*For most patients, disease onset is between ages 35 and 55. Earliest onset is usually not before age 35. Late onset is usually not after age 55. *RVCL affects multiple organs. All patients develop brain and eye disease, leading to disability, vision loss, and premature death. *All patients with RVCL develop kidney and liver disease, with elevated alkaline phosphatase. Some patients develop bone lesions (osteonecrosis) as well as hypothyroidism. Sometimes patients also develop gastrointestinal symptoms or bleeding. *RVCL is associated with progressive deterioration in visual acuity due to multifocal microvascular disease, retinal neovascularization leading, and/or glaucoma. Retinal microvascular disease is noninflammatory and resembles that of diabetic retinopathy. This leads to partial or complete vision loss. *Headaches due to multiple factors including brain lesions, edema, and papilledema. *Mental confusion, loss of cognitive function, loss of memory, slowing of speech and hemiparesis due to brain lesions. Some patients have Jacksonian seizures or grand mal seizures. *Progressive neurologic deterioration unresponsive to<unk>  immunosuppression including corticosteroid therapy and chemotherapeutic agents. *Autopsy typically demonstrates discrete, often confluent, foci of coagulative necrosis in the<unk>  white matter, with intermittent findings of fine calcium deposition within necrotic foci. Additionally, tissues exhibit<unk> c changes involving both arteries and veins of medium and small caliber in the<unk>  white matter. There is fibrinoid necrosis of vessel walls with extravasation of fibrinoid material into adjacent parenchyma present in both necrotic and non-necrotic tissue. Vessels can exhibit obliterative fibrosis in all the layers of vessel walls, as well as perivascular, adventitial fibrosis with limited intimal thickening. *In rare cases, RVCL has been associated with severe disease involving other organs outside the brain and the eye (e.g., osteonecrosis requiring joint replacement, gastrointestinal ischemia leading to bowel resection, or liver failure requiring liver transplantation). Clinical Associations * Raynaud's phenomenon * Anemia * Hypertension * Normocytic anemia * Normochromic anemia * Gastrointestinal bleeding or telangiectasias * Elevated alkaline phosphatase * Chronic kidney disease
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations
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Diffuse unilateral subacute neuroretinitis
Cerebroretinal microangiopathy with calcifications and cysts
Uveitis–Glaucoma–Hyphema syndrome
Chronic relapsing inflammatory optic neuropathy
Acute posterior multifocal placoid pigment epitheliopathy
Late congenital syphilitic oculopathy