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A.L. Mead, T.T. Wong, I.K. Anderson, P.T. Khaw; Maintenance of Long-term Bleb Function by Prolonged Treatment with CAT-152, an Anti-transforming Growth Factor-ß2 (TGF-ß2) Antibody: Enhanced Effects over 5-Fluorouracil (5-FU) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4292.
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Purpose Despite surgical advances and current anti-scarring strategies late bleb failure remains the major barrier to prolonged intraocular pressure (IOP) control after glaucoma filtration surgery (GFS). Few studies have addressed how to maintain long-term bleb function. CAT-152, a human IgG4 that neutralises TGF-ß2, improves GFS outcome in the short term. In this study we examined whether CAT-152 treatment could maintain long-term bleb survival. The effect of CAT-152 was compared to the therapeutic 5-FU, to benchmark the potential clinical benefit of CAT-152. The mechanism of action of CAT-152 was studied in cultured human fibroblasts. Methods The effect of CAT-152 on TGF-ß2 mediated collagen production and α smooth muscle actin (αSMA) expression from human cultures of conjunctival fibroblasts was determined. In a randomised, masked observer study, following modified GFS, 27 rabbits received an intra-operative and prolonged post-operative course of subconjunctival injections (100µl) of CAT-152 (1mg/ml), 5-FU (50mg/ml) or placebo (18 injections: Day 0-42). Bleb characteristics and reaction to treatment were assessed until day 45. Results TGF-ß2 caused a concentration dependent increase in collagen production and αSMA expression in conjunctival fibroblasts, which was completely inhibited by CAT-152. Repeated treatment with CAT-152 maintained bleb function for 45 days in 3 of 9 rabbits and markedly enhanced bleb survival compared to 5-FU or placebo (log rank p<0.001). Median bleb survival (days): CAT-152 41, 5-FU 27 and placebo 17. 5-FU caused corneal epitheliopathy (p=0.003). Conclusions Maintenance of long-term bleb function and morphology is achieved by combined intra-operative and repeated post-operative CAT-152. Efficacy is enhanced and the risk of side effects is reduced with CAT-152 treatment compared to 5-FU. CAT-152 appears to inhibit TGF-ß2 mediated collagen production and myofibroblast differentiation in the bleb tissue. Prolonged administration of CAT-152 may provide a novel, safe approach to the maintenance of bleb function after GFS and enable long-term IOP control.
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