Assessment of Plasma Cytokine Profile Changes in Bevacizumab-Treated Retinopathy of Prematurity Infants

Abstract

We compared changes of plasma angiogenesis cytokine profiles in infants who were treated with intravitreal injection of bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) with age-matched preterm non-ROP infants. Thirteen infants with type 1 ROP and 13 age-matched preterm non-ROP infants were included. Blood samples were collected prior to treatment (time 0) and 6 weeks after the treatment (time 42). Plasma levels of nine cytokines from the angiogenesis growth factor panel and seven soluble cytokine receptors were measured using a magnetic multiplex assay. Plasma cytokine profiles changed from time 0 to time 42 in both groups. In bevacizumab-treated ROP infants, the following plasma angiogenesis growth factor and soluble cytokine receptor levels decreased significantly: soluble VEGF-A (sVEGF-A; P = 0.0001), sVEGF-D (P = 0.04), angiopoietin-2 (Ang-2; P = 0.002), sVEGF receptor 1 (R1) and R2 (P = 0.005), soluble IL-6 receptor (sIL-6R; P = 0.002), soluble glycoprotein 130 (spg130; P = 0.0001), and soluble TNF receptor (sTNFR) I and II (P = 0.0001). The following factors and receptors increased significantly: sVEGF-C (P = 0.05), placental growth factor (PlGF; P = 0.02), endothelin-1 (ET-1; P = 0.0001), and FGF-1 (P = 0.02). At time 42, sVEGF-A, sgp130, sIL-6R, sTNFR I, and sTNFR II were lower, and ET-1 level was higher, in bevacizumab-treated ROP infants compared to age-matched non-ROP infants. The results suggest that bevacizumab treatment resulted in significant angiogenic cytokine profile changes in infants with severe ROP. The long-term clinical impact of these changes should be studied carefully.