Hydroxychloroquine is a crucial treatment for rheumatic diseases due to its relative safety, tolerability, and affordability. It remains a cornerstone in managing patients with systemic lupus erythematosus (SLE), offering benefits such as improved survival and prevention of SLE flares and damage. However, hydroxychloroquine has been associated with irreversible visual loss due to retinal toxicity. Hydroxychloroquine retinal toxicity is far more common than previously considered; an overall prevalence of 7.5% was identified in patients receiving hydroxychloroquine for >5 years, rising to almost 20% after 20 years of treatment.
The prevalence of hydroxychloroquine retinopathy varies, with older screening methods showing a lower prevalence (<2%) compared to more sensitive techniques that detect early stages of the disease (≤8%). The primary predictors of hydroxychloroquine retinopathy have been identified as high-dose use (>5 mg/kg) and long-term treatment (>5 years). However, existing evidence primarily comes from retrospective prevalence studies, and data on the dose-response relationship with outcomes remains scarce.
A recent study published in JAMA Network Open has highlighted key factors associated with an increased risk of hydroxychloroquine retinopathy. This study suggests that the risk of hydroxychloroquine retinopathy is higher in older individuals, females, patients having stage 3 or more CKD and those undergoing tamoxifen treatment. On the other hand, the risk is lower in individuals who are younger than 45 years at the start of hydroxychloroquine treatment and in males. Race and ethnicity also play a role in the development of retinopathy.
The study was led by Dr. Jorge and colleagues, and they examined 4,677 patients who began hydroxychloroquine treatment between July 1, 1997, and December 31, 2020, with up to 15 years of follow-up. Of these patients (mean age 52.4 years; 82.9% women), 125 developed hydroxychloroquine retinopathies. Significant risk factors included older age at initiation, with hazard ratios (HRs) of 2.48 for ages 45-54, 3.82 for ages 55-64, and 5.68 for ages 65 and older, compared to those under 45 years. Women had a higher risk than men (HR, 3.83), as did patients with chronic kidney disease stage 3 or higher (HR, 1.95) and those using tamoxifen (HR, 3.43). Asian (HR, 15.02) and Black patients (HR, 5.51) were more likely to develop pericentral retinopathy compared to non-Hispanic White patients. Age was a significant risk factor for retinal damage from HCQ use. Ethnic disparities were noted, with Asian and Black patients showing a higher likelihood of developing pericentral retinopathy compared to non-Hispanic whites, with hazard ratios of 15.02 and 5.51, respectively.
The researchers emphasized the importance of these findings for patients receiving long-term hydroxychloroquine therapy, especially those with SLE and other rheumatic and dermatologic conditions. HCQ-induced retinal toxicity is irreversible and can continue to progress even after the cessation of the treatment. The study highlights the need for prompt screening and serial monitoring, with the utilization of imaging modalities. This is paramount to prevent HCQ retinopathy and prevent subsequent vision loss or significant visual impairment.
References
- Jorge AM, Melles RB, Marmor MF, Zhou B, Zhang Y, Choi HK. Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes. JAMA Network Open. 2024 May 9;7(5):e2410677.
- Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy — implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018 Dec;14(12):693–703.
- Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye (Lond). 2017 Jun;31(6):828–45.