Faculty Collaboration Database

Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial. Am J Ophthalmol 2016 Aug;168:13-23

Date

05/01/2016

Pubmed ID

27130369

Pubmed Central ID

PMC5482180

DOI

10.1016/j.ajo.2016.04.017

Scopus ID

2-s2.0-84971351125 (requires institutional sign-in at Scopus site)   62 Citations

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.

Author List

Campochiaro PA, Hafiz G, Mir TA, Scott AW, Zimmer-Galler I, Shah SM, Wenick AS, Brady CJ, Han I, He L, Channa R, Poon D, Meyerle C, Aronow MB, Sodhi A, Handa JT, Kherani S, Han Y, Sophie R, Wang G, Qian J

MESH terms used to index this publication - Major topics in bold

Aged
Angiogenesis Inhibitors
Aqueous Humor
Bevacizumab
Cross-Over Studies
Delayed-Action Preparations
Dexamethasone
Diabetic Retinopathy
Drug Implants
Eye Proteins
Female
Glucocorticoids
Humans
Intercellular Signaling Peptides and Proteins
Macular Edema
Male
Middle Aged
Prospective Studies
Visual Acuity