Dilraj Grewal MD

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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
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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
  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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Material Methods

• 5 glaucoma patients undergoing bilateral
  trabeculectomy were enrolled from the glaucoma
  clinic after written informed consent.
• The patients had an IOPgt21mmHg 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
  Dec13(6)454-60.

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Material Methods

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

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Results

• At one-week and 4-weeks following trabeculectomy,
  blebs injected with subconiunctival bevacizumab
  demonstrated less vascularity.
• Average pre-op IOP was 264mmH and at 4 weeks
  post surgery was 123mmHg 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.

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

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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.