Stephen J. Aldington

A Simple Risk Stratification for Time to Development of Sight-Threatening Diabetic Retinopathy

OBJECTIVE The American Diabetes Association and the English NHS Diabetic Eye Screening Program recommend annual screening for diabetic retinopathy (DR) with referral to ophthalmology clinics of patients with sight-threatening DR (STDR). Using only longitudinal data from retinal photographs in the population-based NHS Diabetic Eye Screening Program in Gloucestershire, we developed a simple means to estimate risk of STDR. RESEARCH DESIGN AND METHODS From 2005, 14,554 patients with no DR or mild nonproliferative DR only at two consecutive annual digital photographic screenings were categorized by the presence of DR in neither, one, or both eyes at each screening and were followed for a further median 2.8 years. RESULTS Of 7,246 with no DR at either screening, 120 progressed to STDR, equivalent to an annual rate of 0.7%. Of 1,778 with no DR in either eye at first screening and in one eye at second screening, 80 progressed to STDR, equivalent to an annual rate of 1.9% and to a hazard ratio (HR) of 2.9 (95% CI 2.2–3.8) compared with those with no DR. Of 1,159 with background DR in both eyes at both screenings, 299 progressed to STDR equivalent to an annual rate of 11% and an HR of 18.2 (14.7–22.5) compared with individuals with no DR. CONCLUSIONS Combining the results from 2 consecutive years of photographic screening enables estimation of the risk of future development of STDR. In countries with systematic screening programs, these results could inform decisions about screening frequency.

Epidemiological issues in diabetic retinopathy

There is currently an epidemic of diabetes in the world, principally type 2 diabetes that is linked to changing lifestyle, obesity, and increasing age of the population. Latest estimates from the International Diabetes Federation (IDF) forecasts a rise from 366 million people worldwide to 552 million by 2030. Type 1 diabetes is more common in the Northern hemisphere with the highest rates in Finland and there is evidence of a rise in some central European countries, particularly in the younger children under 5 years of age. Modifiable risk factors for progression of diabetic retinopathy (DR) are blood glucose, blood pressure, serum lipids, and smoking. Nonmodifiable risk factors are duration, age, genetic predisposition, and ethnicity. Other risk factors are pregnancy, microaneurysm count in an eye, microaneurysm formation rate, and the presence of any DR in the second eye. DR, macular edema (ME), and proliferative DR (PDR) develop with increased duration of diabetes and the rates are dependent on the above risk factors. In one study of type 1 diabetes, the median individual risk for the development of early retinal changes was 9.1 years of diabetes duration. Another study reported the 25 year incidence of proliferative retinopathy among population-based cohort of type 1 patients with diabetes was 42.9%. In recent years, people with diabetes have lower rates of progression than historically to PDR and severe visual loss, which may reflect better control of glucose, blood pressure, and serum lipids, and earlier diagnosis.

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.

The influence of background diabetic retinopathy in the second eye on rates of progression of diabetic retinopathy between 2005 and 2010

Purpose:  The Gloucestershire Diabetic Eye Screening Programme offers annual digital photographic screening for diabetic retinopathy to a countywide population of people with diabetes. This study was designed to investigate progression of diabetic retinopathy in this programme of the English NHS Diabetic Eye Screening Programme.

Practical Manual of Diabetic Retinopathy Management

This practical clinical manual covers the diagnosis, treatment – both medical and surgical – and long–term management of eye problems in people with diabetes. Aimed at the MDT involved in the care of patients with diabetes, it emphasizes the importance of regular screening and early diagnosis and presents evidence–based guidance.

A simple algorithm to estimate the time to development of sight-threatening diabetic retinopathy

Abstract Background More than 3 million people with diabetes in the UK are at risk of vision loss because of diabetic eye disease. Present UK recommendations specify annual diabetic eye screening in those aged 12 years or older with diabetes. Patients identified with potentially sight-threatening diabetic retinopathy are referred to ophthalmology services. Those with no retinopathy and those with non-referable retinal microvascular damage continue to be invited for annual screening irrespective of risk. Models for risk stratification require clinical information, including a measure of glycaemic control that may not be available to screening programmes. With use of data only from retinal photographs we aimed to identify patients at low, intermediate, and high risk of those offered annual appointments, to inform discussion about potential changes to recommended screening intervals. Methods We reviewed all patients referred from primary care to one local screening programme with assessable images of both eyes from at least three screening episodes between Jan 1, 2005, and Dec 31, 2010. Digital images were captured after dilation and were graded by a central quality assured team with NHS diabetic eye screening programme protocols. We included patients who at the first and second (index) screenings had no retinopathy or microaneuryms in one or both eyes. They were followed up until any sight-threatening diabetic retinopathy was detected or until the last available photograph with no sight-threatening diabetic retinopathy. Patients were categorised by presence of microaneuryms in neither, one, or both eyes at each screening. We excluded those with any missing data. By design, no confounding variables were included in the model. We derived life table survival plots with Kaplan-Meier estimates and calculated hazard ratios (HRs) with Cox proportional hazards models. We used log logistic models to estimate the proportion of patients with microaneuryms every year after baseline. Data were analysed with SAS (version 9.1). Findings From 2005, 18–254 patients with non-referable diabetic retinopathy at two consecutive screenings were available, of whom 3700 had no further assessable images. Hence 14–554 patients were followed up for further median 2·8 years (IQR 1·3–3·3). Their median age was 65 years (IQR 56–73), and 8188 (55%) were men. Of 7246 with no evidence of retinal microvascular damage at both screenings, 120 progressed to sight-threatening diabetic retinopathy, 0·7% by 1 year. Of 1778 with microaneuryms in neither eye at first screening and in one eye at second screening, 80 progressed to sight-threatening diabetic retinopathy, 1·9% by 1 year (HR 2·9, 95% CI 2·2–3·8). Of 1159 with microaneuryms in both eyes at both screenings, 299 progressed to sight-threatening diabetic retinopathy, 11% by 1 year (HR 18·2, 95% CI 14·7–22·5). Those in higher risk groups were more likely to progress to more serious diabetic retinopathy than were those in lower risk groups. Interpretation This screening programme of a mainly northern European population has robust quality controlled imaging and grading. Hence it needs to be validated in other populations and programmes to be generalisable. Two sequential image sets can differentiate levels of risk and could modify the interval for screening. The addition of these data to clinical indices could improve risk stratification compared with either method alone. Funding None