Retinal histopathological changes following intravitreal injection of different doses of bevacizumab: an electron microscopic study

ABSTRACT

To determine the retinal toxicity of intravitreal bevacizumab in rabbits by electron microscopy. Six albino rabbits received one injection of intravitreal bevacizumab in one eye, and no injection [control] in the fellow eye. Two rabbits received 1.25 mg in 0.05 ml, two received 2.5 mg in 0.1 ml, and two received 5mg in 0.2 ml. for each dose of bevacizumab, one rabbit was sacrificed one day after injection, and the other one week later. The retina was then examined by transmission electron microscopy. The control eyes showed no abnormality. At 1.25 mg there was no change compared with controls. At 2.5 mg, there was mild transient cytoplasmic degeneration in the inner segments of the photoreceptors and the horizontal cells of the outer nuclear layer. At 5mg, there was, in addition to the changes above, marked cytoplasmic degeneration of the retinal pigment epithelial [RPE] cells with shrinkage of the nucleus, and numerous vacuoles in the nerve fiber layer. At one week, there was significant resolution of these changes. There was no evidence of bevacizumab toxicity to the rabbit retina after a single intravitreal injection of 1.25 mg. At 2.5mg, there were mild transient changes, whereas definite toxicity to the RPE cells and nerve fiber layer were seen at 5mg. The maximum recommended dose of intravitreal bevacizumab is therefore 2.5 mg