April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Angiofibrotic Response to Bevacizumab on Fibrovascular Membranes in Proliferative Diabetic Retinopathy
Author Affiliations & Notes
  • Chunhua Jiao
    Department of Ophthalmology & Wynn Institute for Vision Research, University of Iowa, Iowa City, IA
  • Christine Spee
    Doheny Eye Institute, University of Southern California Keck School of medicine, Los Angeles, CA
  • Shikun He
    Doheny Eye Institute, University of Southern California Keck School of medicine, Los Angeles, CA
  • Robert Mullins
    Department of Ophthalmology & Wynn Institute for Vision Research, University of Iowa, Iowa City, IA
  • Dean Eliott
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • David R Hinton
    Doheny Eye Institute, University of Southern California Keck School of medicine, Los Angeles, CA
  • Elliott H Sohn
    Department of Ophthalmology & Wynn Institute for Vision Research, University of Iowa, Iowa City, IA
  • Footnotes
    Commercial Relationships Chunhua Jiao, None; Christine Spee, None; Shikun He, None; Robert Mullins, None; Dean Eliott, Genentech (C); David Hinton, Fibrogen, Inc. (C); Elliott Sohn, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5821. doi:
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    • Get Citation

      Chunhua Jiao, Christine Spee, Shikun He, Robert Mullins, Dean Eliott, David R Hinton, Elliott H Sohn; Angiofibrotic Response to Bevacizumab on Fibrovascular Membranes in Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5821.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

We have previously reported the effect of bevacizumab on vitreous levels of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in eyes operated on for traction retinal detachment (TRD) due to proliferative diabetic retinopathy (PDR). To better characterize the angiofibrotic response, we assessed the morphologic and biochemical alterations of extracted fibrovascular membranes in these eyes after VEGF inhibition.

 
Methods
 

In a randomized, controlled, prospective trial (www.clinicaltrials.gov NCT01270542) of 20 eyes (n=10 controls, n=10 given preoperative bevacizumab 3-7 days prior to diabetic traction detachment surgery), epiretinal membranes were excised at the time of vitrectomy. The membranes were snap frozen and sectioned at 9 µm. Sections were immunofluorescent stained with anti-CTGF or anti-VEGF antibody followed by antibody specific for endothelial cells (CD31), myofibroblasts (smooth muscle actin [SMA]), or cytokeratin. Quantitative and co-localization analysis of antibody content was obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of H&E sections, and TUNEL staining was also performed on membranes. Multiple sections for each membrane were averaged for each eye. Data were analyzed using a paired student t-test to compare two groups.

 
Results
 

The bevacizumab group had a greater than 25% reduction in co-localization in the CD31-CTGF and cytokeratin-CTGF studies compared to controls. There was no change in VEGF colocalization between the treated and controls. High baseline levels of fibrosis were observed in both groups. Cell apoptosis increased 51.34% (p=0.05) in bevacizumab-treated fibrovascular membranes (20.02%) compared to controls (9.75%).

 
Conclusions
 

Intravitreal bevacizumab 1.25 mg administered within one week of surgery significantly suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF expression in fibrotic diabetic traction membranes. Bevacizumab may result in apoptosis within fibrovascular membranes. High baseline levels of fibrosis in both groups may explain the relative resistance of switching from angiogenesis to fibrosis in this study.

     
Keywords: 499 diabetic retinopathy • 697 retinal detachment • 503 drug toxicity/drug effects  
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