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PURPOSE: To report two cases of ibrutinib-related uveitis and review the literature to date. METHODS: We report two cases of ibrutinib-related uveitis using CARE guidelines and review the cases reported in the literature. RESULTS: Case 1) A 55-year-old female with recurrent primary central nervous system lymphoma presented with bilateral decreased visual acuity, photophobia, and floaters that started one month after initiating oral treatment with ibrutinib. Chronic non-granulomatous bilateral anterior-intermediate uveitis with macular edema was identified. Secondary causes were ruled out, and a presumptive diagnosis of ibrutinib-related uveitis was made. Case 2) A 57-year-old female with Waldenström macroglobulinemia who was treated with ibrutinib for two years presented with bilateral blurred vision, photophobia, red eyes, and floaters. A diagnosis of non-granulomatous, noninfectious panuveitis with bilateral cystoid macular edema was made. Secondary causes were ruled out, and ibrutinib toxicity was the most likely cause. CONCLUSION: Ibrutinib-related uveitis is a novel and under-diagnosed clinical entity. The most frequent clinical presentation in the literature is bilateral, non-granulomatous, anterior, and intermediate uveitis. Macular edema is a frequent complication. Uveitis usually requires topical treatment and the suspension of ibrutinib. Switching to second-generation Bruton tyrosine kinase inhibitors is proposed as a potential therapeutic alternative.
Assuntos
Adenina , Piperidinas , Humanos , Feminino , Adenina/análogos & derivados , Adenina/efeitos adversos , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Tomografia de Coerência Óptica , Acuidade Visual , Inibidores de Proteínas Quinases/efeitos adversos , Uveíte/induzido quimicamente , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/diagnóstico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Edema Macular/induzido quimicamente , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Angiofluoresceinografia , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/diagnósticoRESUMO
INTRODUCTION: Axial spondyloarthritis (AxSpA) is a chronic inflammatory condition primarily affecting the axial skeleton. Peripheral features such as peripheral arthritis (PA) and dactylitis are common in AxSpA disease. This study aimed to investigate the independent impact of these manifestations on patient presentation and disease outcomes within an Irish AxSpA cohort. METHODS: 912 Irish AxSpA patients were analyzed in this study. Disease outcomes in patients with and without peripheral arthritis or dactylitis were compared using univariate and multivariate methods. The prevalence of extra-spinal manifestations was further assessed in relation to AxSpA disease duration. RESULTS: 30.2% of patients reported PA, while 6.6% had dactylitis. PA and dactylitis were strongly linked, with 70% of patients presenting with dactylitis also showing features of PA. Psoriasis was more common in both patients with PA (OR 2.2, P < 0.001) and dactylitis (OR 3.38, P < 0.001). Dactylitis, but not PA was strongly linked to uveitis (OR 2.91, P < 0.001) and inflammatory bowel disease (OR 3.15, P < 0.001), while PA was associated with worse patient functioning and reduced quality of life. PA, but not dactylitis was linked with increased AxSpA disease duration. DISCUSSION: Despite high concurrence of PA and dactylitis in AxSpA patients, each manifestation is independently associated with worse outcomes. While some of these overlapped, several outcomes are specific to either PA or dactylitis. Due to its strong association with uveitis and inflammatory bowel disease, an early presentation of dactylitis may represent a unique subset of patients and serve as a valuable predictive marker for the later onset of these conditions.
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Espondiloartrite Axial , Humanos , Feminino , Masculino , Adulto , Irlanda/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Espondiloartrite Axial/epidemiologia , Prevalência , Artrite/epidemiologia , Psoríase/epidemiologia , Psoríase/complicações , Uveíte/epidemiologia , Uveíte/etiologia , Uveíte/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Articulações dos Dedos/patologia , Qualidade de VidaRESUMO
Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).
