BackgroundThe use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection.MethodsWithin the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology–Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02–7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.FindingsNo differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively.InterpretationThe addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of ‘duration of therapy’ and ‘age at stopping therapy’.

BackgroundThe incidence of uveitis associated with juvenile idiopathic arthritis (JIA) varies around the world. Our aim was to investigate the incidence and predictors of uveitis in a Nordic population-based cohort.MethodsConsecutive JIA cases from defined geographical areas in Denmark, Finland, Sweden and Norway with disease onset between January 1997 to June 2000 were followed for median 98 months in this prospective longitudinal cohort study. Potential clinical and immunological predictors of uveitis were identified with logistic regression analysis.ResultsUveitis occurred in 89 (20.5%) of the 435 children with regular ophtalmologic follow-up among the 500 included. Chronic asymptomatic uveitis developed in 80 and acute symptomatic uveitis in 9 children. Uveitis developed at a median interval of 0.8 (range − 4.7 to 9.4) years after onset of arthritis. Predictors of uveitis were age < 7 years at JIA onset (Odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5), presence of antihistone antibodies (AHA) > 15 U/ml (OR 4.8 (1.8 to 13.4)) and antinuclear antibodies (ANA) (OR 2.4 (1.5 to 4.0)). Mean combined IgM/IgG AHA was significantly higher in the uveitis group (19.2 U/ml) than in the non-uveitis group (10.2 U/ml) (p = 0.002). Young age at JIA onset predicted uveitis in girls (p < 0.001), but not in boys (p = 0.390).ConclusionEarly-onset arthritis and presence of AHA in girls, as well as presence of ANA in both genders, were significant predictors of chronic uveitis. The high incidence of uveitis in this long-term Nordic JIA cohort may have severe implications in a lifelong perspective.

ABSTRACT.Purpose: To study the associations between serum 25-hydroxy-vitamin D (25(OH)D) levels, vitamin D administration and intraocular pressure (IOP). Methods: The design of the study included a nested case-control study and a randomized controlled intervention trial. In the first part, healthy Caucasians with high or low serum 25(OH)D levels were recruited from a populationbased study. IOP of the right eye was measured by the use of a rebound tonometer. In the second part, those with low serum 25(OH)D levels were randomized to receive either capsules of vitamin D 3 20 000 IU twice per week or placebo for 6 months before IOP was measured again. Results: Intraocular pressure in the 87 participants with low serum 25(OH)D levels (mean 40.1 ± 12.9 nm) did not differ from IOP in the 42 participants with high serum 25(OH)D levels (mean 85.1 ± 14.0 nm) (15.9 ± 3.3 mmHg versus 15.6 ± 3.1 mmHg, p = 0.56, independent t-test). After intervention, IOP decreased by )0.8 ± 2.1 mmHg (p = 0.017, paired t-test) in the vitamin D group (n = 39) and )0.8 ± 2.5 mmHg (p = 0.059) in the placebo group (n = 39), but the change was not significantly different between the groups (p = 0.92, independent t-test). Conclusion: This study in healthy participants revealed no associations between serum 25(OH)D levels and IOP, and administration of vitamin D 3 to participants with low levels of 25(OH)D did not affect IOP. These results do not support a role of vitamin D in the regulation of IOP.

Purpose: To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA). Design: Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIAassociated uveitis (JIA-U) 18 years after the onset of JIA.Participants: A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden.Methods: Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data.Main Outcome Measures: Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications.Results: Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1e1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6e274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2e7.7). Decreased visual acuity (VA) <6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA <6/12.Conclusions: Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.