Autoimmune Ocular Surface Disorders: From Molecular Immunopathogenesis to Regenerative and Surgical Therapeutics

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren's syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms-including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial-mesenchymal transition-culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling-alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells-are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases-from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions.