Fundamentals in diabetes. Part 2: Diabetic retinopathy

The prevalence of diabetes continues to increase significantly across the world, currently affecting almost 285 million people. In the UK alone, 2.6 million people are diagnosed with the condition, and this number is expected to reach >4 million by 2025 (Diabetes UK, 2010) – the majority of cases being type 2 diabetes associated with ageing, obesity, population growth and sedentary lifestyles (King et al, 1998). 

Diabetes is the leading cause of blindness in people of working age in the UK (Department of Health, 2003), and diabetic retinopathy remains a leading cause of blindness across the world (Congdon et al, 2003; Fong et al, 2004). Diabetes immediately increases the risk of developing a broad spectrum of vascular complications, of which cataracts and diabetic retinopathy are the most common. Apart from affecting vision, diabetic retinopathy also increases the risk of life-threatening systemic vascular complications (Donnelly et al, 2000).

This article – the second in a series on the fundamental pathophysiology of diabetes complications – explores the underlying mechanisms responsible for the development and progression of diabetic retinopathy, as well as classification, screening and the role of the DSN in caring for people with the condition.

Epidemiology
Diabetic retinopathy is the most common complication in type 1 diabetes and nearly all people with the condition will have developed some degree of retinopathy 15–20 years after diagnosis (Klein et al, 1984). Similarly, more than 60% of people with type 2 diabetes will have evidence of retinopathy during this period (Johansen et al, 1994; Aiello et al, 1998). Numerous epidemiological studies – such as the Diabetic Retinopathy Study (DRS; DRS Research Group, 1981), the Wisconsin Epidemiological Study on Diabetic Retinopathy (Klein et al, 1984), the Early Treatment Diabetic Retinopathy Study (ETDRS; ETDRS Research Group, 1985), the Diabetic Retinopathy Vitrectomy Study (DRVS; DRVS Research Group, 1990), the Diabetes Control and Complications Trial (DCCT; DCCT Research Group, 1993), and the UK Prospective Diabetes Study (Kohner et al, 1993) – have reported important relevant data that have played a significant role in identifying related risk factors as well as providing guidelines for the management of diabetic retinopathy.

A review on the epidemiology of diabetic retinopathy and macular oedema has also reported that studies that are of sufficient size to stratify for age and duration of eye disease have clearly shown an increase in diabetic retinopathy in older people with long-standing diabetes (Williams et al, 2004).

Pathophysiology and classification
Diabetic retinopathy is a progressive microangiopathy characterised by small-vessel damage and occlusion (Riordan-Eva and Whitcher, 2008). The earliest pathological changes are thickening of the capillary endothelia basement membrane and reduction of the number of pericytes (cells associated with the outer wall of small blood vessels). Chronic exposure to risk factors such as hyperglycaemia and hypertension leads to a cascade of biochemical and physiological changes that ultimately results in microvascular damage and retinal dysfunction.

Diabetic retinopathy can be classified as either non-proliferative (background and pre-proliferative) or proliferative. During the non-proliferative stage, early retinal damage occurs from abnormal permeability and/or non-perfusion of capillaries that leads to the formation of micoaneurysms (Engerman, 1989), which results in the leaking of fluid that collects around the macula (macular oedema) (Figure 1 gives a schematic representation of the human eye).

Proliferative diabetic retinopathy develops due to occlusion of retinal capillaries that leads to retinal ischaemia. Neovascularisation follows, whereby fragile new blood vessels proliferate on the surface of the retina causing haemorrhage. Blood then accumulates in the vitreous cavity resulting in visual impairment. Box 1 outlines the stages of retinopathy.

Risk factors for diabetic retinopathy
A number of factors increase the risk of diabetic retinopathy:

