title: Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.
abstract: OBJECTIVE
  To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer.
  
  
  METHODS
  Retrospective observational case series.
  
  
  METHODS
  Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG).
  
  
  RESULTS
  Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss.
  
  
  CONCLUSIONS
  These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision.
authors.affiliation: Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California. Electronic address: lbleung@stanford.edu.
authors.forename: Loh-Shan B
authors.initials: LS
authors.lastname: Leung
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University/Stanford Cancer Institute, Palo Alto, California.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Neal
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University/Stanford Cancer Institute, Palo Alto, California.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.affiliation: Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Marmor
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004596:Electroretinography; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000175:diagnosis; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D006886:Hydroxychloroquine; D000069347:Erlotinib Hydrochloride