Abstract
Purpose :
To measure aqueous pro-permeability factors (PPFs) in patients with diabetic macular edema (DME) at several time points after injection of a dexamethasone implant or a vascular endothelial growth factor (VEGF)-neutralizing protein and correlate levels with changes in central subfield thickness (CST) to identify PPFs that may contribute to DME.
Methods :
Twenty patients with DME were randomized to receive an injection of dexamethasone implant or a VEGF-neutralizing protein. Aqueous taps and SD-OCT were done at baseline and every 4 weeks for 28 weeks. A protein array was used to measure aqueous levels of 55 vasoactive proteins. There was a cross-over at week 16.
Results :
After dexamethasone implant injection there was significant correlation between changes in levels of 13 vasoactive proteins with changes in CST, insulin-like growth factor binding protein-1 (IGFBP-1, r=0.47, p<0.001), prolactin (r=0.45, p=0.001), matrix metalloprotein-9 (MMP-9, r=0.45 p<0.001), endocrine gland-VEGF (EG-VEGF, r=0.43, p<0.001), endostatin (r=0.41, p=0.001), angiopoietin-2 (r=0.40, p=0.001), IGFBP-3 (r=0.36 p=0.003), persephin (r=0.35, p<0.008), macrophage inhibitory protein-1a (MIP-1a, r=0.34, p=0.008), thrombospondin-2 (r=0.33, p=0.009), hepatocyte growth factor (HGF, r=0.31, p=02), interleukin-8 (IL-8, 0.30, p=0.03), and CXCL16 (r=0.29, p<0.02). Many of the patients had chronic DME and little or no CST reduction after injections of a VEGF neutralizing-protein resulting in a negative correlation between changes in CST and changes in VEGF levels, but there was a positive correlation between changes in levels of 3 other proteins, IGFBP-3 (r=0.435, p=0.001), prolactin (r=0.369, p=0.013), and MMP-9 (r=0.29, p=0.025).
Conclusions :
Many vasoactive proteins are reduced after injection of a dexamethasone implant in patients with DME and increase as edema recurs. Since levels of IGFBP-3, prolactin, and MMP-9 also correlate with CST after anti-VEGF injection, it is possible that their modulation is secondary to changes in edema and not causally related. Among the edema-correlating proteins, 5 are known to be pro-permeability and/or proangiogenic and have high priority for further study, HGF, EG-VEGF, angiopoietin-2, interleukin-8, and CXCL16. This is particularly true for HGF and EG-VEGF which were previously correlated with edema reduction in retinal vein occlusion.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.