Aqueous humor cytokine levels in patients with diabetic macular edema refractory to anti-VEGF treatment

PURPOSE: To determine aqueous cytokines association with response to intravitreal bevacizumab (IVB) injection in diabetic macular edema (DME). METHOD: We compared the concentrations of IL (interleukin)-1β, IL-2, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor of 64 naïve DME patients with those of 13 cataract patients. Factors associated with central subfield thickness (CST) in DME patients were identified. DME patients were then subgrouped in terms of responsiveness to three IVB injections; cytokine concentrations were compared, and factors associated with responsiveness were identified. RESULTS: Levels of IL-2, IL-8, PlGF, and VEGF were significantly elevated in DME patients (p = 0.007, p < 0.001, p < 0.001, and p = 0.004 respectively). Regression analysis showed that the preoperative CST was associated with the preoperative best-corrected visual acuity and the aqueous IL-10 level (p < 0.001, p = 0.006, respectively). Of the 64 DME patients, 28 (43.75%) exhibited either CST < 300 μm or reduction in CST ≥ 50 μm after three consecutive IVB injections. On sub-group analysis, the mean IL-8 concentration was higher in the refractory group than in the responsive group, and multivariate logistic regression analysis showed that the IL-8 was the only factor associated with responsiveness (OR = 0.95, p = 0.017). CONCLUSIONS: The IL-8 concentration in the aqueous humor was associated with responsiveness to IVB in DME patients.