We Need to Be Better Prepared for Hydroxychloroquine Retinopathy

From the first discovery of chloroquine by Hans Andersag at Bayer in 1939 and later development of its hydroxyl and less toxic formhydroxychloroquine (HCQ), thesemedicationshave been one of the most abundantly used around the world and have been instrumental in saving countless lives from malaria. Hydroxychloroquine is currently listed in the World Health Organization Model List of EssentialMedicines as a disease-modifying agent for rheumatoid arthritis. Its use is becoming ubiquitous for a variety of autoimmune disorders fromlupus to rheumatoidarthritis andnowfinding itsway into dermatology and oncology.1 There are more than 50 studies evaluating HCQ in various disorders includingmany tumors. With the results of the LUMINA (Lupus in Minorities: Nature vsNurture) trial showing clear benefit ofHCQuse bydecreasing mortality and end organ damage, HCQ use has significantly increased and is being advocated by the rheumatology community with clinical trials reporting its use in 50% of patientswith lupus,with tertiary care centers reporting the rate ofupto90%(BaltimoreLupusCohort;MichelePetri,MD,MPH, Johns Hopkins Hospital, written communication, June 25, 2014). Given the increasing use ofHCQ and retinopathy being the only absolute contraindication for its use, it is more critical than ever to advocate for screening, detection, and prevention of retinopathy. Of note, most of these screenings are not performed by retina specialists but by general ophthalmologists.2 The American Academy of Ophthalmology recently issuedrevisedguidelines includingtherecommendationofmore sensitive tests suchasmultifocal electroretinography, spectraldomain optical coherence tomography, and fundus autofluorescence. Although advanced screening is not recommended until 5 years of receivingHCQ, considering the number of patients receiving themedication and the actual practice of performing those tests everyyear adds significant cost to theoverall health care system.2 In an article in JAMA Ophthalmology, Melles and Marmor3 suggest that approximately 350 000 patients in theUnitedStates should receiveanannual eye screeningwhenapplying the current guidelines.However, thatnumbermaybemuchhigher ifweadd the currentuse inbothadult and juvenile rheumatoid arthritis, not to mention the newly found use in oncology, where it may end up being used in higher than normal doses, and in some cases for maintenance, resulting in high cumulative doses.4 Melles and Marmor3 report retinopathy in 7.5% of longterm HCQ users screened with modern techniques, which is about 3 times higher than previous estimates. Those previous estimates had been primarily based on clinical examination and visual fields. Current widespread presence and use of optical coherence tomography as a sensitive and reproducible test,whichevenallowsexact anatomical placementof follow-up scans, may prove to be more sensitive and allow detection of changes well before bull’s-eye maculopathy has developed. Suchprecise investigation of the retinalmorphology does not, however, make functional tests obsolete since a recent studybyMarmorandMelles5 suggests thatvisual field loss can actually be a more sensitive marker than the loss of the ellipsoid zone on optical coherence tomography. There is extensive discussion in the literature (comprehensively summarized byMelles andMarmor3) about the use of ideal and real bodyweight.Within the rheumatology community, there may be a new drive to guide the dose based on blood levels, rather thanbodyweight. Insteadof using it as an adjunct, it should be a primary method to achieve a steady state, which would address both compliance and overdosing inhigh-riskpatients.Mostof thediscussionaboutbodyweight is trying to find a balance between the safety and efficacy of HCQ, but to our knowledge, no randomized studies have shown that dosing based on either ideal or real bodyweight is superior for thedisease itself.The retrospective studyofMelles andMarmor3 suggests that the real bodyweight is abetter predictor of toxic effects but not essentially better at striking the best balance between safety and efficacy. How do we deal as ophthalmologists with HCQ being increasingly used and finding new indications? We need to acknowledge thatHCQ reducesmortality anddecreases end organ damage in lupus6 and need to be prepared that HCQ will Related article page 1453 Research Original Investigation Toxic RetinopathyWith Hydroxychloroquine Therapy