Extending the diabetic retinopathy screening intervals in Singapore: methodology and preliminary findings of a cohort study.

BACKGROUND: The Diabetic Retinopathy Extended Screening Study (DRESS) aims to develop and validate a new DR/diabetic macular edema (DME) risk stratification model in patients with Type 2 diabetes (DM) to identify low-risk groups who can be safely assigned to biennial or triennial screening intervals. We describe the study methodology, participants' baseline characteristics, and preliminary DR progression rates at the first annual follow-up. METHODS: DRESS is a 3-year ongoing longitudinal study of patients with T2DM and no or mild non-proliferative DR (NPDR, non-referable) who underwent teleophthalmic screening under the Singapore integrated Diabetic Retinopathy Programme (SiDRP) at four SingHealth Polyclinics. Patients with referable DR/DME (> mild NPDR) or ungradable fundus images were excluded. Sociodemographic, lifestyle, medical and clinical information was obtained from medical records and interviewer-administered questionnaires at baseline. These data are extracted from medical records at 12, 24 and 36 months post-enrollment. Baseline descriptive characteristics stratified by DR severity at baseline and rates of progression to referable DR at 12-month follow-up were calculated. RESULTS: Of 5,840 eligible patients, 78.3% (n = 4,570, median [interquartile range [IQR] age 61.0 [55-67] years; 54.7% male; 68.0% Chinese) completed the baseline assessment. At baseline, 97.4% and 2.6% had none and mild NPDR (worse eye), respectively. Most participants had hypertension (79.2%) and dyslipidemia (92.8%); and almost half were obese (43.4%, BMI ≥ 27.5 kg/m2). Participants without DR (vs mild DR) reported shorter DM duration, and had lower haemoglobin A1c, triglycerides and urine albumin/creatinine ratio (all p < 0.05). To date, we have extracted 41.8% (n = 1909) of the 12-month follow-up data. Of these, 99.7% (n = 1,904) did not progress to referable DR. Those who progressed to referable DR status (0.3%) had no DR at baseline. CONCLUSIONS: In our prospective study of patients with T2DM and non-referable DR attending polyclinics, we found extremely low annual DR progression rates. These preliminary results suggest that extending screening intervals beyond 12 months may be viable and safe for most participants, although our 3-year follow up data are needed to substantiate this claim and develop the risk stratification model to identify low-risk patients with T2DM who can be assigned biennial or triennial screening intervals.

Evaluation of care with intravitreal aflibercept treatment for UK patients with diabetic macular oedema: DRAKO study 24-month real-world outcomes.

BACKGROUND/ OBJECTIVES: DRAKO (NCT02850263) was a 24-month, prospective, observational, multi-centre cohort study that enrolled patients diagnosed with diabetic macular oedema (DMO) including central involvement. The study aimed to evaluate standard of care intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the 12-month outcomes for patients with prior anti-vascular endothelial growth factor (VEGF) treatment for DMO other than IVT-AFL (C2), and 2-year outcomes for both anti-VEGF treatment-naïve patients (C1) and C2 patients. METHODS: Study eyes were treated with IVT-AFL as per local standard of care. Mean changes in best-corrected visual acuity (BCVA) in ETDRS letters and central subfield thickness (CST) were stratified by baseline factors. Changes in diabetic retinopathy assessments, glycated haemoglobin A1c levels and vision-related quality of life (QoL) were evaluated alongside numbers of injections administered and safety outcomes. RESULTS: For C1, mean (SD) changes from baseline in BCVA of +0.7 (12.7) letters and CST of -123.3 (104.3) µm were observed at Month 24. For C2, mean (SD) changes from baseline for BCVA of + 0.2 (10.2) letters and -0.3 (13.0) letters, and CST of -79.1 (137.6) µm and -91.6 (132.9) µm, were observed at 12 and 24 months, respectively. In Year 2, C1 and C2 patients received a mean of 3.7 and 4.3 injections, respectively. CONCLUSIONS: Year 2 results indicate that IVT-AFL is an effective treatment for DMO in real-world UK clinical practice, despite relatively low injection numbers. The high baseline visual acuity and QoL scores were maintained and there was further improvement in anatomical outcomes.

