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Objective: Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA, using a genome‐wide association study in 522 children with JIA. Methods: Two cohorts of JIA patients with ophthalmologic follow‐up data were genotyped. Data were then imputed using a genome‐wide imputation reference panel, and an HLA‐specific reference panel was used for imputing amino acids and HLA types in the major histocompatibility complex (MHC). After imputation, genome‐wide and MHC‐specific analyses were performed, and a reverse immunology approach was utilized to model antigen presentation at 13 common HLA–DRβ1 alleles. Results: Presence of the amino acid serine at position 11 (serine 11) in HLA–DRβ1 was associated with an increased risk of uveitis in JIA patients (odds ratio [OR] 2.60, P = 5.43 × 10−10) and was specific to girls (Pfemales = 7.61 × 10−10 versus Pmales = 0.18). Serine 11 resides in the YST motif in the peptide‐binding groove of HLA–DRβ1; all 3 amino acids in this motif are in perfect linkage disequilibrium and show identical association with disease. Quantitative prediction of binding affinity revealed that HLA–DRβ1 alleles with the YST motif could be distinguished on the basis of discernable peptide‐binding preferences. Conclusion: These findings highlight a genetically distinct, sexually dimorphic feature of JIA with uveitis as compared to JIA without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA–DRβ1 in the development of uveitis in JIA. The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight‐threatening complications of uveitis in children with JIA. [ABSTRACT FROM AUTHOR]

Background/aims To evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis (IU). Methods Open-label, prospective, controlled, randomised multicentre trial. Patients were randomised in a 1:1 ratio to either the treatment group (prednisolone plus EC-MPS) or control group (prednisolone monotherapy). Patients in the control group who relapsed within 6 months changed to the crossover group (prednisolone plus EC-MPS). Maximum treatment duration was 15 months. The primary endpoint was the time to first relapse in the treatment group and control group. Results Forty-one patients at eight sites were analysed. Twenty-two patients were allocated to the treatment group, with 19 patients in the control group. A first relapse occurred in 9 patients (40.9%) in the treatment group and 15 patients (78.9%) in the control group (p=0.03). The median time to the first relapse was >15 months for the treatment group and 2.8 months for the control group (p=0.07). The probability of relapse-free survival at month 15 was estimated to be 52.9% in the treatment group and 19.7% in the control group (p=0.01). 15 patients changed to the crossover group. Of these, only four patients developed a second relapse. No safety concerns arose during the trial. Only one patient had to discontinue EC-MPS due to increased liver enzymes. Conclusion EC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU. Trial registration number EUDRACT number: 2009-009998-10, Results. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the preferred practice respective diagnosis, treatment, and complications in patients with acute retinal necrosis in Germany.Methods: The uveitis-section of the German Ophthalmologic Society developed a questionnaire with 12 questions concerning patients with acute retinal necrosis seen in the 5 years up to August 2009.Results: In total, 35 eye hospitals answered the questionnaire and reported 213 patients with acute retinal necrosis. Diagnosis was made clinically in 86%. Anterior chamber tap, vitreous biopsy, diagnostic vitrectomy, and serology were performed for confirmation. Therapy was started with acyclovir in all institutions, and continued with ganciclovir, foscarnet and brivudine in some cases. Intravitreal injections were performed in 46%. Additional oral steroids were given in 80%. A following oral antiviral treatment was performed in 94%.Conclusions: Relevant variations were seen in diagnosis and treatment practices. The survey outlines the need for a unique diagnostic and therapeutic guideline. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma is a common vision-threatening complication of uveitis. We investigated the outcome of canaloplasty in patients with chronic uveitis and uncontrolled secondary glaucoma. Methods: This was a retrospective study of 12 patients with medically uncontrolled secondary glaucoma who underwent canaloplasty (14 treated eyes), with follow-up of ≥ 24 months. The primary outcome measure was complete and qualified (requirement for anti-glaucomatous medication) surgical success rates, as determined by a reduction in intraocular pressure (IOP) and the need for anti-glaucomatous medication. Secondary outcome measures were uveitis activity, best-corrected visual acuity (BCVA), vision-threatening complications, and secondary glaucoma surgery. Results: Canaloplasty resulted in a significant IOP reduction, from a mean preoperative baseline level of 27.1 ± 12.3 mmHg to a mean of 14.5 ± 4.3 mmHg ( p = 0.01) at 24 months. Complete success (limit of 15 mmHg) was achieved in six patients and qualified success in one patient. However, failure was noted in five patients, two of whom required additional glaucoma surgery. Topical anti-glaucomatous medications were reduced from 2.7 ± 1.2 (mean ± SD) at baseline to 0.6 ± 1.2 at 24 months ( p = 0.007). Uveitis activity did not increase after surgery. BCVA was not reduced; cataract progressed in two patients. Conclusion: At 2-year follow-up, overall success rate was 58 % (IOP ≤ 15 with or without medication), and surgery failed in 5 eyes, 2 eyes requiring additional glaucoma surgery. No harmful complications or worsening of uveitis activity were noted. [ABSTRACT FROM AUTHOR]

