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

In 30 seconds

This systematic review and random-effects meta-analysis examined hydroxychloroquine retinopathy (HCQ-R) prevalence, cumulative incidence, and risk factors in adults with rheumatic diseases receiving long-term hydroxychloroquine, using observational studies that screened with spectral-domain optical coherence tomography. Nineteen studies were included: 18 cohorts and one case-control study. Pooled HCQ-R prevalence was 5.1% (95% CI 3.9-6.5), and cumulative incidence rose with duration, reaching 5.6% (95% CI 3.2-9.6) at 15 years. Higher daily dose, chronic kidney disease, female sex, and Asian versus White ethnicity were associated with increased risk.

Key findings

• Pooled HCQ-R prevalence was 5.1% (95% CI 3.9-6.5) across studies from 2008 to 2023.
• 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.
• Daily dose >5 mg/kg actual body weight was associated with higher risk (HR 4.32 [2.80-6.65]); chronic kidney disease was also associated (HR 1.94 [1.27-2.96]).
• Female sex (HR 3.78 [1.90-7.48]) and Asian versus White ethnicity (HR 1.67 [1.07-2.62]) were associated with higher HCQ-R risk.

Why it matters

The pooled estimates show that retinopathy risk increases over prolonged hydroxychloroquine exposure and is associated with dose and patient characteristics. These findings help frame the balance between ongoing treatment and ocular risk, and highlight factors that may be relevant when assessing risk and planning surveillance in long-term users.

What to keep in mind

The evidence came from observational studies, so reported risk-factor associations do not establish causation. The review included only studies using spectral-domain optical coherence tomography and English full texts.