Waldenstrom’s macroglobulinemia is a chronic lymphoproliferative disorder characterized by IgM overproduction and plasmacytoid lymphocyte proliferation. Common sites of infiltration include bone marrow, lymph nodes, and spleen.  CNS involvement is exceptionally uncommon. We present a rare case of optic neuritis secondary to Waldenstrom’s macroglobulinemia.

A 65-year-old man with a history of chronic myelomonocytic leukemia and smoldering Waldenstrom’s macroglobulinemia presented with left-sided progressive blurry vision and painful eye movements. Initial examination demonstrated left afferent pupillary defect with red/yellow desaturation. Visual acuity was 20/70 OS and 20/25 OD. Fundoscopic examination revealed bilateral optic disc edema. MRI brain/orbits demonstrated abnormal intra-orbital optic nerve enlargement and enhancement, left greater than right, suggestive of leukemic optic neuropathy. Serum IgM was markedly elevated. The constellation of symptoms and work-up supported the diagnosis of hyperviscosity syndrome associated with Waldenstrom’s macroglobulinemia. Plasmapheresis was initiated resulting in reduction in serum IgM levels and improvement in visual symptoms.  The patient was discharged home and transitioned to zanabrutinib, prednisone, and rituximab, with continual gradual symptomatic improvement.

Overproduction of monoclonal pentameric immunoglobulin IgM is the hallmark of Waldenstrom’s macroglobulinemia. There are a variety of systemic symptoms that occur as a result of lymphoplasmacytoid infiltration and IgM deposits. CNS involvement, such as retinopathy and neuropathy, has rarely been reported from hyperviscosity and vascular hyperpermeability. Fundoscopic examination typically reveals dilatation of retinal veins, hemorrhage, and macular/optic disc edema. Our patient had a history of smoldering Waldenstrom’s macroglobulinemia, and the presenting signs of hyperviscosity syndrome were decreased visual acuity and optic disc edema. Plasmapheresis is the first-line treatment in the acute phase and aims to decrease IgM levels; this is routinely followed by maintenance chemotherapy. This case highlights rare CNS complications of hyperviscosity syndrome associated with Waldenstrom’s macroglobulinemia and the significance of immediate treatment in prevention of serious morbidities.