Kinetics of the long-term antibody response after meningococcal C vaccination in patients with juvenile idiopathic arthritis: a retrospective cohort study.

OBJECTIVES: The kinetics of the antibody response induced by meningococcal serogroup C (MenC) conjugate vaccination was analysed in patients with juvenile idiopathic arthritis (JIA) to assess their long-term protection against MenC disease. METHODS: In The Netherlands, a nationwide catch-up campaign was performed in 2002 during which children aged 1-19 years, including JIA patients, received the MenC conjugate vaccination. From 127 JIA patients, IgG antibody concentrations against MenC-polysaccharide were determined by a fluorescent-bead-based immunoassay in 402 serum samples collected between 2002 and 2010. Using a hierarchical linear regression model, the 8 years course of MenC-specific antibodies was analysed in four age groups (13-19, 9-12.9, 5-8.9 and 1-4.9 years), and in patients starting with methotrexate or biologicals. In 65 randomly selected samples, the correlation of MenC-specific IgG concentrations with serum bactericidal assay (SBA) titres was assessed. MenC-specific IgG concentrations at 4.2 years after vaccination were compared with those of 1527 age-matched healthy controls. RESULTS: MenC-specific IgG concentrations postvaccination were highest in patients aged 13-19 years at time of vaccination. Antibodies gradually waned over time in patients, but their estimated concentrations at 4.2 years postvaccination were similar to those measured in controls. MenC-specific IgG concentrations correlated well with SBA titres (r=0.72, p<0.001). By contrast with methotrexate, starting treatment with biologicals induced a trend towards accelerated decline of MenC-specific antibodies. CONCLUSIONS: Persistence of MenC-specific IgG antibodies in JIA patients is similar to healthy controls, but treatment with biologicals may induce accelerated antibody waning, resulting in unprotected patients who may need revaccination.

Subfoveal serous retinal detachment in patients with uveitic macular edema.

OBJECTIVE: To assess the clinical characteristics and effect on visual acuity (VA) of a subfoveal serous retinal detachment (SRD) associated with macular edema (ME) in patients with uveitis. METHODS: Clinical and optical coherence tomograph characteristics were retrospectively assessed in 37 patients with uveitic ME with a subfoveal SRD (case individuals) and 61 patients with uveitic ME without a subfoveal SRD (control individuals), matched for uveitis location, sex, and age. Scans of the case and control individuals took place between September 19, 2003, and July 21, 2008. RESULTS: Patients with a subfoveal SRD had a shorter history of uveitis (P = .03) and ME (P = .03) and a lower VA (P = .003). Mean total retinal thickness (TRT) in cases exceeded that of controls (449 vs 326 µm; P < .001). The median subfoveal SRD duration was 2 months, and 29 of 36 SRDs (81%) had disappeared at the 3-month follow-up examination. The improvement in VA and the decrease in TRT after 3 months were better in the subfoveal SRD group than in the control group (P = .001 for VA and P = .001 for TRT), resulting in similar VA and TRT after 3 months. CONCLUSIONS: A subfoveal SRD was associated with lower VA and developed typically in the early stages of uveitis and ME. The subfoveal SRD and VA reacted favorably to treatment with periocular and systemic steroids and/or oral acetazolamide.

Distinct cytokine patterns in the aqueous humor of children, adolescents and adults with uveitis.

PURPOSE: To determine the immune mediator profile in relation to age in the aqueous humor (AqH) of patients with uveitis. METHODS: AqH of children, adolescents, and adults with uveitis was analyzed for 16 immune mediators. RESULTS: No significant differences were found for IL-8, RANTES, and IP-10. The concentrations of the remaining 13 mediators were significant lower in adults compared with children and adolescents, except for IL-6, which was higher. CONCLUSIONS: Various immune mediators are present in higher concentrations in AqH of children and adolescents with different uveitis entities compared with that of adults, except IL-6, which was higher in adults.

Risk factors for the development of cataract requiring surgery in uveitis associated with juvenile idiopathic arthritis.

PURPOSE: To identify the possible risk factors for the development of cataract requiring surgery in children with juvenile idiopathic arthritis (JIA)-associated uveitis. DESIGN: Retrospective cohort study. METHODS: Data of 53 children with JIA-associated uveitis, of whom 27 had undergone cataract extraction (CE), were obtained. The main outcome measure, the interval between the onset of uveitis and the first CE (U-CE interval), was examined in relation to clinical and ophthalmologic characteristics and treatment strategies before CE. RESULTS: A shorter U-CE interval was found for children with posterior synechia vs those without posterior synechia (hazard ratio [HR], 3.57; 95% confidence interval [CI], 1.33 to 10.00). No significant difference was found for children in whom the uveitis was the first manifestation of JIA vs those in whom arthritis was the first manifestation of JIA (HR, 1.59; 95% CI, 0.63 to 4.00) and children treated with periocular corticosteroid injections vs those not treated with periocular corticosteroid injections (HR, 3.23; 95% CI, 0.95 to 11.11). Children treated with methotrexate (MTX) had a longer U-CE interval than children not treated with MTX (HR, 0.29; 95% CI, 0.10 to 0.87). CONCLUSIONS: The risk factor for development of early cataract requiring surgery in children with JIA-associated uveitis is the presence of posterior synechia at the time of diagnosis of uveitis. However, early treatment with MTX is associated with a mean delay in the development of cataract requiring surgery of 3.5 years.

