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Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial
Journal article   Open access   Peer reviewed

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

Peter A Campochiaro, Gulnar Hafiz, Tahreem A Mir, Adrienne W Scott, Ingrid Zimmer-Galler, Syed M Shah, Adam S Wenick, Christopher J Brady, Ian Han, Lingmin He, …
American journal of ophthalmology, Vol.168, pp.13-23
08/2016
DOI: 10.1016/j.ajo.2016.04.017
PMCID: PMC5482180
PMID: 27130369
url
https://www.ncbi.nlm.nih.gov/pmc/articles/5482180View
Open Access

Abstract

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

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