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Concept: Uveitis

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BACKGROUND: Uveitis is an autoimmune disease of the eye that refers to any of a number of intraocular inflammatory conditions. Because it is a rare disease, uveitis is often overlooked, and the possible associations between uveitis and extra-ocular disease manifestations are not well known. The aim of this study was to characterise uveitis in a large sample of patients and to evaluate the relationship between uveitis and systemic diseases. METHODS: The present study is a cross-sectional study of a cohort of patients with uveitis. Records from consecutive uveitis patients who were seen by the Uveitis Service in the Department of Ophthalmology at the Medical University of Vienna between 1995 and 2009 were selected from the clinical databases. The cases were classified according to the Standardization of Uveitis Nomenclature Study Group criteria for uveitis. RESULTS: Data were available for 2619 patients, of whom 59.9% suffered from anterior, 14.8% from intermediate, 18.3% from posterior and 7.0% from panuveitis. 37.2% of all cases showed an association between uveitis and extra-organ diseases; diseases with primarily arthritic manifestations were seen in 10.1% of all cases, non-infectious systemic diseases (i.e., Behcet’s disease, sarcoidosis or multiple sclerosis) in 8.4% and infectious uveitis in 18.7%. 49.4% of subjects suffering from anterior uveitis tested positively for the HLA-B27 antigen. In posterior uveitis cases 29% were caused by ocular toxoplasmosis and 17.7% by multifocal choroiditis. CONCLUSION: Ophthalmologists, rheumatologists, infectiologists, neurologists and general practitioners should be familiar with the differential diagnosis of uveitis. A better interdisciplinary approach could help in tailoring of the work-up, earlier diagnosis of co-existing diseases and management of uveitis patients.

Concepts: Medicine, Epidemiology, Medical terms, Infection, Rheumatoid arthritis, Ophthalmology, Ankylosing spondylitis, Uveitis

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Background Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. Methods This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. Results The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). Conclusions In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Concepts: Therapeutic effect, Pharmacology, Clinical trial, Assessment, Glucocorticoid, Ophthalmology, Prediction interval, Uveitis

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PurposeTo analyze the incidence and clinical course of patients developing progressive ocular inflammation following anti-tubercular therapy (ATT) for presumed ocular tuberculosis (TB).MethodsRetrospective analysis of medical records of patients who received ATT for presumed ocular TB and completed at least 12 months follow-up after initiation of ATT. The diagnosis of presumed ocular TB was based on presence of ocular signs suggestive of TB, evidence of past tubercular infection, and exclusion of mimicking clinical entities. All patients received a combination of ATT and corticosteroid therapy. Primary outcome measure was progression (worsening) of ocular inflammation, defined as a two-step increase in level of inflammation (anterior chamber/ vitreous) or the appearance of new lesions following initiation of ATT.ResultsA total of 106 patients (64 male, 42 female) received ATT for presumed ocular TB. Twenty-six (24.5%) patients developed progressive intraocular inflammation following ATT. Primary diagnoses in these patients were: anterior uveitis (n=1), intermediate uveitis (n=9), retinal vasculitis (n=3), serpiginous-like choroiditis (n=7), multifocal choroiditis (n=2), and pan-uveitis (n=4). Following progressive inflammation, diagnosis was revised in two patients (7.7%)-both responded to alternative therapy. Of the rest, majority (n=16; 61.5%) resolved with escalation of corticosteroid therapy. Five patients (19.2%)-all having intermediate uveitis-required therapeutic vitrectomy for resolution. Three patients (11.5%) had persistent inflammation at end of follow-up period.ConclusionProgressive inflammation following ATT for presumed ocular TB is common. It generally resolves on escalation of corticosteroid therapy. Cases not responding to increased immunosuppression need to be re-investigated to rule out a nontubercular cause.Eye advance online publication, 1 March 2013; doi:10.1038/eye.2013.5.

Concepts: Vasculitis, Corticosteroid, Retina, Ophthalmology, Progressive lens, Sarcoidosis, Uveitis, Escalation

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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, © 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.

Concepts: Inflammation, Regression analysis, Evaluation, Medical signs, Eye, Ophthalmology, Uveitis, Vitreous humour

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To determine the effect of an injectable fluocinolone acetonide implant (FAi) in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis.

