Aim: To prospectively study plasma levels of vascular endothelial growth factor (VEGF-A), its soluble receptors sVEGFR-1, sVEGFR-2, and soluble Tie2 in premature infants. To identify their changes related to the onset of retinopathy of prematurity (ROP).
Methods: Blood samples of 63 preterm infants born at a postmenstrual age (PMA) of 23 to 32 weeks were obtained between five days and 15 weeks after birth. 42 infants had no ROP, two had stage 1, nine stage 2 and ten stage 3. Of these, four infants were treated with retinal photocoagulation. VEGF-A, sVEGFR-1, sVEGFR-2, and sTie2 were measured in the plasma with a sandwich-enzyme-immunoassay using factor-specific monoclonal mouse antibodies. We compared the time course of concentrations plotted by kernel smoothing in infants with and without ROP and analysed a paired subgroup with ANOVA.
Results: ROP patients had raised plasma levels of sVEGFR-2 and sTie2 compared to premature infants without ROP. VEGF-A and sVEGFR-1 levels were similar in both groups. Analysis of a subgroup with pairs of measurements, one before 32 weeks and one after 36 weeks, showed a significant increase in sTie2 after 36 weeks of PMA independent of ROP (p=0.03).
Conclusion: This is the first study to measure plasma levels of angiogenic factors in ROP. Similar VEGF-A plasma levels in infants with and without ROP suggest that pathogenic retinal angiogenesis in ROP is mainly driven by local VEGF-A synthesis. Elevated plasma levels in active ROP were observed for sVEGFR-2 and sTie2. These rises have yet to be confirmed as predictive values for ROP.