Radwan Almousa, Konstantinos Samaras, Saj Khan, Damian Lake Subconjunctival 10 mg of Bevacizumab treatment for corneal noevascularization. Radwan Almousa, Konstantinos Samaras, Saj Khan, Damian Lake The CorneoPlastic Unit and Eye Bank Queen Victoria Hospital East Grinstead,UK. The authors have no proprietary or commercial interest in any material discussed in this article

of all VEGF-A isoforms.2 Bevacizumab treatment for CN had been reported with variable vascularization regression response.3,4 CN response to Avastin is dose and time (contact time) dependent.5 We report the use of 10mg of subconjunctival (SC) Avastin, which is higher than previously reported treatment doses for CN. Methods: This is a retrospective review of the case notes of 5 patients who had bevacizumab subconjunctival injection for CN. The study was conducted in a tertiary referral centre in the south east of England. The etiology behind the CN and length of the time elapsed between the beginning of CN and Avastin injection were noted, as well as any side effects. Introduction:The angiogenic privilege of the cornea is essential for corneal transparency, good vision and transplant success. Corneal neovasularization (CN) could lead to corneal scarring, lipid deposition, reduced vision, and loss of corneal immune privilege, thereby worsening the prognosis of subsequent corneal transplant. Various treatments were tried to control CN, of which corticosteroids have been the mainstay, though they carry the potential risk of glaucoma, cataract, and precipitating infection. Vascular endothelial Growth factor (VEGF)-A is a key modulator of corneal angiogenesis and lymphangiogenesis.1 Bevacizumab (Avastin®) is a murine monoclonal antibody that inhibits the action

Results: Patients basic characteristics and etiology of CN.

Time interval between CN and bevacizumab injection, and regression of corneal neovascularization. Figure1: A-Patient 2: preinjection B-Patient 2 in six weeks post injection, regression of blood vessels and lipid keratopathy

Figure 2:A Preinjection Discussion: CN occurs when the balance between angiogenic and antiangiogenic factors shifts toward angiogenic factors. Cornea with NV shows higher concentration of VEGF and pharmacologic strategies to suppress corneal angiogenesis are needed. The inhibitory effects of bevacizumab is time (contact time) and dose- dependent, hence we have chosen to use subconjunctival injection of Avastin to provide more contact time and we have used higher doses than previous reports. Still, only one patient showed partial regression (figure 1). The other patients showed no regression (figure 2). These results echoed previous reports that bevacizumab is effective in active neovascularization, but not established corneal NV.3,4 B-One month post injection Case 5: no change in CN or lipid keratopathy

There were no side effect for Avastin treatment in our series There were no side effect for Avastin treatment in our series. Mild hypertension was the only adverse event identified for intravitreal injection6 Although, recently there were reports of corneal epithelial defect and thinning in relation to topical Avastin.7 Our series have the inheritance weakness of retrospective study with variable follow-ups. The observer was not blinded when reviewing patients photographs. There were no quantitative measurement of CN. Our study does show that even with higher dose of Avastin subconjunctival injection, effectiveness would be reduced in case of established neovascularization. We recommend using 10mg subconjunctival Avastin for only new active neovascularization to achieve therapeutic effects. References: Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D’Amore PA, Dana MR, Wiegand SJ, Streilein JW. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest. 2004;113:1040-1050. Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun. 2005;333:328-335. Doctor PP, Bhat PV, Foster CS. Subconjunctival bevacizumab for corneal neovascularization. Cornea. 2008;27:992-995. Awadein A. Subconjunctival bevacizumab for vascularized rejected corneal grafts. J Cataract Refract Surg. 2007;33:1991-1993. Kim TI, Kim SW, Kim S, Kim T, Kim EK. Inhibition of experimental corneal neovascularization by using subconjunctival injection of bevacizumab (Avastin). Cornea. 2008;27:349-352. Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twelve-week results of an uncontrolled open-label clinical study. Ophthalmology. 2005;112:1035-1047. Kim SW, Ha BJ, Kim EK, Tchah H, Kim TI. The effect of topical bevacizumab on corneal neovascularization. Ophthalmology. 2008;115:e33-38. Epub 2008 Apr 24.