Transcript Off-label subconjunctival Bevacizumab

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
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GREWAL EYE INSTITUTE
CHANDIGARH, INDIA
Financial Disclosures
None of the authors have any financial interest in this
presentation
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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.
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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
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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 antiVEGF 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.
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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).
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.
Material & Methods
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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.
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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)
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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
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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.
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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.