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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 INSTITUTECHANDIGARH, INDIA

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Financial Disclosures

None of the authors have any financial interest in this

presentation

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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

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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

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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).

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.

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Off-label subconjunctival Bevacizumab (1 mg/0.1ml in

temporal-base of bleb) was administered at the end of

trabeculectomy.

Material & Methods

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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

Day 1 IOP OU

10mmHg

Week 2IOP OU 10mmHg

Week 4IOP OU

10mmHg

Pre OpIOP OU 26

mmHg

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

red hue)

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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

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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.