Risk of hydroxychloroquine retinopathy increases with longer use and higher dosage

1. In this retrospective cohort study, the incidence of hydroxychloroquine retinopathy was 2.5% at 10 years, increasing to 8.6% at 15 years in adults with rheumatic or dermatological diseases. 

2. The risk of hydroxychloroquine retinopathy increased to 21.6% after 15 years of use for those receiving greater than 6mh/kg per day compared to 2.7% at 5mg/kg per day or lower.

Evidence Rating Level: 2 (Good)

Study Rundown: Hydroxychloroquine is a disease-modifying anti-rheumatic drug (DMARD) commonly used to treat rheumatological or dermatological conditions such as lupus and rheumatoid arthritis. However, a major concern with its long-term use is the development of hydroxychloroquine retinopathy, which can be vision-threatening. For this reason, screening is often carried out after five years of use and guidelines often recommend keeping doses low to prevent its development. Notably, large studies with available longitudinal follow-up to characterize its specific incidence and risk profile are not yet available. The purpose of this study was to investigate the risk of hydroxychloroquine retinopathy with long-term hydroxychloroquine use and to characterize the dose-response risk. Results of the study found that the incidence of hydroxychloroquine retinopathy was 2.4% after a median of 8.9 years of use, and 8.6% after 15 years. The incidence also increased with increasing doses and was higher among participants with preexisting advanced chronic kidney disease as well as those who were older at the time of starting on hydroxychloroquine. Although there could have been misclassification of exposure due to medication non-adherence, this study offers several strengths due to its long duration of follow-up, large sample size, and incorporation of expert ophthalmologists to grade SD-OCT findings with high interrater reliability.

Click to read the study in AIM

In-Depth [retrospective cohort study]: This study was a retrospective cohort study of adults who received hydroxychloroquine treatment for rheumatic or dermatological reasons to evaluate the long-term risk profile for incident retinopathy. Persons older than 18 years old within the Kaiser Permanente Northern California (KPNC) health system who have been registered within KPNC for at least six months prior to initiating hydroxychloroquine with at least five years of continuous involvement with KPNC thereafter were included in the review (n=3,325). The primary outcome of interest was retinopathy diagnosed on spectral domain optical coherence tomography (SD-OCT). Results of the primary analysis found that 2.4% of participants developed retinopathy (n=81) after a median hydroxychloroquine use of 8.9 years. A total of 69% of cases that developed retinopathy were mild (n=56), 21% were moderate (n=17), and 12% were severe (n=8). After 20 years of initiation of hydroxychloroquine, 11.5% of participants developed retinopathy from either hydroxychloroquine or non-hydroxychloroquine retinopathy. Overall, the incidence of retinopathy increased with higher weight-based doses, among those with advanced chronic kidney disease, and over 55 years old at the time of hydroxychloroquine initiation. Specifically, the risk of hydroxychloroquine retinopathy increased to 21.6% after 15 years of use for those receiving greater than 6mh/kg per day compared to 2.7% at 5mg/kg per day or lower. Findings also support existing recommendations to maintain hydroxychloroquine dosage to below 5mg/kg per day when possible. This study provided insight into the longitudinal ophthalmological risks of hydroxychloroquine use.

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