Assuntos
Linfócitos B , Ativação Linfocitária , Sarcoidose , Humanos , Sarcoidose/imunologia , Sarcoidose/sangue , Sarcoidose/diagnóstico , Linfócitos B/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Países Baixos/epidemiologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico , Uveíte/imunologia , Uveíte/sangue , Uveíte/diagnóstico , Fator Ativador de Células B/sangue , Indonésia , Biomarcadores/sangue , Tuberculose/imunologia , Tuberculose/sangue , Tuberculose/diagnósticoRESUMO
PURPOSE: This study reports the outcomes of the 0.18-mg intravitreal fluocinolone acetonide implant in the treatment of pediatric noninfectious uveitis. METHODS: A retrospective cohort study was performed on patients under 18 years old who received fluocinolone acetonide implant between June 1, 2020 and March 1, 2023. Data collected included demographics, uveitis diagnosis, use of anti-inflammatory therapy, visual acuity, intraocular pressure, and grading of uveitis activity. Uveitis recurrence was defined as increased inflammation that required additional anti-inflammatory therapy. RESULTS: Eleven eyes from seven patients were included in this study. One patient (one eye) had a diagnosis of immune recovery uveitis and the remaining six patients (10 eyes) had pars planitis. The rate of remaining recurrence-free was 82% at 6 months, 60% at 12 months, and 60% at 24 months. Two of the six phakic eyes at baseline required cataract extraction during follow-up. Two of the four eyes that did not have intraocular pressure-lowering surgery before implantation required surgery in follow-up. CONCLUSION: The 0.18-mg fluocinolone acetonide implant has a similar efficacy for the treatment of pediatric uveitis, particularly pars planitis, as in the adult population, although with higher rates of ocular hypertension requiring intervention.
Assuntos
Implantes de Medicamento , Fluocinolona Acetonida , Glucocorticoides , Injeções Intravítreas , Uveíte , Acuidade Visual , Humanos , Fluocinolona Acetonida/administração & dosagem , Estudos Retrospectivos , Feminino , Masculino , Criança , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/fisiopatologia , Glucocorticoides/administração & dosagem , Adolescente , Pré-Escolar , Seguimentos , Pressão Intraocular/fisiologia , Pressão Intraocular/efeitos dos fármacos , Resultado do Tratamento , Relação Dose-Resposta a DrogaRESUMO
Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.
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Artrite , Biomarcadores , Proteômica , Sarcoidose , Sinovite , Lágrimas , Uveíte , Humanos , Lágrimas/metabolismo , Biomarcadores/metabolismo , Uveíte/metabolismo , Uveíte/genética , Uveíte/diagnóstico , Feminino , Masculino , Artrite/genética , Artrite/metabolismo , Sinovite/metabolismo , Sinovite/genética , Sarcoidose/genética , Sarcoidose/metabolismo , Adulto , Proteômica/métodos , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Pessoa de Meia-Idade , Mutação , Proteoma/metabolismo , Doenças Hereditárias AutoinflamatóriasRESUMO
Blau syndrome is an autosomal dominant chronic inflammatory disease, which may begin with skin manifestations in the first months of life, alerting physicians to the diagnosis. This case reports a patient diagnosed jointly by pediatric dermatology and rheumatology consultants at two years of age.
Assuntos
Artrite , Sarcoidose , Sinovite , Uveíte , Humanos , Sinovite/genética , Sinovite/diagnóstico , Uveíte/diagnóstico , Sarcoidose/diagnóstico , Sarcoidose/patologia , Artrite/diagnóstico , Pré-Escolar , Masculino , Feminino , Artrite Infecciosa/diagnóstico , Doenças Hereditárias AutoinflamatóriasRESUMO
Objectives: Behçet uveitis (BU) is a potentially blinding disorder. The main determinant of visual prognosis is early and appropriate treatment that provides rapid suppression of inflammatory attacks, control of subclinical inflammation, and prevention of new attacks. Our study aimed to determine the Turkish uveitis specialists' approach regarding the treatment choices and management of special situations such as pregnancy, vaccination, and surgical planning in BU patients, and to increase information sharing and raise awareness of issues where knowledge is lacking. Materials and Methods: A web-based survey including 16 questions about the treatment approach in ocular involvement of Behçet's disease was sent via e-mail to uveitis specialists in Türkiye. Based on the answers of 49 ophthalmologists who responded to the survey, we evaluated the approaches of uveitis specialists in our country to initiating treatment, selecting therapeutic agents, monitoring, switching and stopping treatment, and special situations such as surgical planning, vaccination, and pregnancy in BU patients. Results: Uveitis specialists in our country mostly act in accordance with the guidelines in the decision to start treatment, selection of therapeutic agents, and monitoring the safety of treatment in BU. However, there is a lack of information about the therapeutic approach in pregnancy and vaccination practices. It was also observed that there is no consensus on the precautions to be taken before cataract surgery. Conclusion: Our study has shown that there is a need for more detailed and widespread information sharing on treatment in preparation for ocular surgery, safety monitoring, drug use during pregnancy, and vaccination in BU patients.
