The likelihood of developing retinopathy on hydroxychloroquine medication is markedly increased by several independent risk factors, including long-term use and high-dose regimens. Also, the presence of chronic kidney disease almost doubles the risk. Hydroxychloroquine (HCQ) is a key treatment for rheumatic diseases but may cause retinal toxicity in certain patients. To identify risk factors for HCQ retinopathy, data from Kaiser Permanente Northern California consortium was used to ascertain a cohort of 4,899 patients with incident HCQ use of at least 5 years between 1997 and 2020. All participants had at least one Spectral-Domain Optical Coherence Tomography (SD-OCT) scan after 5 years of treatment.1 Each SD-OCT was reviewed by an expert ophthalmologist who graded existing HCQ retinopathy into mild, moderate, or severe. A second expert evaluation was done for all pathologies and a sample of normal findings. Cases were matched by age, sex, and time of the first start on HCQ with up to five controls. “The main exposure of interest was HCQ use, and a key strength of this study was that we utilized pharmacy dispensing records to obtain detailed information of HCQ dose and the duration of use, and we assessed the dose in mg/day and weight-based dosing in mg/kg of bodyweight per day,” highlighted Dr. April Jorge (Massachusetts General Hospital). Candidate risk factors included age, sex, weight, diabetes, chronic kidney disease, and medication with other retinal toxins. Amid the nearly 5,000 incident users, 164 cases of HCQ retinopathy were found, of which 100 were mild in severity, 38 moderate, and 26 severe. In this nested case-control study, the mean age was 56, and more than 90% were female; 48% of participants took HCQ for rheumatoid arthritis, followed by 16% due to systemic lupus erythematosus. A conditional logistic regression identified various risk factors for retinopathy. “We observed a dose-response relationship with an increase in odds of retinopathy associated with increased weight-based dosing category,” said Dr. Jorge. “Using less than or equal to 4 mg/kg as the reference group, the odds ratio ranged from 2.76 for a dose between 4 -5 mg/kg up to 7.36 for using ≥6 mg/kg/day.” She added that there were also increased odds (OR 2.96) with each additional 100 mg/day and each other 5 years of use. Moreover, chronic kidney disease (≥ stage 3) doubled the odds of retinopathy. “Patients with these additional risk factors may warrant closer monitoring, and this should also be a consideration when prescribing medication,” Dr. Jorge recommended.
- Jorge A. Risk factors for hydroxychloroquine retinopathy and its subtypes – prospective adjudication analysis of 4,899 incident users. Abstract 0989, ACR Convergence 2021, 3-10. November.
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