title: Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging.
abstract: OBJECTIVE
  Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment.
  
  
  OBJECTIVE
  To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation.
  
  
  METHODS
  A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California.
  
  
  METHODS
  Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles.
  
  
  METHODS
  Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects.
  
  
  METHODS
  Retinal toxic effects.
  
  
  RESULTS
  Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients).
  
  
  CONCLUSIONS
  Preservation of the external limiting membrane carries a positive prognostic value in hydroxychloroquine toxic effects because it may be associated with regeneration of the photoreceptor layer and with potential functional visual improvement on static perimetry. The patterns of abnormal FAF persist despite cessation of the medication, with enlargement of the total area of abnormal FAF being the hallmark of severe toxic effects. Relative foveal resistance in hydroxychloroquine toxic effects was supported by this case series. These findings emphasize the importance of early detection and the need for correlating clinical observations with multimodal imaging, particularly FAF and spectral domain optical coherence tomography.
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Mihai
authors.initials: M
authors.lastname: Mititelu
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Wong
authors.forename: Marie
authors.initials: M
authors.lastname: Brenner
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryar
authors.forename: Lee M
authors.initials: LM
authors.lastname: Jampol
authors.forename: Amani A
authors.initials: AA
authors.lastname: Fawzi
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D012160:Retina / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000503:physiopathology; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D028761:Withholding Treatment
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine