The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal

Ophthalmology. 2003 Jul;110(7):1321-6. doi: 10.1016/S0161-6420(03)00409-3.


Purpose: To define the risk of hydroxychloroquine (HCQ)-related retinal toxicity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who are receiving recommended dosages of the drug (< or =6.5 mg/kg/day).

Design: Prospective cohort study, from 1985 to 2000.

Participants: Greek patients with RA (n = 335) and SLE (n = 191) treated with HCQ, 400 of whom had completed at least 6 years of treatment.

Methods: Ophthalmologic evaluation was performed every 6 months from 1985 to 1995, and yearly thereafter. This consisted of best-corrected visual acuity, color vision testing, static central visual field testing, fundoscopy, electroretinography, and fluorescein angiography, when indicated.

Main outcome measures: Fundus lesions attributed to HCQ.

Results: No HCQ retinal toxicity was noted in any of the 526 patients during the first 6 years of treatment. Two (3.4%) of the first 58 long-term (>6 years) treated patients developed HCQ-related maculopathy at 8 and 6.5 years of treatment, despite regular ophthalmologic evaluation. On follow-up 7 and 9 years after cessation of HCQ treatment, both patients had stable eye disease. No HCQ retinal toxicity was observed in the subsequent 342 patients who were treated for >6 years. Overall, the incidence of HCQ-related retinopathy in 400 patients who were treated with recommended dosages of the drug for a mean of 8.7 years was reduced to 0.5%.

Conclusions: After a baseline ophthalmic examination to confirm the absence of preexisting fundus pathology, patients with normal renal function may receive HCQ at a maximal daily dosage of 6.5 mg/kg and continue safely for 6 years. However, annual screening is recommended in patients who have taken the drug, even in recommended doses, for >6 years.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Cohort Studies
  • Color Perception
  • Electroretinography
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Greece / epidemiology
  • Humans
  • Hydroxychloroquine / adverse effects
  • Hydroxychloroquine / therapeutic use*
  • Incidence
  • Lupus Erythematosus, Systemic / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Retina / drug effects
  • Retina / pathology
  • Retinal Diseases / chemically induced
  • Retinal Diseases / diagnosis
  • Retinal Diseases / epidemiology*
  • Risk Factors
  • Vision Tests
  • Visual Acuity
  • Visual Fields


  • Antirheumatic Agents
  • Hydroxychloroquine