A Practical Manual of Diabetic Retinopathy Management

List of contributors

Stephen J. Aldington

Retinopathy Research and Professional Development Manager, Gloucestershire Hospitals NHS Foundation Trust, UK

Honorary Associate Professor, University of Warwick Medical School, UK

Abdallah A. Ellabban

Lecturer, Department of Ophthalmology, Suez Canal University, Egypt

Ahmed Sallam

Staff Surgeon, Jones Eye Institute

Assistant Professor of Ophthalmology

University of Arkansas for Medical Sciences, USA

Peter H. Scanlon

Consultant Ophthalmologist, Gloucestershire and Oxford Eye Units

Senior Research Fellow, Harris Manchester College

University of Oxford

Visiting Professor of Medical Ophthalmology

University of Gloucestershire, UK

Jonathan Shaw

Associate Professor, Baker IDI Heart and Diabetes Institute, Melbourne, Australia

Peter van Wijngaarden

Consultant Ophthalmologist, Centre for Eye Research

Australia, Royal Victorian Eye and Ear Hospital

Australia Ophthalmology, Department of Surgery

University of Melbourne, Australia

Charles P. Wilkinson

Professor of Ophthalmology, Johns Hopkins University

Emeritus Chairman, Department of Ophthalmology

Greater Baltimore Medical Center, USA

Prologue

Peter H. Scanlon

The scope of the problem of the epidemic of diabetes

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. The International Diabetes Federation (IDF) publishes the Diabetes Atlas¹ and has forecast a rise from the current level of 387 million people worldwide in 2014 to 592 million by 2035. The current level in 2014 is equivalent to 1 in 12 people in the world having diabetes, and 48.3% of these people are believed to be undiagnosed.

In 2000, Karvonen et al.² reported a global variation in the incidence in different populations; the overall age-adjusted incidence of type 1 diabetes varied from 0.1/100,000 per year in China and Venezuela to 36.8/100,000 per year in Sardinia and 36.5/100,000 per year in Finland. The 2014 estimates¹ for the prevalence of type 1 diabetes are 500,000 children aged under 15 years with type 1 diabetes worldwide, the largest numbers³ being in Europe (129,000) and North America (108,700), with the numbers have increased in most of the IDF regions.

The International Diabetes Federation has estimated¹ the prevalence of diabetes in 2014 in 20–79 age groups and projected this to an estimate in 2035 (Fig. 1).

Fig 1 World map showing rising incidence and prevalence of diabetes.

Table 1

Individual publications⁴–¹⁰ from each region have described how these figures were arrived at. The report from the Western Pacific region was noteworthy because this region is home to one-quarter of the world's population, and includes China with the largest number of people with diabetes (98.41 million) as well as the Pacific Islands countries with the highest prevalence rates (Tokelau 37.49%, Federated States of Micronesia 35.03%, Marshall Islands 34.89%).

The prevalence of sight-threatening diabetic retinopathy worldwide

It is difficult to compare the many studies that have recorded the incidence and prevalence of diabetic retinopathy (DR) or sight-threatening or vision-threatening diabetic retinopathy (STDR or VTDR) because of the difference in examination techniques and the different definitions, particularly of STDR and VTDR (see Fig. 2).

Fig. 2 World map showing high prevalence of diabetic retinopathy (DR) and proliferative DR.

Table 2

The map in Fig. 2 uses data from the following studies.

1. In 2012, Yau et al.¹¹ reviewed a total of 35 studies (1980–2008) which provided data from 22,896 individuals with diabetes, and found that the overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular oedema and 10.2% (10.1–10.3) for VTDR.

2. In the USA, Zhang et al.¹² reported that the estimated prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was 28.5% (95% CI, 24.9–32.5%) and 4.4% (95% CI, 3.5–5.7%) among US adults with diabetes, respectively.

3. In Saudi Arabia, Ghamdi et al.¹³ reported that the prevalence of any DR was 34.6% but what was noticeable was the high level of STDR of 17.5%, which was mostly due to high levels of referable maculopathy (15.9%) and may be related to the high number with poor glycaemic control.

4. Burgess et al.¹⁴ reported a systematic literature review of studies of diabetic retinopathy and maculopathy in Africa. A total of 62 studies from 21 countries were included. In population-based studies, the reported prevalence range in patients with diabetes was 30–31.6% for any DR, 0.9–1.3% for PDR and 1.2–4.5% for any maculopathy.

5. Thomas et al.¹⁵ reported results from the Welsh Screening Programme in the UK. The prevalence of any DR and sight-threatening DR in those with type 1 diabetes was 56.0% and 11.2%, respectively, and in type 2 diabetes was 30.3% and 2.9%, respectively.

6. Wu et al.¹⁶ reported on the prevalence of diabetic retinopathy in mainland China. The prevalence of DR, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was 23% (95% CI: 17.8–29.2%), 19.1% (95% CI: 13.6–26.3%), and 2.8% (95% CI: 1.9–4.2%) in people with diabetes.

7. Wong et al.¹⁷ reported from the Singapore Malay Eye Study that the overall prevalence of any retinopathy was 35.0% (95% CI, 28.2–43.4%), the overall prevalence of macular oedema was 5.7% (95% CI, 3.2–9.9%), PDR 4.9% (95% CI, 2.7–8.8%) and the overall prevalence of vision-threatening retinopathy was 9.0% (95% CI, 5.8–13.8%).

8. Rema et al.¹⁸ reported that the overall prevalence of DR in the population of known diabetic subjects in Chennai, India was 20.8% (95% CI: 18.7–23.1%) and 5.1% (95% CI: 3.1–8.0%) in subjects with newly detected diabetes.

9. Villena et al.¹⁹ reported from a hospital-based photographic screening programme in Peru that DR was detected in 282 patients (23.1%) (95% CI: 20.71–25.44%); 249 patients (20.4%) (95% CI: 18.1–22.6%) had non-proliferative DR and 33 (2.7%) (95% CI: 1.8–3.6%) had proliferative DR.

10. In the Australian Diabetes, Obesity and Lifestyle study (AusDiab) of 11,247 adults > 25 years in 42 randomly selected areas of Australia, Tapp et al.²⁰ showed a prevalence of any DR of 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of PDR was 2.1% in those with known DM.

Of note, three studies²¹–²³ have demonstrated that, if one screens for type 2 diabetes in different populations, the prevalence of diabetic retinopathy in screen-positive patients (7.6%, 6.8% and 9%) is much lower than the prevalence in the known population of people with diabetes.

In 1997, Kernell et al.²⁴ reported the youngest child in the literature (11.8 years) at that time with pre-proliferative DR from Sweden.

In 1999, Donaghue et al.²⁵ described the youngest child reported in the literature to have background diabetic retinopathy at that time (1999): 7.9 years (duration 5.6 years, HbA1c 8.9%) from Australia.

Incidence of DR

In 2008 and 2009, Klein et al.²⁶,²⁷ reported on the 25-year cumulative progression and regression of diabetic retinopathy and cumulative incidence of macular oedema (MO) and clinically significant macular oedema (CSMO) in type 1 patients in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. The 25-year cumulative rate of progression of DR was 83%, progression to proliferative DR was 42%, and improvement of DR was 18%; the 25-year cumulative incidence was 29% for ME and 17% for CSME.

In 2009, Wong et al.²⁸ conducted a systematic review of rates of progression of diabetic retinopathy in people with both type 1 and type 2 diabetes during different time periods. The article concluded that, since 1985, diabetic patients have lower rates of progression to proliferative diabetic retinopathy and severe visual loss. These findings may reflect an improvement in medical management of the diabetes and associated risk factors.

Advances in management of diabetes

Advances in the management of diabetes have had a substantial impact on diabetic retinopathy. These are discussed in detail in Chapter 2 on diabetes.

The demonstration by the Diabetes Control and Complications Trial¹⁴ that retinopathy in type 1 diabetes could be reduced by intensive treatment of blood glucose has led to much better control and retinopathy progression has been reduced. Studies²⁹,³⁰ in the early 1990s showed the link between hypertension in type 1 diabetes and a higher occurrence of retinopathy and of progression of pre-existing retinopathy.

A similar demonstration in the United Kingdom Prospective Diabetes Study³¹ (UKPDS) that in type 2 diabetes the development of retinopathy (incidence) was strongly associated with baseline glycaemia and glycaemic exposure, and progression was associated with hyperglycaemia (as evidenced by a higher HbA1c), has led to better control in type 2 diabetes and in a reduction in retinopathy progression. The UKPDS³² also demonstrated that high BP is detrimental to each aspect of diabetic retinopathy in type 2 diabetes and that a tight BP control policy reduces the risk of clinical complications from diabetic eye disease (Fig. 3).

Fig. 3 (a) Uncontrolled hypertension in a person with diabetes: right macula colour photo showing flame haemorrhages and cotton wool spots. (b) The result of treating the hypertension in this person.

Advances in management of diabetic retinopathy

Since Spalter³³ described the photocoagulation of circinate maculopathy in diabetic retinopathy, clear evidence for the efficacy of laser treatment for diabetic eye disease has been shown from the Diabetic Retinopathy Study³⁴–³⁸ and the Early Treatment Diabetic Retinopathy Study³⁹–⁴⁷. In 1981 they reported³⁶ that photocoagulation, as used in the study, reduced the two-year risk of severe visual loss by 50% or more (Fig. 4).

Fig. 4 Stable treated eye after panretinal photocoagulation for NVD.

