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.

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.

Screening for diabetic retinopathy: new perspectives and challenges.

Although the prevalence of all stages of diabetic retinopathy has been declining since 1980 in populations with improved diabetes control, the crude prevalence of visual impairment and blindness caused by diabetic retinopathy worldwide increased between 1990 and 2015, largely because of the increasing prevalence of type 2 diabetes, particularly in low-income and middle-income countries. Screening for diabetic retinopathy is essential to detect referable cases that need timely full ophthalmic examination and treatment to avoid permanent visual loss. In the past few years, personalised screening intervals that take into account several risk factors have been proposed, with good cost-effectiveness ratios. However, resources for nationwide screening programmes are scarce in many countries. New technologies, such as scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness. Additionally, emerging evidence suggests that retinal imaging could be useful for identifying individuals at risk of cardiovascular disease or cognitive impairment, which could expand the role of diabetic retinopathy screening beyond the prevention of sight-threatening disease.

Direct Ophthalmic Healthcare Resource Use among Patients with Geographic Atrophy in a Large Cohort from the United Kingdom.

PURPOSE: To estimate the direct ophthalmic healthcare resource use in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). DESIGN: Retrospective analysis of anonymized data derived from electronic medical records (EMRs) acquired at 10 clinical sites in the United Kingdom. PARTICIPANTS: Patients aged ≥50 years with ≥1 eye with a clinical record of GA or, for comparison, bilateral early/intermediate AMD. Four subgroups were identified: GA in both eyes (GA:GA); GA in 1 eye, choroidal neovascularization (CNV) in the fellow eye (GA:CNV); GA in 1 eye with early or intermediate AMD in the fellow eye (GA:E); and early/intermediate AMD in both eyes (E:E). METHODS: The EMRs were analyzed to derive the median number of visits over the first 2 years after diagnosis of GA or early/intermediate AMD. Clinical tests recorded at visits were used to calculate estimated costs (payer perspective) of monitoring. Analyses were restricted to patients with an initial diagnosis on or after January 1, 2011, to represent present day monitoring and costs associated with AMD. MAIN OUTCOME MEASURES: Median number of visits and estimated monitoring costs per patient (in £) over the first 2 years among patients with ≥2 years of follow-up and in the individual subgroups. Intravitreal treatment costs in the GA:CNV group were excluded. RESULTS: For all 3 GA subgroups (n = 1080), the median number of visits over the first 2 years was 5, and monitoring costs were £460.80 per patient. The GA:CNV subgroup (n = 355) had the highest number of visits (median, 15), with a cost of £1581, compared with the GA:E subgroup (n = 283; median 4 visits; cost ∼£369) and the GA:GA subgroup (n = 442; median 3 visits; cost ∼£277). Ophthalmic tests were conducted most frequently in the GA:CNV subgroup. Visits and costs in the E:E subgroup (n = 6079) were lower. CONCLUSIONS: Resource use in patients with GA varies considerably and is strongly influenced by the concomitant presence of CNV and lack of monitoring strategies for GA.

Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy (EMERALD).

INTRODUCTION: Diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) are the major causes of sight loss in people with diabetes. Due to the increased prevalence of diabetes, the workload related to these complications is increasing making it difficult for Hospital Eye Services (HSE) to meet demands. METHODS AND ANALYSIS: Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy (EMERALD) is a prospective, case-referent, cross-sectional diagnostic study. It aims at determining the diagnostic performance, cost-effectiveness and acceptability of a new form of surveillance for people with stable DMO and/or PDR, which entails multimodal imaging and image review by an ophthalmic grader, using the current standard of care (evaluation of patients in clinic by an ophthalmologist) as the reference standard. If safe, cost-effective and acceptable, this pathway could help HES by freeing ophthalmologist time. The primary outcome of EMERALD is sensitivity of the new surveillance pathway in detecting active DMO/PDR. Secondary outcomes include specificity, agreement between new and the standard care pathway, positive and negative likelihood ratios, cost-effectiveness, acceptability, proportion of patients requiring subsequent full clinical assessment, unable to undergo imaging, with inadequate quality images or indeterminate findings. ETHICS AND DISSEMINATION: Ethical approval was obtained for this study from the Office for Research Ethics Committees Northern Ireland (reference 17/NI/0124). Study results will be published as a Health Technology Assessment monograph, in peer-reviewed national and international journals and presented at national/international conferences and to patient groups. TRIAL REGISTRATION NUMBER: NCT03490318 and ISRCTN:10856638.

Cost-effectiveness of digital surveillance clinics with optical coherence tomography versus hospital eye service follow-up for patients with screen-positive maculopathy.

BACKGROUND: Annually 2.7 million individuals are offered screening for diabetic retinopathy (DR) in England. Spectral-Domain Optical Coherence Tomography (SD-OCT) has the potential to relieve pressure on NHS services by correctly identifying patients who are screen positive for maculopathy on two-dimensional photography without evidence of clinically significant macular oedema (CSMO), limiting the number of referrals to hospitals. We aim to assess whether the addition of SDOCT imaging in digital surveillance clinics is a cost-effective intervention relative to hospital eye service (HES) follow-up. METHODS: We used patient-level data from the Gloucestershire Diabetic Eye Screening Service linked to the local digital surveillance programme and HES between 2012 and 2015. A model was used to simulate the progression of individuals with background diabetic retinopathy (R1) and diabetic maculopathy (M1) following DR screening across the clinic pathways over 12 months. RESULTS: Between January 2012 and December 2014, 696 people undergoing DR screening were found to have screen-positive maculopathy in at least one eye for the first time, with a total of 766 eyes identified as having R1M1. The mean annual cost of assessing and surveillance through the SD-OCT clinic pathway was £101 (95% CI: 91-139) as compared with £177 (95%CI: 164-219) under the HES pathway. Surveillance under an SD-OCT clinic generated cost savings of £76 (95% CI: 70-81) per patient. CONCLUSIONS: Our analysis shows that SD-OCT surveillance of patients diagnosed as R1M1 at DR screening is not only cost-effective but generates considerable cost savings.

