The Basic And Clinical Study Of The Inhibition Effect Of Anti-VEGF Drug On Corneal Neovascularization

Purpose To establish a stable and efficient animal CNV model of alkali burn.To investigate the inhibitory effect of intrastromal injection of Conbercept on corneal neovascularization(CNV)of rabbits induced by alkali burns and to explore the relevant mechanisms.To confirm the inhibitory effect in the process of human CNV caused by various causes.Method Basic experiment:To explore the methods of alkali burn to establish CNV rabbits and select a stable and efficient method.After successful modeling,choose 45 rabbits(45 eyes)that CNV was established by alkali burns.The rabbits were randomly divided into the experimental group,the control group,and the blank group.The experimental group was given an intrastromal injection of Conbercept(10mg/ml,0.05ml)2 weeks after modeling while the control group was given normal saline and the blank group was given nothing.Observe and photograph the cornea of the rabbits each week.The corneal epithelial defect was observed after sodium fluorescein staining.The area of CNV was calculated.Three rabbits were randomly selected from each group 2,3,4,5 and 6 weeks after modeling.Enzyme-linked immunoassay(ELISA)was used to detect the content of vascular endothelial growth factor(VEGF)in the aqueous humor.Immunofluorescence was used to observe expressions of VEGF,vascular endothelial growth factor receptor(VEGFR),placental growth factor(PLGF),and alpha-smooth muscle actin(?-SMA).Clinical trial:The patients with CNV were divided into virus infection group,transplantation group,chemical injury group and thermal burn group according to the etiology.Intrastromal injection was given to the patients.The length,diameter and area of CNV were observed.The best corrected visual acuity(BCVA)and intraocular pressure changes were recorded.Results Basic experiment:The CNV models of rabbits can be established stably and efficiently by alkali burns using 1 mol/L NaOH solution.In the experimental group there was a significantly inhibition of the growth of CNV and the expression of VEGF,VEGFR and PLGF were decreased after intrastromal injection of Conbercept,which suggesting that intrastromal injection of Conbercept can play an effective anti-CNV role.The area and healing speed of corneal epithelial defect in experimental group after injection of Conbercept are compared with those in control group and control group.There was no significant difference between the blank group and the experimental group.The expression of ?-SMA in the cornea of the experimental group was down regulated after injection,which indicated that the cornea scar formation could be reduced by injection of Conbercept into the cornea matrix.Clinical experiment:After intrastromal injection of Conbercept,the area,length and diameter of CNV decreased significantly(P?0.05).Cornal edema decreased as the corneal transparency improved.The best corrected visual acuity improved.All the results suggested that intrastromal injection of Conbercept can effectively inhibit CNV caused by various causes and significantly improve the visual acuity of patients.Conclusion A stable and effective CNV model of corneal alkali burn can be established by alkali burns by covering a 6.5mm-diameter filter paper with lmol/L NaOH solution for 40 seconds on the cornea.Intrastromal injection of Conbercept to rabbits can effectively inhibit the expression of VEGF,PLGF and VEGFR,so as to inhibit CNV caused by alkali burns.It can inhibit the expression of ?-SMA and the formation of corneal scar.Intrastromal injection of Conbercept showed obviously effect on CNV patients caused by various causes.It can inhibit the growth of CNV,reduce the formation of corneal scar.And has no obvious complications.The method of inhibiting CNV by intrastromal injection has good auxiliary effect on the treatment of multiple primary corneal diseases with CNV.It proved to be effectively in controlling the development of primary corneal diseases.