Abstract
OBJECTIVE: To characterize the relationships between in vivo confocal microscopy (IVCM) - derived corneal immune - neural metrics, and systemic cytokines and ocular surface findings in Sjögren's syndrome-associated dry eye disease (SS-DED), and to identify variables independently associated with SS-DED status. METHODS: A retrospective case - control study was conducted (Jan 2019 - Jan 2022), including 120 SS-DED patients and 88 healthy controls. Corneal dendritic cell density (DCD), inflammatory cell density (ICD), and nerve fiber density (NFD) were quantified by IVCM. Tear break-up time (BUT), corneal fluorescein staining (FL), Schirmer test, and Ocular Surface Disease Index (OSDI) were assessed using standard protocols. Variables independently associated with SS-DED were identified using multivariable logistic regression, and their discrimination performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Compared to controls, SS-DED patients showed significantly higher levels of IL-1β, IL-6, TNF-α, DCD, and ICD, and lower NFD levels (all P<0.001). DCD correlated positively with IL-1β, BUT, FL, and OSDI (P<0.05), while NFD correlated negatively with BUT and FL (P<0.001). ICD positively correlated with IL-1β, IL-6, TNF-α, and DCD (all P<0.001). Multivariate regression analysis identified IL-1β (OR=1.249, P<0.001), OSDI (OR=1.074, P=0.033), DCD (OR=1.411, P=0.002), and ICD (OR=1.006, P=0.018) as independent factors associated with SS-DED. Among them, DCD demonstrated the highest discriminative power (AUC=0.886; specificity 98.75%; sensitivity 65.00%). CONCLUSION: Elevated IL-1β, OSDI, DCD, and ICD levels are independent risk factors for SS-DED. Among these factors, DCD exhibited superior predictive performance over the others and may be a biomarker for SS-DED diagnosis and disease monitoring.