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PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Azatioprina , Neoplasias , Humanos , Estudos Retrospectivos , Metotrexato , Adalimumab , Inibidores de Calcineurina , Infliximab , Ácido Micofenólico/uso terapêutico , Estudos de Coortes , Inibidores do Fator de Necrose Tumoral , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Ciclosporina/uso terapêutico , Antimetabólitos , Alquilantes , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Behcet disease is a systemic vasculitis, which may involve the eyes and central nervous system. The true prevalence of neurological involvement is not precisely known but may be associated with ocular involvement. This study investigates the association between Behcet uveitis and neuro-Behcet disease. METHODS: A retrospective single-center analysis was conducted for consecutive patients with Behcet uveitis at the Massachusetts Eye Research and Surgery Institution. Uveitis characteristics, neurological symptoms, fluorescein fundus angiography, and MRI results were recorded. RESULTS: Our population included 108 patients with Behcet uveitis, and 26 (24.1%) were found to have neurological involvement associated with Behcet disease. Optic nerve leakage on fundus angiography and neurological symptoms were associated with an increased risk of neurological involvement. Three cases (11.5%) were nonparenchymal, while 23 (88.5%) were parenchymal with lesions in the cortex, subcortical white matter, thalamus, basal ganglia, and brainstem. CONCLUSIONS: There is a high comorbidity between ocular and neurological involvement in Behcet disease. Careful assessment of neurological symptoms and baseline fluorescein fundus angiography are recommended for patients with Behcet disease. MRI has a high diagnostic yield and should be pursued if there is concern for progressive or pre-existing neurological involvement.
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BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.
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Antineoplásicos , Conjuntivite Alérgica , Doença Enxerto-Hospedeiro , Ceratoconjuntivite , Antineoplásicos/efeitos adversos , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/tratamento farmacológico , Olho , Humanos , Qualidade de Vida , LágrimasRESUMO
PURPOSE: To identify prognostic factors for poor visual outcomes in patients with isolated retinal vasculitis and to elucidate the outcome of immunosuppressive treatment without the use of antituberculosis drugs for patients with retinal vasculitis associated with a positive QuantiFERON-TB Gold In-Tube (QFT) test. METHODS: A retrospective chart review was performed of patients presenting with retinal vasculitis. After the diagnosis of active retinal vasculitis had been confirmed by fluorescein angiography and other possible causes of retinal vasculitis had been excluded, patients were categorized into two groups by their QFT result. Potential associated factors between the poor and good visual outcome groups were statistically analyzed by the chi-square test and logistic regression model with generalized estimating equations. RESULTS: Seventy-three eyes (48 patients) were enrolled in this study. After univariate analysis, multivariate logistic regression analysis was performed and revealed that logMAR visual acuity at the initial visit ( P = 0.01) and outer retinal disruption ( P = 0.03) were the two factors significantly associated with poor visual outcomes. Systemic corticosteroids were administered without the use of antituberculosis drugs to all 16 cases of presumed tuberculous retinal vasculitis associated with positive QFT (26 eyes), 10 (63%) of whom were given nonsteroidal immunosuppressive drugs and achieved inflammatory control and treatment success. CONCLUSION: Risk factors leading to poor visual outcome in patients with isolated retinal vasculitis have been identified. Immunosuppressive treatment without antituberculosis drugs seems to be a promising regimen for selected patients with presumed tuberculous retinal vasculitis under vigilant care.
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Vasculite Retiniana , Tuberculose , Corticosteroides/uso terapêutico , Antituberculosos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Prognóstico , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tuberculose/diagnósticoRESUMO
Regulatory T cells (Tregs) are necessary to prevent autoimmune disease. As such, stable FoxP3 expression is required for the proper function of Tregs in the control of autoimmune disease. Different Treg subsets that utilize different mechanisms of suppression have been identified. The T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif (TIGIT) is a relatively new Treg cell marker that has a suppressive function. We have previously identified the adenosine 2A receptor (A2Ar) as a requirement for the emergence of Tregs following resolution of autoimmune disease. Using a FoxP3-GFP-Cre reporter mouse, we identify FoxP3 and 'exFoxP3' cells, show FoxP3 and not exFoxP3 cells are suppressive. We further show FoxP3 cells express TIGIT, and are induced through A2Ar in healthy volunteers, but not patients with autoimmune disease. Furthermore, we show Tregs emerge in the target tissue at the onset of autoimmune disease in an A2Ar-dependent manner. In summary, we identify a novel subset of TIGIT+ Tregs that are induced through stimulation of the A2Ar.
