Title: Glaucoma Risk Prediction in ocular hypertension (GRIP): a cohort study using electronic medical records to validate a risk predictor and determine the cost-effectiveness of different monitoring schemes according to risk of conversion to glaucoma
Funder: Public Health Agency, NI

Abstract: Glaucoma is a common eye condition that can lead to loss of vision if not identified and treated early. One factor which can increase the chance of developing glaucoma is ocular hypertension (high eye pressure), which is usually detected during an eye health test at the optometrist. Eye pressure is considered to be high if it is above 21 mmHg. _x000D_ In the UK around 1.3 million adults have ocular hypertension, and although many of these people will not develop glaucoma, treatment may be required to stop this happening. It is expected that the number of people with ocular hypertension will increase in the future. Those with the condition are typically monitored in hospital eye services, which are costly to the NHS and can be inconvenient for patients. Current guidance in the UK recommends treatment with eye drops if the eye pressure is greater than 24 mmHg, but it is not known if people with mild elevation of eye pressure (22-23 mmHg) may benefit from treatment. For patients, treatment means having laser treatment and/or using eye drops on a daily and lifelong basis, which patient engagement work performed by the research team revealed to be ‘inconvenient and impractical without knowing if it stops the progression to glaucoma’. Having a tool that can help doctors identify those at the greatest risk of progressing from ocular hypertension to glaucoma would both support clinical decision-making, and improve information that can be given to patients regarding the status of their condition. Although a ‘glaucoma risk calculator’ has previously been developed from data from two trials (called OHTS-EGPS), the National Institute for Heath and Care Excellence (NICE) does not recommend this for use in the NHS, because it is biased and has not been tested in UK patients. _x000D_ In 2017 NICE identified ‘Risk tools to identify risk of developing chronic open angle glaucoma and risk of sight loss’ as a top research recommendation. Another top research recommendation was: “What is the clinical and cost effectiveness of treating an IOP of 22 or 23 mmHg in people with normal optic discs and visual fields?” Our research aims to answer these research priorities by improving the OHTS-EGPS risk calculator and investigating if it is valuable to treat people with IOP of 22 or 23 mmHg. For this purpose we will review the NHS electronic medical records of over 23,000 people who have ocular hypertension and have been monitored at eleven hospital eye services across the UK. By reviewing vision tests (called visual field tests) we will be able to determine whether glaucoma developed. Together with data acquired in routine hospital visits we aim to improve and validate the glaucoma risk calculator so that it is suitable for use in the NHS. _x000D_ We will then explore the value for the NHS of using a UK validated risk prediction tool for different follow-up intervals, according to risk. Patients values and experiences regarding management of ocular hypertension will be explored with focus groups and interviews and their preferences will be formally assessed. This is crucial to understand how best we can incorporate this tool within NHS standard clinical practice, optimise the management of people with ocular hypertension and reduce costs related to the management of the condition. Our team includes experienced clinicians, researchers and two PPI members. Glaucoma UK charity will provide advice. Plans for dissemination of the results and impact have been detailed.

Lay abstract: Background: POAG is a chronic eye disease and a leading cause of blindness; OHT, defined as an IOP > 21 mmHg, is a risk factor for POAG. A POAG risk predictor, the OHTS-EGPS model, is available but it’s generalisability to a UK population is uncertain._x000D_ _x000D_ Aim: To validate and update a risk predictor of OHT and to model the cost-effectiveness of alternative monitoring frequencies and pathways according to glaucoma risk._x000D_ Specific objectives: 1) to validate and update the OHTS-EGPS risk prediction model in a UK population with OHT; 2) to assess the relative efficiency of alternative monitoring pathways for people with OHT according to glaucoma risk compared with standard practice; 3) to determine the clinical and cost effectiveness of treating people with OHT with IOP of 22 or 23 mmHg._x000D_ _x000D_ Methods: Retrospective data analysis of electronic medical records of OHT patients from 11 Hospital Eye Services (HES). Conversion to POAG will be defined as two consecutive and reliable VFs with Glaucoma Hemifield Test ‘outside normal limits’._x000D_ _x000D_ Risk factors: age, ethnicity, IOP, vertical cup-to-disc ratio, central corneal thickness, VF pattern standard deviation, family history of glaucoma, systemic hypertension, diabetes mellitus, sex, and treatment. We will explore the role of Optical Coherence Tomography._x000D_ _x000D_ Sample: We will have access to over 42,000 patients with OHT and at least 5 years of follow-up. From this cohort we will have complete data including series of visual field tests from 20,000 patients._x000D_ _x000D_ Primary outcome: conversion to glaucoma in at least one eye within 5 years. _x000D_ _x000D_ Model updating and validation: The OHTS-EGPS risk prediction model will be applied to calculate the predicted risk of developing glaucoma in 5 years for each patient. For ocular predictors we will use the mean value of both eyes. Model performance will be assessed in terms of discrimination and calibration. Based on the outcome of the validation, we will update the model by adjusting the baseline risk, re-estimating regression coefficients, and exploring the addition of new candidate predictors. _x000D_ _x000D_ Sample size: We anticipate a conversion rate to POAG of 0.5% per year among low risk untreated OHT and 1% per year among high risk and treated OHT. Based upon person years of follow-up within centres and a conservative 0.5% per year conversion rate we anticipate 500 events which will be adequate to analyse our 11 candidate predictors._x000D_ _x000D_ Economic evaluation: we will (1) characterise the current cost of monitoring people with OHT; (2) conduct a model-based cost-utility evaluation comparing alternative treatment and monitoring strategies, with deterministic and probabilistic sensitivity analyses. We will do subgroup analysis for people with IOP of 22 and/or 23 mmHg. We will estimate the increased severity of glaucoma associated with delayed diagnosis in less frequent monitoring intervals. We will evaluate the acceptability of and preferences for new models of eye care based on the risk prediction._x000D_ _x000D_ Timeline: Duration: 24 months. Prefunding: protocol development and ethics approval. Months 1-6: data collection; Months 7-21: data cleaning and analysis, online calculator development, economic evaluation; Months 22-24: report writing and dissemination. _x000D_ _x000D_ Anticipated impact: An updated risk prediction tool will inform effective and efficient OHT management in the NHS. Dissemination will include scholarly outputs, and a knowledge transfer day with relevant stakeholders

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE