Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

Background: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. Methods: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. Findings: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). Interpretation: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. Funding: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership

Successful application of ancient DNA extraction and library construction protocols to museum wet collection specimens

Millions of scientific specimens are housed in museum collections, a large part of which are fluid preserved. The use of formaldehyde as fixative and subsequent storage in ethanol is especially common in ichthyology and herpetology. This type of preservation damages DNA and reduces the chance of successful retrieval of genetic data. We applied ancient DNA extraction and single stranded library construction protocols to a variety of vertebrate samples obtained from wet collections and of different ages. Our results show that almost all samples tested yielded endogenous DNA. Archival DNA extraction was successful across different tissue types as well as using small amounts of tissue. Conversion of archival DNA fragments into single-stranded libraries resulted in usable data even for samples with initially undetectable DNA amounts. Subsequent target capture approaches for mitochondrial DNA using homemade baits on a subset of 30 samples resulted in almost complete mitochondrial genome sequences in several instances. Thus, application of ancient DNA methodology makes wet collection specimens, including type material as well as rare, old or extinct species, accessible for genetic and genomic analyses. Our results, accompanied by detailed step-by-step protocols, are a large step forward to open the DNA archive of museum wet collections for scientific studies

Diabetic cataract removal: postoperative progression of maculopathy—growth factor and clinical analysis

BACKGROUND: Diabetic cataract extraction can be frequently complicated by macular oedema, progression of retinopathy, or development of iris neovascularisation. The pathogenesis of these complications may be the result of changes in the concentration of angiogenic and anti‐angiogenic cytokines in the immediate postoperative period. The study aims to prospectively analyse this. METHODS: Uneventful phacoemulsification with intraocular lens implant was performed in seven eyes of six patients with diabetic retinopathy ranging from severe non‐proliferative to quiescent proliferative. Patients were reviewed 1 day, 1 week, 1 month, and 3 months after surgery with fundus fluorescein angiography (FFA) and aqueous sampling. Each sample was analysed for VEGF, HGF, Il‐1 β (pg/ml), and PEDF (μg/ml) by sandwich ELISA. RESULTS: Clinically significant macular oedema (CSMO) occurred in one patient although increased macular hyperfluorescence occurred in three patients on FFA at 1 month. VEGF 165 concentration increased 1 day after surgery from a median baseline of 68 pg/ml (range 22–87 pg/ml) to 723 pg/ml (range 336–2071) at day 1. By 1 month it had decreased to 179 (range 66–811 pg/ml). HGF concentrations steadily increased over the month while IL‐1 β and PEDF concentrations demonstrated an acute rise on day 1 after surgery and then IL‐1β returned to baseline concentrations while PEDF decreased to below baseline. CONCLUSION: These results confirm altered concentrations of angiogenic and antiangiogenic growth factors after cataract surgery, which may induce subclinical and clinical worsening of diabetic maculopathy