Background/Purpose: Autoimmune uveitis is an inflammatory disorder of the eye that is associated with significant morbidity, including vision-threatening complications and chronic reliance on immunosuppressive therapies. Evaluation of ocular inflammation is largely based on clinical ophthalmic examinations. Our aim is  to discover potential biomarkers of disease through biological samples such as aqueous humor (AQH), blood and tear fluid.

Methods: We obtained AQH samples paired with tears and blood from adult and pediatric patients with uveitis or non-inflammatory conditions undergoing eye surgery at Boston Children’s Hospital, Massachusetts Eye Research & Surgery Institution, and Cincinnati Children’s Hospital Medical Center. We also collected clinical information such as slit-lamp examinations to grade uveitis activity at the time of surgery. Cytokine and immune-related protein content of biological samples was assessed through Olink proximity extension multiplex immunoassay. The intraocular cytokine profiles of (AQH samples were compared across patients by generalized linear models (LIMMA) on log₂ transformed data and assigned inflammatory scores based on the sum of normalized cytokine values. Samples were grouped by uveitis subtype and AQH inflammatory scores. Paired AQH and blood samples and paired AQH and tear samples collected at the time of surgery were evaluated for overlapping inflammatory protein content. Immune-related protein expression in the blood and tear samples were correlated to AQH inflammatory scores.

Results: We evaluated AQH samples from controls (n=16) and patients with anterior uveitis (n=16), intermediate uveitis (n=2), posterior uveitis (n=4), and panuveitis (n=7). At the time of sample collection, all patients had near-quiet disease activity on slit-lamp examination with anterior chamber cell grades between 0 and 0.5+ by SUN criteria. Non-inflammatory control patients displayed low cytokine levels in their AQH, while 44% of patients with anterior uveitis (n=7) and 57% of patients with panuveitis (n=4) had evidence of ongoing inflammation. The cytokine profile did not overlap between paired AQH and tears (n=7) or paired AQH and blood samples (n=14). There was also no direct correlation between immune-related proteins in the blood or tears with their paired AQH inflammatory scores, although some markers such as IL7 and CSF3 in the blood and VEGFA in the tears trended towards significance. Notably, pediatric uveitis patients showed more AQH inflammation compared to adults, as 86% of children with anterior uveitis and 100% of children with panuveitis had AQH inflammation, compared to 11% and 50% in adults, respectively.

Conclusion: Our findings demonstrate that ~50% of anterior and panuveitis patients have elevated inflammatory protein levels in AQH despite having quiescent clinical examinations. Strikingly, the majority of pediatric patients with anterior and panuveitis exhibited subclinical eye inflammation, in contrast to adults with uveitis. This emphasizes the need for more sensitive methods of assessing uveitis activity by examination or imaging-based methods, as well as identifying reliable biomarkers of disease activity.

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/inflammatory-markers-of-autoimmune-uveitis-in-the-eye-tears-and-blood/