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

Rob J. Van Geest, Sarit Y. Lesnik-Oberstein, H. Stevie Tan, Marco Mura, Roel Goldschmeding, Cornelis J F Van Noorden, Ingeborg Klaassen, Reinier O. Schlingemann

Research output: Contribution to journalArticle

Abstract

Introduction: 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.

Original languageEnglish (US)
Pages (from-to)587-590
Number of pages4
JournalBritish Journal of Ophthalmology
Volume96
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

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Connective Tissue Growth Factor
Diabetic Retinopathy
Vascular Endothelial Growth Factor A
Fibrosis
Bevacizumab
Vitrectomy
Blindness
Retina
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

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. / Van Geest, Rob J.; Lesnik-Oberstein, Sarit Y.; Tan, H. Stevie; Mura, Marco; Goldschmeding, Roel; Van Noorden, Cornelis J F; Klaassen, Ingeborg; Schlingemann, Reinier O.

In: British Journal of Ophthalmology, Vol. 96, No. 4, 04.2012, p. 587-590.

Research output: Contribution to journalArticle

Van Geest, Rob J. ; Lesnik-Oberstein, Sarit Y. ; Tan, H. Stevie ; Mura, Marco ; Goldschmeding, Roel ; Van Noorden, Cornelis J F ; Klaassen, Ingeborg ; Schlingemann, Reinier O. / 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. In: British Journal of Ophthalmology. 2012 ; Vol. 96, No. 4. pp. 587-590.
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abstract = "Introduction: 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.",
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AU - Mura, Marco

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