Three patients developed the sudden onset of total blindness several months after treatment with oral CCNU and low-dose whole-brain radiation. The anterior visual system was included in the radiation field in all patients. Radiotherapy was given for a frontal-lobe glioblastoma multiforme, for central nervous system prophylaxis in a patient with oat cell carcinoma of the lung, and for a parietal-lobe glioblastoma multiforme. None of the neoplasms involved the anterior visual system. The radiation dose ranged from 3000 to 4650 rad and the oral CCNU dosage from 300 mg to 1050 mg. Patients 1 and 2 also received other chemotherapeutic agents. Patient 3 who was treated only with oral CCNU and cranial irradiation died. At autopsy the brain showed a widely infiltrating residual high-grade glioma as well as patchy coagulative necrosis with swollen s o n s and dystrophic calcifications. The optic chiasm showed severe demyelination, axonal loss, and hyalinized vessels. Synergism between oral CCNU and radiation may account for the blindness produced.
Cancer 59:901-907, 1987.
RANIAL IRRADIATION is associated with brain and C visual system vasculitis and necrosis when doses above 5000 rad are used,'-* even when used without concomitant chemotherapy. In a recent study, approximately 20% of optic nerves exposed to radiation greater than 6000 rad developed radiation injury.' However, only a few welldocumented cases of visual loss in patients receiving less than 5000 rad, as in our patients, are reported.','' Chemotherapeutic agents used singly such as vincristine and methotrexate have not been reported to cause damage to the anterior visual system despite their well-recognized neurotoxicity. ' '-I6 However, vincristine and methotrexate when used in combination chemotherapy regimens possibly produce visual ~o s s . ' ~-~'
In addition, these agents when used in conjunction with 2000 to 3600 rad of wholebrain irradiation in cases of central nervous system (CNS) leukemia or medulloblastoma probably cause neurotoxicity including occasional toxicity to the anterior visual ~y s t e m . ~~-~~ Few reports on the toxicity of CCNU[ 1-(2chloroethyl)-3-cyclohexyl-1 -nitrosoureal exist although a From the Departments of