Disengagement and loss to follow-up in intravitreal injection clinics for neovascular age-related macular degeneration.

BACKGROUND/OBJECTIVES: Timely assessment and treatment of patients with neovascular AMD (nAMD) are crucial to preservation of vision. Loss to follow up (LTFU) in these patients is a problem but this has not been systematically investigated. SUBJECTS/METHODS: A retrospective review of electronic medical records of patients with nAMD first treated with anti-VEGF therapy from 1st Jan 2014 to 31st Dec 2018, was conducted in January 2021. Any patient not seen for more than 12 months was classed as no longer attending. RESULTS: Of the 1328 patients who attended between 2014 and 2018, 348 had failed to attend and were eligible for inclusion in this study. Reasons noted for discontinuation of care: discharged by clinician (33.3%), died (20.7%), moved to another unit outside of area (17.5%), stopped attending due to ill-health (13.5%), discharged due to failure to attend (5.6%) and patient choice to no longer attend (4.6%). There were 16 (4.6%) who did not receive any further appointments despite clinician request for follow-up. After 5 years, 50.5% of patients were no longer attending for treatment. Age was a factor in failure to attend, with 7 out of 12 patients aged >100 years no longer being followed up, compared to 1 out of 11 of 50-59 year-olds. CONCLUSIONS: When analysing visual outcomes in an AMD service it is important to characterise the patients who are lost to follow up. The outcomes for this group may be avoidably poor and understanding the factors influencing LTFU rate is crucial to addressing shortcomings in a hospital AMD service.

Serum glial fibrillary acidic protein and neurofilament light chain as biomarkers of retinal neurodysfunction in early diabetic retinopathy: results of the EUROCONDOR study.

AIMS: Neurodegeneration and glial activation are primary events in the pathogenesis of diabetic retinopathy. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of underlying neuroinflammatory and neurodegenerative disease processes. The aim of the present study was to assess the usefulness of these serum biomarkers for the identification and monitoring of retinal neurodysfunction in subjects with type 2 diabetes. METHODS: A case-control study was designed including 38 patients from the placebo arm of the EUROCONDOR clinical trial: 19 with and 19 without retinal neurodysfunction assessed by multifocal electroretinography. GFAP and NfL were measured by Simoa. RESULTS: Serum levels of GFAP and NfL directly correlated with age (r = 0.37, p = 0.023 and r = 0.54, p < 0.001, respectively). In addition, a direct correlation between GFAP and NfL was observed (r = 0.495, p = 0.002). Serum levels of GFAP were significantly higher at baseline in those subjects in whom neurodysfunction progressed after the 2 years of follow-up (139.1 ± 52.5 pg/mL vs. 100.2 ± 54.6 pg/mL; p = 0.04). CONCLUSIONS: GFAP could be a useful serum biomarker for retinal neurodysfunction. Monitoring retinal neurodysfunction using blood samples would be of benefit in clinical decision-making. However, further research is needed to validate this result as well as to establish the best cutoff values.

Evaluation of standard-of-care intravitreal aflibercept treatment practices in patients with diabetic macular oedema in the UK: DRAKO study outcomes.

BACKGROUND/OBJECTIVES: DRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti-vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL. METHODS: Mean changes in best-corrected visual acuity and central subfield thickness were measured and stratified by baseline factors, including ethnicity and administration of five initial monthly injections within predefined windows. Clinic visits were classified as treatment only (T1), monitoring assessment only (T2), combined visits (T3) or post-injection visits with no treatment or assessment (T4). RESULTS: Median time from decision to treat to treatment was 6 days. As a percentage of total visits, T1, T2, T3 and T4 were 7%, 42%, 48% and 3% for C1 and 11%, 39%, 48% and 2% for C2. Most IVT-AFL injections were administered by healthcare professionals (HCPs) other than doctors (C1, 57.4%; C2, 58.5%). The percentage of treatments associated with a procedure-related adverse event where at least 75% of injections were completed by the same injector role were similar for doctors and other HCPs (C1, 1.1% and 0.8%; C2, 0.7%, and 1.0%). CONCLUSIONS: Results indicate that upon DMO diagnosis, patients were treated promptly, and most visits were combined (treatment and assessment) or monitoring only. Most IVT-AFL was administered by non-physicians with a similar treatment-related safety profile as IVT-AFL administered by physicians.

