title: The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.
abstract: OBJECTIVE
  Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques.
  
  
  OBJECTIVE
  To reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug.
  
  
  METHODS
  Retrospective case-control study in an integrated health organization of approximately 3.4 million members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography.
  
  
  METHODS
  Hydroxychloroquine use for at least 5 years.
  
  
  METHODS
  Retinal toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage, as well as statistical measures of risk factors and prevalence.
  
  
  RESULTS
  Real body weight predicted risk better than ideal body weight and was used for all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption (odds ratio, 5.67; 95% CI, 4.14-7.79 for >5.0 mg/kg) and with duration of use (odds ratio, 3.22; 95% CI, 2.20-4.70 for >10 years). For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease (odds ratio, 2.08; 95% CI, 1.44-3.01) and concurrent tamoxifen citrate therapy (odds ratio, 4.59; 95% CI, 2.05-10.27).
  
  
  CONCLUSIONS
  These data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of 5.0 mg/kg of real body weight or less is associated with a low risk for up to 10 years. Knowledge of these data and risk factors should help physicians prescribe hydroxychloroquine in a manner that will minimize the likelihood of vision loss.
authors.affiliation: Kaiser Permanente, Redwood City Medical Center, Redwood City, California.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Melles
authors.affiliation: Byers Eye Institute, Stanford University, Palo Alto, California.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Marmor
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001835:Body Weight; D016022:Case-Control Studies; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012372:ROC Curve; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine