Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography

Am J Ophthalmol. 2007 May;143(5):801-809. doi: 10.1016/j.ajo.2006.12.042. Epub 2007 Mar 6.


Purpose: To assess decreased retinal function associated with high cumulative doses of hydroxychloroquine using multifocal electroretinography (mfERG).

Design: Retrospective cross-sectional study.

Methods: Sixty-two patients referred for evaluation of hydroxychloroquine retinal toxicity. Controls were 67 normal eyes of 67 patients referred for a variety of conditions in the other eye. Visual symptoms, duration of treatment, daily hydroxychloroquine dose (milligrams and milligrams per kilogram), cumulative dose, condition for which the drug was taken, visual acuity, retinal examination, visual fields, and mfERG amplitude. The average mfERG amplitude was calculated for five concentric rings. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the other rings (e.g., R(1)/R(2), R(1)/R(3)) were compared with limits derived from control eyes.

Results: The incidence of characteristic mfERG abnormalities in patients referred for evaluation with cumulative hydroxychloroquine doses of more than 1250 g was nearly 50%. It was 2.8 times that found in patients with cumulative doses less than 1250 g. Significant abnormalities were seen with cumulative doses as low as 400 g. The mfERG abnormality most commonly detected was an increased R(1)/R(2) ratio. Cumulative dose was more predictive of mfERG abnormalities than daily dose (either in milligrams or milligrams per kilogram) or duration of treatment.

Conclusions: Functional testing of the retina with mfERG shows locally decreased retinal function in a large fraction of patients referred for evaluation who have taken high cumulative doses of hydroxychloroquine. A prudent mfERG testing strategy is proposed.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy
  • Child
  • Cross-Sectional Studies
  • Electroretinography / methods*
  • Female
  • Humans
  • Hydroxychloroquine / adverse effects*
  • Lupus Erythematosus, Systemic / drug therapy
  • Male
  • Middle Aged
  • Retina / drug effects*
  • Retina / pathology
  • Retinal Diseases / chemically induced*
  • Retinal Diseases / diagnosis*
  • Retrospective Studies
  • Sjogren's Syndrome / drug therapy
  • Visual Acuity
  • Visual Fields


  • Antirheumatic Agents
  • Hydroxychloroquine