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Doenças Autoimunes/imunologia , Receptor A2A de Adenosina/metabolismo , Receptores Imunológicos/metabolismo , Retinite/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Uveíte/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor A2A de Adenosina/genéticaRESUMO
PURPOSE: To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with anterior uveitis of longer than 3 months' duration followed up at United States tertiary uveitis care facilities. METHODS: Estimation of remission incidence and identification of associated predictors used survival analysis. MAIN OUTCOME MEASURES: Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or-for patients who did not return for follow-up after 90 days-remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied. RESULTS: Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% (95% confidence interval [CI], 30.4%-35.2%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95% CI, 0.44-0.83), bilateral uveitis (aHR, 0.75; 95% CI, 0.59-0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56-0.88), and glaucoma surgery (aHR, 0.63; 95% CI, 0.45-0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95% CI, 0.21-0.60) and synechiae (aHR, 0.62; 95% CI, 0.41-0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age ≥40 years vs. <40 years: aHR, 1.29; 95% CI, 1.02-1.63). CONCLUSIONS: Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course.
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Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Administração Oftálmica , Administração Oral , Adulto , Doença Crônica , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Uveíte Anterior/diagnóstico , Uveíte Anterior/fisiopatologia , Adulto JovemRESUMO
PURPOSE: To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy. DESIGN: Multicenter, randomized, double-masked, vehicle-controlled trial. PARTICIPANTS: Patients with neurotrophic persistent epithelial defect with or without stromal thinning. METHODS: The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 µg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat. MAIN OUTCOME MEASURES: The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8. RESULTS: Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient. CONCLUSIONS: Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.
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Córnea/inervação , Úlcera da Córnea/tratamento farmacológico , Fator de Crescimento Neural/uso terapêutico , Doenças do Nervo Trigêmeo/tratamento farmacológico , Administração Oftálmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Úlcera da Córnea/fisiopatologia , Método Duplo-Cego , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/patologia , Feminino , Fluorofotometria , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/administração & dosagem , Fator de Crescimento Neural/efeitos adversos , Soluções Oftálmicas , Proteínas Recombinantes , Resultado do Tratamento , Doenças do Nervo Trigêmeo/fisiopatologia , Acuidade Visual/fisiologia , Cicatrização/efeitos dos fármacosRESUMO
PURPOSE: To assess the safety and efficacy of an intravitreal fluocinolone acetonide (FA) insert to manage inflammation associated with chronic noninfectious posterior uveitis. DESIGN: Multicenter, randomized, prospective, doubled-masked, sham-controlled, 3-year phase 3 clinical trial. PARTICIPANTS: One hundred twenty-nine participants with recurrent noninfectious posterior uveitis were assigned randomly to FA insert (n = 87) or sham injection (n = 42). The more severely affected eye in participants with bilateral disease was designated as the study eye. METHODS: The insert (FA, 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, OCT, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28 and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. RESULTS: The 6-month (28% and 91%) and 12-month (38% and 98%) uveitis recurrence rates were significantly lower (P < 0.001) with FA insert vs. sham, respectively. Fewer recurrences per study eye (mean, 0.7 vs. 2.5), lower incidence of 15-letter or more decrease in best-corrected visual acuity (14% vs. 31%), and reduced systemic (19% vs. 40%) and local (7% vs. 62%) uveitis adjunctive treatments were observed with FA insert vs. sham, respectively. The FA insert group showed higher rates of cataract. Intraocular pressure-lowering treatment use was similar between groups. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. CONCLUSIONS: Chronic noninfectious posterior uveitis was managed successfully in this study population; FA insert eyes experienced fewer uveitis recurrence episodes, required fewer adjunctive treatments, and demonstrated less visual acuity loss compared with sham eyes. The FA insert treatment group showed higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an office setting.
