-169537

RESUMO

Fundamento y objetivo Desarrollar recomendaciones basadas en la mejor evidencia disponible y experiencia sobre el uso de inmunodepresores en pacientes con uveítis anterior (UA) no infecciosa no neoplásica. Material y métodos: Se seleccionó un grupo multidisciplinar de 5 expertos, que en la primera reunión de grupo nominal, acordó el alcance, usuarios y apartados del documento. Posteriormente, se realizó una revisión sistemática de la literatura sobre la eficacia y seguridad de los inmunodepresores en pacientes con UA no infecciosa no neoplásica. En la segunda reunión de grupo nominal, se generaron 33 recomendaciones en base a la evidencia encontrada en la revisión sistemática y a la experiencia de los expertos. Mediante la metodología Delphi, el grado de acuerdo con las recomendaciones se extendió a 25 expertos más que votaron según una escala de uno (total desacuerdo) a 10 (total acuerdo). El acuerdo se definió como una puntuación ≥7 en al menos el 70% de los participantes. El nivel de evidencia y grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford. Resultados: Se aceptaron las 33 recomendaciones generadas. Se incluyen recomendaciones específicas para pacientes con UA no infecciosa no neoplásica, así como para distintas líneas de tratamiento. Conclusiones: En los pacientes con UA no infecciosa no neoplásica, estas recomendaciones sobre el uso de inmunodepresores pueden servir como guía que ayude en la toma de decisiones terapéuticas, dada la ausencia de estudios con potencia estadística suficiente, u otros algoritmos universalmente aceptados sobre los que apoyar dichas decisiones (AU)


Background and objective: To develop recommendations on the use of immunodepressors in patients with non-infectious, non-neoplastic anterior uveitis (AU) based on best evidence and experience. Material and methods: A multidisciplinary panel of five experts was established, who, in the first nominal group meeting defined the scope, users, and chapters of the document. A systematic literature review was performed to assess the efficacy and safety of immunosuppressors in patients with non-infectious, non-neoplastic AU. All the above was discussed in a second nominal group meeting and 33 recommendations were generated. Through the Delphi methodology, the degree of agreement with the recommendations was tested also by 25 more experts. Recommendations were voted on from one (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and degree of recommendation was assessed using the Oxford Centre for Evidence-based Medicine's Levels of Evidence. Results: The 33 recommendations were accepted. They include specific recommendations on patients with non-infectious, non-neoplastic AU, as well as different treatment lines. Conclusions: In patients with non-infectious, non-neoplastic AU, these recommendations on the use of immunosuppressors might be a guide in order to help in the treatment decision making, due to the lack of robust evidence or other globally accepted algorithms (AU)


Assuntos
Humanos , Uveíte/terapia , Algoritmos , Planos e Programas de Saúde/organização & administração , Inflamação/prevenção & controle , Inflamação/terapia , Policondrite Recidivante/complicações , Sarcoidose/complicações , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , Uveíte/economia , Técnica Delfos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Psoríase/complicações
8.
Medicine (Baltimore) ; 96(42): e8045, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29049193

RESUMO

BACKGROUND: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). METHODS: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). RESULTS: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. CONCLUSIONS: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.


Assuntos
Imunossupressores/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Adalimumab/uso terapêutico , Adulto , Anticorpos Monoclonais/uso terapêutico , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Med Clin (Barc) ; 149(12): 552.e1-552.e12, 2017 Dec 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28911893

