Abstract

Hydroxychloroquine (HCQ) is a fundamental therapy in juvenile-onset systemic lupus erythematosus (SLE), yet data on HCQ-related retinal toxicity in children are limited and primarily extrapolated from adult studies. Understanding pediatric-specific timing, risk factors, and reversibility of toxicity is essential for optimizing monitoring strategies. This study aimed to characterize HCQ-associated retinal toxicity in children with SLE and to evaluate exposure-related risk patterns. This retrospective cohort included 87 patients diagnosed with SLE before age 18 and treated with HCQ for at least 6 months at a tertiary pediatric rheumatology center between June 2016 and June 2025. Demographic features, HCQ dosing, exposure duration, ophthalmologic screening intervals, and toxicity outcomes were extracted from electronic records. Retinal toxicity was defined by ophthalmologic assessment, primarily based on automated visual field testing, with structural imaging (OCT/FAF) reviewed when available. The cohort was predominantly female (82.8%). Median age at diagnosis and HCQ initiation was 13 years (IQR 10–15). Median HCQ exposure was 80 months (IQR 52–100.5). Retinal toxicity occurred in 16.1% of patients and typically manifested as isolated functional abnormalities without structural changes on OCT or FAF. Toxicity developed after a median of 37.5 months (IQR 13.25–64.25), with cumulative risks of 8.2%, 9.5%, and 12.2% at 36, 48, and 60 months, respectively. Doses >5 mg/kg/day were significantly associated with toxicity (p=0.00045). Following HCQ withdrawal, 64.3% of affected patients showed clinical or functional improvement. Hydroxychloroquine-related retinal toxicity in juvenile-onset SLE may appear earlier than suggested by adult-based models and often begins as reversible functional impairment. Accurate weight-based dosing and vigilant ophthalmologic monitoring—potentially at intervals shorter than adult guidelines—may help detect toxicity at a reversible stage and protect long-term visual outcomes in children.

Key words: Hydroxychloroquine, lupus erythematosus, systemic, pediatrics, retinal toxicity