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Implantes de Medicamento , Fluocinolona Acetonida/administração & dosagem , Glucocorticoides/administração & dosagem , Uveíte Posterior/diagnóstico , Uveíte Posterior/tratamento farmacológico , Doença Crônica , Método Duplo-Cego , Humanos , Injeções Intravítreas , Estudos Prospectivos , Recidiva , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte Posterior/microbiologia , Acuidade Visual/fisiologiaRESUMO
PURPOSE: Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis. METHODS: Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography. RESULTS: Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure. CONCLUSION: A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.
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Edema Macular/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Triancinolona Acetonida/administração & dosagem , Uveíte/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Corioide , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Humanos , Injeções , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Acuidade Visual , Adulto JovemRESUMO
PURPOSE: Vision-threatening ocular inflammation can be a devastating complication of granulomatosis with polyangiitis (GPA). Here we performed a retrospective observational study to describe the safety and efficacy of treating scleritis and uveitis with either cyclophosphamide or rituximab in GPA. METHODS: A chart review of patients diagnosed with GPA-associated scleritis or uveitis, treated with either cyclophosphamide or rituximab as the final therapy at our clinic, was conducted. A total of 1 year of follow-up visits was required for inclusion in the study. RESULTS: Thirteen patients (19 eyes) suffering from GPA-associated scleritis and/or uveitis were identified. As the final therapy, rituximab was administered to 9 patients and cyclophosphamide to 4. Mean duration of follow-up was 55 months (range 16-23 months). Remission was observed in all patients. Three patients had a flare of scleritis after the completion of therapy, and they were restarted on their respective agents. One patient had a flare of retinal vasculitis during rituximab therapy. One patient on cyclophosphamide experienced transient leukopenia. No adverse side effects of rituximab were noted throughout the course of treatment. CONCLUSIONS: Cyclophosphamide and rituximab are safe and effective agents for controlling scleritis and uveitis associated with GPA, with eventual progression towards steroid-sparing remission.
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Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/complicações , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Esclerite/tratamento farmacológico , Uveíte/tratamento farmacológico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To assess long-term effectiveness of rituximab therapy for refractory noninfectious uveitis affecting the posterior segment. METHODS: Retrospective case series. Patients diagnosed with recalcitrant noninfectious posterior uveitis who were treated with rituximab intravenous infusions between 2010 and 2015 were included. Patients underwent best-corrected visual acuity testing and fluorescein angiography evidence of disk or vascular staining at 6, 12, 18, and 24 months. Patients had at least 24 months of follow-up. RESULTS: Eleven patients (21 eyes) with refractory posterior uveitis treated with intravenous rituximab were included. Nine (81.8%) patients were female. Mean follow-up was 29.3 ± 7.8 months. rituximab was administered as complementary therapy because of previous inefficacy of other therapies in 7 (63.7%) patients, and it was the only treatment in four (36.3%) patients who did not tolerate other drugs. Inflammation signs by fluorescein angiography were controlled in nine (81.8%) patients at the end of follow-up. Baseline best-corrected visual acuity was 20/80 (logarithm of the minimal angle of resolution 0.6 ± 0.4), and final best-corrected visual acuity was 20/40 (0.3 ± 0.5) (P = 0.005). No significant side effects were reported. CONCLUSION: Rituximab therapy was associated with stability and remission of recalcitrant noninfectious posterior uveitis in patients who did not tolerate or did not respond to other therapies.
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Resistência a Medicamentos/efeitos dos fármacos , Terapia de Imunossupressão/métodos , Imunossupressores/farmacologia , Disco Óptico/patologia , Rituximab/administração & dosagem , Uveíte Posterior/tratamento farmacológico , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte Posterior/diagnóstico , Adulto JovemRESUMO
PURPOSE: To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis. DESIGN: Retrospective, multicenter, cohort study. PARTICIPANTS: Patients aged ≥18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. METHODS: Demographic, ocular, and treatment data were extracted from medical records of uveitis cases. MAIN OUTCOME MEASURES: Prevalent and incident OHT with intraocular pressures (IOPs) of ≥21 mmHg, ≥30 mmHg, and increase of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT). RESULTS: Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21 mmHg and OHT ≥30 mmHg are 14.4% (95% confidence interval [CI], 13.4-15.5) and 5.1% (95% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors for incident OHT ≥30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [≥8×/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT. CONCLUSIONS: Ocular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.
