Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial

Am J Ophthalmol. 2016 Aug:168:13-23. doi: 10.1016/j.ajo.2016.04.017. Epub 2016 Apr 27.

Abstract

Purpose: The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro-permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME.

Design: Prospective, randomized crossover clinical trial.

Methods: Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral-domain optical coherence tomography (SDOCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Crossover at week 16 provided changes in protein levels after each intervention in all 20 patients.

Results: After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including 3 known PPFs: angiopoietin-2 (r = 0.40, P = .001), hepatocyte growth factor (HGF; r = 0.31, P = .02), and endocrine gland-VEGF (EG-VEGF, r = 0.43, P < .001). Reduction of prolactin, insulin-like growth factor binding protein-3, and matrix metalloproteinase-9 correlated with edema reduction after injection of a VEGF-neutralizing protein as well as dexamethasone implant, suggesting their modulation is likely secondary to changes in edema rather than causative.

Conclusions: Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multifactorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factors to chronic DME.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Aqueous Humor / metabolism
  • Bevacizumab
  • Cross-Over Studies
  • Delayed-Action Preparations / therapeutic use
  • Dexamethasone / therapeutic use*
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Drug Implants
  • Eye Proteins / metabolism*
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Macular Edema / drug therapy*
  • Macular Edema / metabolism*
  • Macular Edema / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Visual Acuity

Substances

  • Angiogenesis Inhibitors
  • Delayed-Action Preparations
  • Drug Implants
  • Eye Proteins
  • Glucocorticoids
  • Intercellular Signaling Peptides and Proteins
  • Bevacizumab
  • Dexamethasone