Paraneoplastic syndromes with ocular manifestations: Immunopathogenesis, clinical presentation, and oncologic implications

Paraneoplastic syndromes with ocular manifestations are rare but clinically significant immune-mediated disorders that may precede the diagnosis of malignancy. They arise from immune cross-reactivity between tumor and ocular antigens, leading to retinal or optic nerve damage through autoantibodies, cellular immunity, or soluble mediators. This narrative review summarizes current evidence on immunopathogenesis, clinical presentation, diagnostic approach, and oncologic implications. A literature search of PubMed, Scopus, and Web of Science was conducted for publications from January 2000 to September 10, 2025. Because of heterogeneity in study design and outcomes, the evidence was synthesized qualitatively. Ocular paraneoplastic syndromes most commonly present with subacute bilateral visual dysfunction, including vision loss, photopsias, scotomas, nyctalopia, and dyschromatopsia. Cancer-associated retinopathy is typically linked to antiretinal antibodies and rapid photoreceptor dysfunction, while melanoma-associated retinopathy is associated with metastatic melanoma, TRPM1 antibodies, and an electronegative electroretinogram. Paraneoplastic optic neuropathy, including CRMP5-associated forms, may mimic inflammatory or infectious optic nerve disease and requires careful differential diagnosis. Management relies on prompt detection and treatment of the underlying malignancy together with immunomodulatory therapy tailored to the ocular phenotype. Immune checkpoint inhibitors further complicate diagnosis and management, underscoring the need for multidisciplinary care.