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T.T. Wong, A.L. Mead, P.T. Khaw; Long Term Modulation of Ocular Scarring by Matrix Metalloproteinase Inhibition - Comparison with Mitomycin-C Treatment following Experimental Glaucoma Filtration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4291.
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Purpose: Matrix metalloproteinases (MMPs) are important modulators of the healing response. Excess post-operative scarring following glaucoma surgery leads to surgical failure and poor intraocular pressure control. We investigated whether MMP inhibition could modulate long-term subconjunctival scarring following glaucoma surgery. Methods: Using an experimental model of filtration surgery, the effect of subconjunctival injections of Ilomastat on post-operative healing was determined and compared to Mitomycin-C. Intraocular pressure and clinical signs of scarring were recorded. Results: Surgical outcome was significantly improved with Ilomastat (Log Rank p=0.001) compared to vehicle. Treatment with Ilomastat resulted in bleb survival comparable to MMC-treated animals (Log Rank p=0.0163). Mean bleb survival in the three treatment groups were as follows, vehicle 15.2 days; Ilomastat 50.2 days, and MMC 56.3 days. Ilomastat treatment resulted in the development of diffuse functioning blebs that retained normal conjunctival appearance. This contrasted with the cystic, avascular appearance of MMC blebs. Intraocular pressure remained low post-operatively with both Ilomastat and MMC (Log rank p=0.033). Conclusions: The long-term healing response following surgery can be effectively modulated by inhibiting MMP activity. Not only did Ilomastat improve surgical outcome, its long-term anti-scarring effect was comparable to MMC. However, unlike MMC treatment, Ilomastat treated blebs were diffuse and retained normal conjunctival appearance. By targeting these enzymes, a novel method of modulating wound healing may be developed and prove to be a valuable alternative to the use of antiproliferatives such as MMC in the control of long-term scarring in the eye.
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