September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial
Author Affiliations & Notes
  • Tahreem Aman Mir
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Adrienne Scott
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Lingmin He
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Roomasa Channa
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Catherine Mayerle
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • James T Handa
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Saleema A. Kherani
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Yong S. Han
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Guohua Wang
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Jiang Qian
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Peter A Campochiaro
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3267. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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