The Effect Of A Water Soluble Matrix Metalloproteinase Inhibitor On Prolonging Bleb Survival In An Experimental Animal Model

Abstract

Purpose: : The perioperative application of a sustained release matrix metalloproteinase inhibitor (MMPi) is a potential non-toxic alternative to mitomycin C (MMC) for prolonging bleb survival in glaucoma surgery. One key challenge in development is to optimise the pharmacokinetics to ensure drug concentrations are maintained to inhibit the scarring process. We aimed to determine whether marimastat, a highly water soluble MMPi (3.38 mg/ml), was able to prolong bleb survival in an experimental animal model.

Methods: : A randomised, prospective, masked, single observer in vivo study over 30 days was conducted. Glaucoma filtration surgery was performed on 18 New Zealand White rabbits. The rabbits received perioperatively one of three potential subconjunctival treatments, randomised according to a Latin Square

Results: : The marimastat treated rabbits had blebs that failed at a median of 24 days (range 21 - 24). The sterile water treated group failed at a median of 18 days (range 12 -21). Of the MMC treated group one animal had a bleb that failed at day 27 and the other 5 survived until day 30. The differences in bleb survival between the MMC and marimastat groups, and the marimastat and water groups were statistically significant (log rank p = 0.001 and 0.01 respectively).

Conclusions: : Marimastat implants do appear to prolong bleb survival in this animal model but may release too quickly. Further research is needed to refine drug release to optimise the effects of marimastat.

Keywords: wound healing • enzymes/enzyme inhibitors • conjunctiva