Cytokines, chemokines and soluble adhesion molecules in aqueous humor of children with uveitis.

Uveitis in childhood is a visual threatening disease with a complication rate of more than 75%. Despite extensive research, the etiology of uveitis is still unclear although the general opinion is now that uveitis is a T-cell mediated disease. The purpose of this study was to investigate the profile of cytokines, chemotactic cytokines (chemokines) and soluble adhesion molecules in the aqueous humor (AqH) of children with uveitis in order to identify the factors that control the immune response in the eye. In this clinical laboratory investigation we analyzed, with a multiplex immunoassay, 16 immune mediators in the AqH of 25 children with uveitis and 6 children without uveitis. Increased levels of interleukin-2 (IL-2), IL-6, IL-10, IL-13, IL-18, interferon-gamma, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, RANTES, IL-8 and interferon-inducible 10-kDa protein were found in the AqH of children with uveitis compared with controls. No significant differences were found for IL-1 beta, IL-4, IL-12 p-70, soluble vascular cell adhesion molecule 1 and Eotaxin. Lower levels of IL-10 and IL-8 were found in quiet stage uveitis (surgical) samples compared with active uveitis (diagnostic) samples and in samples of patients treated with methotrexate (MTX) compared with samples of patients not treated with MTX. Lower levels of IL-10 were as well found in samples taken during the first 3 months after the diagnosis of uveitis than samples taken later during the disease process. No significant differences were found between patients treated with or without topical or systemic (perioperative and long term) corticosteroids. In conclusion, in children with uveitis, multiple intraocular cytokines, chemokines and soluble adhesion molecules are increased in the AqH regardless of active or inactive inflammation. Whether the IL-8 and IL-10 levels in AqH of children with uveitis are correlated with uveitis activity, early or late phase of the course of the disease and systemic treatment with MTX needs further investigation in a bigger study population.

Rubella virus-associated uveitis in a nonvaccinated child.

PURPOSE: To report presumed Fuchs heterochromic uveitis (FHU) associated with Rubella virus (RV)-specific intraocular antibody production in a child who was not vaccinated against rubella. DESIGN: Observational case report. METHODS: We examined a 13-year-old boy with chronic anterior uveitis complicated by mature cataract. Two aqueous humor (AH) samples taken with an interval of four weeks were analyzed for intraocular antibody production against RV by calculation of the Goldmann-Witmer coefficient. RESULTS: The patient showed all the clinical signs for FHU: iris atrophy, stellate keratic precipitates, and cataract. Analysis of the AH demonstrated intraocular antibody production against RV in two sequential samples. CONCLUSIONS: The data show that RV-associated uveitis can already present during childhood. Moreover, this finding suggests that nonvaccinated children may be at risk to develop uveitis after RV infection.

Ocular hypertension and secondary glaucoma in children with uveitis.

PURPOSE: To identify the risk factors for ocular hypertension and secondary glaucoma in children with uveitis. DESIGN: Retrospective observational case series of 147 patient records. PARTICIPANTS: Two hundred fifty-six eyes of 147 children with uveitis diagnosed before the age of 16 years. METHODS: Data were obtained from the medical records of children with uveitis evaluated at our institute from 1990 through 2004. MAIN OUTCOME MEASURES: Localization and course of uveitis (acute or chronic), underlying systemic disease, onset of ocular hypertension, onset of secondary glaucoma, treatment with steroids, antinuclear antibodies (ANAs), lens extractions, number of blind eyes at onset and during follow-up, and the duration of follow-up. RESULTS: Elevated intraocular pressure developed in 35% of children with pediatric uveitis regardless of the form or type of uveitis during a follow-up of 5 years. Secondary glaucoma, however, developed more frequently in juvenile idiopathic arthritis-associated uveitis (38%) compared with other forms of uveitis (11%) and more frequently in children with uveitis who were ANA positive (42%) than in those who were ANA negative (6%). Elevated intraocular pressure occurred in two thirds of all children within the first 2 years after the diagnosis of uveitis. Except for patients with juvenile idiopathic arthritis-associated uveitis, periocular steroid injections represented an additional risk factor for secondary glaucoma, but this risk was limited to the early phase of the disease process. CONCLUSIONS: In children with uveitis in this series, juvenile idiopathic arthritis-associated uveitis and ANA-positive uveitis without evidence of arthritis are the most important risk factors for developing secondary glaucoma.