Assuntos
Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/terapia , Turquia/epidemiologia , Feminino , Uveíte/diagnóstico , Uveíte/terapia , Uveíte/etiologia , Imunossupressores/uso terapêutico , Masculino , Gravidez , Inquéritos e Questionários , AdultoRESUMO
PURPOSE: To investigate changes to the vitreoretinal interface in uveitis with multimodal imaging including adaptive optics. METHODS: Four eyes (four patients) affected by fovea-attached (subtype 1A) or fovea-sparing epiretinal membranes (ERMs) on spectral-domain optical coherence tomography or visible internal limiting membrane (ILM) on infrared scanning laser ophthalmoscope (SLO) fundus imaging were recruited in this pilot study. The microstructure of the vitreoretinal interface was imaged using flood-illumination adaptive optics (FIAO), and the images were compared with the cross-sectional spectral-domain optical coherence tomography data. RESULTS: Adaptive optics images revealed multiple abnormalities of the vitreoretinal interface, such as deep linear striae in ERM, and hyperreflective microstructures at the location of ERMs and ILMs. The cone mosaic was imaged by FIAO and was found altered in the four eyes with ERMs or visible ILM. The same four eyes presented alteration of photopic 30 Hz flicker that was reduced in amplitude indicating cone inner retinal layer dysfunction. CONCLUSION: FIAO imaging can identify specific patterns associated with ERMs and ILMs. Correlating FIAO imaging of the vitreomacular interface with the structural alterations seen in FIAO at the level of the outer retinal structures can help understand the cause of significant macular dysfunction associated with ERM.
Assuntos
Membrana Epirretiniana , Imagem Multimodal , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Membrana Epirretiniana/diagnóstico , Projetos Piloto , Oftalmoscopia/métodos , Corpo Vítreo/patologia , Corpo Vítreo/diagnóstico por imagem , Uveíte/diagnóstico , Adulto , Acuidade Visual , Idoso , Estudos Transversais , Membrana BasalRESUMO
OBJECTIVES: TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when to stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. METHODS: In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. RESULTS: 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoarticular JIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent oligoarticular JIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). CONCLUSIONS: Younger age at onset, uveitis, duration of tapering, and non-persistent oligoarticular JIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.
Assuntos
Adalimumab , Artrite Juvenil , Etanercepte , Uveíte , Humanos , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/diagnóstico , Feminino , Masculino , Criança , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/etiologia , Estudos Retrospectivos , Itália/epidemiologia , Adolescente , Pré-Escolar , Etanercepte/efeitos adversos , Etanercepte/administração & dosagem , Etanercepte/uso terapêutico , Adalimumab/uso terapêutico , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Lactente , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Fatores de Risco , Recidiva , Fatores de Tempo , Resultado do Tratamento , Exacerbação dos Sintomas , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
PURPOSE OF REVIEW: This article intends to briefly discuss AIDS, summarize the current literature on immune recovery uveitis, describe its ocular manifestations and complications, and tackle its complex management. RECENT FINDINGS: The clinical picture of immune recovery uveitis is still evolving. Up to today, there are still no definite criteria for immune recovery uveitis, and although closely associated with cytomegalovirus retinitis and HIV/AIDS, there are several cases of similar intraocular response in non-HIV patients. The exact pathology for this paradoxical inflammatory reaction remains unclear; however, there is an interest in identifying biomarkers to determine underlying mechanisms and identify patients at risk. The management of this disease also remains a challenge and no standardized treatment approach exists currently. SUMMARY: Immune recovery uveitis is an important cause of visual morbidity particularly in HIV/AIDS patients receiving highly active antiretroviral. It is a paradoxical reaction that is frequently associated with a prior cytomegalovirus retinitis infection. Although it can be a transient and self-limiting process, there is a complex decision on the timing of antiviral treatment and the initiation of antiretroviral treatment to prevent immune recovery uveitis. Furthermore, a substantial challenge arises in balancingtreatment decisions for complications in refractory cases.
