Antibody-Related Mechanisms in Ocular Diseases: Autoimmunity, Malignancy, and Therapeutic Targeting

Antibodies in ocular disease have heterogeneous biological meanings: they may act as direct pathogenic effectors, systemic diagnostic biomarkers, indicators of B-cell clonality, or therapeutic agents. This distinction is particularly important in the eye, where immune privilege and the blood–ocular barrier restrict tissue access, whereas inflammation may permit entry of immunoglobulins, complement, and immune cells or support local humoral responses. This narrative review integrates antibody and B-cell biology across autoimmune and paraneoplastic retinopathies, aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, ocular mucous membrane pemphigoid, ocular myasthenia gravis, thyroid eye disease, systemic autoimmune and fibroinflammatory disorders with ocular involvement, and B-cell malignancies including vitreoretinal and ocular adnexal lymphoma. We distinguish the evidence for direct antibody pathogenicity from disease association and emphasize that a positive result is interpretable only in relation to the ocular phenotype, assay platform, titer, specimen compartment, and orthogonal confirmation. Serum testing, ocular-fluid analysis, electrophysiology, multimodal imaging, cytology, histopathology, immunophenotyping, immunoglobulin clonality, and molecular testing have complementary roles. Therapeutic strategies include B-cell or B-lineage depletion, complement inhibition, cytokine- or receptor-directed monoclonal antibodies, insulin-like growth factor-1 receptor blockade, and emerging FcRn- or plasma-cell-directed approaches; however, regulatory status and ocular-specific evidence vary substantially among diseases. A mechanistically stratified framework may reduce overdiagnosis, improve recognition of malignant masquerade syndromes, and support more precise selection of targeted therapy.