Latanoprost treatment for open angle glaucoma. The United Kingdom Glaucoma Treatment Study: a multicentre, randomised, placebo-controlled clinical trial

BACKGROUND: Treatment of open-angle glaucoma (OAG) aims to prevent vision loss by lowering intraocular pressure (IOP), yet there has been no previous placebo-controlled medical treatment trial assessing vision function preservation. Observation periods in previous (unmasked) trials assessing visual function have typically been at least 5 years. The aim of this study was to assess vision preservation by latanoprost treatment compared to placebo. METHODS In this randomised, triple-masked, placebo-controlled trial, patients with newly-diagnosed OAG were enrolled at 10 UK centres (tertiary referral centres, teaching hospitals, and district general hospitals) between Feb 2007 and Mar 2010. Eligible patients were randomly allocated (1:1) to receive either latanoprost 0·005% or placebo eye drops, provided in identical bottles, once daily to both eyes. Randomization was in permuted blocks stratified by participating centre. The primary hypothesis was that latanoprost treatment reduces incident visual field (VF) deterioration, compared with placebo, by 50% over 2 years. The primary outcome was VF deterioration: 3 locations in the Pattern Deviation Glaucoma Change Probability maps worse than baseline in 2 consecutive VFs, present in 2 consecutive VF pairs. The primary analysis was VF survival in the intention-to-treat population. The trial was terminated in July 2011 on the recommendation of the independent data monitoring committee following an interim analysis. Trial registration number: ISRCTN96423140. FINDINGS: 516 patients were randomised and data on all subjects with post-allocation data (461) were analysed. 18 serious adverse events were reported, none attributable to the study drug. Baseline mean (SD) IOP was 19·6 (4·6) mmHg and 20·1 (4·8) mmHg, and IOP reduction at 24 months 3·8 (4·0) mmHg and 0·9 (3·8) mmHg, in the latanoprost and placebo groups, respectively. Incident VF deterioration (95% CI) by 24 months was 15·0% (10·8, 20·0) in the latanoprost group and 24·8% (19·5, 30·7) in the placebo group (P=0·007). VF survival was significantly longer in the latanoprost group: at 24 months, adjusted hazard ratio (HR) 0·44 (0·28, 0·69) (P=0·0003). The difference between treatment groups was evident after only 12 months, HR 0·47 (0·23, 0·95) (P=0·035). INTERPRETATION: This is the first placebo-controlled trial to demonstrate VF preservation with an IOP-lowering agent in OAG. The study design enabled a relatively short observation period. FUNDING: Pfizer Inc.; UK National Institute for Health Research Biomedical Research Centre