Retinal Complications in Patients with Systemic Lupus Erythematosus Treated with Antimalarial Drugs

Objective: Hydroxychloroquine (HCQ) and chloroquine (CQ) are key drugs in systemic lupus (SLE) and related diseases. Retinal toxicity remains the most worrisome complication. We studied factors potentially associated with retinal toxicity, using case-control analyses.

Methods: Within our SLE clinic cohort, we identified patients with retinal changes using the Systemic Lupus International Collaborating Clinics Damage Index. We confirmed HCQ/CQ retinopathy with chart review, and selected up to 3 SLE controls for each case, matched by age at SLE diagnosis and SLE duration.

Results: Over an average 12.8 years of followup, within 326 patients exposed to antimalarial drugs, 18 (5.5%) developed retinal toxicity. The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years (maximum 33 yrs). Median HCQ/CQ duration was statistically similar in cases [19 yrs, interquartile range (IQR) 14-20] and controls (16 yrs, IQR 11-22), likely due to our matching on SLE duration. Versus controls, cases tended to have more renal disease (cases 22.2%, controls 14.8%) and were slightly less likely to be white (cases 61.1%, controls 74.1%), but neither variable reached statistical significance. Among patients with retinal toxicity, the number previously exposed to CQ was more than 3 times that in controls.

Conclusion: Just over 5% of patients developed antimalarial retinal complications, over an average of 12.8 years. No cases were detected in the first 5 years of therapy. Past CQ use was more common in cases versus controls. Future studies using larger cohorts are under way to better define the roles of therapy duration, race/ethnicity, and other factors.