Abstract
Purpose: :
To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls at two time points.
Methods: :
One hundred and twenty New Zealand white rabbits underwent two full thickness cutaneous wounds using standard 6mm dermatologic punch biopsies. Following this, the rabbits were randomly assigned to one of three treatment groups each consisting of forty rabbits. Each group received intravitreal injections in the left eye consisting of 1.25 mg/0.05 ml bevacizumab, 0.5 mg/0.05 ml ranibizumab, or 0.05 ml of normal saline. Twenty rabbits from each agent group underwent wound harvesting on day 7 and twenty on day 14. The tensile maximal load for each harvested wound specimen was measured using wound tensiometry by mounting each specimen into the grips of a TestResources mechanical tester. A linear mixed model with random intercepts was fit to compare the difference in max load between treatment groups and the control group. Dunnett-Hsu’s method for multiple comparisons was used to adjust for multiple hypothesis tests.
Results: :
On day 7 the following wound tension reading means with standard error and 95% confidence intervals in dynes were found: saline placebos 8.25 +/- 0.86 (6.52, 9.97) , bevacizumab 7.80 +/- 1.01 (5.79, 9.81) (p=0.922), and ranibizumab 5.46 +/- 0.85 (3.74, 7.18) (p=0.048). On day 14 the following wound tension reading means with standard error and 95% confidence intervals in dynes were found: saline placebos 7.34 +/- 0.55 (6.24, 8.44), bevacizumab 6.05 +/- 0.54 (4.97, 7.14) (p=0.18), and ranibizumab 7.99 +/- 0.54 (6.91, 9.08) (p=0.60).
Conclusions: :
In our study only intravitreal ranibizumab was found to exert a statistically significant inhibition of cutaneous wound tensile strength at day 7 compared to placebo controls. At day 14 neither agent produced any significant effect on tensile wound strength 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 ranibizumab therapy during the peri-operative period.
Keywords: retina • wound healing • neovascularization