Pergamon Int. J. Radiation Oncology Biol. Phys.. Vol. 30, No. 4. pp. 765-773, 1994 Copyright 0 1994 Elwier Science Ltd Printed in the USA. All rights reserved 0360-3016/94 $6.00 + .OO 0360-3016(94)E0240-K ?? Clinical Original Contribution RADIATION RETINOPATHY AFTER EXTERNAL-BEAM IRRADIATION: ANALYSIS OF TIME-DOSE FACTORS JAMES T. PARSONS, M.D.,* FRANK J. BOVA, PH.D.,* CONSTANCE R. FITZGERALD, M.D.,+ WILLIAM M. MENDENHALL, M.D.* AND RODNEY R. MILLION, M.D.* *Department of Radiation Oncology, University of Florida College of Medicine; and +Private Practice of Ophthalmology, Gainesville, FL Purpose: To investigate the risk of radiation-induced retinopathy according to total radiation dose and fraction size, based on both retrospective and prospectively collected data. Methods and Materials: Between October 1964 and May 1989, 68 retinae in 64 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 26 years; mean, 9 years; median, 8 years). Results: Twenty-seven eyes in 26 patients developed radiation retinopathy resulting in visual acuity of 20/200 or worse. The mean and median times to the onset of symptoms attributable to retinal ischemia were 2.8 and 2.5 years, respectively. Fourteen of the injured eyes developed rubeosis iridis and/or neovascular glaucoma. Radiation retinopathy was not observed at doses below 45 Gy, but increased steadily in incidence at doses > 45 Gy. In the range of doses between 45 and 55 Gy, there was an increased risk of injury among patients who received doses per fraction of > 1.9 Gy (p = .09). There was also a trend toward increased risk of injury among patients who received chemotherapy (two of two vs. four of ten in the 45-51 Gy range; p = .23). The lowest dose associated with retinopathy was 45 Gy delivered to a diabetic patient by twice-a-day fractionation. The data did not suggest an increased risk of radiation retinopathy with increasing age. Conclusion: The current study suggests the importance of total dose as well as dose per fraction, and adds support to a small body of literature suggesting that patients with diabetes mellitus or who receive chemotherapy are at increased risk of injury. A sigmoid dose-response curve is constructed from our current data and data from the literature. Adverse effects of radiotherapy, Head and neck neoplasms, Injuries to retina. INTRODUfXION Between October 1964 and May 1989, 157 patients un- derwent radiation therapy at the University of Florida for primary extracranial tumors that required irradiation of the eyes or optic nerves. ,411 had a minimum of 3 years of posttreatment follow-up. The current study reports on a subset of these 157 patients consisting of 64 patients in whom 68 retinae were exposed to therapeutic irradiation by techniques that did not produce severe dry-eye com- plications (i.e., cornea1 injury), but which placed the retina at risk of injury. Patients whose entire orbit was irradiated to a high dose and who developed blindness secondary to severe dry eye syndrome were excluded from the current analysis, as were patients in whom only the optic nerves, but not the retina, were irradiated. This study differs from that published in 1983 (23) by including a greater number of patients and longer follow- up. Additionally, during the last 17 years all curatively treated patients in whom the eyes or optic nerves were irradiated had pretreatment and routine follow-up ophthalmologic examinations whether symptomatic or not, thus allowing prospective collection of data regarding radiation injury, as well as early detection and manage- ment of complications. In addition, off-axis dosimetry taken from contours through the level of the eyeball has been routinely performed during the last 10 years, ob- viating the need for retrospective reconstruction of do- simetry in many cases. METHODS AND MATERIALS Patient population Patients were identified for inclusion in the current analysis by a review of the radiation records, simulation films, and portal films of all patients who underwent ir- Reprint requests to: Jarnets T. Parsons, M.D., Department of Radiation Oncology, University of Florida Health Science Cen- ter, P. 0. Box 100385, Gainesville, FL 32610-0385. Accepted for publication 22 April 1994.