Improving the screening of risk factors in diabetic retinopathy.

INTRODUCTION: In 2002, Diabetic Retinopathy was reported as the leading cause of blindness in the working age group. The introduction of systematic screening programs in the UK has reduced visual loss and blindness due to diabetic retinopathy, but it does still occur with catastrophic consequences for the individual. AREAS COVERED: The author conducted an ongoing search for articles relating to diabetic retinopathy since 2000 utilizing Zetoc Alert with keywords and contents page lists from relevant journals. This review covers the risk factors for loss of vision due to diabetic retinopathy and discusses ways in which the awareness of these risk factors can be used to further reduce visual loss. Some risk factors such as glycemic and B/P control are well known from landmark trials. This review has included these factors but concentrated more on the evidence behind those risk factors that are not so clearly defined or so well known. EXPERT OPINION: The major risk factors are well known, but one continues to find that people with diabetes lose vision in situations in which a better awareness of the risks by both the individual with diabetes and the health workers involved may have prevented the visual loss.

Testing the performance of risk prediction models to determine progression to referable diabetic retinopathy in an Irish type 2 diabetes cohort.

BACKGROUND /AIMS: To evaluate the performance of existing prediction models to determine risk of progression to referable diabetic retinopathy (RDR) using data from a prospective Irish cohort of people with type 2 diabetes (T2D). METHODS: A cohort of 939 people with T2D followed prospectively was used to test the performance of risk prediction models developed in Gloucester, UK, and Iceland. Observed risk of progression to RDR in the Irish cohort was compared with that derived from each of the prediction models evaluated. Receiver operating characteristic curves assessed models' performance. RESULTS: The cohort was followed for a total of 2929 person years during which 2906 screening episodes occurred. Among 939 individuals followed, there were 40 referrals (4%) for diabetic maculopathy, pre-proliferative DR and proliferative DR. The original Gloucester model, which includes results of two consecutive retinal screenings; a model incorporating, in addition, systemic biomarkers (HbA1c and serum cholesterol); and a model including results of one retinopathy screening, HbA1c, total cholesterol and duration of diabetes, had acceptable discriminatory power (area under the curve (AUC) of 0.69, 0.76 and 0.77, respectively). The Icelandic model, which combined retinopathy grading, duration and type of diabetes, HbA1c and systolic blood pressure, performed very similarly (AUC of 0.74). CONCLUSION: In an Irish cohort of people with T2D, the prediction models tested had an acceptable performance identifying those at risk of progression to RDR. These risk models would be useful in establishing more personalised screening intervals for people with T2D.

Epidemiology of moderately severe and severe non-proliferative diabetic retinopathy in South West England.

AIMS: To estimate the incidence of early treatment diabetic retinopathy study (ETDRS) level 47 and 53 and progression to treatment with panretinal photocoagulation (PRP) for proliferative DR (PDR). METHODS: Log-linear regression was used to estimate the incidence of level 47-53 or worse for 33,009 people with diabetes (PWD) in Gloucestershire during 2013-2016 by calendar year and diabetes type, based on the first recording. Progression was analysed in Gloucestershire and Bristol with a parametric survival analysis examining the association of baseline and time-varying demographic and clinical factors on time to PRP after the first recording of level 47-53. RESULTS: Incidence decreased from 0.57 (95% confidence intervals (CI) 0.48-0.67) per 100 PWD in 2013 to 0.35 (95% CI 0.29-0.43) in 2016 (p < 0.001). For progression, 338 eligible PWD from Gloucestershire and 418 from Bristol were followed for a median of 1.4 years; 78 and 83% had Type 2 diabetes and a median (interquartile range) of 15 (10-22) and 17 (11-25) years duration of diagnosed diabetes respectively. Three years from the incident ETDRS 47-53, 18.9% and 17.2% had received PRP respectively. For Gloucestershire, severe IRMA and updated mean HbA1c were associated with an increase in the risk of initiating PRP (hazard ratio 3.14 (95% CI: 1.60-6.15) and 1.21 (95% CI: 1.06-1.38 per 10 mmol/mol) respectively). CONCLUSION: This study provides additional understanding of this population and shows that a high proportion of patients with ETDRS levels 47-53 need to be monitored as they are at high risk of progressing to PDR.

Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes.

OBJECTIVES: DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. METHODS: Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. RESULTS: A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of -119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA < 70 letters. Mean number (SD) of injections in year one was 6.4 (2.1). No significant adverse events were recorded. CONCLUSION: Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.

Prevalence and incidence of diabetic retinopathy (DR) in the UK population of Gloucestershire.

PURPOSE: To estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR). METHODS: Electronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log-linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses. RESULTS: Across the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56-75) years (median (interquartile range)), 57% male, 5 (1-10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate-severe NPDR were statistically significant risk factors associated with progression to PDR. CONCLUSIONS: Incidence and prevalence of DR decreased between 2012 and 2016 in this well-characterized population of the UK.

Standardization of Optical Coherence Tomography Angiography Imaging Biomarkers in Diabetic Retinal Disease.

Optical coherence tomography Angiography (OCT-A) represents a revolution in the noninvasive evaluation of retinal and choroidal circulation especially in detecting early clinical signs of diabetic retinal disease (DRD). With appropriate use, OCT-A characteristics and measurements have the potential to become new imaging biomarkers in managing and treating DRD. Major challenges include (a) provision of standardized outputs from different OCT-A instruments providing standardized terminology to correctly interpret data; (b) the presence of artifacts; (c) the absence of standardized grading or interpretation method in the evaluation of DRD, similar to that already established in fundus photography; and (d) establishing how OCT-A might be able to provide surrogate markers to demonstrate blood retinal barrier breakdown and vascular leakage, commonly associated with DRD. In fact, OCT-A guidelines for DRD are still evolving. The outputs of quantitative OCT-A data offer a unique opportunity to develop tools based on artificial intelligence to assist the clinicians in diagnosing, monitoring, and managing patients with diabetes. In addition, OCT-A has the potential to become a useful tool for the evaluation of cardiovascular diseases and different neurological diseases including cognitive impairment. This article written by the members of Diabetic Retinopathy expert committee of the European Vision Clinical Research network will review the available evidence on the use of OCT-A as an imaging biomarker in DRD and discuss the limits and the current application as well as future developments for its use in both clinical practice and research trials of DRD.

A Multitask Deep-Learning System to Classify Diabetic Macular Edema for Different Optical Coherence Tomography Devices: A Multicenter Analysis.

OBJECTIVE: Diabetic macular edema (DME) is the primary cause of vision loss among individuals with diabetes mellitus (DM). We developed, validated, and tested a deep learning (DL) system for classifying DME using images from three common commercially available optical coherence tomography (OCT) devices. RESEARCH DESIGN AND METHODS: We trained and validated two versions of a multitask convolution neural network (CNN) to classify DME (center-involved DME [CI-DME], non-CI-DME, or absence of DME) using three-dimensional (3D) volume scans and 2D B-scans, respectively. For both 3D and 2D CNNs, we used the residual network (ResNet) as the backbone. For the 3D CNN, we used a 3D version of ResNet-34 with the last fully connected layer removed as the feature extraction module. A total of 73,746 OCT images were used for training and primary validation. External testing was performed using 26,981 images across seven independent data sets from Singapore, Hong Kong, the U.S., China, and Australia. RESULTS: In classifying the presence or absence of DME, the DL system achieved area under the receiver operating characteristic curves (AUROCs) of 0.937 (95% CI 0.920-0.954), 0.958 (0.930-0.977), and 0.965 (0.948-0.977) for the primary data set obtained from CIRRUS, SPECTRALIS, and Triton OCTs, respectively, in addition to AUROCs >0.906 for the external data sets. For further classification of the CI-DME and non-CI-DME subgroups, the AUROCs were 0.968 (0.940-0.995), 0.951 (0.898-0.982), and 0.975 (0.947-0.991) for the primary data set and >0.894 for the external data sets. CONCLUSIONS: We demonstrated excellent performance with a DL system for the automated classification of DME, highlighting its potential as a promising second-line screening tool for patients with DM, which may potentially create a more effective triaging mechanism to eye clinics.

Diagnostic Accuracy of Monitoring Tests of Fellow Eyes in Patients with Unilateral Neovascular Age-Related Macular Degeneration: Early Detection of Neovascular Age-Related Macular Degeneration Study.

PURPOSE: To evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared with fundus fluorescein angiography (FFA) to detect onset of active macular neovascularization in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD). DESIGN: Prospective diagnostic accuracy cohort study conducted in 24 eye clinics in the United Kingdom over 3 years. PARTICIPANTS: Older adults (>50 years) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD. METHODS: Self-reported vision, Amsler, clinic-measured visual acuity (VA), fundus assessment, and spectral domain OCT. The reference standard is FFA. MAIN OUTCOME MEASURES: Sensitivity and specificity of the 5 index tests. RESULTS: Of 552 participants monitored for up to 3 years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were self-reported vision much worse (5), distortion on Amsler (33), 10-letter decrease in acuity from baseline (36), fundus examination (64), and OCT (110). Percentage index test sensitivities were: self-reported vision 4.2 (95% confidence interval [CI], 1.6-9.8); Amsler 33.7 (95% CI, 25.1-43.5); VA 30.0 (95% CI, 22.5-38.7); fundus examination 53.8 (95% CI, 44.8-62.5); and OCT 91.7 (95% CI, 85.2-95.6). All 5 index test specificities were high at 97.0 (95% CI, 94.6-98.5), 81.4 (95% CI, 76.4-85.5), 66.3 (95% CI, 61.0-71.1), 97.6 (95% CI, 95.3-98.9), and 87.8 (95% CI, 83.8-90.9), respectively. The combination of OCT with one other index test that was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination. CONCLUSIONS: Tests of self-reported change in vision, unmasking of new distortion, measurements of acuity, and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

Multimodal imaging interpreted by graders to detect re-activation of diabetic eye disease in previously treated patients: the EMERALD diagnostic accuracy study.

BACKGROUND: Owing to the increasing prevalence of diabetes, the workload related to diabetic macular oedema and proliferative diabetic retinopathy is rising, making it difficult for hospital eye services to meet demands. OBJECTIVE: The objective was to evaluate the diagnostic performance, cost-effectiveness and acceptability of a new pathway using multimodal imaging interpreted by ophthalmic graders to detect reactivation of diabetic macular oedema/proliferative diabetic retinopathy in previously treated patients. DESIGN: This was a prospective, case-referent, cross-sectional diagnostic study. SETTING: The setting was ophthalmic clinics in 13 NHS hospitals. PARTICIPANTS: Adults with type 1 or type 2 diabetes with previously successfully treated diabetic macular oedema/proliferative diabetic retinopathy in one/both eyes in whom, at the time of enrolment, diabetic macular oedema/proliferative diabetic retinopathy could be active or inactive. METHODS: For the ophthalmic grader pathway, review of the spectral domain optical coherence tomography scans to detect diabetic macular oedema, and seven-field Early Treatment Diabetic Retinopathy Study/ultra-wide field fundus images to detect proliferative diabetic retinopathy, by trained ophthalmic graders. For the current standard care pathway (reference standard), ophthalmologists examined patients face to face by slit-lamp biomicroscopy for proliferative diabetic retinopathy and, in addition, spectral domain optical coherence tomography imaging for diabetic macular oedema. OUTCOME MEASURES: The primary outcome measure was sensitivity of the ophthalmic grader pathway to detect active diabetic macular oedema/proliferative diabetic retinopathy. The secondary outcomes were specificity, agreement between pathways, cost-consequences, acceptability and the proportion of patients requiring subsequent ophthalmologist assessment, unable to undergo imaging and with inadequate quality images/indeterminate findings. It was assumed for the main analysis that all patients in whom graders diagnosed active disease or were 'unsure' or images were 'ungradable' required examination by an ophthalmologist. RESULTS: Eligible participants with active and inactive diabetic macular oedema (152 and 120 participants, respectively) and active and inactive proliferative diabetic retinopathy (111 and 170 participants, respectively) were recruited. Under the main analysis, graders had a sensitivity of 97% (142/147) (95% confidence interval 92% to 99%) and specificity of 31% (35/113) (95% confidence interval 23% to 40%) to detect diabetic macular oedema. For proliferative diabetic retinopathy, graders had a similar sensitivity and specificity using seven-field Early Treatment Diabetic Retinopathy Study [sensitivity 85% (87/102), 95% confidence interval 77% to 91%; specificity 48% (77/160), 95% confidence interval 41% to 56%] or ultra-wide field imaging [sensitivity 83% (87/105), 95% confidence interval 75% to 89%; specificity 54% (86/160), 95% confidence interval 46% to 61%]. Participants attending focus groups expressed preference for face-to-face evaluations by ophthalmologists. In the ophthalmologists' absence, patients voiced the need for immediate feedback following grader's assessments, maintaining periodic evaluations by ophthalmologists. Graders and ophthalmologists were supportive of the new pathway. When compared with the reference standard (current standard pathway), the new grader pathway could save £1390 per 100 patients in the review of people with diabetic macular oedema and, depending on the imaging modality used, between £461 and £1189 per 100 patients in the review of people with proliferative diabetic retinopathy. CONCLUSIONS: For people with diabetic macular oedema, the ophthalmic grader pathway appears safe and cost saving. The sensitivity of the new pathway to detect active proliferative diabetic retinopathy was lower, but may still be considered acceptable for patients with proliferative diabetic retinopathy previously treated with laser. Suggestions from focus group discussions should be taken into consideration if the new pathway is introduced to ensure its acceptability to users. LIMITATIONS: Lack of fundus fluorescein angiography to confirm diagnosis of active proliferative diabetic retinopathy. FUTURE WORK: Could refinement of the new pathway increase its sensitivity to detect proliferative diabetic retinopathy? Could artificial intelligence be used for automated reading of images in this previously treated population? TRIAL REGISTRATION: Current Controlled Trials ISRCTN10856638 and ClinicalTrials.gov NCT03490318. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology AssessmentVol. 25, No. 32. See the NIHR Journals Library website for further project information.

More and more people are developing diabetes. Diabetic macular oedema and proliferative diabetic retinopathy are complications of diabetes, which could cause blindness. Thus, people with diabetic macular oedema and proliferative diabetic retinopathy need to be treated in a timely manner and reviewed in clinic for life. The population in the world is ageing. As a result, there are more people with eye diseases. There are also more treatments now for people with eye diseases. The workload in hospitals is increasing, making it difficult for the NHS to cope with the demand. There are not enough ophthalmologists (eye doctors) to look after patients. Delayed appointments and treatment mean that patients may lose sight. The goal of EMERALD (Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy) was to see if patients with treated and stable diabetic macular oedema or proliferative diabetic retinopathy could be followed by 'ophthalmic graders', who are not doctors but are trained to diagnose diabetic macular oedema and proliferative diabetic retinopathy. In EMERALD, trained ophthalmic graders examined photographs of the back of the eye of people with diabetic macular oedema and proliferative diabetic retinopathy. They checked if diabetic macular oedema and proliferative diabetic retinopathy remain inactive. If so, patients could continue follow-up with the ophthalmic graders. If diabetic macular oedema or proliferative diabetic retinopathy were active, graders would immediately refer patients to ophthalmologists. EMERALD found that graders were excellent at detecting diabetic macular oedema, and this could give ophthalmologists time to see other patients. Graders were not quite as good at detecting active proliferative diabetic retinopathy. However, considering that patients had already had treatment, this may still be safe. Patients participating in focus group discussions mentioned that they would prefer to see ophthalmologists, so they could ask questions about their eye condition. If this was not possible, they would like to have immediate results from graders and still see the ophthalmologist from time to time.

