For Better HCQ Retinopathy Guidelines, Include Prescribing Physicians

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Guidelines to prevent retinopathy caused by a drug to treat autoimmune disease must be developed jointly by ophthalmologists and prescribing physicians, journal authors say.

Three times in the last 20 years, the American Academy of Ophthalmology has updated guidelines for dosing of hydroxychloroquine (HCQ) and recommendations for detecting retinopathy at the earliest possible stage; as tests for finding asymptomatic HCQ retinopathy have improved the condition had be founder earlier, and the AAO’s limits on safe dosing have declined.

But as noted in a recent editorial in the American Journal of Ophthalmology, “Rethinking the Hydroxychloroquine Dosing and Retinopathy Screening Guidelines,” there was a problem with this process, which led poor uptake of the recommendations: the prescribing physicians who would have to manage the autoimmune disease were left out of the process, “but must live with the ramifications of the guidelines.”

The authors are ophthalmologist David J. Browing, M.D., Ph.D.; rheumatologist Naoto Yokogawa, M.D.; ophthalmologist Paul B. Greenberg, M.D., MPH; and ophthalmologist Elliot Perlman, M.D.

“Hydroxychloroquine is effective in many autoimmune diseases, particularly in patients with systemic lupus erythematosus (SLE),” authors of the new editorial note. “Hydroxychloroquine is recommended to all SLE patients, unless contraindicated, due to the multiple beneficial effects on survival, disease activity, and the risks of organ damage and thromboembolic episodes.”

While there are alternatives to HCQ, these may cost more and have more side effects, the authors said. And, the 2016 guidelines in particular failed to adequately account for the challenge that prescribing physicians face as the obesity epidemic intensifies, and the gap between real body weight and ideal body weight increases.

Thus, prescribing physicians faced with the 2016 update were in a tight spot: if they failed to adhere to the AAO guidelines, they would appear to be ignoring patient safety, when in fact doctors and patients “are making calculated decisions balancing the risks of HCQ retinopathy with damage to other organ systems.”

Early and frequent testing for HCQ retinopathy is still important, the authors write, but finding this condition at the earliest possible stage should be “an important subsidiary goal, not the primary goal.” The mission of the of the prescribing physician managing autoimmune disease and the ophthalmologist should be the same: “controlling systemic disease without endangering vision.”


A prospective study is needed to clarify the point at which retinopathy progresses despite stopping HCQ. Absent those results, the current recommendation to stop HCQ at the first sign of trouble must be reconsidered. New guidelines, which would reflect input from prescribing physicians, would “reflect a more nuanced approach,” and acknowledge that evidence is limited.

The authors pointed to six questions they said need answers to settle current controversies in HCQ dosing:

  • Can dosing be based on blood levels?
  • How does HCQ distribute between adipose tissue (fat) and lean tissue?
  • What are the key indicators at which HCQ retinopathy progresses even if the drug is stopped?
  • What are the relative sensitivities and specificities of tests for HCQ retinopathy?
  • How can renal disease be measured in HCQ dosing?
  • What is the connection between cumulative HCQ dose and HCQ risk?

Prospective studies are needed to answer these questions. In the meantime, specialists who care for patients with autoimmune disease must take part in the AAO committee that revises the next set of guidelines, the authors said. “By acknowledging the complementary roles of prescribers and ophthalmologists, this approach will lead to wider acceptance of guidelines and better care for our patients,” they said.

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