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Invest Ophthalmol Vis Sci 2002;43: E-Abstract 3332.
© 2002 ARVO

Anti-TGFß2 Antibody (CAT-152) as a New Post-Operative Modulator of Scarring after Experimental Glaucoma Filtration Surgery

AL Mead1, TT L Wong1, IK Anderson2, MF Cordeiro1 and PT Khaw1

1 Wound Healing Research Unit Institute of Ophthalmology London United Kingdom
2 Cambridge Antibody Technology Melbourn Cambridge United Kingdom

Commercial Relationships:   A.L. Mead, Cambridge Antibody Technology F; T.T.L. Wong, None; I.K. Anderson, None; M.F. Cordeiro, None; P.T. Khaw, None.

Abstract

Purpose: We have demonstrated that a novel human monoclonal antibody that neutralises Transforming Growth Factor ß2, CAT-152 (lerdelimumab), improves glaucoma filtration surgery outcome by inhibiting subconjunctival fibrosis. This was first shown in our experimental model of aggressive scarring, using a regimen of both intra- and post-operative subconjunctival injections of CAT-152. CAT-152 is currently undergoing multicentre clinical trials. The purpose of the present study was to determine if post-operative application of CAT-152 alone could prevent scarring, and to compare CAT-152 with 5-fluorouracil (5-FU), the current gold standard post-operative anti-scarring agent. Methods: In a randomised, masked observer study, following modified glaucoma surgery, 54 rabbits were randomly allocated to receive a post-operative course of seven subconjunctival injections (100µl) between days 2 and 14 of CAT-152 (1mg/ml), 5-FU (50mg/ml) or no treatment. Bleb characteristics, successful drainage and local reaction to treatment were assessed. Animals were sacrificed on days 10, 21 and 30 and the tissue was processed to demonstrate subconjunctival architecture and extracellular matrix deposition. Results: CAT-152 significantly improved surgical outcome compared to 5-FU and control (log rank p<0.001). Mean bleb survival (days): CAT-152 24.6, 5-FU 19.5 and control 16.8. CAT-152 treatment improved bleb morphology (p<0.05) and was well tolerated. 5-FU prolonged the duration of corneal epitheliopathy(p<0.01). Conclusions: Post-operative administration of CAT-152 significantly improved surgical outcome and reduced the risk of corneal side effects compared to the gold standard anti-scarring agent 5-FU. These findings suggest that CAT-152 may have a potential therapeutic role as a post-operative agent to prevent subconjunctival scarring after glaucoma filtration surgery.

Keywords: 631 wound healing • 423 growth factors/growth factor receptors • 316 animal model

© 2002, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.




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