Title: Efficacy of the Telescopic Mirror Implant for Age-related Macular Degeneration: The MIRROR Trial
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: BACKGROUND: Despite the availability of new improved therapies for the “wet” form of AMD, no treatment exists for those who fail to respond to intravitreal or laser therapies and for the “atrophic” form of the disease. External low vision aids remain the main avenue for rehabilitation but tolerability and use can be limited. A novel approach is the use of implantable intraocular magnifiers however due to the paucity of robust clinical information, none are currently available on the NHS. This proposal seeks to evaluate the efficacy and safety of a new intraocular magnifying device (OriLens). DESIGN: We plan a multicentre randomised controlled trial. The OriLens telescopic device will be implanted in one eye in Group 1 as a secondary surgical procedure. Group 2 will receive standard of care. POPULATION: Participants eligible for the trial will have bilateral advanced stable AMD and have had uncomplicated bilateral cataract surgery with IOL implantation and will have a visual acuity of between 6/60 and 6/240 bilaterally. All eligible participants will undergo Nd:YAG capsulotomy in the study eye. INTERVENTION: Eligible participants will be randomized to one of two groups. Group 1: Secondary implantation with the OriLens, refraction and low vision rehabilitation and Group 2: Refraction and low vision rehabilitation. OUTCOMES: The Primary Outcome measure will be best-corrected distance visual acuity at 12 months with refraction with a conventional near vision reading addition but no external low vision aids. Secondary Outcomes will be vision-specific quality of life using the Impact of Vision Impairment Profile (IVI), health-related quality of life status (EQ-5D-5L), quality adjusted life years (QALY) gain, best corrected near visual acuity, reading speed, associated costs and cost-effectiveness (QALY). Safety will be assessed by surgical complication rate and endothelial cell count. The Mechanistic part of the study will evaluate the effect of parameters such as scar size, location of PRL, implantation in the dominant/non-dominant eye and binocular visual function on the visual outcome. ASSESSMENTS: Eligibility will be determined at the screening visit. Surgery in Group 1 will take place at Day 0, surgical review on Days 1 and 7 and study visits at 1, 3, 6 and 12 months. STATISTICAL ANALYSIS AND SAMPLE SIZE: Sample size is calculated on the assumption that the telescope is capable of providing a 10-letter improvement on a Log-based chart i.e ETDRS from baseline and that standard care ie: cataract surgery without the magnifying device will improve visual acuity by a mean (SD) of 1.94 (13.4) letters, 59 participants in each group would be required to detect a 8.06 letter difference between the 2 groups at 90% power, giving 66 per group accounting for 10 attrition. Analyses will be on an intention-to-treat basis and at a significance level of 0.05. The comparison of best-corrected distance visual acuity (and other continuous outcomes) between the treatment and standard care groups will be investigated using analysis of covariance, adjusting for the minimisation factors, baseline and other co-variates where appropriate. DURATION OF STUDY: The study will run for 42 months. RECRUITMENT RATE: Ten centres will be required. The first 6 months will be spent in setup and in the initiation and training of staff at selected sites. The recruitment phase is 18 months with 12 months follow-up and 6 months for analysis of data, writing of report and dissemination of results

Lay abstract: This study will address a key priority for Age-Related Macular Degeneration (AMD) research identified through the priority-setting partnership between patients, carers and doctors known as the James Lind Alliance. The priority question asks “Are there ways of restoring sight loss for people with AMD?". There are approximately 600,000 individuals in the UK with AMD and who are subsequently visually impaired. Despite the availability of new improved treatments by injection for the “wet” form of AMD, no treatment exists for “atrophic or dry” AMD or for those who fail to respond to intravitreal or laser therapies. AMD typically leads to loss of central vision and low vision aids can be successful in some users however limitations include small field of view and difficulties with hand-eye co-ordination. Recently a novel approach has been the use of an implantable magnifying lens into the eye. This is often described as an intraocular telescope. These devices are placed inside the eye at the time of cataract surgery or as a separate procedure. The devices have several potential advantages ie: more natural scanning technique and are more cosmetically appealing as they are placed inside the eye. Several intraocular telescopes have recently become available but limited evidence is available in terms of how useful these are. The National Institute for Health and Care Excellence (NICE) has been unable to make a recommendation for their routine use in the NHS. A novel device (OriLens) uses mirrors in its design, which allows a significant reduction in the size of the lens implant but maintains a high magnification and causes less reduction of the peripheral visual field. The reduced size of magnifying lens (telescopes) also offers the potential for an easier and safer surgery and faster recovery than other magnifying lenses (telescopes) currently available. The aim of this trial is to provide good quality evidence to these questions 1. How good is the OriLens in improving vision and quality of life? 2. How safe is the OriLens? 3. Which patients do well with the device? The study will involve 132 people with severe sight loss from AMD who have had bilateral cataract surgery. After consenting, patients will be for their suitability to participate in the study. Once confirmed that they fulfil the inclusion criteria to participate in the trial, each participant will be randomly assigned into one of two groups. Group 1: Patients will receive the OriLens magnifying lens during an operation, will be tested for new glasses, provided with any necessary supplementary spectacles, and have low vision training. Group 2: Patients will be tested for new glasses, provided with appropriate spectacles and LVAs, and will have low vision training. Surgery within the trial will be in one eye only which will be selected after testing with an external telescope. The main outcome will be distance visual acuity after 1 year, but this study will compare a set of measurable outcomes for all participants, including reading acuity, reading speed, quality of life and safety. The study will take place over a 3 and a half-year period across several health centres in the UK. The applicants and team overseeing this research include experienced clinicians and researchers. In addition the team has the full support of the Northern Ireland Clinical Trials Unit (NICTU) and Clinical Research Network (NICRN). Costs include time for investigators, research staff and project manager, telescopic lens, meetings, publication and presentation of results to Patient Groups and at scientific meetings.

Research activity codes: 5.3 MEDICAL DEVICES;6.3 MEDICAL DEVICES
Health categories: EYE