Transient Bevacizumab (Avastin)-Induced Alterations in Rat Eyes

Abstract

Aims: To study the histopathological, biochemical and functional effects of intravitreal bevacizumab on the rat eye, with special emphasis on its immediate pro-inflammatory features eventually associated with cellular oxidative burden. Methods: Histopathological evaluation was performed 24 h, 1 and 4 weeks after bevacizumab (75 μg/rat eye) or saline intravitreal injection, as well as biochemical analysis of oxidative stress-related markers and electroretinograms. Results: Bevacizumab induces a transient inflammatory reaction together with a modification of the b-wave amplitude and latency of the electroretinogram. No changes were observed in any of the oxidative stress markers studied at any time after injection. Conclusion: Intravitreal bevacizumab injection per se generates an immediate, transient and mild inflammation of the rat eye, which is not associated with oxidative stress in ocular tissues.

Effects of Bevacizumab (Avastin®) on the Electroretinogram of Isolated Rat Retina

“…The concentrations used in our study (the clinical therapeutic concentration and twice this concentration) did not show toxicity on retinal function. Therefore, in concordance with previous in vivo studies of lack of ocular toxicity after intravitreal injection of bevacizumab in animal models [24][25][26][27][28][29] , our in vitro results support the retinal safety of bevacizumab on retinal function.…”

“…Histopathological evaluation, biochemical analysis and ERGs were performed 24 h, 1 and 4 weeks after injection. These authors reported a significant increase in the ERG b-wave amplitude and latency 24 h after intravitreal injection that subsequently disappeared [29] . In contrast to the studies mentioned above, we did not observe any change in the ERGs in rats 24 h after intravitreal injection of bevacizumab at 1 mg/ml of vitreous (data not shown).…”

“…Two in vivo studies in rodents have evaluated the effects of intravitreal bevacizumab on retinal function in normal retina [28,29] . Heiduschka et al [28] showed that intravitreally injected bevacizumab does not have any toxic effects on the mouse retina and its function as shown by electroretinography.…”

“…In this study, a decrease in ERG amplitudes was detected 24 h after injection, which recovered gradually thereafter, and was attributed to the trauma of intravitreal injection [28] . Sancho-Tello et al [29] evaluated the effects of intravitreal injection of 75 g bevacizumab (approx. 1.3 mg/ml of vitreous) in rats.…”

“…Studies using in vivo electrophysiological testing and histopathological analysis have been performed in rabbits [24][25][26][27] and rodents [28,29] . Only one study has evaluated in vitro the effects of bevacizumab on retinal function in pieces of isolated bovine retinas [30] .…”