title: Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.
abstract: BACKGROUND
  Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo.
  
  
  METHODS
  In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140.
  
  
  RESULTS
  We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug.
  
  
  CONCLUSIONS
  This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period.
  
  
  BACKGROUND
  Pfizer, UK National Institute for Health Research Biomedical Research Centre.
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. Electronic address: david.garway-heath@moorfields.nhs.uk.
authors.forename: David F
authors.initials: DF
authors.lastname: Garway-Heath
authors.affiliation: Department of Optometry and Visual Science, City University, London, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Crabb
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Catey
authors.initials: C
authors.lastname: Bunce
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Lascaratos
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Amalfitano
authors.affiliation: Huddersfield Royal Infirmary, Huddersfield, UK.
authors.forename: Nitin
authors.initials: N
authors.lastname: Anand
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Augusto
authors.initials: A
authors.lastname: Azuara-Blanco
authors.affiliation: Hinchingbrooke Hospital, Huntingdon, UK.
authors.forename: Rupert R
authors.initials: RR
authors.lastname: Bourne
authors.affiliation: Norfolk and Norwich University Hospital, Norfolk, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Broadway
authors.affiliation: Birmingham Heartlands and Solihull, Birmingham, UK.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cunliffe
authors.affiliation: Bristol Eye Hospital, Bristol, UK.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Diamond
authors.affiliation: Sunderland Eye Infirmary, Sunderland, UK.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Fraser
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Tuan A
authors.initials: TA
authors.lastname: Ho
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Martin
authors.affiliation: Cheltenham General Hospital, Cheltenham, UK.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: McNaught
authors.affiliation: Birmingham Heartlands and Solihull, Birmingham, UK.
authors.forename: Anil
authors.initials: A
authors.lastname: Negi
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Krishna
authors.initials: K
authors.lastname: Patel
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; Department of Optometry and Visual Science, City University, London, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Russell
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Ameet
authors.initials: A
authors.lastname: Shah
authors.affiliation: Bristol Eye Hospital, Bristol, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Spry
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Edward T
authors.initials: ET
authors.lastname: White
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Wormald
authors.affiliation: National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Wen
authors.initials: W
authors.lastname: Xing
authors.affiliation: University Hospitals Leuven, Leuven, Belgium.
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Zeyen
mesh_terms: D060433:Administration, Ophthalmic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D053208:Kaplan-Meier Estimate; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D016896:Treatment Outcome; D014794:Visual Fields / Q000187:drug effects; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost