title: A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy.
abstract: BACKGROUND
  In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF and VEGF in the eye is associated with this angiofibrotic switch. This study investigated whether anti-VEGF agents induce accelerated fibrosis in patients with PDR, as predicted by this model.
  
  
  METHODS
  CTGF and VEGF levels were measured by ELISA in 52 vitreous samples of PDR patients, of which 24 patients had received intravitreal bevacizumab 1 week to 3 months before vitrectomy, and were correlated with the degree of vitreoretinal fibrosis as determined clinically and intra-operatively.
  
  
  RESULTS
  CTGF correlated positively, and VEGF correlated negatively with the degree of fibrosis. The CTGF/VEGF ratio was the strongest predictor of fibrosis. Clinically, increased fibrosis was observed after intravitreal bevacizumab.
  
  
  CONCLUSIONS
  These results confirm that the CTGF/VEGF ratio is a strong predictor of vitreoretinal fibrosis in PDR, and show that intravitreal anti-VEGF treatment causes increased fibrosis in PDR patients. These findings provide strong support for the model that the balance of CTGF and VEGF determines the angiofibrotic switch, and identify CTGF as a possible therapeutic target in the clinical management of PDR.
authors.affiliation: Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Van Geest
authors.forename: Sarit Y
authors.initials: SY
authors.lastname: Lesnik-Oberstein
authors.forename: H Stevie
authors.initials: HS
authors.lastname: Tan
authors.forename: Marco
authors.initials: M
authors.lastname: Mura
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.forename: Cornelis J F
authors.initials: CJ
authors.lastname: Van Noorden
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Klaassen
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D055513:Connective Tissue Growth Factor / Q000187:drug effects / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism / Q000601:surgery
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; D000068258:Bevacizumab