Purpose:
Connective tissue growth factor (CTGF) is a fibrosis inducer that is elevated in proliferative diabetic retinopathy. The goal of this study was to determine the expression of vascular endothelial growth factor (VEGF) and CTGF in membranes causing diabetic traction detachment with regard to vascular endothelial cells, myofibroblasts, and cytokeratin.
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. Volocity software (version 5.4) allowed quantitative and co-localization analysis of antibody content obtained through immunofluorescence confocal microscopy. Multiple sections for each membrane were averaged for each eye.
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. See figure for complete results.
Conclusions:
Intravitreal bevacizumab 1.25 mg administered within one week of surgery may decrease VEGF and CTGF expression in diabetic traction membranes. VEGF inhibition decreases co-expression of CTGF but not VEGF in vascular endothelial cell and cytokeratin stains. Attenuation of fibrovascular activity in membranes might provide scientific rationale for performing surgery within 7 days of preoperative adjunctive bevacizumab for diabetic traction detachment.
Clinical Trial:
http://www.clinicaltrials.gov NCT01270542
Keywords: diabetic retinopathy • retinal detachment • cytokines/chemokines