An exploration of the effects of bevacizumab on the corneal epithelium and endothelium : an in vitro and clinical study

The avascular nature of the cornea is disrupted when corneal neovascularization (NV) causes the formation of new blood vessels onto the ocular surface resulting in opacification and subsequent blindness. The third most common cause of blindness worldwide is corneal disease and corneal NV is present in almost every case. Approximately 4.14% of patients who require eye care present with corneal NV and the major causes are infectious diseases, extended wear of contact lenses and vascular response to corneal transplantation. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, plays the most critical role in the development of several retinal neovascular diseases, as well as in corneal NV. Its inhibition by anti-VEGF agents has proven to be successful in the management of these conditions. The most widely used therapeutic agent is bevacizumab (Avastin®), a full-length recombinant humanized monoclonal antibody against VEGF, due to its cost-effectiveness. Despite the widespread use of bevacizumab in ophthalmology, its use is considered off-label. Therefore, ongoing studies into the safety of this drug for the eye is important. Given that bevacizumab was initially used to treat retinal neovascular diseases, its safety for retinal cells is more robustly established. More recently, it has been studied as an off-label topical treatment for corneal NV. The safety and biocompatibility of bevacizumab on the cornea must be ensured for off-label use, particularly as there has been evidence for potential corneal cytotoxicity resulting in delayed epithelial wound healing. It is speculated that topical bevacizumab possibly interferes with the adhesion between the corneal epithelium and the basement membrane, leading to increased risk of corneal epithelial defects. In this thesis, the primary objective is to investigate the effects of bevacizumab on the corneal epithelium and endothelium, focusing on two aims: 1) examine the cytotoxic effects of bevacizumab on the viability and metabolism of human corneal epithelial cells and endothelial cells, and 2) evaluate the adverse effects of intravitreal bevacizumab on the cornea in patients and report on the risk factors involved in developing corneal epithelial defects.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat