Translating the UK Glaucoma Treatment Study

The results from the United Kingdom Glaucoma Treatment Study (UKGTS), which provide strong evidence for the vision-preserving benefit of intraocular-pressure-lowering topical medications, should help clinicians to make more informed choices about the day-to-day management of their glaucoma patients, according to David F Garway-Heath MD, FRCOphth. “The UKGTS results provide strong evidence for the vision-preserving effects of IOP lowering by latanoprost. A 20% IOP reduction was associated with a relative risk reduction of visual field progression by 50%. Some patients progress rapidly and close monitoring and treatment escalation may be needed, whereas other patients may not need immediate treatment because they are at low risk of visual disability during their lifetimes,” he told delegates at a Glaucoma Day session at the XXXV ESCRS Congress in Lisbon, Portugal. Dr Garway-Heath, International Glaucoma Association Professor of Ophthalmology at the UCL Institute of Ophthalmology, London, UK, said that UKGTS is the first randomised, triple-masked, placebo-controlled trial to assess the benefit of topical treatment for reduction of loss of vision in patients with open-angle glaucoma (OAG). “There was a lack of evidence of the protective effect of prostaglandins in the scientific literature. We were interested in rectifying that and looking at quality of life and visual field progression for our patients, not simply IOP alone, which is the way most glaucoma drugs are evaluated in clinical trials,” said Dr Garway-Heath. Another motivation for the UKGTS is the current duration of glaucoma clinical trials, said Dr Garway-Heath. “The typical observation periods for therapeutic trials with visual field deterioration as an outcome are four years or longer. Longer trials increase the cost of drug development and delay bringing benefit to patients. We wanted to see if we could design a trial that would help shorten that timeline and bring treatments more quickly to patients,” he said. In order to achieve this, the study was designed to measure progression quickly, drawing on research by Professor David Crabb at City, University of London, that shows that identification of progression is improved by clustering tests at the beginning and end of a two-year follow-up period compared to the traditional three VF tests per year evenly spaced over the same period. The primary hypothesis of the UKGTS was that treatment with a topical prostaglandin analogue (latanoprost) reduces the incidence of VF deterioration events compared with placebo by 50% over a two-year observation period, said Dr Garway-Heath. He noted that the design was modelled closely on the Early Manifest Glaucoma Trial (EMGT) in order to facilitate future meta-analysis of the data. Baseline mean intraocular pressure was 19.6mmHg in 258 patients in the latanoprost group and 20.1mmHg in 258 controls. At 24 months, the mean reduction in IOP was 3.8mmHg in 231 patients in the latanoprost group and 0.9mmHg in 230 patients in the placebo group. “The pressure reduction of almost 20% for the latanoprost group is less than that usually seen in clinical trials. This is because pharmaceutical companies usually put in patients with very high IOPs in order to achieve large pressure reductions. By contrast, our patients were newly diagnosed without a pressure criterion,” he said. Visual field preservation was also significantly longer in the latanoprost group than in the placebo group, noted 
Dr Garway-Heath. “The relative risk reduction was 50%, so it is a strong treatment effect on VF progression. To put it in context, it means that we need to treat eight patients with glaucoma in order to prevent one VF progression in a two-year time period,” he said. In terms of translating the results to real-life practice, Dr Garway-Heath said that it is important to treat glaucoma patients on an individual level, monitoring them with quality of life, likely visual disability and life expectancy in mind. He pointed out that based on the UKGTS data, two-thirds of patients have no measurable progression without any treatment over a two-year period. “Even with longer follow-up in the EMGT trial, one-third of patients after seven years had no measurable progression. That is a lot of patients who are not going to get a lot worse even if the treating physician does nothing,” he said. Treatment intensity can be low in low-risk patients, but they need to be followed for progression. Other patients may progress rapidly despite treatment, in which case careful monitoring and greater treatment intensity are called for, he said. While the treatment target is typically a compromise between reducing the risk of symptomatic vision loss and the adverse consequences of therapy, patient preferences should also be taken into account, said Dr Garway-Heath. “At the end of the day, treatment is the patient’s choice – we need to advise patients of the risks of symptomatic vision loss, match the treatment intensity to the risk, and monitor for progression,” he concluded. David F Garway-Heath: 
david.garway-heath@moorfields.nhs.uk

Tags: glaucoma