Childhood Uveitis Research Articles

Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.

A41: The Effects of Youngsters' Eyesight on Quality of Life as a Measure of Uveitis Activity, Visual Function and Vision Related Quality of Life in Childhood Uveitis

Background/Purpose:The Effects of Youngsters Eyesight on Quality of Life (EYE‐Q) is a valid instrument that measures visual function and vision related quality of life (QOL) in children with ocular disease. Our objective is to determine whether the EYE‐Q is valid in children with uveitis.Methods:Children with uveitis (JIA‐associated uveitis (JIA‐U) and idiopathic uveitis (IU)) who have had a slit lamp examination within one month of completing the EYE‐Q were included. We collected data related to uveitis clinical characteristics and the ocular examination (LogMAR visual acuity (VA), intraocular pressure (IOP), and # of cells) in the worse and better eye. Questionnaires were completed on overall QOL (Pediatric QOL Inventory—MPedsQL), and vision (EYE‐Q). We determined associations between the EYE‐Q and the ocular exam using Spearman's correlation coefficients.Results:There were 19 children with JIA‐U and 17 with I‐U included with a total of 42 ocular examinations performed. Females comprised 75%, with a mean age of diagnosis of 5.6 (SD = 3.6) years. There were 29 (80%) children with bilateral disease, with varied uveitis locations (anterior (69%), intermediate (25%), and panuveitis (6%)), and numerous ocular complications (synechiae (53%), cataracts (44%), band keratopathy (25%), cystoid macular edema (22%), and glaucoma (6%)). At time of examination, 28% were being treated with oral methotrexate, 52% with subcutaneous methotrexate, 14% with infliximab, and 2% with adalimumab. There were 71% of children on eye drops, 59% on ocular steroids, and 2% on mydriatics. Mean PedsQL score was 80.9 ± 15.6. Mean EYE‐Q score was 3.1 ± 0.6. Slit lamp examination showed worse LogMAR VA in children with I‐U compared to JIA‐U but similar IOP and # of cells (Table ).For both the child and parent reports, the EYE‐Q had moderate correlations with LogMAR VA and the PedsQL, and mild to no correlations with # of cells and IOP (Table ). The PedsQL had mild to no correlations with LogMAR VA, # of cells and IOP. Ocular examinations in children with uveitis Ophthalmology exam Uveitis (n=21) JIA‐U (n=21) Worse eye Intraocular pressure, mean±SD 17.9 ± 7.9 17.6 ± 7.3 LogMar visual acuity, mean±SD 0.75 ± 0.67 0.18 ± 0.20 Slit lamp exam Cells, N (%) 0 (<1 cell in field) 11 (73.3%) 11 (55.5%) 0.5+ (1–5 cells in field) 1 (6.7%) 2 (10.0%) 1+ (6–15 cells in field) 1 (6.7%) 3 (15.0%) 2+ (16–25 cells in field) 0 (0.0%) 4 (20.0%) 3+ (26–50 cells in field) 2 (13.3%) 0 (0.0%) Better Eye Intraocular pressure, mean±SD 12.9 ± 5.0 13.9 ± 4.4 LogMar visual acuity, mean±SD 0.31 ± 0.38 0.07 ± 0.12 Slit lamp exam Cells, N (%) 0 (<1 cell in field) 13 (86.7%) 16 (80.0%) 0.5+ (1–5 cells in field) 0 (0.0%) 1 (5.0%) 1+ (6–15 cells in field) 1 (6.7%) 1 (5.0%) 2+ (16–25 cells in field) 0 (0.0%) 2 (10.0%) 3+ (26–50 cells in field) 1 (6.7%) 0 (0.0% Correlation of the EYE‐Q and PedsQL with standard measures of uveitis activity EYE‐Q child (range 0–4) R [95% CI] P value Better Eye LogMAR VA −0.36 (−0.66−0.06) 0.089 Cells −0.16 (−0.56−0.31) 0.501 IOP 0.167 (−0.28−0.55) 0.463 Worse Eye LogMAR VA −0.51 (−0.75−(−0.12)) 0.010 Cells 0.063 (−0.39−0.49) 0.795 IOP −0.16 (−0.54−0.29) 0.492 PedsQL Total scale 0.66 (0.32–0.84) <0.001 EYE‐Q parent (range 0–4) Better Eye LogMAR VA −0.31 (−0.56−0.004) 0.050 Cells −0.07 (−0.49−0.37) 0.751 IOP 0.06 (−0.46−0.22) 0.457 Worse Eye LogMAR VA −0.35 (−0.59−(−0.04)) 0.027 Cells −0.14 (−0.45−0.21) 0.411 IOP −0.14 (−0.46−0.22) 0.457 PedsQL Total scale 0.52 (0.23−0.72) <0.001 PedsQL (range 0‐100) Better Eye LogMAR VA 0.03 (−0.30−0.35) 0.867 Cells −0.21 (−0.51−0.15) 0.240 IOP 0.05 (−0.32−0.41) 0.792 Worse Eye LogMAR VA −0.13 (–0.43–0.21) 0.434 Cells −0.25 (−0.54−0.11) 0.169 IOP 0.13 (–0.25–0.47) 0.494 Spearman's correlation coefficients p–value <0.05 Mild correlations: R <0.3; Moderate correlations: R = 0.3–0.7; Strong correlation: R = >0.7 Effects of Youngsters Eyesight on QOL LogMAR visual acuity intraocular pressure Pediatric Quality of Life InventoryConclusion:The EYE‐Q is an important instrument in the measurement of QOL and function in children with uveitis. Since many children with active disease are asymptomatic, the EYE‐Q may not reflect the presence of active disease based on the slit lamp examination, but can detect changes in vision related to function and QOL. Since the EYE‐Q demonstrated moderate correlations with standard measures of QOL and function, whereas the PedsQL showed mild to no correlations, the EYE‐Q may be an important component of the global assessment of visual function and QOL in this population.

