Avastin Eye Drops Inhibition Of Corneal Neovascularization Experimental And Clinical Research

BackgroundCorneal transparency is based on banlance of low levels of vascular endothelial growth factor and high levels of anti-vascular endothelial growth factor,but corneal inflammation and chemical burn will break the steady-state, resulting in pathological corneal neovascularization [1]. Not only seriously affect vision, but also corneal allograft rejection occurred in high-risk factors after transplantation. On the one hand, Corneal neovascularization can enhance the defense capabilities of the cornea and promote repair of injury and inflammation; but on the other hand, the loss of normal corneal transparency lead to vision loss or even an important cause of blindnessAngiogenesis is characterized substances in alkali and other chemical burns,and is related to the loss of vision. In our country the CNV which caused by ocular trauma (especially a serious chemical burn) is a very common eye's disease, accounting for the whole 10% of corneal diseases.So, the loss of vision is currently facing one of the most prominent problem in ophthalmology in China[2].It has been study the pathogenesis of CNV and preventive measures for a long time, but the treatment of CNV is still difficult Although many treatment methods has been used,such as glucocorticoids, non-steroidal anti-inflammatory drugs, heparin, Cyclosporin A, methotrexate, thalidomide [3-6] and so on,but there is still a lack of a very safe and effective drug treatment.Glucocorticoid which is the main treatment CNV drugs, but caused glaucoma, cataracts and other side effects.Therefore, It is significant to develope new effective and safe drugs to inhibit corneal neovascularization.PurposeIn this study, the aim of experiment is through the established two corneal neovascularization models induced by corneal alkali burn and suture method in rabbit to compare effect of inhibition for the CNV for different stimulate factors in the different periods of time after accepting the treatment of Avastin eye drops, and be compared with steroid eye drops;There collect 24 case of corneal neovascularization induced by different causes in clinical , and observe the inhibition of corneal neovascularization and security after application of Avastin eye drops.MethodsExperimentⅠ:Avastin eye drops inhibite corneal neovascularization induced by corneal alkali burn on rabbit(1) Alkali burn method (1mol/LNaOH solution) induced the generation of corneal neovascularization;(2 After alkali burns in seven days, each group give the corresponding drug drops, 4 times / d, a total of 14 days;(3)Observed and recorded through the slit lamp after alkali burn corneal 7d,21d,28d,56d, repeatedly performed standardized digital slit-lamp pictures and calculate the area of corneal neovascularization; RT-PCR detecte the expression of corneal tissue VEGFmRNA; immunohistochemistry detecte the expression of corneal tissue VEGF protein; enzyme-linked immunosorbent assay detecte the expression of aqueous VEGF.Experiment II: Avastin eye drops inhibite corneal neovascularization induced by corneal suture on rabbit(1) suture-induced corneal angiogenesis;(2), (3) are the same as with the ExperimentⅠ. Avastin eye drops inhibite corneal neovascularization on human(1) Standards into line with the patients, and this treatment on a voluntary basis;(2) Delivery: Avastin eye drops, 4 times / day; a total of 14 days.(3) fter administration, observed and recorded through the slit lamp, repeatedly performed standardized digital slit-lamp pictures and calculate the area of corneal neovascularization in 7d,14d; observed and asked patients; evaluate security. Results:ExperimentⅠ:(1). the successful prepare the model of corneal neovascularization induced by corneal alkali burn on rabbit;(2). Each group be gave different drug therapy after 14d, at different time points, corneal neovascularization were significantly shorter and sparser in Avastin group than that in the control group; RT-PCR test results, in the 21d,28d,the expression of corneal tissue VEGFmRNA in Avastin group lower than those in the control group; ELISA assay shows that VEGF in the aqueous humor in 21d in Avastin group was significantly lower than that in the control group.It shows that this drug can effectively penetrate into the cornea so that decreased the VEGF in the aqueous.Experiment II:(1)Successful prepare the model of corneal neovascularization induced by suture on rabbit;(2) Each group be gave different drug therapy after 14d, at different time points, corneal neovascularization were significantly shorter and sparser in Avastin group than that in the control group; RT-PCR test results, in the 21d,28d,the expression of corneal tissue VEGFmRNA in Avastin group lower than those in the control group; ELISA assay shows that VEGF in the aqueous humor in 21d in Avastin group was significantly lower than the control group.Experiment III:(1)Into 24 cases of patients who meet the criteria, a total of 31 eyes.(2) In 31 cases of eye disease, Average corneal neovascularization area is 60.70±21.08% in 7 days and 40.26±21.52% in 14 days,respectively decreased than before treatment 39.30%and 59.74%. In 31 patients, 18 cases of patients visual acuity improved in varying degrees respectively.(3) In 31 cases of eye disease, drug safety evaluation are 0. So far it not observed corneal edema, corneal epithelial loss, corneal ulcer not healing, pigment uveitis, iris atrophy and the phenomenon of lens injury; no systemic adverse reactions, skin allergies and toxic injury. Conclusion:After acute inflammation of corneal alkali burn, Avastin eye drops drops can effectively control the growth of new blood vessels, and can reduce the area of neovascularizationTherefore, there provides a good drug to corneal neovascularization in the clinical.Period in non-acute inflammation, regardless of physical factors or chemical factors stimulate the corneal neovascularization, Avastin eye drops can have subsided neovascularization.However,after stopping use the drug, it will continue the growth of new blood vessels in a model of corneal neovascularization induced by corneal suture.Therefore, corneal neovascul- arization induced by different factors should provide a different time and method of administration.Human corneal neovascularization Caused by different factors , Avastin eye drops will enable to degrade corneal neovascularization.In a short period of time it has no adverse reactions and a good security.