Retinal Toxicity Evaluation Of Intravitreal Bevacizumab (Avastin) In Albino Rabbit Eyes

Objective:To evaluate the retinal toxicity of intravitreal Bevacizumab (Avastin) in albino rabbit eyes.Methods:Sixteen New Zealand albino rabbits/thirty-two eyes were divided into four groups byrandom. Three groups were prepared for Avastin experiment, named A, B, C. Each groupreceived intravitreal injection Avastin dose at 1.25mg/0.05ml, 2.5mg/0.1ml and6.25mg/0.25ml respectively. The other group named D served as a control, and acceptedintravitreal injection 0.9％normal saline 0.1ml. After 1, 2 and 4 weeks, flicker full fieldelectroretinagram (ERG), light and electron microscopic tests were recorded for toxicitystudy. Use K Independent Samples Nonparametric Tests for statistical analysis.Results:After intravitreal injection Avastin 1, 2 and 4 weeks, the ERG patterns of each groupwere normal, including rod response, maximal combined response, oscillatory potentials,cone response and 30 Hz flicker response. There was no significant difference betweenstudy eyes and control eyes by statistical analysis of amplitude and implicit time.(P＞0.05).There was no histologic retinal toxicity evidence of each group observed by lightmicroscopy in any stage of the study. The retinal layers in all eyes were intact with nosign of cellular disorganization, retinal inflammation or bleeding.By electron microscopic observation, there was no evident retinal toxicity being testedboth at group A and B (1.25mg/0.05ml and 2.5mg/0.1 ml), except for minimalmitochondrial electron density decrease in the inner segments of photoreceptors. But at group D (6.25mg/0.25ml), significant mitochondrial swelling and hydropic changes wereseen in the inner segments of photoreceptors by electron microscopy. And there was noimprovement of the pathological changes in four weeks.Conclusions:Administration of intravitreal Avastin at dose of 1.25mg and 2.5mg were safe in thealbino rabbit model. Retinal function, histology and ultramicrostructure tests showed nosigns of retinal toxicity. For vitreous volume of rabbit is about 1/3～1/2 than human, ourstudy supported the safety of intravitreal injection Avastin at dose of 1.25mg for humanbeings. But there was evident retinal toxicity revealed at dose of 6.25mg in rabbit eyes.Significant mitochondrial swelling and hydropic changes in the inner segments ofphotoreceptors were detected by electron microscopic assessment. It also could beindirectly extrapolate to humans, for reducing or avoiding retinal toxicity of Avastincumulation, the repeating interval should not be too short, the single dose and thefrequency of injection should not be too high.