Title: Low vs. high-intensity occlusion therapy for mild/moderate amblyopia: A randomised, controlled feasibility trial
Funder: Department of Health and Social Care

Abstract: Aims To conduct a feasibility study comparing low versus high-intensity occlusion regimens, in children aged 4-17 years with mild/moderate amblyopia. Background Amblyopia (lazy eye) is a neuro-developmental condition causing reduced visual function predominantly in one eye. It affects approximately 3.6% (230,000) children under 7 years in the UK. Current gold-standard treatment involves full-time glasses wear if required and monitoring for improvement over time (commonly 3-6 months). 75% of cases require additional treatment by penalisation of the 'fellow', better-seeing eye, commonly achieved using a patch (occlusion therapy). To reduce the burden of occlusion, treatment is aimed at delivering the minimum effective dose (in hours) per day. However, adherence to treatment remains poor, and 67% of children with mild/moderate amblyopia do not achieve equal vision with part-time occlusion. It is not known if initial low-intensity occlusion (2 hours daily) prolongs treatment, increases total prescribed dose and treatment costs, and negatively impacts final visual outcomes. Evidence suggests that high-intensity (full-time) occlusion could yield faster responses and better outcomes, but there are limited contemporary data available about outcomes from high-intensity treatments to design a randomised-controlled trial (RCT). Thus, I plan to undertake a randomised-controlled, single-blinded feasibility trial of low versus high-intensity occlusion to inform the design of a future RCT. Methods Patients, their parents, and the public were involved in the study design. Children aged 4 years and older, with mild/moderate amblyopia will be randomised into treatment groups using computer-generated permuted block randomisation, stratified by site and age, and will be asked by DEP to perform either 'treatment-as-usual' (TAU, 2 hours daily occlusion, increasing to 6 hours in cases of arrested improvement and residual amblyopia, monitored every 8-12 weeks) or full-time occlusion (FTO) monitored every 5 weeks (1 week). Examiners will be masked to the treatment group. Visual acuity (VA) and objective (dose-monitored) and subjective adherence to treatment will be measured every visit. Approximately 200 eligible children are seen each year at Moorfields Eye Hospital. Based on previous research, we anticipate achieving a sample of 60 children. Semi-structured interviews with all children and their parents will explore barriers to treatment adherence, and willingness to be randomised. Views will be sought from 30 clinicians about barriers to, and likelihood of, uptake of high-intensity treatment into clinical practice. The Fellowship will be used to build on collaborations with clinicians, psychologists, implementation scientists, health economists, and clinical trial units to deliver a future trial and build relationships for a future programme of amblyopia treatment research. Anticipated impact and dissemination Data from this feasibility study will be used in a planned future RCT to address unanswered questions about treatment optimisation and improving outcomes in children with amblyopia. Findings will be co-presented with a patient representative at relevant national and international clinical and scientific meetings and published in peer-reviewed journals. A summary of findings will be published for patients via hospital newsletter and Orthoptists through professional networks, utilising social media to raise awareness. Publication 'BITEs' (Brokering Innovation Through Evidence) will be used to engage the public in research findings.

Lay abstract: AIM This study will compare low vs. high treatment doses for patching (occlusion therapy) children with lazy eye (amblyopia) to support the design of a future study. BACKGROUND Amblyopia is an eye and brain condition that affects about 230,000 children under 7 years in the UK. It affects the way eyesight develops, causing blurred vision. It is commonly caused by misalignment of the eyes (squint) and/or a need for glasses. Amblyopia usually only affects one eye. Commonly, children aged 4-5 years in the UK are tested through school-entry vision screening. Children with reduced vision are then referred to a hospital or community eye service. Treatment is most effective in children under 8 years. The first stage of treatment involves prescribing glasses, if required, and monitoring if vision improves over time (usually 3-6 months) as the brain adapts to a clear image. In children whose vision does not improve to normal levels with glasses alone, further treatment is required. This is most commonly achieved by covering the better-seeing or normal eye for a number of hours per day, called 'patching' or 'occlusion therapy'. Patching is often difficult for children and many suffer from bullying. Treatment is often unsuccessful. Research over the last 20 years has focussed on investigating the minimum number of hours of patching required each day to achieve a treatment effect. Evidence shows 2 hours daily patching (low-intensity treatment) works, but usually takes a number of months, and sometimes years. Adherence to treatment drops dramatically over time. It costs the NHS approximately 314m to treat 230,000 children with amblyopia. Full-time patching (high-intensity treatment) could produce faster improvements in vision, and better final outcomes, shortening treatment and reducing costs, but there isn't enough information about the treatment to appropriately design a clinical trial to compare low vs. high-intensity patching. Patients, their parents and the public have been involved in the design of the proposed study, and will provide oversight of all future work. RESEARCH QUESTION In children aged 4 years and older with amblyopia, does low or high-intensity patching produce a better vision outcome? This study will provide the necessary information to address this question in a clinical trial. METHODS I will: Conduct a small-scale feasibility study to see if it's possible to run a larger trial.I will approach children and their families at Moorfields Eye Hospital and ask them to take part in the study. They will be randomly asked to perform either low or high-intensity patching. Treatment will be monitored with an electronic device in their patch. Children will have their vision tested in clinics for 12 months. Develop ways to address known problems with treatment adherence.I will interview patients and their parents and work together with the public, psychologists and specialist implementation scientists to improve treatment adherence. Design a clinical trial and apply for funding.I will use the results from the feasibility study to design the future trial. I will also ask patients and the public about important issues when designing the trial. I will seek funding from the NIHR, National Eye Research Centre (UK) and National Institutes of Health (US). OUTCOMES Assessment of whether full-time patching is acceptable/achievable, and methods for improving treatment adherence. A fully-designed future clinical trial, capable of assessing whether low vs. high intensity patching: Improves vision outcomes Decreases treatment duration Reduces treatment costs Presentation of findings at/through: National and international clinical and scientific meetings (co-presented with a patient representative) Peer-reviewed journals Patient newsletters Social media Publishing Brokering Innovation Through Evidence (BITEs)

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: EYE