Chloroquine and Hydroxychloroquine Toxicity

We have read with interest the article on retinal toxic reaction secondary to chloroquine and hydroxychloroquine use, finding it to be both comprehensive and informative.¹ Of particular interest were the data on drug dosage calculation for actual and lean body weight and the use of novel methods of imaging to identify signs of a toxic reaction. The article prompted us to review our patients with a diagnosis of a chloroquine or hydroxychloroquine toxic reaction and the relevant risk factors in these cases (Table).

All our patients were treated with quinolones for either discoid lupus erythematosus or rheumatoid arthritis. All 3 patients presented with difficulty reading secondary to either reduced near acuity and/or paracentral scotomas. Two of the patients also complained of reduced color vision. On examination, cornea verticillata was seen in 1 patient and all 3 had a bull's eye maculopathy. Spectral-domain ocular coherence tomography (OCT) imaging demonstrated paracentral loss of the photoreceptor layer and the outer highly reflective band, and rings of reduced and increased fundus autofluorescence were identified on blue autofluorescence imaging.

Two of the 3 patients were taking a “toxic” quinolone dose according to lean body weight calculations, with the remaining patient being close to the “toxic” dose when using lean body weight. None of the patients were obese and the body mass index ranged from 22 to 25 (calculated as weight in kilograms divided by height in meters squared).

Our small series supports the conclusions of the article by Michaelides et al.¹ Growing evidence supports quinolone dosage based on lean body weight in all patients and adjustment of the daily dosage, using the range of commercially available preparations, to keep the daily dosage within the “safe” range. There is also increasing evidence to support the use of fundus autofluorescence and spectral-domain OCT to identify signs of a retinal toxic reaction as soon as possible. Early diagnosis is particularly important given the risk of slow progression after administration of the drug is stopped. In 2 of our 3 patients, visual difficulties progressed during follow-up, which continued for a mean of 4.5 years. This is in keeping with the findings of the Michaelides et al article in which progression was noted in 6 of 10 patients and up to a maximum of 7 years after stopping treatment.¹

The recently revised American Academy of Ophthalmology guidelines advocate screening and recommend the use of at least 1 investigation such as spectral-domain OCT, fundus autofluorescence, and/or multifocal electroretinography for patients taking chloroquine or hydroxychloroquine for longer than 5 years.² By contrast, the current Royal College of Ophthalmologists guidelines from October 2009 do not advocate screening but recommend the use of Amsler chart and central visual field testing to detect early disease after referral of symptomatic patients to an ophthalmologist.³ For patients who have been undergoing continuous treatment for more than 5 years, an individual arrangement with the local ophthalmologist is advocated.³ The data from the Michaelides et al article and our series would support screening for these patients with greater use of autofluorescence imaging and spectral-domain OCT to identify early disease.