1. Diabetes duration – the duration of diabetes is the major risk factor for the development of diabetic retinopathy (Klein et al, 1984).
2. Glycaemic control – the DCCT (DCCT Research Group, 1993) has shown that in people with type 1 diabetes, good glycaemic control reduces the risk of progression of diabetic retinopathy and delays the onset of retinopathy in those who do not have retinal changes at the time of presentation. In people with type 2 diabetes, the UKPDS (Kohner et al, 1993) has shown that good glycaemic control can also delay the progression of retinopathy.
3. Hypertension – studies have indicated that high diastolic blood pressure in young people (Klein et al, 1984) and higher systolic blood pressures in older people (Kohner et al, 1993) can worsen diabetic retinopathy. Recommended target blood pressure levels are ≤130/80 mm/Hg for people with type 2 diabetes and ≤135/85 mmHg for people with type 1 diabetes (NICE, 2005; 2009); however, targets may vary according to local guidelines and protocol.
4. Pregnancy – this has been associated with worsening of diabetic retinopathy, therefore dilated retinal examination is essential during the course of pregnancy. Intrinsic hormonal changes in pregnancy and the need for rapid tightening of glycaemic control throughout pregnancy has also been found to have a strong association with worsening retinopathy. Various factors influence the progression of diabetic retinopathy in pregnancy, including: being in a pregnant state; duration of diabetes; degree of retinopathy at conception; presence of existing hypertension and metabolic control before and during pregnancy (Klein et al, 1990; DCCT Research Group, 2000).
5. Hyperlipidaemia – data from the ETDRS suggest that lipid-lowering may reduce the risk of visual loss in people with diabetic retinopathy (Chew et al, 1996). Target total cholesterol levels of <4 mmol/L are now recommended for people with type 2 diabetes (NICE, 2009).
6. Cigarette smoking – this an additional risk factor and its effect on cardiovascular disease is well known.
7. Age – retinopathy is uncommon in type 1 diabetes before the age of 13 years. The onset of puberty may influence retinopathy, although the duration of diabetes is a significant factor. In those with older onset type 1 diabetes there is an increased frequency of retinopathy in those aged <50 years (Klein et al, 1984). Approximately 21% of people with type 2 diabetes have retinopathy at diagnosis, and their retinopathy is believed to have begun at least 6.5 years before diagnosis of diabetes (Harris et al, 1992).
8. Ethnicity – data from population-based studies suggest that the prevalence and severity of diabetic retinopathy are both higher in African American, Hispanic and south Asian people than in white people, and are not fully accounted for by differences in the distribution of retinopathy risk factors (Wong et al, 2006; Raymond et al, 2009). For example, in the UK Asian Diabetes Study (Raymond et al, 2009) of 1035 people with type 2 diabetes (421 south Asian and 614 white European), the authors showed that after controlling for retinopathy risk factors, south Asian people were more likely to have diabetic retinopathy than white people. 

Screening
Current screening recommendations are that all people aged >12 years with diabetes need to be invited for annual screening (Scanlon, 2008). Digital retinal photography with mydriasis (dilating the pupil using eye drops – usually tropicamide 1% – prior to retinal photography) should be used as the gold standard screening test to detect diabetic retinopathy. There should also be an appropriate referral service in place whereby if any abnormalities are detected these can then be addressed either in hospital clinics or in primary care. 

The screening programme may vary in its delivery regionally depending on the availability of resources and patterns of provision. It may involve GPs, optometrists, hospital physicians and other healthcare professionals. The UK National Screening Committee is responsible for screening programmes in each region.

Management and implications for diabetes nurses
People with diabetes should have their eyes reviewed annually as an integral part of their diabetes care management regardless of the presence of diabetic retinopathy. Emphasis should focus more on prevention and monitoring than treatment. This comes with highlighting the importance of education in relation to diabetes and lifestyle issues surrounding its management.

Following initial assessment of the individual with diabetic retinopathy, the following elements should be covered in the consultation:

• Glycaemic control.
• Blood pressure.
• Lifestyle (including smoking cessation, basic dietary review, physical activity and alcohol consumption).
• Current medication.
• Baseline biomedical parameters (HbA_1c level, renal function, lipid profile and urine albumin excretion).
• Provision of individual diabetes education, including self-monitoring of blood glucose.

The risk of visual impairment and blindness may be reduced by advising people with diabetes on self-care strategies and enrolling them on structured education programmes (NICE, 2003). Programmes such as DESMOND (Diabetes Education and Self-management for Ongoing and Newly Diagnosed) for people with type 2 diabetes and DAFNE (Dose Adjustment for Normal Eating) for those with type 1 diabetes, have been designed to enable these individuals to self-manage their condition successfully. Currently, no topical pharmaceutical preparations are available for the treatment of diabetic retinopathy, although research is still ongoing.

Setting up a diabetes eye clinic service is an innovative and challenging venture, and can prove to be a new learning curve for DSNs. It can also help develop management and interpersonal skills as well as create good working relationships within both the ophthalmic and diabetes clinics. Box 2 highlights how this service can be implemented within a clinical area.

Conclusion
Diabetic retinopathy is a chronic but treatable complication of diabetes. DSNs can play a key role in targeting these screened-positive individuals who present with high but modifiable risk factors (poor glycaemic control, cardiovascular risk). 

The increasing prevalence of diabetes is already having an impact on financial constraints in the NHS. Screening for diabetic eye disease and early detection at a time when it is asymptomatic when followed by interventions can lead to improved outcomes and also play an important part in reducing healthcare costs and improve quality of life for people with diabetes.

Acknowledgements
The authors would like to thank June James (Nurse Consultant in Diabetes, Department of Diabetes and Endocrinology, University Hospitals of Leicester NHS Trust) for her help with this article.