Determinants of Baseline Ophthalmic Screening and Its Association with Long-Term Treatment Persistence in Patients with Rheumatic Diseases Initiating Hydroxychloroquine: A Nationwide Cohort Study

Purpose: Hydroxychloroquine (HCQ) is a cornerstone therapy for various rheumatic diseases (RDs), but prolonged exposure carries a risk of irreversible retinal toxicity. Current guidelines recommend baseline ophthalmic screening to ensure safety and support treatment longevity. This study aimed to evaluate real-world adherence to baseline screening, identify its determinants, and assess its association with long-term HCQ treatment persistence. Patients and Methods: We conducted a nationwide retrospective cohort study using the South Korean Health Insurance Review and Assessment Service (HIRA) database. Adult patients with RDs who initiated HCQ between 2014 and 2018 and maintained therapy for ≥ 30 consecutive days were included. Baseline ophthalmic screening was defined as fundoscopy or optical coherence tomography (OCT) performed within 12 months of HCQ initiation, a pragmatic window reflecting real-world clinical practice. Determinants of screening were identified using multivariable logistic regression, and the association between screening and HCQ persistence was analyzed using Cox proportional hazards models. Results: Of the 19,876 patients included, only 32.5% underwent baseline screening. Independent predictors of higher screening rates included older age, female sex, treatment initiation at tertiary or general hospitals, a later initiation year, and a diagnosis of systemic lupus erythematosus, Sjögren’s syndrome, or Behçet’s disease. Conversely, concomitant use of conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids predicted lower rates. During follow-up, baseline ophthalmic screening was independently associated with significantly improved HCQ persistence (adjusted HR for discontinuation: 0.91; 95% CI: 0.88– 0.94); this relationship held true specifically for patients undergoing baseline OCT (adjusted HR: 0.93; 95% CI: 0.88– 0.98). Conclusion: These findings highlight the gap between guideline recommendations and real-world practice. The observed association between baseline ophthalmic screening, particularly utilizing OCT, and improved HCQ persistence suggests that such screening may potentially serve as an indicator of comprehensive clinical management within routine practice.