Abstract
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