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. Each uveitis subtype is categorized by the affected region of the eye and is associated with different autoimmune disorders with distinct immunopathology (i.e. juvenile arthritis, sarcoidosis and Behcet’s disease). However, it is unclear how these differences translate into differences in intraocular pathology. Here, we sought to evaluate the intraocular cytokine profile within each uveitis subtype.

Methods: We obtained intraocular fluid samples from patients at Boston Children’s Hospital and Massachusetts Eye Research & Surgery Institution with uveitis or non-inflammatory controls undergoing eye surgery. We also collected clinical information such as slit-lamp examinations and medications at the time of surgery. Cytokine content in the aqueous humor was assessed through the Olink proteomics platform, which utilizes proximity extension assay technology to detect 45 cytokines through a multiplex immunoassay. To identify differences in the presence of specific cytokines, we used generalized linear models (LIMMA) on log₂ transformed data. Each uveitis subtype was compared to the controls using Bayesian post-hoc testing. Thresholds for differential cytokine levels were adjusted p< 0.05 and fold change >1.

Results: We collected aqueous humor samples from control patients (n=10) and patients with anterior uveitis (n=13), 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 cells grades between 0 and 0.5+ by SUN criteria. As expected, non-inflammatory control patients displayed low cytokine levels in their aqueous humor. Anterior uveitis and panuveitis had elevated cytokine expression, while intermediate uveitis and posterior uveitis showed cytokine levels comparable to controls, reflecting the anatomical regions affected by each uveitis subtype. Patients with anterior uveitis segregated into two groups, those with increased inflammatory cytokines (n=6) and those without (n=7). However, there were no significant differences in examination findings or medication usage between these two groups. Among the inflamed anterior uveitis samples, there was significant upregulation of TNF, IL-17, IL-10, IL-6, CXCL9 and IL-15, as well as several chemokines and matrix metalloproteinases compared to controls. Panuveitis also displayed a similar pattern of cytokine upregulation with no significant differences in expression between inflamed anterior uveitis and panuveitis.

Conclusion: While ophthalmic examinations indicated near-quiet clinical disease activity at the time of surgery, panuveitis patients and a subset of anterior uveitis patients displayed persistent inflammation within their intraocular fluid. Further, the similarities in the intraocular cytokine profile between anterior uveitis and panuveitis suggest convergence in inflammatory pathways.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/intraocular-cytokine-profiling-of-autoimmune-uveitis/