Immunological Interplay at the Ocular Surface of Stevens-Johnson Syndrome, Ocular Cicatricial Pemphigoid, and Ocular Graft Versus Host Disease.

Rare ocular surface inflammatory disorders (OSIDs), such as ocular cicatricial pemphigoid (OCP; 1.3-2/million), Stevens-Johnson Syndrome (SJS; 1-5/million), and ocular graft versus host disease (oGVHD; occurring in >50% of chronic GVHD cases) share overlapping clinical phenotypes. Their defining features include conjunctival cicatrization and chronic inflammation. An incomplete understanding of the underlying immunopathogenesis of these conditions has hindered the development of targeted therapies, leaving patients at risk of permanent vision loss and highlighting the need to define distinct ocular immune profiles. Existing literature indicates elevated levels of neutrophils and macrophages/monocytes, along with major increases in their related secretory factors, IL-8 (P < 0.05) and TNF-α (P < 0.05), at the ocular surface across all three groups. Whereas both B cells and cytotoxic T cells are elevated in oGVHD, OCP is characterized by elevated B cells and a concomitant reduction in cytotoxic T cells. Apart from neutrophils and macrophages/monocytes, the local immune landscape-especially in SJS-has been underexplored. At the molecular level, extensive studies of tears have reported elevated levels of IL-17, CXCR1 (P < 0.01), CTGF (P < 0.05) in OCP; IFN-α and IFN-γ (P < 0.05) in oGVHD; and MCP-1, MIP-1β (P < 0.05) in SJS. These studies also indicate that sampling methods and patients' medication status may influence immune profile outcomes. Comprehensive immunophenotyping studies, coupled with the establishment of pathological links to respective molecular profiles, could advance understanding of condition-specific disease biology.