Purpose: Secondary glaucoma is a common complication in patients with uveitis. Heidelberg Retina Tomography (HRT) and retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT) are widely used for examining optic nerve head changes. We evaluated these parameters in patients with uveitis and secondary glaucoma and with inflammatory papillary leakage on fluorescein angiography. Methods: Prospective single-center analysis of patients with uveitis, evaluating the impact of optic disc leakage on objective optic disc imaging parameters. Results: Overall, 96 eyes of 59 patients were included. Papillary leakage was found in 42 eyes (43.8 %), and secondary glaucoma was found in 41 eyes (42.7 %). Glaucoma and papillary leakage were present in 12 (29 %) eyes with leakage and in 29 (54 %) eyes without leakage ( p = 0.023). Neuroretinal rim area ( p = 0.004), rim volume on HRT ( p = 0.004), and RNFL thickness on OCT ( p = 0.0008) were significantly increased in eyes with papillary leakage, while RNFL on HRT was unchanged ( p = 0.255). When only eyes with normal IOP were examined, all objective parameters on OCT and HRT were significantly increased, whereas in eyes with secondary glaucoma, there was only a trend in the same direction, which did not reach significance. A comparison of eyes with secondary glaucoma and optic disc leakage to normal eyes with no glaucoma or leakage revealed no difference in any of the parameters. Conclusions: The objective parameters of optic nerve head imaging tools are significantly influenced by papillary leakage. In patients with secondary glaucoma and papillary leakage, these techniques are unable to detect and monitor glaucomatous damage. [ABSTRACT FROM AUTHOR]

Objective: Based on a nationwide database, this study analyzed the influence of methotrexate (MTX), tumor necrosis factor (TNF) inhibitors, and a combination of the 2 medications on uveitis occurrence in juvenile idiopathic arthritis (JIA) patients.Methods: Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating pediatric rheumatologic sites. Patients with a JIA disease duration of <12 months at initial documentation and ≥2 years of followup were included in this study. The impact of antiinflammatory treatment on the occurrence of uveitis was evaluated by discrete-time survival analysis.Results: A total of 3,512 JIA patients (mean ± SD age 8.3 ± 4.8 years, 65.7% female, 53.2% antinuclear antibody positive, and mean ± SD age at arthritis onset 7.8 ± 4.8 years) fulfilled the inclusion criteria. Mean ± SD total followup time was 3.6 ± 2.4 years. Uveitis developed in a total of 180 patients (5.1%) within 1 year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). Disease-modifying antirheumatic drug (DMARD) treatment in the year before uveitis onset significantly reduced the risk for uveitis as follows: MTX: hazard ratio (HR) 0.63, P = 0.022; TNF inhibitors: HR 0.56, P < 0.001; and a combination of the 2 medications: HR 0.10, P < 0.001. Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, P < 0.001).Conclusion: The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. [ABSTRACT FROM AUTHOR]