Many Long-Term Hydroxychloroquine Users Go Unmonitored for Retinopathy

Long-term users of hydroxychloroquine in the UK are not receiving retinal monitoring for hydroxychloroquine retinopathy.

Hydroxychloroquine retinopathy monitoring covers fewer than 4% of long-term users of hydroxychloroquine in the United Kingdom, according to a report published in Eye. The study shows that nearly 40% of patients diagnosed with the complication were already symptomatic at the time of diagnosis.

Researchers conducted a nationwide, prospective case ascertainment study to identify the number of cases and clinical characteristics of hydroxychloroquine retinopathy diagnosed annually in the hospital eye services across the UK. 

They obtained data from the British Ophthalmological Surveillance Unit, which sends monthly reporting cards to approximately 1420 UK ophthalmologists. From 2018 to 2019, the research team sent a standardized questionnaire to reporting ophthalmologists upon notification of a case to collect demographic and clinical data relating to hydroxychloroquine use and retinopathy.

The researchers received reports of  66 cases of hydroxychloroquine retinopathy and received responses to 46 of the case questionnaires, a 73% response rate. After adjusting for the under-ascertainment and under-reporting, the team estimated the potential number of incident cases of hydroxychloroquine retinopathy during the study year was between 24 and 43 cases. 

The increasing use of hydroxychloroquine in developed countries in the past 2 decades and low drug discontinuation rates is likely to increase the incidence of hydroxychloroquine retinopathy in the future given the latent period between treatment initiation and the development of retinopathy.

Of 24 patients with complete or partial datasets available, the researchers reported 14 patients were asymptomatic (61%) and 9 patients were symptomatic (39%). They found the median duration of hydroxychloroquine therapy was 19 years (range, 4-50; interquartile range, 14.5-23), with the most common indication for therapy being systemic lupus erythematosus (n=12), followed by rheumatoid arthritis (n=6), Sjögren syndrome (n=5), mixed connective tissue disease (n=1), and malaria (n=1). 

The researchers say that these data suggest 0.03 to 0.06% of long-term hydroxychloroquine patients in the UK were diagnosed with retinopathy during the study interval, and that retinal monitoring for long-term hydroxychloroquine users had a coverage of between 1.9% and 3.8% during the study interval. 

“The increasing use of hydroxychloroquine in developed countries in the past 2 decades and low drug discontinuation rates is likely to increase the incidence of hydroxychloroquine retinopathy in the future given the latent period between treatment initiation and the development of retinopathy,” according to the researchers. “Increasing access to retinal monitoring using modern retinal imaging techniques will facilitate the detection of early manifestations of hydroxychloroquine retinopathy.”

Limitations of the study included lack of a verification mechanism for the study investigators to confirm the diagnosis of hydroxychloroquine retinopathy, and potential exclusion of possible or mild cases.

References:

Yusuf IH, Han RC, Downes SM, Sharma SM. A nationwide survey of hydroxychloroquine retinopathy presenting to the hospital eye service in the United Kingdom. Eye (Lond).  Published online November 15, 2022. doi:10.1038/s41433-022-02291-0