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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.

Background and Purpose— Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. Methods— A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. Results— Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16–1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97–0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75–0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00–1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09–1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. Conclusions— Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions.

Aims We aimed to use longitudinal data from an established screening programme with good quality assurance and quality control procedures and a stable well‐trained workforce to determine the accuracy of grading in diabetic retinopathy screening. Methods We used a continuous time‐hidden Markov model with five states to estimate the probability of true progression or regression of retinopathy and the conditional probability of an observed grade given the true grade (misclassification). The true stage of retinopathy was modelled as a function of the duration of diabetes and HbA1c. Results The modelling dataset consisted of 65 839 grades from 14 187 people. The median number [interquartile range (IQR)] of examinations was 5 (3, 6) and the median (IQR) interval between examinations was 1.04 (0.99, 1.17) years. In total, 14 227 grades (21.6%) were estimated as being misclassified, 10 592 (16.1%) represented over‐grading and 3635 (5.5%) represented under‐grading. There were 1935 (2.9%) misclassified referrals, 1305 were false‐positive results (2.2%) and 630 were false‐negative results (11.0%). Misclassification of background diabetic retinopathy as no detectable retinopathy was common (3.4% of all grades) but rarely preceded referable maculopathy or retinopathy. Conclusion Misclassification between lower grades of retinopathy is not uncommon but is unlikely to lead to significant delays in referring people for sight‐threatening retinopathy., What's new? A statistical modelling approach can be used to retrospectively evaluate the accuracy of screening programmes for diabetic retinopathy.Our model predicts that misclassification of background retinopathy as no detectable retinopathy is unlikely to lead to clinically significant delays in referring people with sight‐threatening retinopathy.This study adds to a growing body of evidence that suggests screening intervals for people graded as no background retinopathy could be safely extended to 2 or 3 years.

Aims - A National Screening Programme for diabetic eye disease in the UK is in development. We propose a grading and early disease management protocol to detect sight-threatening diabetic retinopathy and any retinopathy, which will allow precise quality assurance at all steps while minimizing false-positive referral to the hospital eye service. Methods - Expert panel structured discussions between 2000 and 2002 with review of existing evidence and grading classifications. Proposals - Principles of the protocol include: separate grading of retinopathy and maculopathy, minimum number of steps, compatible with central monitoring, expandable for established more complex systems and for research, no lesion counting, no ‘questionable’ lesions, attempt to detect focal exudative, diffuse and ischaemic maculopathy and fast track referral from primary or secondary graders. Sight-threatening diabetic retinopathy is defined as: preproliferative retinopathy or worse, sight-threatening maculopathy and/or the presence of photocoagulation. In the centrally reported minimum data set retinopathy is graded into four levels: none (R0), background (R1), preproliferative (R2), proliferative (R3). Maculopathy and photocoagulation are graded as absent (M0, P0) or present (M1, P1). Discussion - The protocol developed by the Diabetic Retinopathy Grading and Disease Management Working Party represents a new consensus upon which national guidelines can be based leading to the introduction of quality-assured screening for people with diabetes.

Summary Aim to establish the degree to which the severity of retinopathy determines the risk for the need for subsequent photocoagulation in those with newly diagnosed Type 2 diabetes mellitus. Methods Of 5102 patients entered into the UK Prospective Diabetes Study (UKPDS), 3709 had good quality retinal photographs that could be graded at entry. They were followed until the end of the study or until lost to follow-up, or until they received photocoagulation. Retinopathy severity was categorized as no retinopathy, microaneurysms (MA) only in one eye, MA in both eyes or more severe retinopathy features. The risk of photocoagulation was assessed in relation to severity of retinopathy at baseline, 3 and 6 years. Results Of the 3709 patients assessed at entry to the UKPDS, 2316 had no retinopathy. Of these 0.2% needed photocoagulation at 3 years, 1.1% at 6 years and 2.6% at 9 years. Those with MA in one eye only (n = 708) were similar, with 0%, 1.9% and 4.7% needing photocoagulation by 3, 6 and 9 years, respectively. Amongst those who had more retinopathy features at entry (n = 509), 15.3% required photocoagulation by 3 years, and 31.9% by 9 years. When those without retinopathy at 6 years (n = 1579) were examined 3 and 6 years later (9 and 12 years after diagnosis), 0.1% and 1.8% required photocoagulation. Those with more severe retinopathy (n = 775) needed earlier treatment, 6.6% after 3 years and 13.3% after 9 years. The commonest indication for laser therapy was maculopathy, but those with more severe retinopathy were more likely to be treated for proliferative retinopathy and to need both eyes treated. Conclusion Few type 2 diabetic patients without retinopathy progress to photocoagulation in the following 3–6 years, while patients with more severe retinopathy lesions need to be monitored closely.

