Studies of Ocular inflammation: Clinical & Translational Research

National Eye Institute

Investigators

Linked publications & trials

Abstract

Uveitis/Intraocular Inflammatory Disease BioBank (iBank) (16-EI-0046) Uveitis is a heterogenous group of diseases where the common denominator is the inflammation in the uveal tissues. While less than half may have associated (other) systemic autoimmune diseases more than half remains undifferentiated. The disease course is unpredictable with remission and flares that can lead to blindness. There are no laboratory or reliable clinical markers of prognosis or predictors of disease activity. Current standard of care is corticosteroids followed by immunomodulatory drugs (non-biologic and biologic) regardless of the clinical subtypes. This approach disregards the possibility that the underlying mechanism or drivers of disease are different in different types of uveitis which is supported by the high failure rates of individual treatments in uveitis (up to 40-50%) and leads to undertreatment of some cases while exposing some patients to unnecessary treatment. Currently the disease is stratified based on anatomical locations (anterior, intermediate and posterior). While this has some implications for vision loss and may be partially helpful clinically its not informative of the underlying mechanism nor its a reliable indicator of disease remission, prognosis or treatment response. The aim of this project is: 1) To identify molecular correlates of disease category and activity through clinical and transcriptional profiling of uveitis patients. 2) To investigate the effects of therapy on uveitis molecular signatures. We have performed high-dimensional flow cytometry on samples as well as single cell sequencing on PBMCs in a cohort of uveitis clinical responders and non-responsers. Lastly, we have performed PBMC bulk RNA sequencing on >300 samples, and proteomics analysis on >150 samples using the SomaLOgic platform. Microbiome in Uveitis (13-EI-0072) Intestinal microbiota emerges as a candidate responsible for priming the immune system in many immune mediated diseases as well as in animal models of uveitis, however, it is not known whether (and how) gut dysbiosis might affect human uveitis. This study introduces the innovative concept of elucidating the role of gut microbiota in human uveitis. While animal models of uveitis indicate gut microbiome may play a role in induction or propagation of disease it is not clear whether or how gut microbiota may contribute to disease pathogenesis in human disease. This study has the potential to help identify patients with the highest risk of uveitis, improve our ability to identify subsets of patients suitable for microbial intervention strategies, predict treatment responders in advance and help devise personalized treatment regimens. The results of this study may help affect disease course in uveitis by manipulating the commensal microbiota and open a new avenue in therapeutics and diagnostics. We have collected over 100 fecal samples from uveitis patients and healthy volunteers and the manuscript is in preparation. A Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis (16-EI-0169) A prospective, non-randomized, uncontrolled, single-center, two-arm pilot study to evaluate ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Eight participants were enrolled and the trial has concluded. Manuscript in preparation. Adalimumab vs. Conventional Immunosuppression for Uveitis (ADVISE) Trial (20-EI-0004) The ADVISE Trial is a randomized, parallel-treatment, comparative effectiveness trial, comparing adalimumab to conventional (small molecule) immunosuppression with antimetabolites and/or calcineurin inhibitors for corticosteroid sparing in the treatment of non-infectious, intermediate, posterior, and panuveitides. The NEI was a site for this multicenter trial.