Relationship of lacrimal gland change and cornea in patients with primary Sjögren's syndrome and non-Sjögren's syndrome related dry eye

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 such as lacrimal gland ultrasonography (LGUS) and in vivo confocal microscopy (IVCM) remain underutilized in diagnosing the disease. 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 suffer from more severe dry eye symptoms, while lacrimal gland changes with the disease development play a role in nerve depletion. Multimodal ophthalmic imaging reveals interconnected lacrimal gland-corneal neuroimmune dysfunction in SSDE, providing diagnostic biomarkers and treatment insights to explore in the future.