Pathological mechanisms of Sjögren’s disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation

Sjögren's disease-related dry eye (SjD‑DE) refers to a form of dry eye disease driven by autoimmune dysregulation in Sjögren's disease (SjD). Compared with primary dry eye, patients with SjD-DE typically present with more pronounced symptoms and signs, along with persistent and refractory disease courses that markedly impair daily functioning and quality of life. Although the precise mechanisms underlying SjD-DE have not been fully elucidated, accumulating evidence indicates that SjD affects not only lacrimal secretion but also multiple components of the ocular surface. In this context, we review recent pathological studies focusing on glandular dysfunction, goblet cell loss, tear film hyperosmolarity, ocular surface inflammation, and corneal nerve pathology in SjD-DE. These pathological alterations are highly interconnected and mutually reinforcing, ultimately driving the "vicious cycle" of ocular surface damage. This review aims to provide insights to support the development of novel non-invasive diagnostic criteria and future therapeutic strategies for SjD-DE.