Long-term low-dose hydroxychloroquine use associated with low risk for retinopathy

A higher hydroxychloroquine dose was associated with progressively greater risk.

Overall risk for retinopathy was low among patients who received hydroxychloroquine for five or more years with guideline-recommended serial retinopathy screening, with most documented cases being mild, a study found.

Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus as well as for other inflammatory diseases but can cause hydroxychloroquine retinopathy, which can lead to permanent vision loss. Researchers studied 3,325 adults who received hydroxychloroquine for five or more years between 2004 and 2020 to define the long-term risk for hydroxychloroquine retinopathy, as well as the degree to which average hydroxychloroquine dose within the first five years of treatment predicts risk. The authors used pharmacy and health records to review hydroxychloroquine dosing and reviewed annual optical scans over time with spectral domain optical coherence tomography (SD-OCT) to find evidence of retinopathy. Any cases were categorized as mild, moderate, or severe. Risk for developing retinopathy after 15 years was then estimated according to average dosing levels of hydroxychloroquine during the first five years of treatment (>6, 5 to 6, or ≤5 mg/kg per day). Results were published Jan. 17 by Annals of Internal Medicine.

In the study, 81 participants developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% after 10 and 15 years, respectively. The risk was greater for those who received a higher dose during the first five years of treatment. The cumulative incidences of retinopathy at 15 years were 21.6% for doses of greater than 6 mg/kg per day, 11.4% for doses of 5 to 6 mg/kg per day, and 2.7% for doses of 5 mg/kg per day or lower. The corresponding risks for moderate to severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively.

The researchers noted that regular screening can identify retinopathy at an early and treatable stage. Risk estimates, combined with the excellent intra-rater reliability of retinopathy outcomes per SD-OCT (κ agreement, 0.80) in the study, suggest that the true incidence of retinopathy is higher than reported before the use of routine screening with SD-OCT, they said.

“Fortunately, we observed that severe bull's-eye retinopathy was rare with routine screening,” the authors continued. “Because most mild and moderate cases are typically asymptomatic and unlikely to progress to severe retinopathy after hydroxychloroquine is withdrawn, our findings suggest that, under current screening recommendations and dosing patterns, loss of visual acuity from hydroxychloroquine retinopathy should be rare.”