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X. Sun, W. Xu, J. Qian, X. Zhang, X. Xu, X. Zhang, H. Liu, P. Rosenfeld; Safety of Repeatedly Intravitreal Injection of Bevacizumab in Rabbit Eyes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4575.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the safety of retina in rabbits after repeatedly intravitreal injection of bevacizumab with different dosage.
Fourteen chinchilla rabbits were randomly divided into experimental group (n=12) and normal control group(n=2). 2.5 mg/0.1 mL and 5.0 mg /0.2 mL of bevacizumab were respectively injected into the right eye of the experimental group. The same volume of NS were injected into the left eyes at the same time. Injections were performed every two weeks and lasted six weeks. Clinical observation and retinal function tests were performed before and 2 days after every injection. The eyes were sacrificed at 1 week and 4 weeks time point after last intravitreal injection. Electron and optical microscope and TUNEL were performed.
After intravitreal injection, slight inflammation was observed in anterior chamber in 5.0 mg experimental group by slit lamp. But no statistical differences of average anterior chamber flash-count was found between control and experimental eyes(P > 0.05).No changes were found by Indirect Ophthalmoscope, B-ultrasonic inspection, ultrasound biomicroscopy and optical coherence tomography. Amplitude and pattern of ERG responses and flash VEP were similar between the control and experimental groups(P > 0.05). Some inflammatory cells were found in the some bevacizumab-injected eyes and NS-injected eyes at 1 weeks time point after injections, and vanished at 4 weeks time point. Electron microscopy shows that there were plasma cell and individual cells with vacuole-like change in 5.0 mg experimental group at 1 week time point after injections. Apoptotic cells were identified in the cone rod layer in every group by TUNEL test. The volume of apoptotic cells was more in 5.0mg-experimental group at 1 weeks time point after injections than that in the normal and experimental control group (P<0.01).
This study reveals that multi-intravitreal injection 5.0mg Bevacizumab may have mild toxicity to the retina in rabbits.
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