Changes in Aqueous Cytokine Levels Following Intravitreal Aflibercept in Treatment-Naive Patients with Diabetic Macular Edema

Purpose: To investigate the changes in aqueous humor cytokine levels in response to short-term aflibercept therapy in treatment-naive patients with center-involving diabetic macular edema (DME). Methods: This is a prospective cohort study that included patients with treatment-naive DME with central subfield macular thickness ≥310 μm on optical coherence tomography from July 2015 to May 2017. Patients received 3 monthly intravitreal aflibercept injections. Aqueous samples for cytokine analysis were obtained before the first and third injections. Levels of various cytokines were measured using multiplex immunoassay. Main outcome measures were changes in aqueous cytokine levels from baseline to month 2. Results: A total of 17 patients were enrolled and 16 completed the study. The mean age was 57.2 ± 8.1 years. The following cytokines were significantly higher at month 2 versus baseline: transforming growth factor-beta (TGF-β)1 (P = 0.004), TGF-β2 (P = 0.017), inducible protein (IP)-10 (P = 0.011), and hepatocyte growth factor (HGF) (P = 0.02). There were significant reductions in the levels of vascular endothelial growth factor (VEGF) (P < 0.001), placental growth factor (PlGF) (P = 0.028), interleukin (IL)-6 (P = 0.011), and platelet-derived growth factor-AA (PDGF-AA) (P = 0.003). Conclusions: In treatment-naive patients with DME, short-term aflibercept therapy not only results in VEGF and PlGF suppression, but also leads to reduced levels of IL-6 and PDGF-AA and higher concentrations of TGF-β1, TGF-β2, HGF, and IP-10.