title: Subjective and objective screening tests for hydroxychloroquine toxicity.
abstract: OBJECTIVE
  To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing.
  
  
  METHODS
  Prospective, single-center, case control study.
  
  
  METHODS
  Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration.
  
  
  METHODS
  Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected.
  
  
  METHODS
  We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group.
  
  
  RESULTS
  Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing.
  
  
  CONCLUSIONS
  Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests.
authors.affiliation: Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: cukrasc@nei.nih.gov.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cukras
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Huynh
authors.affiliation: Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Vitale
authors.affiliation: Office of the Scientific Director, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
authors.affiliation: Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Fredrick L
authors.initials: FL
authors.lastname: Ferris
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland; Section for Translational Research in Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000633:toxicity*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D016022:Case-Control Studies; D003941:Diagnostic Techniques, Ophthalmological; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D006886:Hydroxychloroquine / Q000633:toxicity*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012164:Retinal Diseases / Q000139:chemically induced / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000187:drug effects; D014794:Visual Fields / Q000187:drug effects
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine