1. v Dilraj Grewal MD SPS Grewal MD Rajeev Jain, MD G S Brar MD Evaluation of Sub-Conjunctival Bevacizumab as an antiproliferative agent in Glaucoma Filtering Surgery: Initial Experience GREWAL EYE INSTITUTE CHANDIGARH, INDIA

2. v Financial Disclosures None of the authors have any financial interest in this presentation

3. v To evaluate and compare bleb characteristics and grade bleb photographs following trabeculectomy augmented with Off-label Subconjunctival Bevacizumab using the Moorfields Bleb Grading System. Purpose

4. v Introduction Bleb failure is a major factor limiting the long- term success of trabeculectomy surgery. The process of bleb failure involves vascularization with fibroblast migration and eventual scarring of the fistula tract. Although VEGF is a unique mitogen specific to vascular endothelial cells, the signal cascade leading to fibroblast migration and proliferation involves a dynamic interplay between many proteins. Blocking the neovascular signal cascade with anti- VEGF proteins may lead to a decrease in fibroblast proliferation by affecting the supply of mitogenic cytokines such as fibroblast growth factor carried in by new vessel formation and decreasing the known synergism that exists between VEGF and fibroblast growth factor. BEVACIZUMAB INHIBITS NEOVASCULARIZATION

5. v 5 glaucoma patients undergoing bilateral trabeculectomy were enrolled from the glaucoma clinic after written informed consent. The patients had an IOP>21mmHg and were on maximum tolerated dose of antiglaucoma medication. Subconjunctival Bevacizumab (1 mg in temporal-base of bleb) was administered in surgical eye during trabeculectomy. Trabeculectomy was performed under local anesthesia. Intraocular pressure and bleb photographs were recorded at one, two and four-weeks post-surgery. Slitlamp photographs of bleb site on the superior conjunctiva with eye positioned in inferior gaze were graded according to Moorfields Bleb-Grading System 1 for the parameters of area (grades 1-5), height (grades 1-4) and vascularity (grades 1-5). Material & Methods 1.Wells AP, Crowston JG, Marks J, et al. A pilot study of a system for grading of drainage blebs after glaucoma surgery. J Glaucoma. 2004 Dec;13(6):454-60.

6. v Off-label subconjunctival Bevacizumab (1 mg/0.1ml in temporal-base of bleb) was administered at the end of trabeculectomy. Material & Methods

7. v At one-week and 4-weeks following trabeculectomy, blebs injected with subconiunctival bevacizumab demonstrated less vascularity. Average pre-op IOP was 26±4mmH and at 4 weeks post surgery was 12±3mmHg reduction demonstrating an average reduction of14mmHg for bevacizumab administered blebs. None of the patients required a repeat surgery. No bleb leaks or adverse events were observed in any eye. Results

8. Day 1 IOP OU 10mmHg Week 2 IOP OU 10mmHg Week 4 IOP OU 10mmHg Pre Op IOP OU 26 mmHg

9. Compare the Calibre of Blood vessels, number of Blood vessels, and the cabillary bed (background red hue)

10. v

11. v Since angiogenesis forms an integral part of wound healing which is an unwanted process in the postoperative period after glaucoma filtering surgery, bevacizumab as humanized antibody against vascular endothelial growth factor can be used in combination with conventional filtering surgery. Alternative or adjunctive administration of anti-angiogenic drug bevacizumab would help reduce the rate of bleb failure at an improved risk-benefit ratio. In addition to inhibiting the VEGF responsible for blood vessel endothelial migration and angiogenesis during the proliferative phase of wound healing it also has an inhibitory effect on the synergistic effect of VEGF and Fibroblast growth factor (FGF). The consequent decrease in the fibroblast activity would also inhibit the main factor responsible for bleb failure. This low-cost, safe drug can have a significant role to play in improving the success of GFS and the consequential benefits in terms of improved quality of life and the cost savings on IOP lowering topical drops or re-surgery are significant This strengthens the concept of using angiogenesis inhibitors to inhibit fibroblast cells in bleb healing. Discussion

12. v Conclusion Subconjuctival Bevacizumab is a viable adjunct treatment following trabeculectomy for preventing bleb failure. Its role in reducing the vascularity and area of bleb may help to increase the survival rate and function of blebs specially those exhibiting increased vascularity post surgery.