title: Validation of the colour difference plot scoring system analysis of the 103 hexagon multifocal electroretinogram in the evaluation of hydroxychloroquine retinal toxicity.
abstract: OBJECTIVE
  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.
authors.affiliation: Ophthalmology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Gabrielle S
authors.initials: GS
authors.lastname: Graves
authors.forename: Murtaza K
authors.initials: MK
authors.lastname: Adam
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Stepien
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004596:Electroretinography / Q000187:drug effects / Q000379:methods*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012164:Retinal Diseases / Q000139:chemically induced* / Q000175:diagnosis*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000188:drug therapy; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine
keywords: hydroxychloroquine toxicity; multifocal electroretinography; retinal; toxicity; toxicology