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Hydroxychloroquine and chloroquine retinopathy - recommendations on monitoring

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

  • data have highlighted that hydroxychloroquine retinopathy is more common than previously reported (1,2)
    • the prevalence in long-term users appears to be around 7.5% and depending on dose and duration of therapy can increase to 20-50% after 20 years of therapy. Risk increases for patients taking more than 5mg/kg/day (1). This is important as the only intervention to prevent further damage is stopping the drug. The risk is increased for patients taking more than 5mg/kg/day, those also taking Tamoxifen, and those with renal impairment
      • the retinopathy is manifest as damage to the photoreceptors and subsequent degeneration of the retinal pigment epithelium (RPE) (3)
        • may produce a 'Bull’s eye maculopath'’ and central visual loss
          • is important as the only intervention to prevent further damage is stopping the drug

  • risk is increased for patients taking more than 5mg/kg/day, those also taking tamoxifen, and those with renal impairment (3)
    • most affected patients demonstrate parafoveal toxicity (2-6 degrees from the fovea), some patients may exhibit pericentral toxicity (greater than 7 degrees from the fovea) which necessitates monitoring outside the macula
    • chloroquine retinopathy appears to follow a similar, but more rapid, course when compared to hydroxychloroquine retinopathy

  • Advice (4)
    • recommend that all patients be referred for annual monitoring after five years of therapy and be reviewed annually thereafter whilst on therapy
      • at each monitoring visit, patients should undergo imaging with both spectral-domain optical coherence tomography (SD-OCT) and widefield fundus autofluorescence imaging (FAF)
      • if widefield FAF is not available, FAF can be acquired in several photographic fields to encompass the macula and extra-macular areas

    • patients with abnormalities on either SD-OCT or widefield FAF should undergo central, static, automated visual field testing appropriate to the location of the abnormality seen on SD-OCT or FAF; patients with paracentral defects may benefit from 10-2 visual field testing, and those with paracentral disease may benefit from 30-2 visual field testing
      • patients with structural abnormalities consistent with hydroxychloroquine retinopathy, but with no abnormality identified on repeated visual field testing should undergo multifocal electroretinography

    • monitoring may be started one year after therapy is initiated if additional risk factors exist e.g. very high dose of drug therapy (greater than 5mg/kg/day hydroxychloroquine), concomitant tamoxifen therapy or renal insufficiency (eGFR less than 60ml/min/1.73m2)

    • chloroquine appears to be more retinotoxic than hydroxychloroquine and so we recommend that monitoring begins after one year of therapy for all patients on chloroquine, using the same tests

    • baseline testing for new initiators of hydroxychloroquine or chloroquine is no longer recommended
      • this amendment is supported by recent evidence of a low rate of drug discontinuation as a result of baseline testing (less than 4%)
      • furthermore, it is recognised that a significant proportion of patients discontinue hydroxychloroquine in the first five years of therapy, either due to adverse effects or insufficient clinical response. Adequate monitoring may not be possible with retinal co-pathology
        • may be identified at the first monitoring episode and a discussion with the patient and prescribing physician about the suitability of continued hydroxychloroquine therapy may be arranged
      • is no specific recommendation for patients to arrange annual community optometry assessments, or any specific form of self-assessment, before monitoring commences

    • monitoring
      • may be best incorporated into the hospital eye service via virtual clinics
      • alternatively, they may be commissioned in the community similar to a diabetic retinopathy service
      • results of monitoring should be communicated back to the prescribing doctor, patient and GP as normal, possible or definite hydroxychloroquine retinopathy
      • it is the prescribing doctor's responsibility to ensure their patients are adequately monitored and to act on the results of monitoring
      • a useful aide memoir for these guidelines for hydroxychloroquine is the 5 x 5 rule (ideally keep dosage < 5mg/kg/day and screen after five years of drug use).

Reference:

  • Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA ophthalmology. 2014;132(12):1453-60.
  • Yusuf IH, Foot B, Galloway J, Ardern-Jones MR, Watson SL, Yelf C, et al. The Royal College of Ophthalmologists recommendations on screening for hydroxychloroquine and chloroquine users in the United Kingdom: executive summary. Eye (London, England). 2018;32(7):1168-73.
  • NHS Specialist Pharmacy Service (July 2022). Hydroxychloroquine and chloroquine retinopathy monitoring
  • The Royal College of Ophthalmologists. Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Monitoring Executive Summary. December 2020.

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