Thesis defense Carlyn Kouwenberg

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Childhood uveitis represents a rare group of ophthalmological inflammatory entities with a varied spectrum of clinical presentation and treatment. Physicians face several challenges in the management of this potentially sight-threatening disease. Research into pediatric uveitis has mainly focused on juvenile idiopathic arthritis-associated uveitis (JIA-U), with less information available for clinical management and molecular understanding of other specific subtypes. In this thesis, we studied a variety of aspects of pediatric uveitis beyond JIA-U with the overarching aim to improve the current diagnostic and therapeutic strategies for pediatric uveitis in general.

We provided an increase of knowledge about the clinical course of pediatric patients with idiopathic chronic anterior uveitis. These children showed a higher prevalence of ocular complications compared to children with JIA-U. We also identified younger age as a risk factor for ocular complications within the chronic anterior uveitis cohort.  

Furthermore, we proposed additional diagnostics (retinal nerve fiber layer thickness using optical coherence tomography) and investigated the efficacy and safety of novel treatment options (adalimumab) in pediatric uveitis patients beyond JIA-U. We revealed an upregulation of circulating proteins with key functions in the coagulation and complement cascade in pediatric uveitis patients with retinal vascular involvement. Moreover, these data suggest that the microcirculation might play a role in noninfectious pediatric uveitis. Hence, we conducted exploratory research that revealed nailfold capillaroscopic abnormalities indicating involvement of the systemic microcirculation in pediatric uveitis. This finding supports our believe that pediatric uveitis is not merely an isolated ocular inflammatory condition, but might be a manifestation of a disease affecting the systemic immune system and microcirculation. Moreover, it highlights the importance of a multidisciplinary approach in the management of pediatric uveitis patients to provide the best possible care.
These new insights may serve as a foundation for more personalized interventions and aid in the development of new approaches for treatment.