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.

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.

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.

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.

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.

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.

Correction to: Fundamental principles of an effective diabetic retinopathy screening program.

Authors would like to correct few errors in their publication which are listed below.

Progression from Early/Intermediate to Advanced Forms of Age-Related Macular Degeneration in a Large UK Cohort: Rates and Risk Factors.

PURPOSE: To estimate rates and risk factors for progression to geographic atrophy (GA) or choroidal neovascularization (CNV) among eyes diagnosed with early or intermediate age-related macular degeneration (AMD) in clinical practice. DESIGN: Retrospective cohort analysis of a multicenter electronic medical record (EMR) database from the United Kingdom. PARTICIPANTS: Patients aged 50 years or more with diagnosis of early/intermediate AMD in at least 1 eye (the study eye) and no evidence of CNV or GA in the study eye, from 10 clinical sites using the EMR. METHODS: Anonymized data for 40 543 patients with a diagnosis of early/intermediate AMD were extracted between October 2000 and February 2016 from EMR database records held in the 10 sites. A sample of records randomly selected from each center was used to validate disease definitions. Records were analyzed by subgroup, based on the AMD status of the fellow eye. Multivariate Cox regression models identified other predictors of disease progression. MAIN OUTCOME MEASURES: Progression rate (per 100 person-years) to GA or CNV in study eyes with early/intermediate AMD by fellow eye status and identified risk factors for progression. RESULTS: Study eyes with early/intermediate AMD and a diagnosis of CNV in the fellow eye progressed to CNV fastest (at a rate of 15.2 per 100 person-years), and those with a diagnosis of GA in the fellow eye progressed to GA fastest (11.2 per 100 person-years), compared with the rates per 100 person-years of progression to CNV (3.2-11.9) or GA (2.0-7.8) in the other subgroups. In individuals with bilateral early/intermediate AMD, rates of progression to GA or CNV were 2.0 and 3.2 per 100 person-years, respectively. In the multivariate model, age, female sex, and cardiovascular disease were associated with an increased risk for progression to advanced AMD, whereas diabetes and glaucoma were associated with a decreased rate of progression (hazard ratios, 0.45 and 0.64, respectively). CONCLUSIONS: Progression to GA or CNV was observed frequently in eyes with early/intermediate AMD, with the status of the fellow eye affecting the rate of progression. Novel associations with risk factors were observed and require replication in other cohorts.

Fundamental principles of an effective diabetic retinopathy screening program.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults worldwide. Early detection and treatment are necessary to forestall vision loss from DR. METHODS: A working group of ophthalmic and diabetes experts was established to develop a consensus on the key principles of an effective DR screening program. Recommendations are based on analysis of a structured literature review. RESULTS: The recommendations for implementing an effective DR screening program are: (1) Examination methods must be suitable for the screening region, and DR classification/grading systems must be systematic and uniformly applied. Two-field retinal imaging is sufficient for DR screening and is preferable to seven-field imaging, and referable DR should be well defined and reliably identifiable by qualified screening staff; (2) in many countries/regions, screening can and should take place outside the ophthalmology clinic; (3) screening staff should be accredited and show evidence of ongoing training; (4) screening programs should adhere to relevant national quality assurance standards; (5) studies that use uniform definitions of risk to determine optimum risk-based screening intervals are required; (6) technology infrastructure should be in place to ensure that high-quality images can be stored securely to protect patient information; (7) although screening for diabetic macular edema (DME) in conjunction with DR evaluations may have merit, there is currently insufficient evidence to support implementation of programs solely for DME screening. CONCLUSION: Use of these recommendations may yield more effective DR screening programs that reduce the risk of vision loss worldwide.

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.

Update on Screening for Sight-Threatening Diabetic Retinopathy.

PURPOSE: The aim of this article was to describe recent advances in the use of new technology in diabetic retinopathy screening by looking at studies that assessed the effectiveness and cost-effectiveness of these technologies. METHODS: The author conducts an ongoing search for articles relating to screening or management of diabetic retinopathy utilising Zetoc with keywords and contents page lists from relevant journals. RESULTS: The areas discussed in this article are reference standards, alternatives to digital photography, area of retina covered by the screening method, size of the device and hand-held cameras, mydriasis versus non-mydriasis or a combination, measurement of distance visual acuity, grading of images, use of automated grading analysis and cost-effectiveness of the new technologies. CONCLUSIONS: There have been many recent advances in technology that may be adopted in the future by screening programmes for sight-threatening diabetic retinopathy but each device will need to demonstrate effectiveness and cost-effectiveness before more widespread adoption.

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.

The English National Screening Programme for diabetic retinopathy 2003-2016.

The aim of the English NHS Diabetic Eye Screening Programme 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. In order to achieve the delivery of evidence-based, population-based screening programmes, it was recognised that certain key components were required. It is necessary to identify the eligible population in order to deliver the programme to the maximum number of people with diabetes. The programme is delivered and supported by suitably trained, competent, and qualified, clinical and non-clinical staff who participate in recognised ongoing Continuous Professional Development and Quality Assurance schemes. There is an appropriate referral route for those with screen-positive disease for ophthalmology treatment and for assessment of the retinal status in those with poor-quality images. Appropriate assessment of control of their diabetes is also important in those who are screen positive. Audit and internal and external quality assurance schemes are embedded in the service. In England, two-field mydriatic digital photographic screening is offered annually to all people with diabetes aged 12 years and over. The programme commenced in 2003 and reached population coverage across the whole of England by 2008. Increasing uptake has been achieved and the current annual uptake of the programme in 2015-16 is 82.8% when 2.59 million people with diabetes were offered screening and 2.14 million were screened. The benefit of the programme is that, in England, diabetic retinopathy/maculopathy is no longer the leading cause of certifiable blindness in the working age group.

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.