Aims/hypothesis. To determine whether microaneurysms, in the absence of other lesions, have a predictive role in the progression of diabetic retinopathy in Type II (non-insulin-dependent) diabetes mellitus. Methods. Retinal photographs taken at diagnosis in patients participating in the United Kingdom Prospective Diabetes Study, and thereafter at 3 yearly intervals, were assessed using a modified Early Treatment of Diabetic Retinopathy grading system for lesions of diabetic retinopathy and end points of vitreous haemorrhage and photocoagulation. The number of microaneurysms in each eye was recorded. Results. The changes between diagnosis and later photographs were analysed in 2424 patients at 6 years, 1236 at 9 years and 414 at 12 years. Of the 2424 patients studied in the 6 year cohort 1809 had either no retinopathy or microaneurysms only at entry. In these patients the presence of microaneurysms alone and also the number of microaneurysms had a high predictive value for worsening retinopathy at 3, 6, 9, and 12 years after entry into the study (e. g. at 6 years χ2 for trend = 75 on 1 df, p < 0.001). The predictive value of the presence or absence of microaneurysms and their number at 3 years from diagnosis and subsequent worsening retinopathy was similar to that at entry. Conclusion/interpretation. Microaneurysms are important lesions of diabetic retinopathy and even one or two microaneurysms in an eye should not be regarded as unimportant. [Diabetologia (1999) 42: 1107–1112]

Diabet. Med. 28, 345–351 (2011) Abstract Objective To study the association between baseline retinal microaneurysm score and progression and regression of diabetic retinopathy, and response to treatment with candesartan in people with diabetes. Methods This was a multicenter randomized clinical trial. The progression analysis included 893 patients with Type 1 diabetes and 526 patients with Type 2 diabetes with retinal microaneurysms only at baseline. For regression, 438 with Type 1 and 216 with Type 2 diabetes qualified. Microaneurysms were scored from yearly retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Retinopathy progression and regression was defined as two or more step change on the ETDRS scale from baseline. Patients were normoalbuminuric, and normotensive with Type 1 and Type 2 diabetes or treated hypertensive with Type 2 diabetes. They were randomized to treatment with candesartan 32 mg daily or placebo and followed for 4.6 years. Results A higher microaneurysm score at baseline predicted an increased risk of retinopathy progression (HR per microaneurysm score 1.08, P

Aims TOSCA was an EU-Commission supported international research project designed to develop telescreening services in diabetic retinopathy and glaucoma. This paper describes the quality assurance methods developed for the diabetic retinopathy telescreening service within the TOSCA project. Setting The study was performed in 1895 patients with diabetes between 2000 and 2002 at diabetic retinopathy screening sites in five European countries. Data were analysed centrally. Methods Patients attending each clinic's diabetic retinopathy screening service received standardized retinal photography. The images and associated data were transferred electronically to a remote location for grading. Each photographer uploading images and each grader downloading images for assessment was controlled by a systematic quality management approach. The quality assurance measures defined were image quality, intragrader reliability. A cockpit chart was developed for the management and presentation of relevant results and quality measures. For the intragrader reliability tests, 10% of the images were processed for a second grading. An algorithm for calculating differences between repeated gradings was developed. Results The assessment of image quality for the different sites showed that only 0–0.7% were unassessable. One hundred per cent agreement for both gradings was achieved in 50–85% of graded cases, depending on site and grader, and an agreement better than 95% in 71–100% of cases. Conclusions A telemedicine-supported quality assurance process is practical and advantageous. The cockpit charts have proven to be useful tools when monitoring the performance of a telescreening service. Grader feedback showed high satisfaction with the quality assurance process.

AIMS: To evaluate the introduction of a community-based non-mydriatic and mydriatic digital photographic screening programme by measuring the sensitivity and specificity compared with a reference standard and assessing the added value of technician direct ophthalmoscopy. METHODS: Study patients had one-field, non-mydriatic, 45 degrees digital imaging photography prior to mydriatic two-field digital imaging photography followed by technician ophthalmoscopy. Of these patients, 1549 were then examined by an experienced ophthalmologist using slit lamp biomicroscopy as a reference standard. The setting was general practices in Gloucestershire. Patients were selected by randomizing groups of patients (from within individual general practices) and 3611 patients were included in the study. Patients for reference standard examination were recruited from groups of patients on days when the ophthalmologist was able to attend. The main outcome measure was detection of referable diabetic retinopathy (DR) as defined by the Gloucestershire adaptation of the European Working Party guidelines. RESULTS: For mydriatic digital photography, the sensitivity was 87.8%, specificity was 86.1% and technical failure rate was 3.7%. Technician ophthalmoscopy did not alter these figures. For non-mydriatic photography, the sensitivity was 86.0%, specificity was 76.7% and technical failure rate was 19.7%. CONCLUSIONS: Two-field mydriatic digital photography is an effective method of screening for referable diabetic retinopathy. Non-mydriatic digital photography has an unacceptable technical failure rate and low specificity.

Aims/hypothesis. To determine risk factors related to the incidence and progression of diabetic retinopathy over 6 years from diagnosis of Type II (non-insulin-dependent) diabetes mellitus. Methods. This report describes 1919 patients from within the United Kingdom Prospective Diabetes Study (UKPDS), with retinal photographs taken at diagnosis and 6 years later and with complete data available. Photographs were centrally graded for lesions of diabetic retinopathy using the modified Early Treatment of Diabetic Retinopathy Study Final scale. Risk factors were assessed after 3 months diet from the time of diagnosis of diabetes. Patients were seen every 3 months in a hospital setting. Biochemical measurements were done by a central laboratory. End points of vitreous haemorrhage and photocagulation were confirmed by independent adjudication of systematically collected clinical data. The main outcome measures were incidence and progression of retinopathy defined as a two-step Early Treatment of Diabetic Retinopathy Study (ETDRS) final scale change. Results. Of the 1919 patients, 1216 (63 %) had no retinopathy at diagnosis. By 6 years, 22 % of these had developed retinopathy, that is microaneurysms in both eyes or worse. In the 703 (37 %) patients with retinopathy at diagnosis, 29 % progressed by two scale steps or more. Development of retinopathy (incidence) was strongly associated with baseline glycaemia, glycaemic exposure over 6 years, higher blood pressure and with not smoking. In those who already had retinopathy, progression was associated with older age, male sex, hyperglycaemia (as evidenced by a higher HbA1 c) and with not smoking. Conclusion/interpretation. The findings re-emphasise the need for good glycaemic control and assiduous treatment of hypertension if diabetic retinopathy is to be minimised. [Diabetologia (2001) 44: 156–163]

To the Editor : In the August issue of this journal Looker et al presented results from data analyses of patients from the Scottish Diabetic Retinopathy Screening programme [1]. The principal finding was that transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and who had had two consecutive screens showing no visible retinopathy. We had already published this result in Diabetes Care [2], online in November 2012 and in print in March 2013 but this has not been acknowledged by Looker et al. We recognise that our results were based on data from patients for whom we had no information on the type of diabetes, but they would predominantly have been patients with type 2 diabetes because they were from a populationbased screening programme in England. The transition rates found in the Scottish study are of the same order as those found in our cohort. The authors state that a major strength of the paper is that it uses a centralised quality-controlled grading system and the criteria for referable disease have not altered over the course of the programme. This tends to suggest a single reading centre although they have not expressly stated this. However, Goatman et al [3] reported in 2012 on external quality assurance (EQA) of grading in the Scottish programme in nine reading centres. They reported that there were significant differences in sensitivities and specificities between graders and between reading centres in 2008, when much of the data in the Looker paper would have been collected. This is not alluded to in the Looker paper [1]. The authors discuss several possible reasons for the apparent regression of mild background retinopathy to no visible retinopathy at subsequent examination. However, they do not raise the possibility that this may be due to changes in grading or the differences in sensitivity and specificity between graders enumerated in the EQA paper [3]. These recent results suggest that a 2 year screening interval may be safe in those with type 2 diabetes and no visible retinopathy on two consecutive screens. In our paper [2] this may be deduced from the results. However we also discuss the quality of our grading and the need to validate these results in other populations before implementation of changes in screening intervals. There is no ‘gold standard’ for grading of digital retinal images and hence the introduction of extended intervals in any programme would require validation of any rules in existing datasets, continuing education of graders and robust failsafe procedures, EQA and QA of grading.

We present the methodology for 45 degrees retinal photography and detail the development, application and validation of a new system of 45 degrees field grading standards for the assessment of diabetic retinopathy. The systems were developed for the EURODIAB IDDM Complications Study, part of a European Community funded Concerted Action Programme into the epidemiology and prevention of diabetes (EURODIAB). Assessment of diabetic retinopathy was carried out centrally by a trained reader of colour retinal photographs using the newly-developed system. The system proved to be acceptably accurate, repeatable repeatable and relatively simple to apply. It compared well with the recognised 'gold standard' 7-field 30 degrees stereo photography (assessed using a modified Airlie House classification scheme), against which the new system was validated in a series of 48 eyes. Selection was as a stratified random sample based on clinical retinopathy status: 5, no retinopathy; 25, non-proliferative retinopathy; 16, proliferative or photocoagulated; plus 2, eyes with potentially confounding lesions (vein occlusion). Simple presence of retinal lesions was correctly detected by both systems in 43 of the 48 eyes, giving 100% agreement on detection. Both systems correctly identified the two known cases of confounding vein occlusion. In eyes with diabetic retinopathy (n = 41), when severity was expressed in three groups: mild background, moderate/severe background and proliferative/photocoagulated, at least one grader (out of five) using the new system matched the verified results in 38 out of 31 (93%) eyes and three or more graders matched in 31 (76%) eyes.(ABSTRACT TRUNCATED AT 250 WORDS)