The recent editorial by Browning brings welcome attention to the ophthalmologist’s role in screening for hydroxychloroquine (HCQ) toxicity and the need for careful dosing. However, we are concerned that it perpetuates incorrect information and omits important new evidence.
The concept that ideal body weight should be used to guide HCQ therapy comes from animal studies of very high dosing (primarily in rats) by McChesney that have been cited by Browning and others to suggest that HCQ is not stored in fat. Actually, McChesney’s paper states that “…the concentrations [of HCQ] in skin and fat were just below those of muscle,” indicating that the drug is stored to a similar level in all of these tissues. McChesney also reported that the distribution of chloroquine in monkeys is essentially equivalent in muscle, skin, and fat. We are not aware of any published evidence that supports the notion that obesity is a risk factor for HCQ retinopathy in humans. In fact, our study of 2361 long-term users of HCQ demonstrated that obese patients have a slightly lower risk of toxicity, and that real body weight is more predictive of retinopathy than ideal weight over the full range of body mass index (BMI) from 15 (underweight) to 35 (obese). Moreover, a prospective study of 300 patients showed that regular body weight, but not ideal body weight, correlates with blood levels of HCQ. Using real weight is simpler than performing unnecessary ideal body weight calculations, and we strongly urge that patients stay below a daily dose of 5 mg/kg.
The editorial also fails to alert readers to key information, including the recent publication of updated 2016 American Academic of Ophthalmology (AAO) recommendations for screening HCQ retinopathy. This document emphasizes the importance of daily dose by weight (<5 mg/kg real weight) and demonstrates how the risk rises dramatically with higher doses and prolonged usage of the drug. Beyond dose and duration, the only proven risk factors for toxicity are renal disease and concurrent usage of tamoxifen, so few patients are at “high risk” at the time they begin HCQ. Thus, there is little reason to ignore the recommendation that annual screening can be deferred for 5 years in most patients. Of greater importance, ophthalmologists should be informed about racial differences in the pattern of HCQ toxicity. Asian patients typically show early damage outside the central macula (near the arcades) and can develop serious toxicity before it would be recognized by tests that focus only on the parafovea (10-2 fields or central macular OCT). Wider fields and imaging studies are needed for these patients.
The AAO guidelines define a new standard of care. Routine testing should in general include both automated visual fields (most sensitive) and spectral-domain optical coherence tomography (most specific), along with other confirming modalities, where available.