Risk of Retinopathy Associated with Long-Term Use of Hydroxychloroquine in Patients with Rheumatic Diseases: A Systematic Review and Meta-Analysis.

Abstract

We aimed to estimate the prevalence and cumulative incidence of hydroxychloroquine retinopathy (HCQ-R) and its risk factors among patients receiving long-term HCQ with rheumatic diseases through a systematic review and meta-analysis of observational studies that used spectral-domain optical coherence tomography (SD-OCT) for screening. A systematic search of PubMed, Scopus, Ovid EMBASE, and World Health Organization databases (inception-December 31, 2025) identified observational studies meeting the following criteria: 1) adults with rheumatic diseases on HCQ for at least one year, 2) SD-OCT used for HCQ-R screening, 3) reported HCQ-R prevalence or cumulative incidence or calculable data, 4) reported HCQ-R risk factors as hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs), and 5) English full text. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis estimated pooled prevalence, cumulative incidence, and risk-factor associations. We screened 827 studies from which an overall 19 met inclusion criteria (18 cohort and 1 case-control). Pooled HCQ-R prevalence from 2008 to 2023 was 5.1% (95% CI 3.9-6.5). Pooled cumulative incidence was 0.1% (95% CI 0.0-0.5) at 5 years, 2.6% (95% CI 1.6-4.1) at 10 years, and 5.6% (95% CI 3.2-9.6) at 15 years. Risk factors measured as HR (95% CI) included daily dose >5 mg/kg actual body weight (4.32 [2.80-6.65]), chronic kidney disease (CKD) (1.94 [1.27-2.96]), female sex (3.78 [1.90-7.48]), and Asian vs White ethnicity (1.67 [1.07-2.62]). HCQ-R risk increases with duration and is dose-dependent, reaching 5.6% by 15 years. Findings support dose optimization with intensified screening for higher-risk patients, including those with CKD or those who are female and/or Asian.