Title: DIAbetic Macular Oedema aNd Diode Subthreshold micropulse laser (DIAMONDS)
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: PURPOSE: To evaluate clinical and cost-effectiveness of Diode Subthreshold Micropulse Laser (DSML) compared with standard threshold laser to treat Diabetic Macular Oedema (DMO) with Central Retinal Thickness (CRT) of < 400 microns. DESIGN: Pragmatic, multicentre, allocation concealed, double-masked randomised trial. SETTING: Hospital outpatients (13 Ophthalmic Units in UK). TARGET POPULATION: People with centre involving DMO and central retinal thickness of less than 400 microns. INCLUSION CRITERIA: Adults with type 1 or 2 diabetes and DMO of < 400 microns in central retinal thickness, visual acuity of > 24 Early Treatment Diabetic retinopathy Study (ETDRS) letters (logMAR > 1.2) amenable to laser in one or both eyes. EXCLUSION CRITERIA: Other causes of macular oedema including epiretinal membrane and vitreomacular traction, ineligible for laser, previous laser or anti-VEGF/steroids within the previous six months in the study eye, DMO with central retinal thickness of > 400 microns. CONTROL TREATMENT: Standard threshold laser. HEALTH TECHNOLOGY ASSESSED: DSML. PRIMARY OUTCOME: Best corrected distance visual acuity (BCdVA) in the study eye at 2 years. SECONDARY OUTCOMES (at 2 years): binocular BCdVA; central retinal thickness by optical coherence tomography (OCT), mean deviation (MD) of the Humphrey 10-2 visual field; % of people meeting driving standards, general and visual related quality of life, cost-effectiveness, side effects, number of laser treatments needed, need for additional treatment. MEASURES OF COSTS AND OUTCOMES: A within-trial economic evaluation will compare relative cost-effectiveness of DSML with standard laser based on quality of life estimation, this reflecting the primary and other outcomes, adverse effects and costs of treatment. Results will be expressed primarily as cost per quality adjusted life year from NHS and personal and social services (PSS) perspective. Extrapolation beyond the trial period using decision-modelling will be used to estimate longer-term cost-effectiveness. SAMPLE SIZE: Based on a mean (standard deviation) of 0.08 (0.23) log MAR for best corrected distance VA change from baseline for the standard laser (from Lavinsky et al, 2011) and a permitted maximum difference of 0.1 logMAR (5 ETDRS letters) between groups, the trial requires 113 patients per arm at 90% power and 0.05 level of significance. Accounting for a maximum 15% dropout rate, we aim to recruit 266 patients. TIMETABLE: Setting up: 5 months; recruitment: 15 months; follow-up: 24 months; data analysis: 4 months; report writing: 2 months. Total duration: 50 months EXPERTISE IN THE TEAM: Ophthalmologists with expertise in DMO, methodologists, trialists, health economists, experts in health technology and qualitative assessments, statisticians, service users.

Lay abstract: Diabetic macular oedema (DMO) is the most common cause of irreversible blindness in people with diabetes. DMO results from leakage of fluid into the central part of the retina, the macula, the area responsible for detailed vision. As a result of the retina being “wet” or “swollen” its function is impaired and subsequently there is loss of sight. The National Institute of Health and Care Excellence (NICE) has recommended treatment with laser for people with DMO when the retina is thickened if the thickness is < 400 microns, as measured using a machine called optical coherence tomography (OCT). Laser treatment has been done for decades. Although it is clear that laser is good for people with DMO it can have side effects including paracentral scotomas (small areas around the centre of the vision where one cannot see), reduced color vision, scarring over and under the retina among others. The laser scar might also get bigger over time and if the scar affects the very centre of the retina, the central vision can be reduced. Furthermore, if the laser beam accidentally hits the very centre of the retina it would cause profound central loss of vision. Recently, a new type of laser treatment for DMO was introduced, called diode subthreshold micropulse laser (DSML). This type of laser treatment appears to be at least as good if not better than conventional laser and may have less side effects. So far, however, all studies comparing both types of lasers have been small and short-term (have included small number of patients who were followed for short periods of time) and not all outcomes (characteristics that were looked at to evaluate the effects to the laser) that matter to patients were studied (for instance, quality of life of patients was not evaluated in these studies). Thus, stronger evidence is needed to find out whether DSML is better than conventional threshold laser treatment. This study will investigate how DSML compares with conventional laser for the treatment of patients with DMO in terms of improving vision or preventing sight loss, reducing the amount of fluid (and thus “thickness”) in the retina, improving the quality of life of patients, and reducing side effects and costs, number of treatments needed and need for additional treatment(s) (need to give other treatments in addition to laser). We also know that patients with DMO worry about their the ability to drive so we will compare the effects of the lasers on whether patients achieve driving standards following treatment. This study will include people with DMO with a retinal thickness of < 400 microns. Participants will receive either conventional laser or DSML; who will receive one or the other will be determined by chance. Patients receiving these treatments and the people assessing the response to these treatments will not know which type of laser was done. The research team includes expert clinicians, methodologists, statisticians, health economists, and experts in qualitative research and will be supported by a clinical trials unit and by ophthalmology research networks and patient groups. Patients will be recruited from thirteen NHS hospitals across the UK. Patients (including someone who has been treated for DMO) have been involved in the study design and will collaborate with the research team to assure that the study, its outcomes and recommendations are relevant to patients.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: EYE;METABOLIC AND ENDOCRINE