Concepts: Corticosteroid, Uveitis, Intermediate uveitis, Fluocinolone acetonide

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Noninfectious uveitis results in vision loss and ocular complications without adequate treatment. We compared the risk of developing ocular complications between patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIIPPU) and matched controls.

Concepts: Ophthalmology, Uveitis, Intermediate uveitis

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To better characterize posterior uveitis, vitreous samples from 15 patients were subjected to antibody arrays, and the expression levels of 200 human cytokines were evaluated. Expression was analyzed by 1-way analysis of variance (significance at P < .01), unsupervised cluster algorithm, and pathway analysis.

Concepts: Immune system, Disease, Medical terms, Physician, Ophthalmology, Machine learning, Analysis of variance, Uveitis

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BACKGROUND: Nonetheless biologic modifier therapies are available treatment strategies for sight-threatening uveitis in children, the lack of evidence from head-to-head randomized controlled studies limits our understanding of timing of therapy when to commence therapy, which agent to choose and how long to continue treatment, and, in case of failure, if switching to another anti-TNF-alpha strategy might be eventually an option. Our aim was to compare the efficacy of Adalimumab when used as first anti-TNFalpha therapy versus Adalimumab used after the failure of a previous anti-TNFalpha (Infliximab) in an open-label, comparative, multi-center, cohort study of childhood chronic uveitis. METHODS: 26 patients (14 F, 12 M; median age: 8.6 years) with refractory, non-infectious active uveitis were enrolled. Due to the refractory course of uveitis to previous DMARD treatment, Group 1 received Adalimumab (24 mg/sq mt, every 2 weeks), as first anti-TNFalpha choice; Group 2 received Adalimumab, as second anti-TNFalpha drug, due to the loss of efficacy of Infliximab, administered after a period of at least 1 year. Both groups received Adalimumab for at least 1 year of treatment. Primary outcome was, once remission was achieved, the time to a first relapse. RESULTS: 14 children (10 with JIA, 3 with idiopathic uveitis, 1 with Behcet’s disease) were recruited in Group 1; 12 children (7 with JIA, 3 with idiopathic uveitis, 1 with early-onset sarcoidosis, 1 with Behcet’s disease) in Group 2. Group 2 showed a lower probability to steroid discontinuation during the first 12 months of treatment (Mantel-Cox chi24.12, p<0.04). In long-term follow-up, Group 1 had higher probability of uveitis remission during the time of treatment on Adalimumab (median +/-SE: 18 +/-1.1 vs 4 +/-0.6 months, CI 95%: 15.6-27.5 vs 2.7-5.2, Mantel-Cox chi210.12, p<0.002). CONCLUSIONS: Even if limited to a relatively small group, our study suggests a better efficacy of Adalimumab when used as first anti-TNFalpha treatment in childhood chronic uveitis.

Concepts: Medicine, Randomized controlled trial, Infliximab, Ankylosing spondylitis, Etanercept, Adalimumab, Uveitis, Behçet's disease

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The syndrome of tubulointerstitial nephritis and uveitis (TINU) is a multisystemic autoimmune disorder that may occur in response to various environmental triggers, including drugs and microbial pathogens. Evidence exists of HLA antigen-related genetic predisposition to developing TINU. The resulting inflammation affects chiefly the ocular uvea and renal tubules, although other organs may be involved. TINU is uncommon; only about 200 cases are on record since its original description 40 years ago, although it is possible that new ones are no longer being reported. Although its incidence is highest in children and adolescents, all ages may be affected. Renal and ocular inflammation may be clinically severe and persistent, but the prognosis for the majority of patients with TINU is favorable. Owing to its low prevalence, no standard therapeutic protocols have been established, but most reported cases have been treated with corticosteroids or other immunomodulatory agents. TINU has many features in common with sarcoidosis, the main clinical entity from which it must be distinguished. This article begins with an illustrative case vignette, followed by an overview of the syndrome and current theories regarding its pathogenesis.

Concepts: Immune system, Kidney, Bacteria, Glomerulonephritis, Prevalence, Interstitial nephritis, Sarcoidosis, Uveitis

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Adalimumab was recently approved for the treatment of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

Concepts: Ophthalmology, Uveitis, Intermediate uveitis