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Tahreem Aman Mir, Adrienne Scott, Lingmin He, Roomasa Channa, Catherine Mayerle, James T Handa, Saleema A. Kherani, Yong S. Han, Guohua Wang, Jiang Qian, Peter A Campochiaro; Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3267.
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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.
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.
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).
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.
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