1. CC Teng Effect of Subconjunctival Bevacizumab on Pterygiums Christopher C. Teng, MD 1,2 Lawrence Jacobson, MD 1 1 New York University School of Medicine and 2 Manhattan Eye, Ear and Throat Hospital, New York, New York Supported by an American Society of Cataract and Refractive Surgery (ASCRS) foundation research grant

2. CC Teng Precis: Subconjunctival injection of bevacizumab can cause regression of pterygiums and may serve as a useful adjunctive to medical and surgical management Introduction Pterygia can vary from small, atrophic quiescent lesion to large, rapidly growing fibrovascular lesions. Pathologically, pterygia have been described as elastotic degeneration of collagen with fibrovascular proliferation and are thought to be caused by immunologic, environmental (ultraviolet light exposure) and genetic factors. Pterygia have increased levels of angiogenic growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).

3. CC Teng VEGF is has been shown to play a critical role in angiogenesis. Bevacizumab is a full-length humanized monoclonal antibody against VEGF. Given that bevacizumab works on blocking VEGF in the proliferation of blood vessels, a subconjunctival injection of bevacizumab should cause vessel regression and prevent the formation of new ones. We injected subconjunctival bevacizumab into a pterygium and monitored it for 7 weeks.

4. CC Teng A 54 year-old man presented with a 3+ red, inflamed nasal pterygium on his left eye for 1 month, refractory to naphazoline and artificial tears. The pterygium had been progressively growing for 3 years and was causing frequent episodes of eye irritation. Treatment options were discussed, including non-steroidal and steroid drops, surgery and subconjunctival injection of bevacizumab. The experimental nature of bevacizumab was explained; the patient considered his options and opted for injection. Informed consent was signed and following 1 drop of topical anesthetic and moxifloxacin, 0.05 ml of bevacizumab (1.25 mg per 0.05 ml) was injected into the leading edge of the pterygium. The Case

5. CC Teng The characteristics used to gauge medication efficacy were based on irritation, vascularization and color; graded on a scale of 0 to 4 (0= unremarkable, 1= trace, 2= mild, 3= moderate, 4= diffuse). Pre-injection pterygium grade was irritation= 3, vascularization= 3 and redness= 3. Vision without correction was OD 20/20, OS 20/25. At one week post-injection, irritation improved to a grade of 0, the conjunctiva showed injection= 1 and the vessels comprising the pterygium showed marked regression, improving from 3 prior to injection to 1 after. At 2 weeks, the pterygium maintained this appearance. After 7 weeks, the pterygium regressed to its pre- injection state.

6. CC Teng Pre injection and 1 week post injection Note the regression of corneal neovascularization Pre-injection pterygium: Grade: Irritation= 3, vascularization= 3 redness= 3 Post Injection Pterygium at 1 week: Grade: Irritation= 0, vascularization= 1 redness= 1

7. CC Teng Discussion Pterygiums are composed of proliferating fibrovascular tissue and gradually increase in size over time; new formation of blood vessels must accompany the proliferating tissue. Studies have shown that angiogenic factors are active in pterygium formation, specifically an increase in bFGF and VEGF expression and decrease in pigment epithelium derived growth factor (PEDF), which is an endogenous angiogenic inhibitor.

8. CC Teng We injected bevacizumab, an anti-VEGF inhibitor, into the leading edge of a pterygium and our results demonstrated regression in pterygium vascularization and color, with decreased symptoms of the patient. When the patient presented, he had a vascularization level, irritation level and color of pterygium all graded at 3. One week after the injection his symptoms subsided to 0 and the vascularization and color regressed to 1. This level was maintained for 2 weeks, upon which the pre-injection state gradually returned.

9. CC Teng Subconjunctival bevacizumab was well tolerated and decreased irritation, vascularization and color of the pterygium. Reduction in pterygium vascularization suggests that anti-VEGF therapy may have a role in the treatment of inflamed pterygiums refractory to alternative treatments. Although the duration of improvement was not sustained, the response to treatment was promising and no side effects were noted. Further studies exploring topical and subconjunctival applications of bevacizumab and as an adjunctive to surgical pterygium removal are warranted.

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