Hydroxychloroquine And Chloroquine Screening (2016 AAO Recommendations)

Plaquenil toxicity 1.jpg

The American Academy of Ophthalmology released an updated set of screening recommendations for hydroxychloroquine (Plaquenil) and chloroquine to account for the many studies that have shown the effects of these medications on the retina (1).  It succinctly makes the case for screening, and outlines the evidence for screening methods and parameters to know for screening.

Because this information is pretty important (2), I wanted to highlight some of the key points made by the publication.  I’m sure that this may continue to change and evolve the more we learn; but here are my conclusions:

  • Because of early detection, bull’s-eye maculopathy is not as frequently seen.  We now know that bull’s-eye maculopathy is a late finding and may be associated with vision loss.
  • Asians have a slightly different clinical presentation (3-4).  Several recent studies have shown that instead of the classic perifoveal changes typical of hydroxychloroquine toxicity, Asians with retinal toxicity have a more peripheral pattern.
  • The dose risk is calculated by REAL weight.  Previous recommendations were based on ideal body weight, which is calculated solely on patient age, height, and sex (5).  This apparently resulted in overdosing of thin patients.  Thus, the patient’s real weight is now recommended as the basis for calculating the daily dose per weight (in kg).
  • Doses ≥ 5 mg/kg/day (real weight) of hydroxychloroquine (2.3 mg/kg/day of chloroquine) are associated with higher risk of toxicity.  Doses lower than 5 mg/kg/day have low risk (< 1% for the first 5 years, and below 2% between 5-10 years of use).
  • The longer you use the medication, the higher the risk of toxicity.  After 20 years of use the risk of toxicity is around 20%.  For people using the medication for more than 20 years who do not have any retinal toxicity, the risk of developing toxicity in the next year is around 4%.
  • There are some other risk factors that may increase the risk for toxicity besides dose and duration of use.  These include concurrent renal disease, tamoxifen use, and pre-existing retinal disease.

How To Screen

Baseline Exam

A comprehensive ophthalmology exam should be performed within 1 year of starting hydroxychloroquine or chloroquine.  Visual fields and SD-OCT are not necessary for baseline measurements unless there is pre-existing retinal pathology that needs to be documented.

Annual Screening Exams

These screening exams should start after 5 years of use (prior to then screening exams are not necessary).

  • Screening exams should consist of a comprehensive ophthalmology exam, automated perimetry (10-2, 24-2 or 30-2 in Asians), and SD-OCT of the macula.
  • Optional testing includes fundus autofluorescence and multifocal ERG.

Unproven or Unnecessary Screening Tests

  • Amsler grid
  • Fundus examination/photography:  visible changes to the macula happen late in the disease course.  While it is still prudent to consider a dilated fundus examination for other reasons, it alone is not sufficient for screening.
  • Time-Domain OCT
  • Fluorescein angiography
  • Full-field ERG
  • Color vision
  • EOG

References and Additional Reading

Image credit:  http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/hydroxychloroquine-toxicity/plaquenil-fundus-OD-LRG.jpg

  1. Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF, for the American Academy of Ophthalmology.  Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision).  Ophthalmology 2016;123:1386-1394.
  2. Melles RB, Marmor MF.  The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.  JAMA Ophthalmol 2014;132:1453-60.
  3. Melles RB, Marmor MF.  Pericentral retinopathy and racial differences in hydroxychloroquine toxicity.  Ophthalmology 2015;122:110-6.
  4. Lee DH, Melles RB, Joe SG, et al.  Pericentral hydroxychloroquine retinopathy in Korean patients.  Ophthalmology 2015;122:1252-6.
  5. Marmor MF, Keller U, Lai TY, et al.  Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.  Ophthalmology 2011;118:415-22.

Are there any other important points that should be noted in regards to hydroxychloroquine screening?  Do you have any tips to help remember this information better?  Leave a comment or contact us!