PReS-FINAL-2063: Proposed criteria for activity, damage and impact of juvenile idiopathic arthritis associated uveitis: consensus effort from the multinational interdisciplinary working group for uveitis in childhood (MIWGUC)

Uveitis is the most common extraartricular manifesation of juvenile idiopathic arthritis (JIA) with an.incidence of approx. 10 - 15 per 100,000 children. Uveitis, a potentially blinding disorder, is present in approx 10-18% of JIA patients, with a wide spectrum of presentations. Despite advances in treatment of childhood arthritis there are no definitions for assessment of activity, damage and impact of JIA associated uveitis.

PReS-FINAL-2068: S100 A8/A9 serum levels reflect disease activity in juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common disease associated with uveitis in childhood. S100 proteins have been proven to be valuable biomarkers in different subtypes of JIA as well as in other (auto)inflammatory or autoimmune diseases.

PReS-FINAL-2028: ANA positivity and a younger age at onset, but not disease category, predict the risk of uveitis in italian children with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic anterior uveitis in childhood, and uveitis is the most frequent extra-articular manifestation seen overall in children with JIA. Although it is well-known that ocular involvement is strongly associated with a constellation of particular clinical features, which include the presence of antinuclear antibodies (ANA), young age at disease onset, female sex, and an asymmetric pattern of arthritis, the relative importance of each risk factor is still a matter of debate.

PReS-FINAL-2150: Antiocular antibodies in children with juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common disease associated with uveitis of childhood. The pathogenesis of JIA-associated uveitis (JIAU) is undefined, although there is evidence for a B-cell-mediated autoimmune process with a probably pathogenetic role for autoantibodies.

The Safety and Efficacy of Noncorticosteroid Triple Immunosuppressive Therapy in the Treatment of Refractory Chronic Noninfectious Uveitis in Childhood

To assess the safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious childhood uveitis. Subjects were retrospectively selected from a database. Patients were included if they were diagnosed with chronic, noninfectious uveitis at 16 years of age or under and treated with triple immunosuppressive therapy for at least 6 months (following failure of a combination of 2 immunosuppressants). Patient demographics, diagnoses, duration of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were recorded. Efficacy outcomes for triple therapy were recorded at 6 months. Thirteen patients with bilateral uveitis were included. Using Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%) had a 2-step improvement in anterior chamber cell inflammation (n = 26). In addition, 2 patients required additional oral corticosteroid treatment. There were 4 significant infectious adverse events during a total of 21.9 patient-years (PY) on triple therapy (0.18 events per PY). In this group of children with refractory uveitis, addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.

AB0684 Proposed criteria for activity, damage and impact of juvenile idiopathic arthritis associated uveitis: consensus effort from the multinational interdisciplinary working group for uveitis in childhood (miwguc)

BackgroundUveitis is the most common extraartricular manifesation of juvenile idiopathic arthritis (JIA). Uveitis, a potentially blinding disorder, is present in approx 10-18% of JIA patients, with a wide spectrum of...

Anti-TNF therapy for childhood and adolescent uveitis

Childhood uveitis is the third most common cause of blindness in the pediatric population (1). Numerous side effects of chronic corticosteroid use have prompted a quest for a viable steroid-sparing treatment. Our purpose is to describe the corticosteroid-sparing effect of anti-TNF therapy in chronic childhood and adolescent uveitis. Retrospective longitudinal case series of patients started on anti-TNF therapy for chronic uveitis. Major outcome measures were corticosteroid-sparing success, adverse events, inflammation control, need for and ability to taper concurrent treatments assessed at 1-, 3-, 6-, 12-, 18-, and 24-month intervals. Nineteen eyes of 10 patients who used adalimumab or infliximab and followed for an average of 12 months were identified. Three patients had anterior uveitis and 7 had posterior segment uveitis. All patients with posterior segment inflammation improved significantly with anti-TNF therapy. 84% of eyes with anterior chamber inflammation improved or remained stable. Four patients (40%) required two cycles of therapy due to either relapse or failure. All patients were successfully weaned to systemic steroid dose of less than 7 mg/day without relapse, but 33% required lowdose maintenance steroids. Half of patients required at least one other non-biologic systemic immunosuppressive after 6 months. One serious adverse event (anaphylactic reaction to infliximab) was identified. This is the first study of its kind looking at outcomes for both anterior and posterior uveitis after relatively long term treatment with anti-TNF therapy in children. Anti-TNF antibody biologics improve inflammation control and offer a steroid-sparing therapy in pediatric uveitis patients.

An Evidence-Based Review of Vascular Endothelial Growth Factor Inhibition in Pediatric Retinal Diseases: Part 2. Coats’ Disease, Best Disease, and Uveitis With Childhood Neovascularization

Vascular endothelial growth factor (VEGF) is an important factor in the pathogenesis of multiple retinal neovascular disorders. This report focuses on the quality and depth of new evidence for the use of VEGF inhibitors in selected pediatric ocular diseases, including Coats' disease, Best disease, and childhood uveitis. Because much of the literature comprises case reports and retrospective case series, the level of evidence supporting its use as a primary treatment option, or even as adjuvant therapy, is low. The standard of care is treatment of the underlying disorder to prevent neovascularization (retinal or subretinal), vitreous hemorrhage, or subsequent retinal detachment. However, these complications may not present until late in the disease course. It may then be useful to treat with these agents. Prospective studies are warranted to further elucidate the role of anti-VEGF therapy in these diseases.

Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis–associated uveitis: A consensus effort from the multinational interdisciplinary working group for uveitis in childhood

To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)-associated uveitis. The literature relating to outcome measures used in studies of uveitis in childhood and adolescence was reviewed. A set of core outcomes and domains was established using the Delphi process. This was reviewed by a representative multinational interdisciplinary working group. Nominal group technique consensus was reached on face and content validity of the range and content of the domains. The outcomes and the appropriate instruments for uveitis trials were adapted to the age ranges of patients with JIA-associated uveitis. Consensus was reached that data should be reported at defined time points in longitudinal studies with patients stratified by prognostic markers. Visual acuity testing should be age appropriate. The severity of uveitis (measured as anterior chamber cell grade) and duration of active inflammation should be documented. Visually significant structural complications should be recorded and quantified with standard measures. The responses to treatment and corticosteroid-sparing effects of treatment should be documented. Patient-reported disease activity and age-specific uveitis-related quality of life should be reported using appropriate questionnaires. The proposed outcome measures in JIA-associated uveitis should aid in the standardization and comparison of future RCTs of the treatment regimens for this disease. The proposed outcome measures will be verified in a prospective validation study.

