UNICORNS: Uveitis in childhood prospective national cohort study protocol [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (child- and treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families

Uveitis in childhood : clinical and fundamental developments

This thesis aimed to gain new insights regarding the course and prognosis of uveitis in childhood, the pathogenesis of JIA-uveitis and the treatment of uveitis in children. The role of baseline prognostic factors in JIA-uveitis was studied by a retrospective analysis of 117 affected eyes of 65 patients with JIA-uveitis. Male gender is associated with a complicated course and poor visual prognosis in JIA-uveitis. Uveitis as initial manifestation of JIA is associated with development of posterior synechiae. We investigated the course of JIA-uveitis in a retrospective analysis of 62 patients with JIA-uveitis. High uveitis activity was found at 4-6 years of age, followed by a quiet stage around the age of 9 and 10, after which activity rose again. Administration of systemic medication also increased with age. We attempted to answer the question about the effect of methotrexate therapy in JIA-uveitis and about the risk of relapse of uveitis after its discontinuation. We assessed clinical data of 22 pediatric JIA patients, treated with methotrexate for active uveitis. Eighty-two percent of patients showed improvement of uveitis activity within the first year of methotrexate therapy with a significant steroid-sparing effect. In 69% of patients, in whom methotrexate was discontinued because of inactive uveitis, a relapse of uveitis was observed after a mean time of 7.5 months after the withdrawal. Longer inactivity under methotrexate therapy was independently protective for relapses after the withdrawal. We investigated protein profiles in aqueous humor (n=73) and serum (n=105) samples from 116 children with and without uveitis. We find qualitative and quantitative differences in protein expression in JIA-uveitis compared to the other uveitis entities and the controls, but not to other chronic silent anterior uveitis. One of the protein peaks with qualitative and quantitative differences between groups, m/z 13,762, was associated with activity of uveitis in JIA. This protein was identified as transthyretin. We performed immunohistochemical investigation of iridectomy specimens of two JIA-uveitis patients. Both specimens showed presence of CD4+, CD68+ and CD138+ cells, while CD8+ and CD20+ cells could be detected only in one of them. We investigate prognostic factors in the second most common uveitis entity in children, intermediate uveitis, by retrospective analysis of 35 children with this disease. Younger onset of intermediate uveitis was associated with a complicated course of disease, worse visual outcomes and lower remission rate compared to the older onset group. We assess the effect of an Ahmed glaucoma valve implant on corneal endothelial cell density in children with uveitic glaucoma. This cross-sectional study (80 eyes) shows that Ahmed glaucoma valve implantation is associated with a lower corneal endothelial cell count in eyes with secondary glaucoma independently from the effect of age. The time interval following the implantation was highly correlated with decreased endothelial cell density. We prospectively investigate ocular complications in a cohort of 49 immunocompromised children within 1 year after hematopoietic stem cell transplantation (HSCT). Ocular complications were detected in 27% of patients and included dry eye syndrome(14%), (sub)retinal hemorrhage(12%), optic disc edema(6%), chorioretinal scars(4%), vitritis(2%) and increased intraocular pressure(2%