Efficacy Of Localized Using Vascular Endothelial Growth Factor Inhibitor To Treat Corneal Neovascularization

Purpose:To explore the antiangiogenic effect and security of subconjunctivally and intrastromally injecting the VEGF(vascular endothelial growth factor)inhibitor in animal model and clinical patients.Method:Neovascularization was induced in 30 eyes of 30 rabbits by placing a suture in the corneal stroma.All rabbits were randomly devided into 6 groups.Group 1,2,3 were treated subconjunctivally with VEGF inhibitor 0.05ml,intrastromally with VEGF inhibitor 0.05ml,and subconjunctivally with balanced salt solution 0.05ml 1 week after placing suture.Group 4,5,6 were treat subconjunctivally with VEGF inhibitor 0.05ml,intrastromally with VEGF inhibitor 0.05ml,and subconjunctivally with balanced salt solution 0.05ml 2 week after placing suture.Digital photographs were obtained,neovascularization length(NL),neovasculation area(NA)and vessel caliber(VC)were measured with Image pro plus software.One rabbit was sacrificed randomly in each group before and 1 week,2 weeks,3 weeks after injection.Corneal specimens were analyzed histopathologically and VEGFlevels were measured with ELISA in aqueous humour samples.Prospective study of 6 patients and 6 eyes underwent subconjunctivally and intrastromally injecting the VEGF inhibitor.The follow-up time were 3-12 months.VEGF inhibitor was injected subconjunctivally and intrastromally 0.2ml in all patients.Eyesight,intraocular pressure and digital photographs were recorded,therapeutic effect was evaluated by eyesight,pressure and changes of NL,NA and VC.Results:In digital photographs,NL,NA and VC in group 1 were significantly lower than those in group 3,1 and 2 weeks after injcetion.No statistic difference of NL in group 1 and 3,3 weeks after injection.NL,NA and VC in group 2 were significantly lower than those in group 3,but had no statistic difference with those in group 1,1 week after injection.2 and 3 weeks after injection,NL,NA and VC in group 2 were significantly lower than those in group 1 and 3.NA and VC in group 4 were significantly lower than those in group 6,NL in group 4 had no statistic difference with group 6,4 days,1 week,2 weeks,3 weeks after injection.NA and VC in group 5 were significantly lower than those in group 6,NL in group 5 had no had no statistic difference with group 6,4 days after injection.NL,NA and VC in group 5 were significantly lower than those in group 6,1 week,2 weeks and 3 weeks after injection.The VEGF levels were significantly decreased in group 1 and 2,1 week after injection,and significantly increased in group 1,2 weeks and 3 weeks after injcetion.The VEGF level in group 2 had no statistic difference with group],1 week after injection,and was significantly lower than group 1,2 weeks and 3 weeks after injetion.The VEGF level in group 4 significantly decreased 1 week after injection,significantly increased 2 and 3 weeks after injection.The level in group 4 had no statistic difference with group 6,3 weeks after injection.1w after injection of VEGF inhibitor of 6 patients,the ciliary hyperemia alleviated,the vessels became shorter,the lumen became thinner and part of the small vessels disappeared.The vessels became longer and wider with the time developed.Multiple injections were executed in 4 patients.CNV atrophied and regenerated in each period of treatment.2 patients took keratoplasty after treatment,the implants were clear and recovered well.Conclusions:Subconjunctival and corneal stroma injection of VEGF inhibitor can reduce CNV,mainly in reducing of VC.Intrastromally inject VEGF inhibitor has better effecacy than subconjunctivally injection.Better effecacy can be acquired by injecting VEGF inhibitor in early stage than late stage.Multiple use of VEGF inhibitor is able to maintain its effects providing a good condition of keratoplasty.