The popular antimalarial drug hydroxychloroquine (HCQ) has been a prominent treatment for systemic lupus erythematosus for more than half a century, and most recently it’s also been subject to much scrutiny and debate over its potential merits in treating patients infected by COVID-19. Retinopathy caused by HCQ, though rare, can cause irreversible vision damage or loss, and recent research shows that the longer the treatment duration, the higher the risk. 

A cross-sectional study observed 80 lupus patients (90% female) with a mean age of 31. HCQ therapy duration ranged from 0.3 to 15 years among participants. None complained of visual symptoms; however, it’s important to note that HCQ retinopathy often presents itself asymptomatically in its early stages. Patients underwent the following tests: a series of clinical and laboratory assessments, ophthalmological assessments including a fundus exam, visual field testing and fundus autofluorescence (FAF), the latter being one of the most effective screening methods for this type of retinopathy. 

The researchers found that 11.3% of participants had significant visual field changes, and 6.3% of that group also had abnormal FAF, suggesting the presence of HCQ retinopathy. Those who had normal FAF received a weight-based daily HCQ dose of 4.86, while the mean dose of those with abnormal FAF was 5.28. “There were statistically significant differences between patients who have normal FAF and those who have abnormal FAF as regards the duration of hydroxychloroquine therapy, cumulative dose of HCQ therapy, and decreased the best-corrected visual acuity of both eyes,” the researchers wrote in their paper. 

The incidence of HCQ retinopathy was found to be significantly correlated with the duration and cumulative dose of HCQ therapy; age and daily dose were not statistically significant. However, previous studies have shown weight-based daily dose to be a risk factor. The observed predictors for abnormal FAF cases in this study include duration of HCQ therapy longer than seven years and best-corrected VA of both eyes of 0.5 or less.

“Between the studied risk factors, the HCQ retinopathy depends mainly on the duration of HCQ therapy. This is in agreement with a number of studies related to the risk of retinopathy to increase duration of HCQ treatment,” the researchers wrote. They referenced a previous study, which observed a “1% risk of retinopathy in the first 5 years of HCQ treatment, 1.8% from 6 to 10 years, and 3.3% from 11 to 15 years, so the risk increases after 16 years of use, even after 20 years.”

The latest guidelines from the American Academy of Ophthalmology (2016) and Royal College of Ophthalmologists (2018) recommend dosing a maximum of 5mg/kg per day and keeping treatment duration under five years. There is always some risk of HCQ-induced retinopathy as a result of prolonged HCQ therapy, so make sure to dose your patients appropriately and perform necessary testing and follow-up.

Abdelbaky MSE, Mamoun TAE, Mabrouk FI, Hassan RM. Frequency and risk factors for hydroxychloroquine retinopathy among patients with systemic lupus erythematosus. Egypt J Intern Med. June 8, 2021. [Epub ahead of print].