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Uveíte , Humanos , Uveíte/imunologia , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/complicações , Terapia Antirretroviral de Alta Atividade , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/diagnóstico , Retinite por Citomegalovirus/imunologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Reconstituição Imune , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/complicaçõesRESUMO
OBJECTIVE: This study examined the long-term outcomes of scleral-sutured fixated intraocular lenses (SSIOLs) in patients with uveitis. PATIENTS AND METHODS: Retrospective, consecutive review of uveitis patients with SSIOL fixation from January 2017 to December 2020. SSIOL techniques included four-point fixation with the Akreos A060 or enVista MX60 (Bausch + Lomb) lens, or Hoffman's pockets rescue. RESULTS: Thirteen eyes of 13 patients received an SSIOL (9 AO60, 2 MX60, 2 Hoffman's pockets). Diagnoses included pan- (9), anterior (2), and posterior uveitis (2). Average LogMAR best-corrected visual acuity pre- and postoperatively was 1.01 (Snellen â¼20/200) and 0.50 (Snellen â¼20/60), respectively (P = 0.003). No patients had postoperative SSIOL dislocation or conjunctival suture erosion. Six patients (46%) had uveitis flares postoperatively. Average follow-up was 50.2 months (range = 36.8 to 67.5). CONCLUSION: This series demonstrates a 0% dislocation and suture exposure rate. Risks of uveitis flares postoperatively are high despite aggressive perioperative control but are manageable with current treatments; therefore, patients must be continually monitored. [Ophthalmic Surg Lasers Imaging Retina 2024;55:443-447.].
Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Esclera , Técnicas de Sutura , Uveíte , Acuidade Visual , Humanos , Estudos Retrospectivos , Feminino , Masculino , Esclera/cirurgia , Pessoa de Meia-Idade , Adulto , Uveíte/complicações , Uveíte/cirurgia , Uveíte/diagnóstico , Seguimentos , Implante de Lente Intraocular/métodos , Idoso , Resultado do Tratamento , Adulto Jovem , Fatores de Tempo , Suturas , Desenho de PróteseRESUMO
CONTEXT: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. PURPOSE: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. SETTINGS AND DESIGN: Retrospective multicentric, survey-based study. METHODS: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. RESULTS: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. CONCLUSIONS: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.
Assuntos
Inibidores da Angiogênese , Anticorpos Monoclonais Humanizados , Injeções Intravítreas , Humanos , Índia/epidemiologia , Estudos Retrospectivos , Masculino , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Feminino , Incidência , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Acuidade Visual , Endoftalmite/epidemiologia , Endoftalmite/diagnóstico , Seguimentos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/epidemiologiaRESUMO
Juvenile Idiopathic Arthritis (JIA) is the most common chronic rheumatic disease in childhood, and is associated with uveitis in up to 20-25% of cases. Typically, the uveitis is chronic, asymptomatic, non-granulomatous and anterior. For this reason, screening for uveitis is recommended to identify uveitis early and allow treatment to prevent sight-threatening complications. The management of JIA associated uveitis requires a multidisciplinary approach and a close collaboration between paediatric rheumatologist and ophthalmologist. Starting the appropriate treatment to control uveitis activity and prevent ocular complications is crucial. Current international recommendations advise a step-wise approach, starting with methotrexate and moving on to adalimumab if methotrexate alone is not sufficient to control the disease. If the uveitis remains active despite standard treatment other therapeutic options may be considered including anti-IL6 or other anti-TNF agents such as infliximab, although the evidence for these agents is limited.
Assuntos
Antirreumáticos , Artrite Juvenil , Metotrexato , Uveíte , Humanos , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/etiologia , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Adalimumab/uso terapêutico , Criança , Infliximab/uso terapêuticoRESUMO
Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.
