Effects of bevacizumab in retina and choroid after intravitreal injection into monkey eyes

Objective: Due to its low price, bevacizumab, which binds vascular endothelial growth factor, is currently used off-label for the treatment of over 50 different eye diseases and has been adopted worldwide despite the absence of serious preclinical data. This study examines the effects of intravitreal bevacizumab on monkey eyes with particular focus on choroidal and retinal vessels. Methods: Cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab with or without I-125 labeling. The eyes were enucleated between 1 and 14 days after injection and were investigated by electron microscopy, immunocytochemistry, histochemistry or autoradiography. Untreated and phosphate buffered saline (PBS)-injected monkeys were used as controls. Results: Bevacizumab locally accumulated at high concentration within individual blood vessels. It formed electron-dense deposits inside retinal veins and between red and white blood cells, activated thrombocytes and induced retinal vein thrombosis. Retinal cells like Muller cells, astrocytes and microglia were also activated. High amounts of bevacizumab were found in retinal and choroidal vessels which may interfere with blood flow. Conclusions: The deposits on the retinal vein walls may provide a mechanistic basis for the observed retinal blood flow alterations after bevacizumab treatment in patients.