Validation of the colour difference plot scoring system analysis of the 103 hexagon multifocal electroretinogram in the evaluation of hydroxychloroquine retinal toxicity

Acta Ophthalmol. 2014 Aug;92(5):e377-81. doi: 10.1111/aos.12353. Epub 2014 Feb 7.


Purpose: To evaluate sensitivity, specificity and reproducibility of colour difference plot analysis (CDPA) of 103 hexagon multifocal electroretinogram (mfERG) in detecting established hydroxychloroquine (HCQ) retinal toxicity.

Methods: Twenty-three patients taking HCQ were divided into those with and without retinal toxicity and were compared with a control group without retinal disease and not taking HCQ. CDPA with two masked examiners was performed using age-corrected mfERG responses in the central ring (Rc ; 0-5.5 degrees from fixation) and paracentral ring (Rp ; 5.5-11 degrees from fixation). An abnormal ring was defined as containing any hexagons with a difference in two or more standard deviations from normal (colour blue or black).

Results: Categorical analysis (ring involvement or not) showed Rc had 83% sensitivity and 93% specificity. Rp had 89% sensitivity and 82% specificity. Requiring abnormal hexagons in both Rc and Rp yielded sensitivity and specificity of 83% and 95%, respectively. If required in only one ring, they were 89% and 80%, respectively. In this population, there was complete agreement in identifying toxicity when comparing CDPA using Rp with ring ratio analysis using R5/R4 P1 ring responses (89% sensitivity and 95% specificity). Continuous analysis of CDPA with receiver operating characteristic analysis showed optimized detection (83% sensitivity and 96% specificity) when ≥4 abnormal hexagons were present anywhere within the Rp ring outline. Intergrader agreement and reproducibility were good.

Conclusions: Colour difference plot analysis had sensitivity and specificity that approached that of ring ratio analysis of R5/R4 P₁ responses. Ease of implementation and reproducibility are notable advantages of CDPA.

Keywords: hydroxychloroquine toxicity; multifocal electroretinography; retinal; toxicity; toxicology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy
  • Electroretinography / drug effects
  • Electroretinography / methods*
  • False Positive Reactions
  • Female
  • Humans
  • Hydroxychloroquine / adverse effects*
  • Lupus Erythematosus, Systemic / drug therapy
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • ROC Curve
  • Reproducibility of Results
  • Retinal Diseases / chemically induced*
  • Retinal Diseases / diagnosis*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sjogren's Syndrome / drug therapy
  • Young Adult


  • Antirheumatic Agents
  • Hydroxychloroquine