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Risk factors and diabetic retinopathy progression

The main risk factors for progression of diabetic retinopathy and the evidence linking risk factors, disease progression and incidence of visual loss.
To plan eye care services for people with diabetes, we need to know the incidence of diabetic retinopathy (new cases) in our population.
That is, how many people with diabetes will develop diabetic retinopathy during a specified time period.
There are three main steps to measure the incidence of diabetic retinopathy. 1. We use an agreed case definition and assessment method to define what is, and what is not, diabetic retinopathy. For example, we can use the International Classification of Diabetic Retinopathy (DR) and Diabetic Macular Oedema (DMO) and simple single field 45 degree digital imaging.
We select all the people in a defined population who have diabetes, but do not have visual impairment from diabetic retinopathy. That is, they are disease free.
And 3. We then follow this group (sometimes known as a cohort) for a specified time, for example 10 years, and measure who develops diabetic retinopathy during that time.
To date, most of the population-based incidence studies on diabetic retinopathy (or DR) have taken place in high-income countries. Variations found in this data have highlighted that the risk factors for the development and progression of DR can be divided into non-modifiable and modifiable factors.
Public health interventions to prevent vision loss from DR need to include a screening policy to target those at increased risk and provide health education to minimise that risk.
Non-modifiable risk factors for DR cannot be influenced or changed. Duration of diabetes is a single major risk factor. The longer a person lives with diabetes the higher the risk of developing DR. The cumulative incidence of DR in people with type 1 diabetes has been found to increase from 59% at 4 years to 89% at 10 years to 97% at 25 years. The cumulative incidence in people with type 2 diabetes was found to increase from 26% at 4 years to 66% by 10 years. A decline in the incidence of DR has been noted in some settings after improvements are made to the health management of people with diabetes.
Age. Growth spurts, hormonal, dietary and other changes in the post puberty period mean that teenagers who have type 1 diabetes have a 30% increased risk of developing diabetic retinopathy. This risk is even more significant in males.
Pregnancy for a person with diabetes carries a 50% risk of developing diabetic retinopathy. In women who already have non-proliferative DR there is a 47% chance of the disease progressing to a severe stage. And up to 50% of those will require laser treatment.
Although 29% of women with DR experience regression of the disease in the post-partum period, pregnancy remains a high-risk event. Based on the trends found in DR incidence studies, genetic predisposition and ethnicity have drawn considerable interest as possible non-modifiable risk factors for DR. Some patients are also predisposed to severe diabetic retinopathy even with adequate control.
Modifiable risk factors can be controlled through medication or change in behaviour.
There are several - associated, known and possible - modifiable risk factors for DR: Blood glucose control, blood pressure control, blood lipid levels, body mass index, and smoking Blood glucose control is measured through the glycated haemoglobin, or HbA1c, test. Clinicians measure HbA1c levels to get an overall picture of what a persons average blood sugar levels have been over the previous 2-3 months. The ideal HbA1c level in a person with diabetes is 48 mmol/mol (6.5%).
Evidence shows that for every 1% reduction in HbA1c there is a 40% reduction in risk for the development of the microvascular changes of diabetic retinopathy. On a practical level this 1% reduction means a 25% reduction in the need for laser treatment and a 15% reduction of risk of blindness.
Intensively maintaining levels of blood sugar as close to the ideal as possible (known as good glycaemic control) right from diagnosis is very beneficial for people with diabetes, both in preventing diabetic retinopathy and in delaying the progression of any disease that does develop.
People with diabetes often also have high blood pressure (hypertension). The incidence of visual loss in people with type 2 diabetes is higher when they also have hypertension.
Reducing systolic blood pressure by 10 millimetres of mercury
results in: a 35% risk reduction for developing diabetic retinopathy, a 35% reduction in the need for laser treatment and a 50% reduction of risk for blindness.
Controlling hypertension has been found to have an effect on reducing incidence of DR. Excessive levels of fat (or lipids) in the blood is called hyperlipidaemia. Hyperlipidaemia and obesity are associated with DR but the evidence so far is limited on whether they are risk factors for the disease.
Use of the drug Fenofibrate to reduce cholesterol levels has been found to reduce the risk of requiring laser treatment for proliferative DR. The data varies on smoking as a risk factor for progression of DR. Some studies have found no association whilst others have. Experimental studies have noted that nicotine accelerates diabetic retinopathy. Finally, its important to note that diabetes is associated with early and rapid development of cataracts. Progression of diabetic retinopathy has been associated with cataract surgery. Where possible, pre-operative blood sugar control is required and existing retinopathy stabilised with laser treatment before surgery. When removing dense cataracts, there should be close follow up and management of any diabetic retinopathy progression In summary.
Research has revealed that there are modifiable and non-modifiable risk factors for DR. Control of blood sugar level is the most important modifiable risk factor for reducing the progression of DR. Controlling all the modifiable risk factors for DR is vital and must be considered along with reducing the risk of other complications of diabetes. For example, kidney or heart disease. Physicians and ophthalmologists need to work together to manage people with diabetes over the long term.

People with diabetes are 25 times more likely than the general population to become blind. Diabetes has many manifestations in the eye, of which cataracts and diabetic retinopathy (DR) are the most significant causes of visual impairment and blindness. DR is the leading cause of visual impairment and blindness in working adults under 75 years. Visual impairment due to DR has a significant impact on people with diabetes’ quality of life, compromising their ability to manage their diabetes and increasing the risk of other diabetic complications and a lower life expectancy.

To plan and manage diabetic eye care services, collecting and following patient data over time (longitudinal data) is essential to identify the true extent of diagnosed retinal complications from diabetes in the population. A few large epidemiological studies, mostly from high income countries have provided information on DR incidence and disease progression. These studies, the Wisconsin Epidemiological Study on Diabetic Retinopathy, the Diabetic Retinopathy Study (DRS),the Early Treatment of Diabetic Retinopathy Study (ETDRS), the Diabetes Control and Complications Trial (DCCT), the Diabetic Retinopathy Vitrectomy Study (DRVS), and the UK Prospective Diabetic Survey followed patients for many years and are regarded as “gold standards”. The information provided by these studies has been used to develop guidelines for the care of people with diabetic retinopathy.

However, many of these important large scale studies are now dated. More recent studies have been more limited in scope and have found some confounding or conflicting results due to their smaller sample sizes. In addition, a number of these studies have been clinic-based rather than to population-based. When examining the literature on diabetic eye disease we need to remember that these smaller studies are valuable but that their findings may not be generalisable and may overestimate the frequency and severity of disease.

In this video we examine the main risk factors for DR progression, assess the evidence on risk factors and disease progression and relate the risk factors to the incidence of visual loss from DR. As you watch, consider how incidence data guides the development of appropriate prevention strategies for DR generally and within your setting.

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Diabetic Eye Disease: Building Capacity To Prevent Blindness

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