In 1985, a report³⁹ from the Early Treatment Diabetic Retinopathy Study showed that focal photocoagulation of ‘clinically significant’ diabetic macular oedema (CSMO) substantially reduced the risk of visual loss. Smiddy and Flynn⁴⁸ wrote an excellent review in 1999 when they noted that, according to the Early Treatment Diabetic Retinopathy Study, at least 5% of eyes receiving optimal medical treatment will still have progressive retinopathy that requires laser treatment and pars plana vitrectomy. They also noted that, although vitrectomy improves the prognosis for a favourable visual outcome, preventive measures such as improved control of glucose levels and timely application of panretinal photocoagulation are equally important in the management. Vitrectomy clearly does have a place in the management of diabetic eye disease. Evidence of improving visual results during the last 20 years following vitrectomy have been shown in studies reported by Blankenship and Machemer⁴⁹, Thompson et al.⁵⁰–⁵³, Sigurdsson et al.⁵⁴, Flynn et al.⁵⁵, Nakazawa et al.⁵⁶, Karel and Kalvodova⁵⁷, Harbour et al.⁵⁸, Pendergast et al.⁵⁹, La Heij et al.⁶⁰, Yamamoto et al.⁶¹, Amino and Tanihara⁶², Lewis⁶³, Lahey et al.⁶⁴, Treumer et al.⁶⁵, Schrey et al.⁶⁶, Diolaiuti et al.⁶⁷, Haller et al.⁶⁸, Tao et al.⁶⁹, Gupta et al.⁷⁰ and Ostri et al.⁷¹. However, a restriction in driving field has been reported in over two-thirds of patients in a small series of patients by Barsam and Laidlaw⁷².

Improved postoperative outcomes have recently been reported73–⁷⁵ using VEGF inhibitors preoperatively.

Developments in techniques of laser treatment are discussed Chapter 10 and treatments for DME (e.g. corticosteroids and anti-vascular endothelial growth factor drugs) are described in Chapter 7. Laser photocoagulation remains the standard of care for proliferative diabetic retinopathy, but the anti-vascular endothelial growth factor drugs are now used as a first line of treatment in many centres for centre-involving diabetic macular oedema.

Despite the available treatments, many patients present late in the course of the disease when treatment is more difficult. There have been considerable advances in early detection in the last 10 years with the advent of systematic screening programmes for diabetic retinopathy.

The St Vincent Declaration, a joint initiative on diabetes care and research of the World Health Organisation (Europe) and the International Diabetes Federation (Europe), included 5 year targets for improvement in diabetes outcomes. One of these targets was to reduce diabetes-related blindness by one-third or more over the next 5 years.

In Liverpool, UK on 17–18 November 2005 a conference took place to review progress in the prevention of visual impairment due to diabetic retinopathy in Europe. The conference recommended the following steps in the development of systematic screening programmes for sight-threatening DR.

Step 1: Access to effective treatment: minimum number of lasers per 100,000 population; equal access for all patient groups; and maximum time to treatment from diagnosis 3 months.

Step 2: Establish opportunistic screening: dilated fundoscopy at time of attendance for routine care; annual review; and national guidelines on referral to an ophthalmologist.

Step 3: Establish systematic screening: establish and maintain disease registers; sytematic call and recall for all people with diabetes; annual screening; test used has sensitivity of ≥80% and specificity of ≥90%; and coverage ≥80%.

Step 4: Establish systematic screening with full quality assurance and full coverage: digital photographic screening; all personnel involved in screening will be certified as competent; 100% coverage; quality assurance at all stages; and central/regional data collection for monitoring and measurement of effectiveness.

The establishment of systematic screening in the UK, combined with better management of diabetes and its associated risk factors, has resulted in a report⁷⁶ demonstrating that diabetic retinopathy is no longer the leading cause of blindness in England and Wales.

Practice points

There is an epidemic of diabetes worldwide. The prevalence of diabetic retinopathy is rising as a consequence of the epidemic of diabetes. Effective treatments are available, but are dependent on the stage of diagnosis. Systematic screening programmes can be set up to detect diabetic retinopathy at an appropriate stage to reduce the incidence and prevalence of blindness.

REFERENCE

Please visit www.wiley.com/go/scanlon/diabetic_retinopathy

Acknowledgements

I am grateful to my colleagues in Gloucestershire and Oxford who have assisted in identifying and imaging patients that have provided very useful examples of conditions that have enhanced the quality of this book. In particular, thanks are due to: Lisa Collins (Senior Optometrist), Quresh Mohammed, Emily Fletcher, Rob Johnston, Victor Chong and Samia Fatum (Ophthalmologists), Mike Taylor, Emily Arthur, Seren Stacey-Jones (Medical Photographers), Gwen George, Scott Vallance, Jenny Mason, Tracey Scott, Lewis Smith (Ophthalmic Photographers) and Steve Chave (Informatics