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Purpose: To analyse the effect of intravitreal aflibercept injections on systemic angiopoietin‐2 (Ang2) and vascular endothelial growth factor (VEGF)‐A levels in patients with neovascular age‐related macular degeneration (nAMD). Methods: In a prospective, randomized study, aflibercept (2.0 mg/50 µl) or ranibizumab (0.5 mg/50 µl) was administered intravitreally to 38 treatment‐naive patients. Blood samples were taken before, 7 days after, and 28 days after the first intravitreal therapy. Cytokine levels were measured by enzyme‐linked immunosorbent assay. Twenty‐two age‐ and sex‐matched individuals served as controls. Results: At baseline, there were no significant differences of systemic Ang2 and VEGF‐A levels among the treatment and control groups. After intravitreal aflibercept administration, median (interquartile range: IQR) systemic Ang2 was significantly upregulated from 1819 pg/ml (1262–3099) to 2123 pg/ml (1441–3769; p = 0.011) 7 days after the drug injection and remained non‐significantly elevated at 1944 pg/ml (1431–2546 pg/ml; p = 0.653) 28 days after the drug injection. Median (IQR) systemic VEGF‐A levels were significantly reduced from 43 pg/ml (30–57) to 8 pg/ml (8–8; p < 0.0001) 7 days and 16 pg/ml (8–26; p = 0.001) 28 days after the injection in the aflibercept group. There were no significant effects on systemic VEGF‐A and Ang2 levels in the ranibizumab group at any time point following the first injection. Conclusion: In this study, we report significant systemic upregulation of Ang2 after intravitreal aflibercept administration. This counterregulatory response may represent a potential escape mechanism from antiangiogenic therapy. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the interaction between aflibercept and galectin-1 and evaluate the plasma levels of galectin-1 and vascular endothelial growth factor (VEGF)-A after intravitreal injection of aflibercept in patients with diabetic retinopathy (DR). Methods: Interaction of galectin-1 with aflibercept was determined via immunoprecipitation. Seventeen patients with type 2 diabetes and diabetic macular edema (DME) were each treated with a single intravitreal injection of aflibercept (2.0 mg, 50 µL) monthly for three consecutive months. Plasma galectin-1 and VEGF-A levels were measured just before an injection was administered, 1 week after the first injection, and 2 months after the last injection. Nineteen age- and sex-matched healthy participants served as controls. Results: Irrespective of the tested galectin-1 concentration, 24% of added galectin-1 was precipitated by aflibercept. Baseline plasma concentrations of galectin-1 were 22.0 and 23.0 ng/mL in the control and aflibercept-treated groups, respectively. Systemic galectin-1 levels increased to 27.0 and 24.0 ng/mL at 7 days and 4 weeks, respectively, after treatment. At week 8, plasma galectin-1 levels significantly increased to 36.0 ng/mL. This level persisted for 20 weeks. Systemic VEGF-A levels significantly reduced to below the minimum detectable dose in 16 DME patients at 7 days after treatment. This level persisted for 4 weeks. Plasma VEGF-A levels were reduced at weeks 8 (p = 0.099) and 20 (p = 0.023). Decreased plasma VEGF-A levels were observed in all patients after treatment. Conclusion: We confirmed that physiological aflibercept levels precipitate galectin-1 inin vitroassays. Additionally, systemic upregulation of galectin-1 might be induced by intravitreal aflibercept, which may be relevant in the clinical outcomes of DR treatment. [ABSTRACT FROM PUBLISHER]