抗血管生長因子藥物 bevacizumab 在隱形眼鏡引起之紐西蘭白兔角膜新生血管的療效探討

Abstract

In normal cornea, the avascularity is important for maintaining corneal transparency. Corneal neovascularization induced by various pathological stimuli not only impairs visual accuracy, increases inflammation, increases the risk of graft rejection after corneal transplantation, but also impairs surgical outcome after LASIK. During the pathogenesis of corneal neovascularization, vascular endothelial growth factor (VEGF) plays a key role by controlling vascular endothelial cellular proliferation, migration, tube formation and change of transvascular permeability. In previous studies, prolonged wear of gas impermeable contact lens can induce corneal hypoxia and thus induce corneal neovascularization. In professor Hu and Dr. Chen’s lab, corneal neovascularization could be induced experimentally in New Zealand white rabbits by closed and prolonged wear of gas permeable contact lens. Interestingly, increased VEGF mRNA level was detected in these corneal samples. Clinically, corneal neovascularization is usually controlled by administration of steroid or argon laser photocoagulation. However, the result is not satisfactory. Steroid is well known to induce glaucoma and cataract formation. Argon laser photocoagulation has the potential to damage cornea. Recently, anti-VEGF antibody--- bevacizumab (Avastin) is reported to be safe and effective in treating various types of retinal vascular associated disorders. Besides, the effectiveness of bevacizumab on corneal neovascularization is also reported. Nonetheless, the time point of bevacizumab administration may result in different treatment effects. In this study, we aim to evaluate the possibility of using subconjunctival injection of bevacizumab to control corneal neovasculization induced by closed and prolonged contact lens wear in rabbit model and also to compare the treatment effects of different time points of bevacizumab administration in this animal model. We will also evaluate the formation of pericytes in the mature corneal neovasculization induced by closed and prolonged contact lens wear in rabbit model. Besides, we will also try to find out the intracorneal diffusion of bevacizumab (Avastin) in different treatment groups and also the control group. Finally, we will try to evaluate the effects of bevacizumab in treating corneal neovascularization induced by prolonged contact lens wear, and apply our study results to treat related patients. Our results showed the proof of early but not late subconjunctival injection of bevacizumab in inhibiting corneal neovasculization induced by closed and prolonged contact lens wear in rabbit model. The mature vessels induced by closed and prolonged contact lens wear in rabbits were covered by pericytes. Comparing to normal corneas, the diffusion of bevacizumab in cornea is more transient in both early and late treatment groups. The preliminary results of the animal study provided us a new way and more information for further new methods in treating corneal neovascularization.