Purpose: To investigate the association between aqueous humor (AH) suppressant eye drops and the concentration of aflibercept at 1 month after intravitreal injection. Methods: This retrospective study included 17 eyes of 17 patients with neovascular age-related macular degeneration (nAMD) who used eye drops for their glaucoma and received their first intravitreal aflibercept (IVA) at two centers between July 2013 and November 2020. As controls, we enrolled 40 age-, sex-, and axial length-matched eyes of 40 patients with nAMD who were not using any medication that would affect AH circulation. AH was collected 1 month after the first IVA. Aflibercept levels were measured by enzyme-linked immunosorbent assay and were compared between controls and cases using the Kruskal-Wallis test and Dunn's test. The drugs were categorized into two groups based on their mechanism of action on the AH: outflow drugs (e.g., prostaglandin analog) and inflow drugs (e.g., carbonic anhydrase inhibitor, beta-blockers, and alpha-2 agonists). Results: Mean (interquartile range) aflibercept levels in the AH in controls and in cases who used outflow and inflow drugs were 6.83 ��g/mL (1.94-10.34), 9.93 ��g/mL (2.58-17.44), and 15.95 ��g/mL (7.20-22.57), respectively. A Kruskal-Wallis test showed a significant difference among the control, inflow, and outflow drugs (P = 0.0075). Dunn's test showed that aflibercept levels in the aqueous humor were significantly higher in cases using inflow drugs compared to both controls and cases using outflow drugs (P = 0.0085 and P = 0.044, respectively). Conclusions: Aflibercept levels in the AH 1 month after the first IVA were higher in cases using eye drops that reduce AH secretion than in controls. Translational Relevance: Our results, together with previous studies in animals, suggest that combined use of these eye drops might extend the half-life of intravitreally injected drugs.
