The impact of intravitreal therapy of diabetic macular edema on the local and systemic production of cytokines

Abstract

Purpose: to analyze the levels of cytokines in intraocular fluid (IF) and blood plasma of patients with diabetic macular edema (DME) previously untreated by intravitreal therapy before and after the therapy by angiogenesis inhibitor or a corticosteroid. Material and methods. We examined 90 people — 47 females (52.2 %) and 43 males (47.8 %), mean age 64.54 ± 11.30 years. Of these, 60 had DME, and 30 formed the control group. The levels of 41 cytokines/chemokines in IF were determined by Milliplex® Map Human Cytokine/ Chemokine Panel; while the concentration of IL-18, MCP-1/CCL2, EPO, IL-10, IL-4, IL-6, IL-8, IFNα, VEGF-A in blood plasma was measured by enzyme-linked immunosorbent assay kits (Vector-Best, Russia). Patients with DME received intravitreal injections of an angiogenesis inhibitor (aflibercept. 50 eyes) or a corticosteroid (dexamethasone implant, 30 eyes). Results. Significant differences were revealed in 10 cytokine concentrations between the DME patients and the control group. The concentrations of IL-7, IL-15 and MCP-1/CCL2 levels in IF of DME patients were, respectively, 20.5, 20.3, and 11.02 times higher, than in the control group (р ˂ 0.05). Besides, a pairwise comparison of cytokines concentrations in IF of patients from either treatment group with the controls demonstrated a statistically significant increase in GROα/CXCL1 level. The pairwise comparison also revealed significant differences between the control and the corticosteroid therapy for systemic concentrations of IL-18 (p = 0.017), MCP-1/CCL2 (p = 0.009) and VEGF-A (p = 0.016). Conclusion. A pronounced and significant increase of the levels of a number of cytokines (e.g., IL-7, IL-15. FRACTALKINE/CX3CL1) were only sparsely reported before or remained undetermined at all. Our results on systemic cytokines levels may serve as prerequisite for further research into the role of systemic inflammation in DME pathogenesis. The analysis of associations of our results with those of other clinical biomarkers will contribute to the development of individualized treatment strategies.

Keywords

• diabetic macular edema
• cytokines
• intraocular fluid
• anti-angiogenic treatment