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Hipertensão Ocular/epidemiologia , Uveíte/complicações , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Glucocorticoides/uso terapêutico , Humanos , Incidência , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Uveíte/tratamento farmacológico , Acuidade Visual , Adulto JovemRESUMO
PURPOSE: The purpose was to evaluate the effectiveness and safety of rituximab (RTX) for the treatment of patients with aggressive ocular cicatricial pemphigoid (OCP). METHODS: A review of patient records at a tertiary referral center with biopsy confirmed OCP who presented between 2006 and 2016. Sixty-one eyes of 32 patients with symptomatic OCP who received treatment with RTX monotherapy or RTX in combination with additional immunomodulatory treatment (IMT) were evaluated. Main outcomes included clinically evident remission of disease, the percentage of corticosteroid sparing patients, stage of OCP (Foster), best corrected visual acuity, and treatment complications. Remission was defined as absence of progressive scarring and active ocular inflammation for ≥ 2 months. Partial remission/responding was defined as disease control and clinical improvement for ≥ 2 months. RESULTS: Mean age at the initiation of RTX treatment was 59.1 years (range, 24-80 years) with a median follow-up time after RTX initiation of 32 months (range, 14 to 127 months). Twenty-six patients achieved clinical remission with an average sustained remission of 24.5 months (from 9 months to 84 months). RTX monotherapy was used in six patients, RTX in combination with intravenous immunoglobulin in 14 patients, and RTX with intravenous immunoglobulin and/or with other IMT agent in six patients. Seven eyes (11.5%) of six patients had favorable response to RTX and achieved response and partial remission, while inflammation remained active in the other seven eyes (11.5%) of four patients though there was no progressive scarring. At the last visit, three patients (9.4%) were on topical corticosteroid, three patients (9.4%) were treated with systemic corticosteroid treatments, and the other 26 patients (81.2%) achieved corticosteroid sparing therapy. Five eyes (8.2%) progressed one Foster stage. No other cicatrization progression or worsening of LogMAR visual acuity (p = 0.641) was observed during the follow-up period. Adverse events included leukopenia in three patients (9.4%), anemia in two patients (6.2%), liver enzyme elevation in three patients (9.4%) who were also on another concomitant IMT drug, and Epstein-Barr Virus infection and sinus infection in one patient each (3.1%). No other severe adverse events were noted during the follow-up period. CONCLUSIONS: These retrospective data suggest that RTX is efficacious and well tolerated when included for the treatment of OCP. Controlled studies are necessary to identify the role of this IMT agent in the therapeutic arsenal, especially its optimum dose and duration of administration.
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Túnica Conjuntiva/patologia , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Rituximab/administração & dosagem , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Penfigoide Mucomembranoso Benigno/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To examine the efficacy and safety of infliximab therapy in the treatment for noninfectious intermediate uveitis resistant to conventional immunomodulatory therapy. METHODS: Forty-four eyes of 23 patients with resistant noninfectious intermediate uveitis who were treated with infliximab infusions for a minimum period of 3 months were included. Demographic data, clinical data, and fluorescein angiography and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database between August 2005 and February 2014. Clinical response, improvement in ancillary test findings, and major side effects were evaluated. RESULTS: Nineteen patients (82.6%) achieved remission. The mean duration of treatment to induce remission was 3.99 ± 3.06 months (range, 2-14.7). Cystoid macular edema was the only complication observed during the course of the treatment in 1 eye (2.27%). One patient (4.3%) developed major side effects. None of the patients developed central or peripheral demyelinating neuropathies or multiple sclerosis. At 6 months after remission, logarithm of the minimum angle of resolution visual acuity (P = 0.006) and central macular thickness (P = 0.03) showed significant improvement in patients who achieved remission. CONCLUSION: A significant number of patients achieved remission on infliximab therapy. The incidence of major side effects in our cohort was low.
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Imunoterapia/métodos , Infliximab/uso terapêutico , Uveíte Intermediária/tratamento farmacológico , Adolescente , Adulto , Criança , Feminino , Humanos , Edema Macular/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Tomografia de Coerência Óptica , Uveíte Intermediária/patologia , Uveíte Intermediária/fisiopatologia , Acuidade Visual/fisiologia , Adulto JovemRESUMO
The purpose of this study was to describe a possible causal relationship between ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two middle-aged female patients with already diagnosed OCP were studied in regard to the subsequent onset of conjunctival squamous neoplasia. Their clinical histories, ocular examinations, clinical photographs, and results of biopsies and any ancillary immunofluorescent laboratory evaluation studies were carefully reviewed. One patient had a preinvasive squamous dysplasia and the other an invasive squamous cell carcinoma, both in the unequivocal setting of OCP with bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients had been receiving intensive immunotherapy consisting of some combination of corticosteroids, rituximab, and interferon alpha. Both patients had a positive immunofluorescent study demonstrating immunoreactants at the level of the epithelial basement membrane. Each patient had 2 earlier negative immunofluorescent studies before a third was positive. While rare, there is 1 previous report of an association between OCP and conjunctival squamous neoplasia. The current report provides more data supporting the proposal that this conjunction is more than a random event. Repeat immunofluorescent studies after an initial negative result in a patient with strong clinical signs of OCP are imperative due to the frequency of false negative studies in the context of clinically persuasive disease.
Assuntos
Carcinoma de Células Escamosas/etiologia , Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/etiologia , Penfigoide Mucomembranoso Benigno/complicações , Idoso , Biópsia , Carcinoma de Células Escamosas/diagnóstico , Neoplasias da Túnica Conjuntiva/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Penfigoide Mucomembranoso Benigno/diagnósticoRESUMO
PURPOSE: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at 4 US academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate. MAIN OUTCOME MEASURES: Prevalence and incidence of NV. RESULTS: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13,810 eyes had NV (prevalence = 0.77%, 95% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26,465 eye-years (incidence, 0.33%/eye-year; 95% CI, 0.27-0.41). Factors associated with incident NV include age <35 years compared with >35 years (adjusted hazard ratio [aHR], 2.4; 95% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed >5 years ago, aHR, 2.4 [95% CI, 1.1-5.0] and aHR, 2.6 [95% CI, 1.2-6.0] for diagnosis within <1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95% CI, 2.5-11), and panuveitis (aHR, 4.3; 95% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus. CONCLUSIONS: Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection.
Assuntos
Neovascularização Retiniana/epidemiologia , Neovascularização Retiniana/etiologia , Uveíte/complicações , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
PURPOSE: To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. METHODS: Medical records were reviewed for patients with JIA-associated uveitis who were >16 years old at the final visit (the last visit prior to data collection). RESULTS: In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 ± 11.27 years. The number of eyes with visual acuity of ≤20/50 and ≤20/200 at the final visit was 37 (28 %) and 20 (15 %), respectively; at least one ocular complication was present in 72 % of eyes. Band keratopathy was the most frequent complication (42 %), followed by cataract (25 %), posterior synechiae (22 %), maculopathy (22 %), ocular hypertension (13 %), and hypotony (5 %). At the final visit, patients who were >16 years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were ≤16 years of age. Ongoing inflammation at the final visit was noted in 40 patients (52 %). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. CONCLUSIONS: JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.
Assuntos
Artrite Juvenil/complicações , Medição de Risco/métodos , Centros de Atenção Terciária , Uveíte Anterior/epidemiologia , Baixa Visão/epidemiologia , Acuidade Visual , Adolescente , Adulto , Artrite Juvenil/epidemiologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Morbidade/tendências , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia de Coerência Óptica , Estados Unidos/epidemiologia , Uveíte Anterior/complicações , Uveíte Anterior/diagnóstico , Baixa Visão/diagnóstico , Baixa Visão/etiologia , Adulto JovemRESUMO
PURPOSE: To determine whether classical indocyanine green angiography lesions in patients with birdshot chorioretinitis can be used to monitor disease activity. METHODS: A retrospective case series was performed on 26 eyes in 26 consecutive patients with birdshot chorioretinitis who had at least one indocyanine green angiography performed during disease activity and another during disease quiescence. Using Photoshop, the mean number, area, and area per spot on indocyanine green angiography were compared between disease activity and quiescence using a paired ratio test. RESULTS: The mean total lesion number, area, and area per spot during disease activity were 75.27 spots, 24,525 pixels, and 364 pixels/spots, respectively. The mean total lesion number, area, and area per spot size during disease quiescence were 28.35 spots (P < 0.01), 7,411 pixels (P < 0.01), and 279 pixels/spot (P = 0.12), respectively. CONCLUSION: There was a statistically significant decrease in the mean total area and number of lesions between the time of disease activity and disease quiescence (P < 0.01). Our results suggest that indocyanine green angiography has a role not only in diagnosis but also in monitoring treatment effectiveness; lesions can be reversible with treatment and their reappearance may be an indicator of disease relapse.
