Evaluation and correlation analysis of ocular surface involvement and systemic conditions in patients with rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease in which ocular surface involvement is common but often underrecognized. This study investigated ocular surface changes in patients with RA and their associations with systemic disease features. Twenty-one patients with RA and 25 age- and sex-matched non-disease controls were prospectively enrolled. Ocular surface symptoms and signs, conjunctival impression cytology, and multiplex tear cytokine profiles were assessed. In patients with RA, disease duration, disease activity, autoantibodies, and circulating inflammatory markers were collected and correlated with ocular findings. Public gene-expression datasets from RA synovium and peripheral blood were also analyzed. Dry eye disease (DED) occurred in 42.86% of eyes in patients with RA, predominantly of the mixed subtype. Compared with non-disease controls, patients with RA presented reduced reflex tearing, markedly lower conjunctival goblet cell density, and more severe ocular surface squamous metaplasia. Multiplex tear cytokine profiling revealed significantly increased levels of C-X-C motif chemokine ligand 11 (CXCL11) and interleukin-1β (IL-1β) in RA. Tear CXCL11 levels showed a suggestive positive correlation with IgA rheumatoid factor (RF). In publicly available transcriptomic datasets, CXCL11 expression was significantly elevated in RA synovial tissue from both large and small joints compared with that in osteoarthritic synovium. RA is frequently accompanied by DED and chronic ocular surface inflammation, potentially mediated by tear cytokines and chemokines, and is closely linked to systemic disease status and synovial inflammation. Routine ocular surface screening and combined topical and systemic anti-inflammatory therapy should be considered.