RESUMO

BACKGROUND AND OBJECTIVE: To develop recommendations on the use of immunodepressors in patients with non-infectious, non-neoplastic anterior uveitis (AU) based on best evidence and experience. MATERIAL AND METHODS: A multidisciplinary panel of five experts was established, who, in the first nominal group meeting defined the scope, users, and chapters of the document. A systematic literature review was performed to assess the efficacy and safety of immunosuppressors in patients with non-infectious, non-neoplastic AU. All the above was discussed in a second nominal group meeting and 33 recommendations were generated. Through the Delphi methodology, the degree of agreement with the recommendations was tested also by 25 more experts. Recommendations were voted on from one (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and degree of recommendation was assessed using the Oxford Centre for Evidence-based Medicine's Levels of Evidence. RESULTS: The 33 recommendations were accepted. They include specific recommendations on patients with non-infectious, non-neoplastic AU, as well as different treatment lines. CONCLUSIONS: In patients with non-infectious, non-neoplastic AU, these recommendations on the use of immunosuppressors might be a guide in order to help in the treatment decision making, due to the lack of robust evidence or other globally accepted algorithms.


Assuntos
Imunossupressores/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Tomada de Decisão Clínica/métodos , Técnica Delfos , Esquema de Medicação , Humanos , Uveíte Anterior/diagnóstico , Uveíte Anterior/etiologia
10.
J Med Genet ; 54(1): 38-46, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27609017

RESUMO

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.


Assuntos
Uveíte/genética , Alelos , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Loci Gênicos/genética , Antígenos HLA/genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
11.
Rheumatol Int ; 37(4): 647-656, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27815703

RESUMO

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases.


Assuntos
Inflamação/diagnóstico , Uveíte/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
12.
Int Ophthalmol ; 2016 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-27761762

RESUMO

PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology. Occasionally, triggering causes are identified, such as neoplasms, and they are termed sarcoid-like reactions, which may appear in any sarcoidotic target tissue. Choroidal metastases appear as part of widespread metastatic disease or as the first suggestion of neoplastic disease. They can also be a part of the differential diagnosis of a spectrum of inflammatory eye diseases. We present a case in which a lung carcinoma, pulmonary and eye sarcoid-like reactions, and choroidal metastasis take place in the same patient. CASE REPORT: A 60-year-old male with a past history of pulmonary sarcoidosis and associated anterior uveitis was diagnosed with a lung carcinoma with no regional lymph nodes extension, so that the resection surgery was performed without additional systemic treatment. At the same time, he complained of visual acuity loss and pain in his right eye. An intense ocular inflammatory reaction and a choroidal mass compatible with metastasis were identified. A vitrectomy with an accompanied histological exam of the lesion was deemed inconclusive. Ocular symptoms progressively worsened showing mass growth, and as a result, an enucleation was performed and the histological study subsequently revealed metastasis from his lung carcinoma. CONCLUSION: Sarcoid-like reactions may be due to incipient malignancies. Any diagnosis of sarcoidosis requires ruling out other diseases that can produce secondary sarcoid-like reactions. In addition, any choroidal mass suggestive of metastasis requires exclusion of metastatic disease even in the absence of clinical signs indicating tumor extension.

13.
Ophthalmology ; 123(12): 2618-2625, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27692527

RESUMO

PURPOSE: To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis. DESIGN: Prospective observational study. PARTICIPANTS: Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy. METHODS: All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment. MAIN OUTCOME MEASURES: Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing. RESULTS: Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014). CONCLUSIONS: Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Anti-Idiotípicos/sangue , Uveíte/sangue , Uveíte/tratamento farmacológico , Adalimumab/imunologia , Adolescente , Adulto , Idoso , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/farmacocinética , Formação de Anticorpos/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento , Acuidade Visual
14.
Retina ; 36(9): 1778-85, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27183031

