Patterns and Predictors of Repeated Medication Nonadherence in Glaucoma: A Population-Based Study

Background/Objectives: We aimed to evaluate nonadherence to topical glaucoma therapy and identify risk factors for repeated prescription fulfillment failure in a large national population-based cohort. Methods: The electronic medical records from a large health maintenance organization were retrospectively reviewed for all patients aged 18 years or older with a diagnosis of glaucoma from 2000 to 2023. Data on patients who had purchased at least one anti-glaucoma medication were retrieved. Compliance was defined as prescription fulfillment within predefined expiration windows of 1, 2, and 3 months. Repeated nonadherence was defined as three unfulfilled prescriptions within a 3-month expiration window. Multivariable Cox proportional hazards models were used to identify risk factors for repeated failure. Results: Among 40,200 treated patients, ≥80% cumulative prescription fulfillment was achieved in 80.3% of the population under a 3-month expiration definition. Under a strict 1-month definition, the incidence rate of the third compliance failure was 335 per 1000 person-years. In multivariable Cox analysis, obesity (HR 1.37, 95% CI 1.29–1.45) and current smoking (HR 1.07, 95% CI 1.04–1.11) were independently associated with increased risk of repeated failure. Older age (≥70 years: HR 0.73, 95% CI 0.62–0.87) and higher baseline intraocular pressure (≥25 mmHg: HR 0.65, 95% CI 0.61–0.68) were associated with reduced risk. Initiation with prostaglandin analogs was associated with lower hazard compared with alpha-2 adrenergic agonists (HR 0.53, 95% CI 0.49–0.57), whereas treatment alterations (≥3 changes) were associated with increased hazard (HR 1.64, 95% CI 1.39–1.95). Conclusions: Repeated nonadherence to topical glaucoma therapy is common and is associated with identifiable behavioral and treatment-related factors. Recognition of patients at elevated risk may support targeted strategies to enhance long-term treatment stability.