title: Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease.
abstract: OBJECTIVE
  To evaluate retinal toxicity in patients treated with high-dose hydroxychloroquine (HCQ) (Plaquenil, Sanofi Pharmaceuticals) for chronic graft-versus-host disease (GVHD).
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Twelve patients with chronic GVHD treated with 800 mg/day HCQ between June 2005 and December 2010.
  
  
  METHODS
  Patients in this study underwent ophthalmologic examination yearly and ancillary studies including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG). Evidence of HCQ toxicity was determined by the presence of scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, and confirmed by at least 1 objective test including SD-OCT or mfERG.
  
  
  RESULTS
  Of the 12 patients, 7 were male and 5 were female. Mean age was 49 years. Mean best corrected visual acuity at baseline was 20/25 and remained 20/25 at final follow-up. Median duration of HCQ treatment was 22.8 months. Median adjusted daily dosage was 11.5 mg/kg/day. Seven patients developed vortex keratopathy. No signs of pigmentary retinopathy or bull's-eye maculopathy were found in any of the patients. Three patients developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG. Retinal structure measured by SD-OCT was abnormal in 2 of the 3 patients with retinal toxicity. Colour vision measured by Ishihara plates, as well as by 100 Hue colour test, was abnormal in 2 of the 3 patients with retinal toxicity.
  
  
  CONCLUSIONS
  High-dose HCQ in patients with GVHD was associated with higher incidence and earlier development of retinal toxicity.
authors.affiliation: Department of Ophthalmology, Eye Care Centre, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada?>. Electronic address: edunavajas@gmail.com.
authors.forename: Eduardo V
authors.initials: EV
authors.lastname: Navajas
authors.affiliation: Department of Ophthalmology and Vision Sciences?>
authors.forename: Hatem
authors.initials: H
authors.lastname: Krema
authors.affiliation: Department of Ophthalmology and Vision Sciences?>
authors.forename: Dena S
authors.initials: DS
authors.lastname: Hammoudi
authors.affiliation: Allogeneic Blood and Marrow Transplant Service, Princess Margaret Hospital, University of Toronto.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Department of Ophthalmology and Vision Sciences?>
authors.forename: E Rand
authors.initials: ER
authors.lastname: Simpson
authors.affiliation: Department of Ophthalmology and Vision Sciences, Saint Michael's Hospital, University of Toronto, Toronto, Ont.
authors.forename: Shelley
authors.initials: S
authors.lastname: Boyd
authors.affiliation: Department of Ophthalmology and Vision Sciences?>
authors.forename: Michael
authors.initials: M
authors.lastname: Easterbrook
mesh_terms: D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage / Q000633:toxicity*; D002908:Chronic Disease; D003117:Color Vision Defects / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000633:toxicity*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D012607:Scotoma / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000187:drug effects; D058609:Visual Field Tests
chemical_list: D000962:Antimalarials; D006886:Hydroxychloroquine