The contribution of the English NHS Diabetic Eye Screening Programme to reductions in diabetes-related blindness, comparisons within Europe, and future challenges.

The aim of the English NHS Diabetic Eye Screening Programme (DESP) is to reduce the risk of sight loss amongst people with diabetes by the prompt identification and effective treatment if necessary of sight-threatening diabetic retinopathy, at the appropriate stage during the disease process, with a long-term aim of preventing blindness in people with diabetes.For the year 2009-2010, diabetic retinopathy (DR) was no longer the leading cause of blindness in the working age group. There have been further reductions in DR certifications for WHO severe vision impairment and blindness from 1,334 (5.5% of all certifications) in 2009/2010 to 840 (3.5% of all certifications) in 2018/2019. NHS DESP is a major contributor to this further reduction, but one must also take into account improvements in glycaemic and blood pressure control, timely laser treatment and vitrectomy surgery, improved monitoring techniques for glycaemic control, and vascular endothelial growth factor inhibitor injections for control of diabetic macular oedema. The latter have had a particular impact since first introduced in the UK in 2013.Current plans for NHS DESP include extension of screening intervals in low-risk groups and the introduction of optical coherence tomography as a second line of screening for those with screen positive maculopathy with two dimensional markers. Future challenges include the introduction of automated analysis for grading and new camera technologies.

Prospective evaluation of an artificial intelligence-enabled algorithm for automated diabetic retinopathy screening of 30 000 patients.

BACKGROUND/AIMS: Human grading of digital images from diabetic retinopathy (DR) screening programmes represents a significant challenge, due to the increasing prevalence of diabetes. We evaluate the performance of an automated artificial intelligence (AI) algorithm to triage retinal images from the English Diabetic Eye Screening Programme (DESP) into test-positive/technical failure versus test-negative, using human grading following a standard national protocol as the reference standard. METHODS: Retinal images from 30 405 consecutive screening episodes from three English DESPs were manually graded following a standard national protocol and by an automated process with machine learning enabled software, EyeArt v2.1. Screening performance (sensitivity, specificity) and diagnostic accuracy (95% CIs) were determined using human grades as the reference standard. RESULTS: Sensitivity (95% CIs) of EyeArt was 95.7% (94.8% to 96.5%) for referable retinopathy (human graded ungradable, referable maculopathy, moderate-to-severe non-proliferative or proliferative). This comprises sensitivities of 98.3% (97.3% to 98.9%) for mild-to-moderate non-proliferative retinopathy with referable maculopathy, 100% (98.7%,100%) for moderate-to-severe non-proliferative retinopathy and 100% (97.9%,100%) for proliferative disease. EyeArt agreed with the human grade of no retinopathy (specificity) in 68% (67% to 69%), with a specificity of 54.0% (53.4% to 54.5%) when combined with non-referable retinopathy. CONCLUSION: The algorithm demonstrated safe levels of sensitivity for high-risk retinopathy in a real-world screening service, with specificity that could halve the workload for human graders. AI machine learning and deep learning algorithms such as this can provide clinically equivalent, rapid detection of retinopathy, particularly in settings where a trained workforce is unavailable or where large-scale and rapid results are needed.

Evaluation of a New Model of Care for People with Complications of Diabetic Retinopathy: The EMERALD Study.

PURPOSE: The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. DESIGN: Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. PARTICIPANTS: Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. METHODS: A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). MAIN OUTCOME MEASURES: Primary outcome: sensitivity of the new pathway. SECONDARY OUTCOMES: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. RESULTS: The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%-99%) and specificity of 31% (95% CI, 23%-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%-91%] and 48% [95% CI, 41%-56%], respectively) or UWF images (83% [95% CI, 75%-89%] and 54% [95% CI, 46%-61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%-93%] and 49% [95% CI, 42%-56%], respectively, for UWF versus 80% [95% CI, 69-88%] and 40% [95% CI, 34%-47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists' assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. CONCLUSIONS: The new pathway has acceptable sensitivity and would release resources. Users' suggestions should guide implementation.