Assuntos
Coriorretinite/diagnóstico , Corantes/administração & dosagem , Angiofluoresceinografia , Verde de Indocianina/administração & dosagem , Adulto , Coriorretinopatia de Birdshot , Coriorretinite/tratamento farmacológico , Coriorretinite/fisiopatologia , Eletrorretinografia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Retina/patologia , Estudos Retrospectivos , Campos Visuais/fisiologiaRESUMO
PURPOSE: To describe the clinical course, visual outcome, and prognosis of isolated, idiopathic retinal vasculitis. METHODS: Eighty patients (150 eyes) with isolated, idiopathic retinal vasculitis were included. Demographic data, clinical data, complications at the initial visit and during follow-up, fluorescein angiography, and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution (MERSI) database from September 2005 to February 2015. RESULTS: Seventy-five (93.7%) patients required treatment with immunomodulatory therapy. Of those 75 patients, 60 (75%) patients were able to achieve durable remission. Factors which were independently significant predictive of poor visual outcome were lower initial visual acuity (OR: 3.78; 95% CI: 1.75-8.16; P = 0.001), cystoid macular edema (OR: 5.54; 95% CI: 1.81-16.99; P = 0.003), and macular ischemia (OR: 5.12; 95% CI: 1.12-23.04; P = 0.036). CONCLUSION: The majority (67.25%) of our patients enjoyed a good visual outcome (most recent visit best-corrected visual acuity equal to or better than 20/40 and within one line or better from the baseline) with immunomodulatory therapy. We found that cystoid macular edema, macular ischemia, and lower best-corrected visual acuity during the first consultation visit were significant independent risk factors for poor visual outcome.
Assuntos
Vasculite Retiniana/diagnóstico , Vasculite Retiniana/fisiopatologia , Acuidade Visual/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Angiofluoresceinografia , Humanos , Imunomodulação , Imunossupressores/uso terapêutico , Isquemia/diagnóstico , Isquemia/tratamento farmacológico , Isquemia/fisiopatologia , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Vasculite Retiniana/tratamento farmacológico , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To describe changes in three-dimensional choroidal volume and thickness with full raster scans of enhanced depth imaging optical coherence tomography in patients with birdshot retinochoroidopathy. METHODS: This prospective case series collected spectral domain optical coherence tomography images with the enhanced depth imaging technique from eight eyes of eight patients with birdshot retinochoroidopathy including four active patients (four eyes) and four quiet patients (four eyes). Fifty scans of each patient were manually segmented before automated built-in calibration software was used. RESULTS: Of all active patients, there were no statistically significant differences in the total choroidal volume and mean central choroidal thickness between the active and inactive phase over 6 months of follow-up. Alterations in choroidal parameters were evident and consistent after amelioration of inflammation, whereas the retinal volume and thickness remained stable. Regarding the eight inactive eyes at 6 months, the mean total choroidal volume and mean central choroidal thickness were significantly less than historical controls (P = 0.03 and P < 0.001, respectively). Persistent suprachoroidal hyporeflective space in two patients was noted despite the fact that clinical inflammation completely subsided at 6 months. CONCLUSION: Choroidal volume and thickness changes were consistent with inflammation in patients with birdshot retinochoroidopathy. Patients with inactive birdshot retinochoroidopathy have significant reduction in choroidal volume and thickness than do normal patients.