Comparison of idiopathic and secondary uveitis patients seen in a dual pediatric rheumatology-ophthalmology clinic

Purpose Uveitis is an intraocular inflammatory disease that accounts for 10-15% of all cases of total blindness in the U.S. Although uveitis is more prevalent in adults, children comprise approximately 5% of the uveitis population. The most common etiologies of childhood uveitis are idiopathic, infectious, and rheumatologic. Idiopathic uveitis is the most common cause of pediatric uveitis, while uveitis associated with Juvenile Idiopathic Arthritis (JIA) is the most common secondary cause. In 2005, the physicians of Children’s Mercy’s Hospital created a dual Pediatric Rheumatology and Ophthalmology uveitis clinic for patients with ocular inflammation requiring systemic immunosuppressant therapy. An ophthalmologist and rheumatologist jointly evaluate each patient, and formulate a comprehensive plan with the patient and family. To our knowledge, this is the only pediatric uveitis clinic in the U.S. staffed by the two subspecialties simultaneously. The aim of this study was to determine if the characteristics of ocular involvement differ between severe Idiopathic uveitis (IU) and Secondary uveitis (SU).

The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty

AimThe long-term course of juvenile idiopathic arthritis (JIA)-associated uveitis is not known yet. This study investigates the course and activity of JIA-associated uveitis in childhood and puberty.DesignRetrospective study of the...

Surgical outcomes in refractory uveitic glaucoma

Glaucoma complicating childhood uveitis often proves refractory to medications. Although goniotomy offers effective intraocular pressure (IOP) reduction for selected cases, others fail and require additional surgery. Our purpose was to evaluate outcomes and surgical strategy for refractory uveitic glaucoma cases.

Patterns of childhood-onset uveitis in a referral center in Turkey

PurposeThis study aimed to investigate the frequency and characteristics of childhood-onset uveitis and evaluate the rate and specific causes of visual loss in this population.MethodsThe data of 121 patients (179 eyes) with uveitis starting before ≤16 years and followed up for at least 6 months were retrospectively evaluated. Age at onset, sex, laterality, associated systemic disease, laboratory data, therapeutic strategies, surgeries, final visual acuity, and causes leading to visual acuity ≤20/200 were analyzed.ResultsChildhood-onset uveitis made up 9.6% of our uveitis patients. The mean age at onset was 11.7 years (1–16) and the mean follow-up period was 38.5 months (6–148). Forty-three patients (35.5%) were female and 78 were male (64.5%). The disease was bilateral in 58 (47.9%) and unilateral in 63 (52.1%) patients. Uveitis was mostly (59.5%) seen between 12 and 16 years of age. Pars planitis, observed in 29 (24%) patients, was the leading cause of childhood-onset uveitis. Uveitis was idiopathic in 20 (16.5%) of patients. The most frequently associated diseases were Behcet’s disease (BD) in 20 (16.5%), toxoplasmosis in 16 (13.2%), and juvenile idiopathic arthritis (JIA) in 8 (6.6%) patients. Anterior uveitis was observed in 38 (31.4%), intermediate uveitis in 31 (25.6%), posterior uveitis in 30 (24.8%), and panuveitis in 22 (18.2%) patients. The final visual acuity was ≤20/200 in 32/179 eyes (17.9%) of 27/121 patients (22.3%). The most often ocular complication leading to visual acuity ≤20/200 was optic atrophy and had been observed in 14 of 32 eyes (43.7%). Macular scar observed in five eyes (15.6%) was the second most often complication. Etiological distribution of 27 patients with visual acuity ≤20/200 was as follows: 12 had BD (44.4%), 5 had idiopathic uveitis (18.5%), 4 had pars planitis (14.8%), 3 had toxoplasmosis (11.1%), 2 had JIA (7.4%), and 1 had toxocara (3.7%).ConclusionsAlthough rare, childhood-onset uveitis has a blinding potential and causes visual loss in up to 22.3% of the patients. In endemic areas like Turkey, BD may be the most common uveitis-associated systemic disease and the leading cause of visual loss in childhood uveitis as adulthood.

Étude épidémiologique des uvéites de l’enfant : à propos de 49 cas

To analyze the patterns of pediatric uveitis. A retrospective study of 49children with uveitis, examined from January 2000to December 2009. All patients underwent a complete ophthalmic examination and an etiological search; follow-up varied from six months to seven years. The mean age at onset of uveitis was 11.6years (range, 5-14years). The sex ratio was 1.04. Uveitis was bilateral in 59.20% of the patients, anterior in 22cases (44.9%), intermediate in seven cases (14.3%), posterior in four cases (8.1%), and panuveitis was found in 16cases (32.7%). In 57.2% of the patients, uveitis was idiopathic. Infectious uveitis was responsible for 14.1% of the cases, the most common of which were toxoplasmosis and toxocarosis. Systemic associations were found in 22.5%, with juvenile idiopathic arthritis in 6.2%. A specific ocular entity was responsible for 6.2% of the cases. Ocular complications occurred in 65.3% of the affected eyes, the most common being cataract (24.5%) and cystoid macular edema (20.5%). The final visual acuity was less than 20/200in 18%. Pediatric uveitis is rare but may cause visual loss. In our study, the cause of uveitis in childhood remains most often undiagnosed. Toxoplasmosis and toxocarosis are the most frequent infectious causes. Cataract was the most frequent complication. A strict ophthalmological follow-up is mandatory to improve the prognosis.

