Diabetic Macular Oedema and Diode Subthreshold Micropulse Laser (DIAMONDS): A Pragmatic, Multicentre, Allocation Concealed, Prospective, Randomised, Non-inferiority Double-masked Trial

Background

Laser has been the treatment of choice for people with Diabetic Macular Oedema (DMO) since its beneficial effects were demonstrated by the ETDRS in 1985 [1]. In a recent appraisal [2], The National Institute of Health and Care Excellence (NICE) recommended the continued use of standard threshold laser to treat people with DMO and central retinal thickness of < 400 microns because laser treatment is clinically effective and cost-effective in this patient group. However, conventional laser treatment may have side effects including paracentral scotomas (areas around the central vision in which patients do not see; these may affect the ability to read and drive), enlargement of the laser scar over time with potential visual loss, reduced colour vision and epiretinal membrane/subretinal fibrosis. If conventional laser is accidentally applied to the centre of the retina, profound visual loss would ensue.

Small case series and small randomised trials suggested DSML has comparable or superior efficacy but may have less side effects than conventional laser. Thus, Lavinsky and collaborators [3], in a trial where participants were randomised to receive standard threshold laser (n=42), normal density DSML (n=39) or high density DSML (n=42) showed superiority of the latter with regards to visual acuity improvement and reduced retinal thickness at 12 months follow-up [3]. In a randomised trial with 50 patients with DMO, Vujosevic and colleagues [4] found no differences in terms of visual acuity or central retinal thickness between standard threshold laser and DSML, but a statistically significant increased retinal sensitivity, as measured with microperimetry was achieved following DSML with no laser scars present in the retina, as disclosed by fundus examination and autofluorescence images at 12 months follow-up [4]. Similarly, randomised trials by Kumar and associates [5], Figueira and coworkers [6] and Laursen and associates [7] included 20, 53 and 16 patients respectively, and a follow-up duration of 18 weeks, 12 months and 5 months respectively, found no differences in visual acuity and central retinal thickness between conventional threshold laser and diode subthreshold laser. A recently published review [8] concluded that available data suggested similar or superior efficacy of DSML (when compared with standard threshold laser) with less or no retinal damage. It is possible that DSML may allow for a more standard delivery of treatment to all patients given that it is applied to the entire macular area in a confluent manner, rather than to zones that the treating ophthalmologist may perceive as thickened or to areas of suspected leakage or extrafoveal ischaemia based on fluorescein angiography, reducing/minimising possible variability in the results obtained.

Although published data suggest that DSML may be superior to conventional threshold laser, current knowledge is based on results of randomised trials with small numbers of patients followed for no more than 12 months. Furthermore, important outcomes such as cost-effectiveness of the treatment, effects of the laser on the visual field and patient reported outcomes were not evaluated in these previous studies. Stronger evidence is required to support policy-making and investment decisions.

Rationale for the Study