Long-term dosing of more than 6 mg/kg conferred the highest cumulative incidence of retinopathy at 15 years.

Hydroxychloroquine retinopathy, an irreversible and vision-threatening complication of long-term use, can be arrested with early detection. To quantify risks associated with weight-based hydroxychloroquine dosing (less than 5 mg/kg, 5 to 6 mg/kg or more than 6 mg/kg) and duration of therapy, researchers analysed pharmacy dispensing records and annual optical coherence tomography screening examinations for 3300 patients (mean age, 58 years) in a large California healthcare system. The most common indications for hydroxychloroquine were rheumatoid arthritis, other arthritides and systemic lupus erythematosus. All included patients had taken hydroxychloroquine for at least  five years.

In total, 81 patients (median treatment duration, nine years) developed hydroxychloroquine retinopathy: 10-year and 15-year cumulative incidences of hydroxychloroquine retinopathy were 2.5% and 8.6%, respectively. Two-thirds of cases were mild. A clear dose-response relation was observed between low, moderate and high hydroxychloroquine doses and 15-year cumulative incidence of retinopathy: 2.7%, 11.4% and 21.6%. Older age (i.e. greater than 55 years) at initiation and chronic kidney disease (i.e. stage 3 or worse) were associated significantly with higher cumulative incidence of hydroxychloroquine retinopathy.

Comment: These results support using the lowest possible dose of hydroxychloroquine; in individual patients, dosing requires balancing the benefits against retinopathy risk and stopping the drug at the earliest signs of retinopathy. Strengths of this study include high capture of exposure and outcome data and low likelihood of misclassification; limitations are lack of information on the visual consequences of hydroxychloroquine retinopathy and data on control of underlying disease at each dose.

Rahul B. Ganatra

Melles RB et al. Hydroxychloroquine dose and risk for incident retinopathy: a cohort study. Ann Intern Med 2023 Jan 17; e-pub (https://doi.org/10.7326/M22-2453).