Title: A cross-sectional study to assess the clinical utility of modern visual function assessments in patients with inherited retinal disease
Funder: Department of Health and Social Care

Abstract: Research Question: Can we improve assessments of visual function to make them more appropriate in patients with genetic eye disease? Background Inherited retinal degenerations are the leading cause of blindness in the working age population in the United Kingdom. Retinitis pigmentosa (RP) is the most common type of inherited retinal degeneration. RP causes progressive night-time and peripheral vision loss. Within NHS eyecare the visual acuity letter chart is the most frequently employed test used to measure visual function. However, visual acuity in patients with RP is not affected until end-stages of disease. Visual acuity is therefore a poor visual function marker for many patients with early-to-moderate stage RP. More targeted tests that better reflect the vision changes caused by RP degeneration are required. We have shown alternative visual function tests are more sensitive to earlier visual changes in patients with two specific types of inherited retinal degeneration (choroideremia and RPGR-associated RP). These tests are now being used in current clinical trials. New clinical trials are under development for different types of RP, bringing some urgency to identify degeneration targeting tests of vision for these patients. This project will enable recommendations for more appropriate, more patient focused measures of visual function, that better reflects RP degeneration. Aims and objectives. To investigate the clinical utility of degeneration-targeting visual function tests in patients with retinitis pigmentosa (RP). We will evaluate the usefulness, benefits and limitations of a range of vision tests for use in patients with RP, where they have not been used before. As well as gain understanding of participant opinions about these alternative tests. We will use these results to make testing recommendations for RP clinical trials and subsequent patient care. Methods The project is a cross-section observation study, we will recruit 40 patients with RP and 40 age-matched controls. Each participant will complete a range of carefully selected vision assessments including visual acuity tests, microperimetry assessments and patient-reported outcomes. To explore participants opinions of study tests acceptability, we will purposively recruit a sub-sample of 20-25 study participants to take part in semi-structured telephone interviews. These will be recorded, transcribed, and analysed using thematic analysis. Timelines for delivery (Table 1) The 24-month project (part time &ndash; 2.5 days per week), includes 3 months for study set-up and15 months for data collection (1-2 participants per week). Leaving six months for data analyses culminating in peer-reviewed publications and test recommendations. We will hold at least 7 patient and public involvement meetings via video conferencing, throughout the project to ensure it remains patient focused. Anticipated impact and dissemination We have strong relationships with industry sponsors following our work on current clinical trials and therapeutic development. Therefore, we are uniquely positioned to make evidence-based recommendations that directly impact clinical trial design and subsequent patient care. We will publish our results and recommendations in optometry and ophthalmology peer-reviewed articles. The findings will also be presented at conferences and visual examination recommendations summarised and circulated to relevant regulatory bodies. Widespread dissemination is essential for greater patient benefit.

Lay abstract: Background & Aims In young people, retinitis pigmentosa (RP) remains one of the commonest causes of untreatable sight loss. RP is a group of eye diseases that causes vision loss that starts around the outside and moves inwards towards the centre, resulting in tunnel vision and reduced night-time vision, before leading to severe blindness. In 2020 a new gene therapy treatment for a specific type of RP was approved by the NHS, costing in excess of &pound;650,000 per patient. Despite this, current NHS vision tests are not very effective at measuring the treatment effects. Currently, in NHS eyecare vision is mainly measured using a letter chart. We call this visual acuity. However, this only measures one small part of central vision and is not able to detect vision changes such as tunnel vision caused by RP. A patient with RP, registered severely sight impaired and unable to see to carry out everyday tasks such as getting dressed often have normal visual acuity results. New tests have been designed that could be better at measuring RP vision changes.These include newly designed letter charts and computerised tests to assess the seeing area. Apart from our recent work, these tests have not been used before in patients with RP. This project will investigate which tests are the best ones to use. It will allow us to make recommendations for their use in RP patient care. The project is important and timely because other new, sight-saving treatments are being developed for other types of RP. It is essential we have the right tests that are more likely to show if these new RP treatments are safe and effective. Study Plan The study was developed with the support of a patient and public involvement (PPI) group. The study will take place at Oxford Eye Hospital and will include 40 patients with RP and 40 healthy volunteers. All participants will complete the same vision tests. The analyses will evaluate participant test performance and compare the results to standard visual acuity results. We want to see if the alternative tests can better discriminate between patients and healthy volunteers. We will speak to 20-25 participants after taking part in the study to find out their thoughts and feelings of the study tests. We want to see if any changes are needed to make the tests more RP patient friendly. Throughout the project, the PPI group will meet to discuss the projects progress and participant feedback to make sure the project remains patient focused. To encourage maximum patient benefit we will make sure the results reach as many individuals as possible involved in NHS eyecare and clinical trial development.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE