title: Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: pcampo@jhmi.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gulnar
authors.initials: G
authors.lastname: Hafiz
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Tahreem A
authors.initials: TA
authors.lastname: Mir
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Scott
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zimmer-Galler
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Shah
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Wenick
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Brady
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ian
authors.initials: I
authors.lastname: Han
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Lingmin
authors.initials: L
authors.lastname: He
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Roomasa
authors.initials: R
authors.lastname: Channa
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Poon
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyerle
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Aronow
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Akrit
authors.initials: A
authors.lastname: Sodhi
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: James T
authors.initials: JT
authors.lastname: Handa
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Saleema
authors.initials: S
authors.lastname: Kherani
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Raafay
authors.initials: R
authors.lastname: Sophie
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Guohua
authors.initials: G
authors.lastname: Wang
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001082:Aqueous Humor / Q000378:metabolism; D000068258:Bevacizumab; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004343:Drug Implants; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008269:Macular Edema / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005136:Eye Proteins; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D000068258:Bevacizumab; D003907:Dexamethasone