Changes in Aqueous Angiopoietin-1/2 Concentrations During the Induction Phase of Intravitreal Faricimab Injections for Diabetic Macular Edema

Purpose: The purpose of this study was to investigate the dynamic changes in aqueous concentrations of angiopoietin (Ang)-1/2 and vascular endothelial growth factor (VEGF) during injection in treatment-naïve patients with diabetic macular edema (DME) receiving faricimab during the induction phase (3 consecutive monthly doses) and retrospectively analyze the data. Methods: Thirty-five eyes of 26 patients (age = 63.1 ± 12.9 years) with treatment-naïve DME received faricimab injections monthly, 3 consecutive times. Additionally, 59 eyes of 59 patients (age = 63.9 ± 8.8 years) who underwent cataract surgery were recruited as controls. Aqueous humor samples were collected from each injection or surgery and stored at −80°C, and the concentration of each cytokine was quantified using a multiple enzyme-linked immunosorbent assay (Luminex). The clinical parameters of best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at each visit were also recorded. Results: Three induction phases of faricimab significantly suppressed each aqueous cytokine, rapidly for VEGF, gradually for Ang-2, and slightly for Ang-1. The Ang-1/2 ratio was lower (<1.0) at baseline and gradually increased, but did not reach a control ratio of 1.58. The baseline CFT correlated with VEGF, but not with the Ang-2, Ang-1, or Ang-1/2 ratios. After three injections, CFT did not correlate with VEGF, but it positively correlated with Ang-2 and negatively correlated with Ang-1, and it strongly negatively correlated with the Ang-1/2 ratio. Conclusions: The Ang-1/2 ratio in the aqueous humor significantly negatively correlated with the degree of residual edema after faricimab treatment for DME. Translational Relevance: The Ang-1/2 ratio in aqueous humor is thus a useful biomarker of the treatment response for DME.