Assuntos
Piridinas , Uveíte , Acuidade Visual , Humanos , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Adulto , Acuidade Visual/fisiologia , Uveíte/tratamento farmacológico , Uveíte/fisiopatologia , Uveíte/diagnóstico , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Administração Oral , Triazóis/uso terapêutico , Triazóis/administração & dosagem , Resultado do Tratamento , Janus Quinase 1/antagonistas & inibidores , IdosoRESUMO
BACKGROUND: Hodgkin's lymphoma (HL) is an extremely rare cause of ocular inflammation that is usually not considered in the typical workup of uveitis and other eye diseases. A few cases of ocular inflammation were reported previously showcasing HL with absence of typical symptoms of HL at presentation. Acknowledging the potential ocular inflammation associated with HL can prompt ophthalmologists to broaden their diagnostic approach and collaborate with internal medicine departments to investigate this rare yet significant etiology. CASE PRESENTATION: A 17-year-old Caucasian woman presenting unilateral panuveitis was later diagnosed with HL. The ocular findings were non-necrotizing scleritis, anterior uveitis, vitritis, white/yellowish chorioretinal lesions, papillitis and vasculitis. A left supra-clavicular lymph node biopsy confirmed the diagnosis of nodular sclerosing Hodgkin's lymphoma stage IIB. Other causes of uveitis were excluded. Chemotherapy led to remission of the disease and the ocular lesions became quiescent with persistent pigmented chorioretinal scars. CONCLUSIONS: Hodgkin's lymphoma should be considered in the differential diagnosis of diseases that can occasionally be revealed by unilateral ocular inflammation. A comprehensive, multidisciplinary approach is key to properly assessing such cases.
Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/diagnóstico , Feminino , Adolescente , Diagnóstico Diferencial , Esclerite/diagnóstico , Esclerite/etiologia , Esclerite/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pan-Uveíte/diagnóstico , Pan-Uveíte/tratamento farmacológico , Pan-Uveíte/etiologiaRESUMO
PURPOSE: To determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection. METHODS: Concentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection. RESULTS: One-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&-II, IP-10, MIP-1ß, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+. CONCLUSION: Decreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.
Assuntos
Biomarcadores , Infecções por HIV , Tuberculose Ocular , Uveíte , Humanos , Masculino , Biomarcadores/urina , Feminino , Adulto , Pessoa de Meia-Idade , Uveíte/urina , Uveíte/microbiologia , Uveíte/diagnóstico , Tuberculose Ocular/urina , Tuberculose Ocular/diagnóstico , Infecções por HIV/urina , Infecções por HIV/complicações , Coinfecção/urina , Diagnóstico Diferencial , Soropositividade para HIV/urina , Soropositividade para HIV/complicações , Soronegatividade para HIV , Adulto Jovem , Valor Preditivo dos Testes , Urinálise/métodosRESUMO
Ocular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders.
Assuntos
Sífilis , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Sífilis/tratamento farmacológico , Sífilis/diagnóstico , Fatores Sexuais , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/diagnóstico , Brasil/epidemiologia , Antibacterianos/uso terapêutico , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Idoso , Resultado do TratamentoRESUMO
PURPOSE: Behçet's disease-associated uveitis (BDU) is a severe, recurrent inflammatory condition affecting the eye and is part of a systemic vasculitis with unknown etiology, making biomarker discovery essential for disease management. In this study, we intend to investigate potential urinary biomarkers to monitor the disease activity of BDU. METHODS: Firstly, label-free data-dependent acquisition (DDA) and tandem mass tag (TMT)-labeled quantitative proteomics methods were used to profile the proteomes of urine from active and quiescent BDU patients, respectively. For further exploration, the remaining fifty urine samples were analyzed by a data-independent acquisition (DIA) quantitative proteomics method. RESULTS: Twenty-nine and 21 differential proteins were identified in the same urine from BDU patients by label-free DDA and TMT-labeled analyses, respectively. Seventy-nine differentially expressed proteins (DEPs) were significantly changed in other active BDU urine samples compared to those in quiescent BDU urine samples by IDA analysis. Gene Ontology (GO) and protein-protein interaction (PPI) analyses revealed that the DEPs were associated with multiple functions, including the immune and neutrophil activation responses. Finally, seven proteins were identified as candidate biomarkers for BDU monitoring and recurrence prediction, namely, CD38, KCRB, DPP4, FUCA2, MTPN, S100A8 and S100A9. CONCLUSIONS: Our results showed that urine can be a good source of biomarkers for BDU. These dysregulated proteins provide potential urinary biomarkers for BDU activity monitoring and provide valuable clues for the analysis of the pathogenic mechanisms of BDU.