Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery.
OBJECTIVE
Postoperative subconjunctival wound healing remains the commonest cause of late bleb failure after glaucoma filtration surgery. This study was undertaken to investigate whether the human monoclonal antibody that neutralizes transforming growth factor-beta2 (CAT-152; lerdelimumab) could be used as a postoperative agent to prevent scarring after glaucoma surgery and compared it with 5-fluorouracil (5-FU), to benchmark its potential clinical benefit.


METHODS
In a randomized, controlled, masked-observer study, after modified glaucoma surgery, 48 rabbits were randomly allocated to receive a postoperative course of seven subconjunctival injections of CAT-152 (1 mg/mL), 5-FU (50 mg/mL), or no treatment. Bleb characteristics, the presence of subconjunctival drainage, and local reaction to treatment were assessed. Animals were killed on days 10, 21, and 30. Immunohistochemistry, histologic staining and electron microscopy were performed to demonstrate the mechanism of CAT-152-mediated effects on the extracellular matrix.


RESULTS
CAT-152 significantly improved surgical outcome (log rank test, P < 0.001) and reduced subconjunctival collagen deposition (P < 0.01) compared with 5-FU and control. Median bleb survival was increased in the CAT-152 group (23.5 days) compared with the 5-FU (20 days) and control (16 days) treatment groups. 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
Postoperative administration of CAT-152 significantly improved surgical outcome, reduced subconjunctival scarring, and minimized the risk of corneal side effects compared with the anti-scarring agent 5-FU. These findings suggest that CAT-152 may offer therapeutic benefit as a postoperative agent to prevent subconjunctival scarring after glaucoma filtration surgery.
Mead
Anna L
AL
Wound Healing Unit, Institute of Ophthalmology, London, United Kingdom. a.mead@ucl.ac.uk
Wong
Tina T L
TT
Cordeiro
M Francesca
MF
Anderson
Ian K
IK
Khaw
Peng T
PT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002921:Cicatrix / Q000188:drug therapy* / Q000473:pathology; D003229:Conjunctival Diseases / Q000188:drug therapy* / Q000473:pathology; D005355:Fibrosis / Q000517:prevention & control; D018463:Filtering Surgery; D005901:Glaucoma / Q000601:surgery*; D007267:Injections; D011183:Postoperative Complications / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000276:immunology*; D053781:Transforming Growth Factor beta2; D014945:Wound Healing / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; C475848:Lerdelimumab