ImportanceHydroxychloroquine sulfate ...can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull’s eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques.ObjectivesTo reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug.ResultsReal body weight predicted risk. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption and with duration of use. For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease and concurrent tamoxifen citrate therapy.Conclusions and RelevanceThese data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of 5.0 mg/kg of real body weight or less is associated with a low risk for up to 10 years.