Paraneoplastic syndromes associated with visual loss

The recent literature was reviewed to analyze the developments in the diagnosis, pathogenesis, and immunology of this group of paraneoplastic syndromes. Clinical features and pathologic findings are summarized.

The mechanism of cell death in cancer-associated retinopathy appears to occur through apoptotic pathways. Caspase inhibitors and a calcium antagonist have been used in animal models to block or suppress the effect of the antirecoverin antibodies on the retina with significant response. These agents are possible treatment options for cancer-associated retinopathy. Aberrant expression of recoverin by tumor cells does not necessarily induce antirecoverin antibodies and cancer-associated retinopathy. Many tumors, not just those producing the clinical picture of cancer-associated retinopathy, have been shown to express recoverin. Recoverin appears to play a functional role in tumor cells, and antirecoverin antibodies may have tumor-suppressing effects. Further research into this area may help design epitope-based immunotherapy for patients with recoverin-expressing tumors. Further evidence has emerged to support the initial observation that depolarizing bipolar cells are the likely retinal target in melanoma-associated retinopathy. Intravitreal injection of melanoma-associated retinopathy serum produced electroretinogram changes in animals very similar to the clinical findings in humans. Many new antibodies and antigens had been discovered to be linked to various paraneoplastic syndromes. Anti-collapsing response-mediating protein-5 is likely to be an important one; it was found to be the second most common autoantibody related to paraneoplastic neurologic syndromes.

Further research into the functional role of recoverin in cancer cells may advance our understanding in cancer immunology. Immunotherapy may be possible if a specific epitope of recoverin can be found to contain the antigenic site for antitumor antibodies and not cross-react with retinal antigens. Research into the pathogenesis of the other paraneoplastic syndromes is required for a better understanding and treatment of these rare conditions. The missing link between primary cutaneous melanoma and uveal melanocytes still eludes investigators in bilateral diffuse uveal melanocytic proliferation. The discovery of the missing link may provide us with some understanding of the development of uveal melanoma.