title: [Severe chloroquine- and hydroxychloroquine-induced retinopathy].
abstract: BACKGROUND
  Antimalarial drug-induced retinopathy was first described in the 1950s. Irreversible retinal damage still occurs 50 years later, despite knowledge of the phenomenon. This raises several questions: How aware are physicians of this problem and do they inform their patients? What efficient prevention strategies should be advocated and what are the legal aspects? We present four cases of severe chloroquine- and hydroxychloroquine-induced retinopathy to try to understand what led to these situations.
  
  
  METHODS
  The fist case, a male patient born in 1956, had chloroquine therapy for lupus initiated in 1987, at a dose ranging from 3 to 6 mg/kg per day. In 1992, no toxicity was clinically or electrophysiologically noted. In 1997, macular abnormalities were diagnosed; chloroquine treatment was nevertheless continued. In 2002, the electroretinogram and central visual field examinations were abnormal. Chloroquine treatment was discontinued. In 2005, abnormalities of full-field and multifocal electroretinograms, electro-oculogram, color vision, and visual field confirmed the maculopathy. The second case, a female patient, born in 1956, had chloroquine therapy for rheumatoid arthritis beginning in 1993, at a dose of 5 mg/kg per day. In 1999, 2000, and 2001, electroretinograms were reported as normal. Clinical maculopathy occurred in 2003 and treatment was continued. In January 2004, the central visual field was found abnormal; treatment was discontinued in July 2004. The third case, a female patient born in 1931, had chloroquine therapy for malaria prevention initiated in 1975, at a dose of 1.7 mg/kg per day. No exams were performed after 1983. In 2001, she complained of a left unilateral vision loss. Bilateral maculopathy was clinically found, and confirmed by full-field and multifocal electroretinograms. The fourth case, a female patient born in 1944, had hydroxychloroquine therapy for lupus initiated in 1982 at a dose of 6.9 mg/kg per day. In 2000 and 2002, full-field electroretinograms were reported as normal despite low amplitudes. In 2004, clinical examination was normal, whereas electroretinogram, electro-oculogram, color vision, and central visual field examinations proved severe damage; the treatment was discontinued.
  
  
  CONCLUSIONS
  Retinal damage in these cases was caused by several factors. Treatment was not stopped despite clinically obvious maculopathy in cases 1 and 2. In case 3, no ophthalmologic examinations were performed between 1983 and 2001. In case 4, despite a high cumulative dose, therapy was not discontinued, as also seen in cases 1 and 2, in which ophthalmologic monitoring was not increased. Higher doses than the maximal recommended daily dose occurred in cases 1, 2, and 4.
  
  
  CONCLUSIONS
  Antimalarial drug therapy still requires intensive monitoring to avoid severe retinal damage that can lead to legal blindness. Appropriate examinations should be performed regularly in order to decide whether to taper or stop when damage is still mild, preclinical, or reversible.
authors.affiliation: Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France. isabelle.ingster-moati@lrb.ap-hop-paris.fr
authors.forename: I
authors.initials: I
authors.lastname: Ingster-Moati
authors.forename: E
authors.initials: E
authors.lastname: Bui Quoc
authors.forename: M
authors.initials: M
authors.lastname: Crochet
authors.forename: C
authors.initials: C
authors.lastname: Orssaud
authors.forename: J-L
authors.initials: JL
authors.lastname: Dufier
authors.forename: O
authors.initials: O
authors.lastname: Roche
mesh_terms: D000368:Aged; D000962:Antimalarials / Q000009:adverse effects*; D002738:Chloroquine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012164:Retinal Diseases / Q000139:chemically induced*; D012720:Severity of Illness Index
chemical_list: D000962:Antimalarials; D006886:Hydroxychloroquine; D002738:Chloroquine