RESUMO

PURPOSE: To assess the safety and efficacy of intravitreal dexamethasone implants in the treatment of macular edema secondary to infectious uveitis. METHODS: We retrospectively reviewed clinical records from three uveitis referral units in Spain. The main outcome measures were rate of reactivation of infection, improvements in visual acuity and resolution of macular edema, as measured by optical coherence tomography. RESULTS: We included eight eyes from seven patients with a median age of 64 years (30-75). Etiologies of the infections were Herpes simplex virus-type 1, Varicela-Zoster virus, Treponema pallidum, Brucella mellitensis, Borrelia burgdorferi, Toxoplasma gondii, and cytomegalovirus. Median visual acuity was 20/160 (20/30-20/400) at baseline and 20/70 (20/25-20/200) at the last follow-up visit. Mean macular thickness was 516 µm (115) at baseline and 266.3 µm (40) at the last follow-up visit. Visual acuity improved in 100% of the eyes and none of the eyes showed macular edema at the last follow-up visit. Five patients required reinjections of the implant. Only one patient required antiglaucoma drops for a temporary increase in ocular pressure. There were no cases of reactivation of the infectious ocular disease. Median follow-up time was 18 months. CONCLUSION: In this small case series of eyes with macular edema secondary to infectious uveitis, treatment with dexamethasone intravitreal implants was not associated with reactivation of the infectious ocular disease. Furthermore, significant improvements in visual acuity and macular thickness were observed in our patients.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Edema Macular/tratamento farmacológico , Uveíte/tratamento farmacológico , Adulto , Idoso , Dexametasona/efeitos adversos , Implantes de Medicamento , Feminino , Glucocorticoides/efeitos adversos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico por imagem , Edema Macular/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/diagnóstico por imagem , Uveíte/microbiologia
15.
Semin Arthritis Rheum ; 46(1): 95-101, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27060872

RESUMO

OBJECTIVE: To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). METHODS: Multicenter study of SpA-related uveitis refractory to at least 1 immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. RESULTS: A total of 15 patients (13 men/2 women; 18 affected eyes; mean age 39 ± 6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n = 8), psoriatic arthritis (n = 6) and non-radiographic axial SpA (n = 1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n = 13), sulfasalazine (n = 6), pulses of methylprednisolone (n = 4), azathioprine (n = 3), leflunomide (n = 2), and cyclosporine (n = 1). Overall, 10 of them had also been treated with TNF-α blockers; etanercept (n = 7), adalimumab (n = 7), infliximab (n = 6), and certolizumab (n = 1). GLM was given at the standard dose (50mg/sc/monthly) as monotherapy (n = 7) or in combination with conventional immunosuppressive drugs (n = 8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years [0 (0-0)] was significantly reduced compared to baseline findings [1 (0-3); p = 0.04]. The mean best corrected visual acuity value also improved (0.84 ± 0.3 at 2 years versus 0.62 ± 0.3 at baseline; p = 0.03). Only minor side effects were observed after a mean follow-up of 23 ± 7 months. CONCLUSIONS: Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Espondilartrite/complicações , Uveíte/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Uveíte/etiologia
16.
Ophthalmology ; 123(8): 1632-1636, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27084561

RESUMO

PURPOSE: To describe and analyze the prevalence of spondyloarthritis (SpA) in patients with anterior uveitis (AU). DESIGN: Multicentric, observational, prospective study. PARTICIPANTS: Consecutive patients with AU who were human leukocyte antigen (HLA)-B27 positive or HLA-B27 negative with more than 1 episode of AU separated by at least 3 months were selected. Patients with a previous diagnosis of SpA were excluded. METHODS: Included patients were evaluated by an ophthalmologist and a rheumatologist following a predefined visit schedule. MAIN OUTCOME MEASURES: Sociodemographic and clinical variables including the diagnosis of SpA according to Assessment of SpondyloArthritis International Society (ASAS) criteria and an exhaustive ophthalmological examination (best-corrected visual acuity, intraocular pressure, biomicroscopic examination of the anterior and posterior segment of the eye, cataract evaluation, optical coherence tomography evaluating both the 1-mm central retina thickness and the optic nerve head and retinal nerve fiber layer, and visual field in a dark room with 1 eye patched) were collected. Baseline descriptive, bivariate, and concordance analyses were performed. RESULTS: We included 798 patients, mostly men (59%) with a mean age of 45 years; 60% were AU HLA-B27 positive, and 40% had recurrent negative AU HLA-B27. A total of 50.2% and 17.5% of patients presented axial and peripheral SpA according to ASAS criteria, respectively. Patients with AU who were HLA-B27 positive were more frequently diagnosed with axial (69.8% vs. 27.3%, P < 0.0001) and peripheral SpA (21.9% vs. 11.1%, P < 0.0001) than patients with recurrent negative AU HLA-B27. In general, we did not detect important differences between groups in the ophthalmologic variables. CONCLUSIONS: A large percentage of patients with clinically significant AU have an undiagnosed SpA. This percentage is even higher if the HLA-B27 haplotype is positive.


Assuntos
Espondilartrite/epidemiologia , Uveíte Anterior/epidemiologia , Adulto , Feminino , Antígeno HLA-B27/imunologia , Humanos , Estudos Interdisciplinares , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Prevalência , Estudos Prospectivos , Retina/patologia , Células Ganglionares da Retina/patologia , Espanha/epidemiologia , Espondilartrite/diagnóstico , Espondilartrite/imunologia , Tomografia de Coerência Óptica , Uveíte Anterior/diagnóstico , Uveíte Anterior/imunologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia
17.
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
18.
Expert Opin Investig Drugs ; 25(2): 195-214, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26640977

RESUMO

INTRODUCTION: Several advances have been made in the diagnostic approach and therapeutic management of patients with immune-mediated uveitis over the last few decades, which have to lead to an improvement in the visual prognosis of patients. However, the use of available therapies, including steroids and immunosuppressive drugs, is still associated with limited efficacy and potentially serious side effects. Consequently, efforts have been made to develop novel therapeutic alternatives including new molecules and innovative therapeutic approaches. AREAS COVERED: Herein, the authors provide an updated review of those drugs in the initial phases of evaluation for the treatment of immune-mediated uveitides as well as the latest evidence from basic research. EXPERT OPINION: Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.


Assuntos
Desenho de Drogas , Terapia de Alvo Molecular , Uveíte/tratamento farmacológico , Administração Oftálmica , Animais , Ensaios Clínicos Fase II como Assunto , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Prognóstico , Uveíte/diagnóstico , Uveíte/imunologia
19.
Ocul Immunol Inflamm ; 24(2): 147-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25121345

RESUMO

PURPOSE: To describe the clinical characteristics and to assess visual prognosis of patients with syphilis-associated uveitis in northern Spain. METHODS: Retrospective review of clinical records in eight general uveitis referral centers. RESULTS: Since the year 2000, 50 patients have been diagnosed: 31 men and 19 women; median age was 41 (19-76) years. A total of 34% were co-infected with HIV and 24% presented systemic manifestations of syphilis. Median initial visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20-20/2000) and 20/22 (20/20-20/2000), respectively (p < .0001). The most frequent manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on admission presented worsening of visual acuity at last visit, whereas frequency of worsening in eyes without edema was 7.1% (p = 0.009). CONCLUSIONS: In our series, patients with syphilitic uveitis were more usually middle-aged men and were frequently co-infected with HIV. Although most patients showed posterior segment involvement, visual prognosis was good.


Assuntos
Infecções Oculares Bacterianas/diagnóstico , Sífilis/diagnóstico , Uveíte/diagnóstico , Adulto , Idoso , Antibacterianos/uso terapêutico , Contagem de Linfócito CD4 , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Feminino , Infecções por HIV/diagnóstico , Humanos , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Papiledema/diagnóstico , Prognóstico , Estudos Retrospectivos , Centros de Cuidados de Saúde Secundários , Espanha , Sífilis/tratamento farmacológico , Sífilis/microbiologia , Uveíte/tratamento farmacológico , Uveíte/microbiologia , Carga Viral , Acuidade Visual/fisiologia , Adulto Jovem
20.
Surv Ophthalmol ; 60(6): 575-89, 2015 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26164735

RESUMO

Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy.


Assuntos
Imunossupressores/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Infliximab/uso terapêutico
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