title: Preventing radiation retinopathy with hyperfractionation.
abstract: OBJECTIVE
  The purpose of this study was to determine factors associated with the development of radiation retinopathy in a large series of patients with head-and-neck cancer. In particular, we addressed whether the use of hyperfractionated radiation therapy was effective in reducing the risk of retinopathy.
  
  
  METHODS
  One hundred eighty-six patients received a significant dose to the retina as part of curative radiotherapy. Primary sites included: nasopharynx, 46; paranasal sinus, 64; nasal cavity, 69; and palate, 7. Prescription doses varied depending on primary site and histology. Hyperfractionated (twice-daily) radiation was delivered to 42% of the patients in this study, typically at 1.10 to 1.20 Gy per fraction. The remainder were treated once-daily. Retinal doses were determined from computerized dosimetry plans when available. For all other patients, retinal doses were retrospectively calculated using reconstructed off-axis dosimetry taken from contours through the center of the globes. Retinal dose was defined as the minimum dose received by at least 25% of the globe. The median retinal dose was 56.85 Gy. Patients were followed for a median of 7.6 years.
  
  
  RESULTS
  Thirty-one eyes in 30 patients developed radiation retinopathy, resulting in monocular blindness in 25, bilateral blindness in 1, and decreased visual acuity in 4. The median time to the diagnosis of retinopathy was 2.6 years (range, 11 months to 5.3 years). The actuarial incidence of developing radiation retinopathy was 20% at both 5 and 10 years. The incidence of developing ipsilateral blindness due to retinopathy was 16% at 5 years and 17% at 10 years. Site-specific incidences varied considerably, with ethmoid sinus (9 of 25, 36%), nasal cavity (13 of 69, 19%), and maxillary sinus (6 of 35, 17%) being the most common sites associated with radiation retinopathy. Three of 72 patients (4%) receiving retinal doses less than 50 Gy developed retinopathy. Higher retinal doses resulted in a steady increase in the incidence of retinopathy, with 25 of the 30 cases occurring after 60 Gy or more. Of the patients receiving more than 50 Gy to the retina, hyperfractionation was associated with a significantly lower incidence of radiation retinopathy (37% vs. 13%; p = 0.0037). On multivariate analysis, retinal dose (p < 0.0001), fractionation schedule (p = 0.0003), age (p = 0.0365), and prolonged overall treatment time (p = 0.0213) were significant predictors of radiation retinopathy.
  
  
  CONCLUSIONS
  The incidence of ipsilateral radiation retinopathy after treatment of nasal cavity/paranasal tumors is 20% at 5 and 10 years. Retinal dose and fractionation schedule are the strongest predictors of retinopathy. Hyperfractionated radiotherapy is associated with a significant reduction in the incidence of radiation retinopathy, especially when the retina receives more than 50 Gy.
authors.affiliation: Department of Radiation Oncology, University of Florida College of Medicine, Health Science Center, 2000 SW Archer Road, Gainesville, FL 32608, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Monroe
authors.forename: Niranjan
authors.initials: N
authors.lastname: Bhandare
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001766:Blindness / Q000209:etiology; D002648:Child; D019583:Dose Fractionation, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy; D009669:Nose Neoplasms / Q000532:radiotherapy; D010157:Palatal Neoplasms / Q000532:radiotherapy; D010255:Paranasal Sinus Neoplasms / Q000532:radiotherapy; D011832:Radiation Injuries / Q000150:complications / Q000517:prevention & control*; D012160:Retina / Q000528:radiation effects*; D012164:Retinal Diseases / Q000209:etiology / Q000517:prevention & control*; D014786:Vision Disorders / Q000209:etiology