Impact of Loading Dose Adherence and Long-term Anti-VEGF Persistence on Diabetic Macular Edema Outcomes in a Korean Cohort Study

Purpose: To evaluate the impact of adherence to the initial loading dose (LD) and 1-year persistence of anti-vascular endothelial growth factor (anti-VEGF) therapy on treatment failure in diabetic macular edema (DME). Methods: This retrospective cohort study included patients receiving intravitreal anti-VEGF injections for DME between 2017 and 2021. Patients with prior anti-VEGF treatments or alternative therapies within one year before the index date were excluded. LD adherence was defined as completing three injections within 63 days of treatment initiation. Treatment failure was defined as the first occurrence of alternative treatments post-index date. Multivariable Cox proportional hazards models were performed. Findings: Among 2,239 patients, the persistence rates of anti-VEGF therapy were 45.2%, 24.1%, and 16.8% at 1, 2, and 3 years, respectively. LD adherence was observed in 75.5% of patients. Compared to the LD adherent group, the LD incomplete group had a significantly higher risk of treatment failure (HR = 1.91; 95% CI: 1.06–3.43). However, extending the LD interval up to 180 days did not significantly impact treatment failure (HR = 1.04, 95% CI: 0.59–1.83; P = 0.90). Patients who discontinued treatment within the first year exhibited a 1.62-fold higher risk of treatment failure at three years (HR = 1.62; 95% CI: 1.01–2.60). Implications: Adherence to the initial LD and sustained anti-VEGF therapy are crucial for reducing treatment failure risk in DME patients. Importantly, minor deviations from the standard LD schedule, with intervals extending to 180 days, may not adversely affect the treatment failure. These findings highlight the need for strategies to enhance patient adherence while individualized scheduling flexibility.