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 Dilraj Grewal MD SPS Grewal MD Rajeev Jain, MD G S Brar MD GREWAL EYE INSTITUTE CHANDIGARH, INDIA

Financial Disclosures • None of the authors have any financial interest in this presentation

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

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

Material & Methods • 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 System1 for the parameters of area (grades 1-5), height (grades 1-4) and vascularity (grades 1-5). • 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.

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

Results • 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.

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

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

Discussion • 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.

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.

Dilraj Grewal MD SPS Grewal MD Rajeev Jain, MD G S Brar MD

Dilraj Grewal MD SPS Grewal MD Rajeev Jain, MD G S Brar MD

Presentation Transcript

G S Brar MD Dilraj Grewal MD Rajeev Jain, MD SPS Grewal MD

Daniele Tognetto MD, Pia Leon MD, Paolo Cecchini MD, Silvia Rinaldi MD, Giuseppe Ravalico MD

A Kheirkhah MD, A Izadi MD, R Nazari MD H Hashemi MD, M Jabbarvand MD, H Hashemian MD

Dr. S.Chakravarty MBBS, MD MD

Megan Miller MD, Nancy Schindler MD, John Seal MD, Mark Russo MD

Michael P. Goldman, MD Sandhya S. Brachio, MD

Overview of Sleep Ritu G. Grewal, MD

Ahmet ALANAY, MD Cagatay OZTURK, MD Meric ENERCAN, MD Ibrahim ORNEK, MD Mehmet TEZER, MD

Anil Verma, MD, Nagesh S. Anavekar, MD, Alessandra Meris, MD,

Azmi HAMZAOGLU, MD Cagatay OZTURK, MD Ahmet ALANAY, MD Mehmet TEZER, MD Selhan KARADERELER, MD

Burcu Oktay MD , Sadık Ardıç MD, Hikmet Firat MD, Erdem Akbal MD, Ramazan Akdemir MD

Jane S. Kim MD, Linda Y. Kao MD, Ross Borzykowski MD, Benjamin H. Taragin MD

R Mehanna MD 1 ; AG Machado MD, PhD 2 ; S Oravivattanakul MD 2 ; G Genc MD 2 ; SE Cooper MD, PhD 2

HELVACIOGLU Firat , MD, SENCAN Sadik , MD, OGUZHAN Hasan, MD, YETER Celal, MD

MD’ s Question

Akiko Masai, MD, Tomoichiro Ogawa, MD Takuya Shiba, MD, Hiroshi Tsuneoka, MD

Melissa B Daluvoy MD, Ajoy S Virdi MD, Neelofar Ghaznawi MD,

Daisuke Aizawa,MD Kazutaka Kamiya,MD Tetsuya Ikeda,MD Kimiya Shimizu,MD

Carlos S. Morales, MD; Foula Kontonicolas MD;

Carlos G. Arce MD, Paulo Schor MD, Mauro Campos MD

George O. Waring IV, MD Daniel S. Durrie, MD Miranda Bishara, MD

Mustafa Serinken MD, Cenker Eken MD, Kamil Tunay MD, Yalcin Golcuk MD