Irreversible optic nerve dysfunction associated with central retinal vein occlusion (CRVO) is an unusual but important complication of Waldenstrom Macroglobulinemia (WM). Acute visual loss in CRVO is mainly due the severe macular oedema. However, ischaemic optic neuropathy needs to be considered in patients with CRVO when, (i) there is a relative afferent papillary defect and central scotoma, (ii) the visual acuity is not consistent with the retinal pathology, and (iii) the visual defects persisted despite resolution of macular oedema following treatment of the hyperviscosity state. The ischaemic type of CRVO is associated with a poor visual prognosis and the presenting visual acuity has a prognostic role. We report the first description of irreversible unilateral optic nerve damage associated with CRVO in a patient with WM.