Endocrine Abstracts

Our recent studies have localised 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1), 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 CBX reduced IOP in patients with ocular hypertension (OHT) who are at risk of glaucoma, a leading cause of blindness in the Western world.

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 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.

There was an overall reduction of IOP by 10% following the ingestion of CBX (P<0.0001). Compared to baseline values (right eye (RE) 22.7 (21.6-23.9) mmHg, left eye (LE) 21.5 (20.0-22.9) mmHg (mean, 95% confidence interval), a significant reduction was seen when patients were treated with CBX (RE 20.5 (19.3-21.7) mmHg, p=0.0003, and LE 19.6 (18.5-20.9) mmHg, p=0.0053), but not when the patients were taking placebo or during the intermediate washout stage. Blood pressure remained stable throughout the study.

These data suggest that 11 beta HSD1 may provide a novel therapeutic target for patients with elevated IOP.