1. Effect of pre-op subconjuntival injection of bevacizumab in pterygium surgery Young Jeung Park, M.D. Ph.D. Jong Wook Lee, M.D. Kyoo Won Lee, M.D. Ph.D. Financial Disclosure ： All authors declares no financial interest Cheil Eye Hospital, Daegu, Korea

2. Background Vascular Endothelial Growth Factor (VEGF) - Mediator cytokine of pathological angiogenesis Angiogenesis in pterygiumAngiogenesis in pterygium - Angiogenic stimulators↑, inhibitors↓  the formation and progression of pterygium Application of anti-VEGF therapy  Inducing regression of blood vessels in pterygium  Pterygial recurrence ↓

3. The Effects of the Subconjunctival Injection of bevacizumab (Avastin ® ) in Recurrent Pterygium 1.The maximum effect of subconjunctival injection of pterygium lasted less than 1 month. 2.In ICG, the thickness of conjunctival blood vessels decreased(30.14%).  The subconjunctival injection of bevacizumab 0.2cc was effective for recurrent pterygium 2008 ASCRS poster presentation J. Korean Ophthalmol Soc. 2008 Dec 49(12):1901-1909

4. Purpose To evaluate the effects of pre-op subconjunctival injection of bevacizumab in pterygium surgery.

5. Methods Bevacizumab group: 25 eyes / Control group: 25 eyes Bevacizumab group: Bevacizumab subconjunctival injection (0.2cc): 1~2 weeks pre-op Excision of pterygium and superior conjuntivolimbal autograft Followed up at 1 st week, 2 nd week, 4 th week, and every month thereafter. Bevacizumab groupControl group Recurrent pterygium Primary pterygium Recurrent pterygium Primary pterygium N7187 M:F3:411:72:513:5 Age52.4±8.253.7±10.851.7±4.955.7±9.8 Pterygium grade3333 Follow-up period24.86±3.8026.44±2.3626.86±2.0425.67±2.59 Demography

6. Evaluation 1. Grades of vascularity & Immunohistochemistry for VEGF of tissues obtained from pterygium surgery. 2. Degree of edema in conjuntivolimbal autograft. 3. Ocular and systemic complications. Pictures of grades of vascularity - observed for vessel diameter and vessel density. - Values per picture: (A)=1.0, (B)=1.5, (C)=2.0, (D)=2.5, (E)=3.0 A = 1 B = 1.5 C = 2.0 D = 2.5 E = 3.0 Standard LM (x100, H&E stain) The scoring system of graft edema 0: no edema, equal in thickness to normal conjuntiva 1: mild edema, graft edema within x1 of the corneal thickness under slit-lamp exam. 2: moderate edema, between 1~3 3: severe edema, graft edema above x2 of the corneal thickness under slit-lamp exam. Fisher exact test

7. Comparison vascularization of pterygium tissue obtained from pterygium surgery Bevacizumab groupControl group Pre- avastinAfter-avastin 2 21 1 2 3 Notice the marked decrease in vascularization grade in group with bevacizumab treatment compared to the control group.

8. Average vascular grading score BevacizumabControlP N(recurrent/primary)25(7/18) Vascular grading score (mean±SD) 1.97±0.682.16±0.500.3188 Immunohistochemistry for VEGF of pterygium tissue form pterygium surgery Control groupbevacizumab group (B) represents stronger stain concentration at the apical epithelium, indicating denser concentration of VEGF.

9. Comparison of the graft edema presented at conjuntivolimbal autograft The bevacizumab group exhibits more persistent, and significant graft edema on 2 nd month follow up after surgery

10. A-1 A-2 B-1 B-2 Two Cases of persistent post-surgical graft edema (Bevacizumab group) (A, B-1) shows severe graft edema 3 months after surgery. (A, B-2) shows normal connection between graft vessels and recipient vessels on ICG anterior segment angiography Authors hypothesize that the graft edema may be due to suppression of lymphangiogenesis induced by bevacizumab.

11. Complications Any pterygial recurrence: none Other ocular & systemic complication: none

12. 1. Vascular grading comparison: bevacizumab group/control group : 1.97±0.68/2.16±0.50 2. Pre-op bevacizumab injection group presented lower VEGF stain. → Subconjunctival injection of bevacizumab on pterygium region is effective in reducing the vascular thickness and oncurrence of VEGF in the histologic pterygium region. 3. Persistent auto-graft edema observed at the 8th week post op compared to the control group. → Bevacizumab inhibit lymphangiogenesis as well as angiogenesis. → The delay of surgical wound healing must be put into consideration when using bevacizumab before pterygium surgeries. Conclusions