BackgroundPatients diagnosed with advanced primary open-angle glaucoma are at a high risk of lifetime blindness. Uncertainty exists about whether primary medical management (glaucoma eye drops) or primary surgical treatment (augmented trabeculectomy) provide the best and safest patient outcomes.ObjectivesTo compare primary medical management with primary surgical treatment (augmented trabeculectomy) in patients with primary open-angle glaucoma presenting with advanced disease in terms of health-related quality of life, clinical effectiveness, safety and cost-effectiveness.DesignThis was a two-arm, parallel, multicentre, pragmatic randomised controlled trial.SettingSecondary care eye services.ParticipantsAdult patients presenting with advanced primary open-angle glaucoma in at least one eye, as defined by the Hodapp–Parrish–Anderson classification of severe glaucoma.InterventionPrimary medical treatment – escalating medical management with glaucoma eye drops. Primary trabeculectomy treatment – trabeculectomy augmented with mitomycin C.Main outcome measuresThe primary outcome was health-related quality of life measured with the Visual Function Questionnaire-25 at 2 years post randomisation. Secondary outcomes were mean intraocular pressure; EQ-5D-5L; Health Utilities Index 3; Glaucoma Utility Index; cost and cost-effectiveness; generic, vision-specific and disease-specific health-related quality of life; clinical effectiveness; and safety.ResultsA total of 453 participants were recruited. The mean age of the participants was 67 years (standard deviation 12 years) in the trabeculectomy arm and 68 years (standard deviation 12 years) in the medical management arm. Over 65% of participants were male and more than 80% were white. At 24 months, the mean difference in Visual Function Questionnaire-25 score was 1.06 (95% confidence interval –1.32 to 3.43;p = 0.383). There was no evidence of a difference between arms in the EQ-5D-5L score, the Health Utilities Index or the Glaucoma Utility Index. At 24 months, the mean intraocular pressure was 12.40 mmHg in the trabeculectomy arm and 15.07 mmHg in the medical management arm (mean difference –2.75 mmHg, 95% confidence interval –3.84 to –1.66 mmHg;p < 0.001). Fewer types of glaucoma eye drops were required in the trabeculectomy arm. LogMAR visual acuity was slightly better in the medical management arm (mean difference 0.07, 95% confidence interval 0.02 to 0.11;p = 0.006) than in the trabeculectomy arm. There was no evidence of difference in safety between the two arms. A discrete choice experiment updated the utility values for the Glaucoma Utility Index. The within-trial economic analysis found a small increase in the mean EQ-5D-5L score (0.04) and that trabeculectomy has a higher probability of being cost-effective than medical management. The incremental cost of trabeculectomy per quality-adjusted life-year was £45,456. Therefore, at 2 years, surgery is unlikely to be considered cost-effective at a threshold of £20,000 per quality-adjusted life-year. When extrapolated over a patient’s lifetime in a model-based analysis, trabeculectomy, compared with medical treatment, was associated with higher costs (average £2687), a larger number of quality-adjusted life-years (average 0.28) and higher incremental cost per quality-adjusted life-year gained (average £9679). The likelihood of trabeculectomy being cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life year gained was 73%.ConclusionsOur results suggested that there was no difference between treatment arms in health-related quality of life, as measured with the Visual Function Questionnaire-25 at 24 months. Intraocular pressure was better controlled in the trabeculectomy arm, and this may reduce visual field progression. Modelling over the patient’s lifetime suggests that trabeculectomy may be cost-effective over the range of values of society’s willingness to pay for a quality-adjusted life-year.Future workFurther follow-up of participants will allow us to estimate the long-term differences of disease progression, patient experience and cost-effectiveness.Trial registrationCurrent Controlled Trials ISRCTN56878850.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 25, No. 72. See the NIHR Journals Library website for further project information.