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J. B. Christoforidis, R. Ricketts, S. Bean, C. Pratt, J. Pierce, M. B. Wells, K. La Perle; The Effect of Intravitreal Pegaptanib, Bevacizumab and Ranibizumab on Blood Vessel Formation During Cutaneous Wound Healing in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6150.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of intravitreal pegaptanib, bevacizumab and ranibizumab on blood vessel formation during cutaneous wound healing in a rabbit model and to compare this effect to placebo controls.
Forty New Zealand white rabbits underwent full thickness cutaneous wounds using standard 6mm dermatologic punch biopsies. Following this, the rabbits were randomly assigned to one of four treatment groups each consisting of ten rabbits. Each group received intravitreal injections in the left eye consisting of 0.3 mg/0.1 ml pegaptanib, 1.25 mg/0.05 ml bevacizumab, 0.5 mg/0.05 ml ranibizumab or no injection (placebo). Five rabbits from each group underwent wound harvesting on day 7 and five on day 14. The tissue samples were stained with hematoxylin and eosin and for immunohistochemistry with CD34 (selective for endothelial cells) to stain vessels. The biopsy specimens were then examined for each rabbit. An average neovascularization (ANV) score was obtained by 4 independent observers at the biopsy site margins at 5 contiguous 40x fields .
At week one the following ANV score means with standard deviations were found: placebos 13.2 +/- 1.77, bevacizumad 8.6 +/- 1.04 (p<0.001), ranibizumab 9.2 +/- 1.27 (p<0.001) and pegaptanib 10.23 +/- 1.43 (p<0.002). At week two the following ANV score means with standard deviations were found: placebos 7.64 +/- 0.75 , bevacizumad 7.64 +/- 0.88 (p<0.171) , ranibizumab 4.76 +/- 1.00 (p<0.002) and pegaptanib 6.66 +/- 1.14 (p<0.416).
In our study intravitreal pegaptanib, bevacizumab and ranibizumab were found to exert a statistically significant inhibition of new blood vessel formation at the cutaneous wound margins at one week compared to placebo controls. At two weeks only ranibizumab continued to have a statistically significant effect while pegaptanib and bevacizumab groups had equivalent numbers of blood vessels compared to placebo controls. Since angiogenesis is an integral component of the proliferative phase of wound healing, we encourage clinicians to be observant of their patients' recent surgical history and to consider refraining from the use of intravitreal anti-VEGF therapy during the peri-operative period.
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