Screening Intervals for Diabetic Retinopathy and Implications for Care.

PURPOSE OF REVIEW: The purpose of this study is to review the evidence that lower risk groups who could safely be screened less frequently for sight-threatening diabetic retinopathy (DR) than annually. RECENT FINDINGS: Data have demonstrated that people with no DR in either eye are at a low risk of progression to sight-threatening DR over a 2-year period (event rate 4.8 per 1000 person years), irrespective of whether the screening method is one-field non-mydriatic or two-field mydriatic digital photography. Low risk has been defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with risk factor data. The risk of an extension to 2 years is less than 5 per 1000 person years in a population with a national screening programme, and the general standard of diabetes care is relatively good, whether low risk is defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with other risk factor data. The definition used in different populations is likely to depend on the availability of data.

Development of a cost-effectiveness model for optimisation of the screening interval in diabetic retinopathy screening.

BACKGROUND: The English NHS Diabetic Eye Screening Programme was established in 2003. Eligible people are invited annually for digital retinal photography screening. Those found to have potentially sight-threatening diabetic retinopathy (STDR) are referred to surveillance clinics or to Hospital Eye Services. OBJECTIVES: To determine whether personalised screening intervals are cost-effective. DESIGN: Risk factors were identified in Gloucestershire, UK using survival modelling. A probabilistic decision hidden (unobserved) Markov model with a misgrading matrix was developed. This informed estimation of lifetime costs and quality-adjusted life-years (QALYs) in patients without STDR. Two personalised risk stratification models were employed: two screening episodes (SEs) (low, medium or high risk) or one SE with clinical information (low, medium-low, medium-high or high risk). The risk factor models were validated in other populations. SETTING: Gloucestershire, Nottinghamshire, South London and East Anglia (all UK). PARTICIPANTS: People with diabetes in Gloucestershire with risk stratification model validation using data from Nottinghamshire, South London and East Anglia. MAIN OUTCOME MEASURES: Personalised risk-based algorithm for screening interval; cost-effectiveness of different screening intervals. RESULTS: Data were obtained in Gloucestershire from 12,790 people with diabetes with known risk factors to derive the risk estimation models, from 15,877 people to inform the uptake of screening and from 17,043 people to inform the health-care resource-usage costs. Two stratification models were developed: one using only results from previous screening events and one using previous screening and some commonly available GP data. Both models were capable of differentiating groups at low and high risk of development of STDR. The rate of progression to STDR was 5 per 1000 person-years (PYs) in the lowest decile of risk and 75 per 1000 PYs in the highest decile. In the absence of personalised risk stratification, the most cost-effective screening interval was to screen all patients every 3 years, with a 46% probability of this being cost-effective at a £30,000 per QALY threshold. Using either risk stratification models, screening patients at low risk every 5 years was the most cost-effective option, with a probability of 99-100% at a £30,000 per QALY threshold. For the medium-risk groups screening every 3 years had a probability of 43-48% while screening high-risk groups every 2 years was cost-effective with a probability of 55-59%. CONCLUSIONS: The study found that annual screening of all patients for STDR was not cost-effective. Screening this entire cohort every 3 years was most likely to be cost-effective. When personalised intervals are applied, screening those in our low-risk groups every 5 years was found to be cost-effective. Screening high-risk groups every 2 years further improved the cost-effectiveness of the programme. There was considerable uncertainty in the estimated incremental costs and in the incremental QALYs, particularly with regard to implications of an increasing proportion of maculopathy cases receiving intravitreal injection rather than laser treatment. Future work should focus on improving the understanding of risk, validating in further populations and investigating quality issues in imaging and assessment including the potential for automated image grading. STUDY REGISTRATION: Integrated Research Application System project number 118959. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme.

Influence of primary care practices on patients' uptake of diabetic retinopathy screening: a qualitative case study.

BACKGROUND: The NHS Diabetic Eye Screening Programme aims to reduce the risk of sight loss among people with diabetes in England by enabling prompt diagnosis of sight-threatening retinopathy. However, the rate of screening uptake between practices can vary from 55% to 95%. Existing research focuses on the impact of patient demographics but little is known about GP practice-related factors that can make a difference. AIM: To identify factors contributing to high or low patient uptake of retinopathy screening. DESIGN AND SETTING: Qualitative case-based study; nine purposively selected GP practices (deprived/affluent; high/low screening uptake) in three retinopathy screening programme areas. METHODS: Semi-structured interviews were conducted with patients, primary care professionals, and screeners. A comparative case-based analysis was carried out to identify factors related to high or low screening uptake. RESULTS: Eight possible factors that influenced uptake were identified. Five modifiable factors related to service and staff interactions: communication with screening services; contacting patients; integration of screening with other care; focus on the newly diagnosed; and perception of non-attenders. Three factors were non-modifiable challenges related to practice location: level of deprivation; diversity of ethnicities and languages; and transport and access. All practices adopted strategies to improve uptake, but the presence of two or more major barriers made it very hard for practices to achieve higher uptake levels. CONCLUSIONS: A range of service-level opportunities to improve screening attendance were identified that are available to practices and screening teams. More research is needed into the complex interfaces of care that make up retinopathy screening.