Prevention of flare recurrences in childhood‐refractory chronic uveitis: An open‐label comparative study of adalimumab versus infliximab

To compare the efficacy and safety of adalimumab versus infliximab in an open-label prospective, comparative, multicenter cohort study of childhood noninfectious chronic uveitis. Thirty-three patients (22 females, 11 males, median age 9.17 years) with refractory, vision-threatening, noninfectious active uveitis were enrolled, and received for at least 1 year infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 6-8 weeks) or adalimumab (24 mg/m2 every 2 weeks). The primary outcome was to assess, once remission was achieved, the time of a first relapse. Time to remission, time to steroid discontinuation, and the number of relapses were also considered. Sixteen children (12 with juvenile idiopathic arthritis [JIA], 3 with idiopathic uveitis, and 1 with Behçet's disease) were recruited in the adalimumab cohort and 17 children (10 with JIA, 5 with idiopathic uveitis, 1 with early-onset sarcoidosis, and 1 with Behçet's disease) were recruited in the infliximab group. Cox regression analysis did not show statistically significant differences between the two groups with regard to time to achieve remission and time to steroid discontinuation, whereas a higher probability of uveitis remission on adalimumab during the time of treatment was shown (Mantel-Cox χ2=6.83, P<0.001). At 40 months of followup, 9 (60%) of 15 children receiving adalimumab compared to 3 (18.8%) of 16 children receiving infliximab were still in remission on therapy (P<0.02). Even if limited to a relatively small group, our study suggests that over 3 years of treatment, adalimumab is more efficacious than infliximab in maintaining remission of chronic childhood uveitis.

Behçet Disease in Children

Purpose: To investigate the incidence and clinical characteristics of Behçet disease in children.Methods: The authors retrospectively reviewed the charts of 3382 patients with Behçet disease from October 1986 to December 2005 at Ankara University Medical School Behçet Unit and/or Atmaca private clinic.Results: 110 children were diagnosed with Behçet disease. The 110 children represented 3.3% of the total number of Behçet patients that were reviewed. 62.7% were girls and 37.3% were boys. The mean age at initial manifestation was 11.63 ± 3.46 years and at diagnosis was 14.15 ± 2.13 years. Ocular involvement was found in 30.9% of the children. Of these, 61.8% were bilateral and 38.2% were unilateral. Anterior uveitis was found in 18 eyes (32.8%), posterior uveitis in 24 eyes (43.6%), and panuveitis in 13 eyes (23.6%).Conclusion: Behçet disease should be considered in the differential diagnosis of childhood uveitis, particularly in endemic areas. The collaboration of pediatricians, rheumatologists, dermatologists, ophthalmologists, and other specialists when necessary is required in the diagnosis and management of children with Behçet disease.

Adalimumab (Humira™): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology

Tumor necrosis factor alpha (TNF-α) is a key soluble mediator involved in the inflammatory cascade of many disorders including uveitis. Among the anti-TNF-α agents, one of the most used in immune-mediated diseases, such as inflammatory arthropathies, is adalimumab (Humira™, Abbott Pharmaceutical Inc.), a fully humanized antibody. The purpose of this review is to analyze the main pharmacological and clinical aspects of adalimumab and its efficacy both in systemic and ocular inflammatory disorders. Adalimumab was effective in treating several autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. In recent years, adalimumab has been used successfully in refractory cases of intraocular inflammation. Moreover, this biological agent showed good safety and efficacy profiles in ocular use including childhood uveitis. Switching from other anti-TNF-α agents to adalimumab may offer several advantages, such as easier administration, better patient compliance, and lower rate of adverse events. Adalimumab is a promising drug for the therapy of uveitis, although further studies are needed on its application in uveitis.

Epidemiology and Course of Disease in Childhood Uveitis

Epidemiology and Course of Disease in Childhood Uveitis