Abstract
BACKGROUND: Primary Sjögren's syndrome(pSS) is characterized as an autoimmune disorder mostly involving exocrine glands and pSS related dry eye (SSDE) contributes to a severe subtype of dry eye disease (DED). Emerging imaging tools for ocular surface evaluation such as lacrimal gland ultrasonography (LGUS) and in vivo confocal microscopy (IVCM) remain underutilized in diagnosing the SSDE. This study aims to investigate LGUS-IVCM correlations to map structural-functional relationships in SSDE patients. METHODS: This prospective cross-sectional study enrolled 27 SSDE patients and 12 non-pSS related dry eye (NSSDE) controls, utilizing IVCM and LGUS to assess corneal nerve morphology, immune cell activity, and glandular structural parameters. RESULTS: SSDE patients exhibited greater nerve tortuosity (p = 0.003), dendritic cell density (p < 0.001), and parenchymal echogenicity alterations (p = 0.013) versus NSSDE. For dry eye patients, subbasal nerve density inversely correlated with lacrimal gland area (r = -0.352, p < 0.05), logistic regression confirmed lacrimal gland area as an independent risk factor of nerve depletion. Meanwhile, ROC curve of dendritic cell density and activation strongly predicted SSDE with an AUC of 0.838 and 0.827. CONCLUSION: SSDE patients experience more corneal epithelial injury, with progressive lacrimal gland changes contributing to corneal nerve damage and inflammation. Multimodal ophthalmic imaging elucidates the interconnected lacrimal gland-corneal neuroimmune dysfunction in SSDE, offering potential diagnostic biomarkers and therapeutic targets for future exploration.