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Hydroxychloroquine Dose Associated With Greater Risk of Incident Retinopathy


Patients who took hydroxychloroquine had an overall risk of hydroxychloroquine retinopathy of 8.6% after 15 years.

A higher dose of hydroxychloroquine was associated with a greater risk of incident retinopathy, according to a study published in Annals of Internal Medicine. Overall risk of hydroxychloroquine retinopathy was 8.6% after 15 years in all patients who used the treatment for inflammatory diseases.

Hydroxychloroquine is often used to treat systemic lupus erythematosus and other inflammatory diseases. However, vision-threatening retinopathy is just one of the possible adverse effects of this treatment. This study aimed to estimate the long-term risk of incident hydroxychloroquine retinopathy using the average dose in the first 5 years of use.

Patients from the Kaiser Permanente Northern California (KPNC) integrated health network were included in this study. The database includes spectral domain optical coherence tomography imaging from 2009 on.

Participants who were aged 18 years and older, were enrolled in KPNC, and had started hydroxychloroquine treatment from January 2004 to December 2014 were included in the primary study population. At least 6 months of continuous enrollment in KPNC was required prior to hydroxychloroquine treatment, as was 5 years of continuous enrollment after the start of treatment.

Pharmacy dispensing records were used to assess hydroxychloroquine exposure. The primary study population was classified into 3 body weight–based dosing groups: at most 5, 5 to 6, and more than than 6 mg/kg per day. Patients were included in a dose range if at least 80% of their days were in that dose range.

There were 3325 patients who were included in this study who had started treatment with hydroxychloroquine from 2004 to 2014 and used it for at least 5 years. A total of 65.4% of participants used 5 mg/kg/day or less of hydroxychloroquine, 16.0% used 5 to 6 mg/kg/day, and 18.6% used more than 6 mg/kg/day. The mean age of the participants after 5 years of use was 58 years, 83% were women, and 50% identified as non-Hispanic White.

There were 81 cases of incident hydroxychloroquine retinopathy identified in the population (2.4%), with a median duration of use of 8.9 years (range, 5-16 years). In 10 years, the cumulative incidence of hydroxychloroquine retinopathy was 2.5% and in 15 years it increased to 8.6%, with most cases being mild (69%).

The risk of hydroxychloroquine retinopathy increased for each weight-based dose of the medicine. At 15 years, the cumulative incidences were 2.7% (95% CI, 1.5%-4.8%) in the group who used 5 mg/kg/day or less, 11.4% (95% CI, 4.0%-29.9%) in the group using 5 to 6 mg/kg/day, and 21.6% (95% CI, 14.6% to 31.4%) in the group who received more than 6 mg/kg/day.

A stratified analysis revealed that patients with chronic kidney disease stage 3 or higher and those who were 55 years or older when starting treatment with hydroxychloroquine had a higher cumulative incidence of hydroxychloroquine retinopathy.

There were some limitations to this study. Misclassification of doses could be possible due to nonadherence. Published data had limited information on the functional effect of mild vs moderate vs severe hydroxychloroquine retinopathy.

The researchers concluded that the long-term risk of hydroxychloroquine retinopathy increased in patients who received higher doses of the treatment during the first 5 years of its prescription, with most cases being mild.


Melles RB, Jorge AM, Marmor MF, et al. Hydroxychloroquine dose and risk for incident retinopathy: a cohort study. Ann Intern Med. Published online January 16, 2023. doi:10.7326/M22-2453

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