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CM G Cheung, S Rauz, PI Murray, PM Stewart; Systemic Carbenoxolone Reduces Intraocular Pressure in Patients with Ocular Hypertension . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4079.
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Purpose: Our recent studies have localised 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), an isozyme which activates cortisol from cortisone, to the human ocular non-pigmented ciliary epithelium, and in an open blinded study conducted on healthy male volunteers, systemic inhibition of this isozyme with oral carbenoxolone (CBX) resulted in a 17% reduction of intraocular pressure (IOP). The aim of this study was to evaluate whether inhibition of 11ß-HSD1 reduced IOP in patients with ocular hypertension (OHT) Methods: Sample size calculations, aiming for a power of 0.9, indicated that 20 patients would be needed to demonstrate a significant drop in IOP following ingestion of CBX at a confidence level of 99%. A randomised, double-blind, placebo-controlled, cross-over trial assessing the effects of oral CBX (100mg three times a day for 4 days) or placebo, on IOP in OHT patients was conducted. Patients with systemic hypertension, underlying endocrine disease and those on exogenous steroids were excluded. IOP readings were taken every 10 minutes for 30 minutes at 5pm on days 1 (Baseline), 5 (Treatment A (CBX or placebo) day 4), 15 (Washout day 10) and 19 (Treatment B day 4) of the study. Blood pressure was measured throughout the study. Statistical analysis was by ANOVA. Results: Following ingestion of CBX there was an overall reduction of IOP by 10% when compared to baseline (p < 0.0001). There was a significant reduction in the IOP in each eye when patients were treated with CBX (right eye p = 0.0003, left eye p = 0.0053) but not when they were taking placebo or during the intermediate washout stage. Blood pressure remained stable throughout the study. Conclusion: These data suggest that 11ß-HSD1 could provide a novel target for treating patients with elevated IOP.
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