Juvenile idiopathic arthritis-associated uveitis (JIA-U) is an inflammatory eye disease that affects 20% of children with JIA and can lead to cataracts, glaucoma, vision loss and blindness. Current screening guidelines are designed to identify children at risk for eye disease in JIA. However, pediatric rheumatologists'and ophthalmologists'ability to provide comprehensive screening for uveitis is limited because the guidelines have not been updated to include all juvenile arthritis subtypes and other known risk factors for vision-limiting complications of JIA. Screening in JIA and other related autoimmune diseases of childhood is crucial because early uveitis detection can prevent visual complications and influence therapeutic management. Likewise, institution of early aggressive therapy when needed may avert serious visual complications. To improve health outcomes and quality of life of children with JIA-U, we need a better understanding of risk factors for uveitis, long-term visual outcomes, and the effects of visual and physical disability on children's lives. Early and accurate identification of JIA-U through the identification of risk factors for susceptibility and severity of uveitis, standardization of outcome measures, and elucidation of the significance of HLA risk alleles would improve the evaluation of the impact of JIA-U and the understanding of disease etiology, pathogenesis and outcome. Likewise, an improved risk stratification scheme could reduce unnecessary ophthalmology visits and help us identify children at greater risk for severe eye disease and complications. The objectives of this study are to 1) Identify differences in the clinical characteristics and course of JIA-U in patients of European and African descent in children with JIA to identify clinical and genetic risk markers for uveitis, 2) Examine the risk factors identified over a 4-year prospective study of a cohort of children diagnosed with early JIA to determine which factors are associated with eventual development of uveitis, and provide data on their longitudinal profile, 3) Determine the impact of having both arthritis and uveitis on physical and visual disability, vision-specific QOL, and overall QOL using subjective and objective measures. Using a comprehensive biologic, genetic and psychosocial approach, we hope to develop more widely applicable risk stratification schemes based on JIA subtype, and to identify new risk factors that will identify the populations of children at greatest risk for severe disability and blindness so that interventions can be developed to improve their overall outcome. The candidate is a pediatric rheumatologist and an assistant professor of pediatrics at Emory University. She has obtained a Masters of Science in Clinical Investigation. She is devoted to a career in clinical outcomes research in children with autoimmune eye diseases. She has assembled an outstanding mentoring team with experience in pediatric rheumatology, pediatric ophthalmology, pediatric epidemiology, outcomes research and measurement, which are relevant to her objectives. This mentored award will help her become a successful independent clinician scientist.

Public Health Relevance

Juvenile idiopathic arthritis-associated uveitis (JIA-U) is an inflammatory eye disease that affects 20% of children with JIA. This research will validate known risk factors and identify new risk markers of JIA-U, identifying populations of children at greatest risk for severe disability and blindness. It is anticipated that early detection of JIA-U, regular monitoring for eye disease and complications, and institution of appropriate therapy can significantly improve our children's quality of life and long-term outcomes.

National Institute of Health (NIH)
National Eye Institute (NEI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZEY1)
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Agarwal, Neeraj
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Emory University
Schools of Medicine
United States
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Ogdie, Alexis; Sparks, Jeffrey A; Angeles-Han, Sheila T et al. (2018) Barriers and Facilitators of Mentoring for Trainees and Early Career Investigators in Rheumatology Research: Current State, Identification of Needs, and Road Map to an Inter-Institutional Adult Rheumatology Mentoring Program. Arthritis Care Res (Hoboken) 70:445-453
Angeles-Han, Sheila T; Yeh, Steven; Patel, Purnima et al. (2018) Discovery of tear biomarkers in children with chronic non-infectious anterior uveitis: a pilot study. J Ophthalmic Inflamm Infect 8:17
McCracken, Courtney; Yeh, Steven; Jenkins, Kirsten et al. (2018) Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis. Eye (Lond) :
Angeles-Han, Sheila T; Lo, Mindy S; Henderson, Lauren A et al. (2018) Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken) :
Sood, Arjun B; Angeles-Han, Sheila T (2017) An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis. Curr Treatm Opt Rheumatol 3:1-16
Angeles-Han, Sheila T; Rabinovich, Consuelo Egla (2016) Uveitis in children. Curr Opin Rheumatol 28:544-9
Henderson, Lauren A; Zurakowski, David; Angeles-Han, Sheila T et al. (2016) Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. Pediatr Rheumatol Online J 14:9
Angeles-Han, Sheila T; McCracken, Courtney; Yeh, Steven et al. (2015) The Association of Race With Childhood Uveitis. Am J Ophthalmol 160:919-928.e1
Angeles-Han, Sheila T; Yeh, Steven; McCracken, Courtney et al. (2015) Using the Effects of Youngsters' Eyesight on Quality of Life Questionnaire to Measure Visual Outcomes in Children With Uveitis. Arthritis Care Res (Hoboken) 67:1513-20
Angeles-Han, Sheila T; McCracken, Courtney; Yeh, Steven et al. (2015) Characteristics of a cohort of children with Juvenile Idiopathic Arthritis and JIA-associated Uveitis. Pediatr Rheumatol Online J 13:19

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