Summary

Diabetic retinopathy is characterised by damage to the microvasculature supplying the eye due as a result of diabetes mellitus. It can result in progressive loss of vision. Diabetic retinopathy is one of the leading causes of preventable blindness in the working-age population. It predominantly arises from chronic hyperglycaemia which causes metabolic and vascular changes within the retina.

Aetiology

The aetiology of diabetic retinopathy is multifactorial and is associated with several factors:

• Overproduction of vascular endothelial growth factor (VEGF): chronic hyperglycaemia induces retinal hypoxia, which in turn causes an overproduction of vascular endothelial growth factor (VEGF). This promotes the growth of new, fragile blood vessels (a process known as neovascularisation), and increases the permeability of existing blood vessels, leading to macular oedema.
• Polyol Pathway Activation: In hyperglycaemic conditions, glucose is converted to sorbitol via the enzyme aldose reductase. Accumulation of sorbitol causes osmotic stress, leading to cell swelling and dysfunction, particularly in the retinal nerve cells and vascular endothelial cells.
• Advanced Glycation End-products (AGEs): Chronic exposure to high glucose levels results in the non-enzymatic glycation of proteins, forming AGEs. These compounds accumulate on cells and extracellular matrix, leading to vascular stiffness, altered protein function, and the induction of pro-inflammatory pathways.
• Protein Kinase C (PKC) Activation: Hyperglycaemia activates the diacylglycerol-PKC pathway. Certain isoforms of PKC are associated with increased vascular permeability, altered blood flow, and the production of growth factors, contributing to diabetic retinopathy.
• Oxidative Stress: Excess glucose metabolism generates reactive oxygen species (ROS), leading to oxidative stress. This promotes inflammation, damages cellular structures, and triggers apoptotic pathways, all of which contribute to retinal injury.

Other contributory factors:

• Duration of diabetes: The longer a person has diabetes, the higher the risk of developing diabetic retinopathy. Most individuals with type 1 DM and a significant proportion of those with type 2 DM will show some signs of retinopathy after 20 years of disease.
• Hypertension: high blood pressure is a risk factor for diabetic retinopathy. High blood pressure can exacerbate the microvascular damage in the retina. It is important to manage blood pressure optimally in individuals with diabetes to reduce risk of progression.
• Dyslipidaemia: altered lipid profiles, particularly elevated levels of low-density lipoprotein (LDL) cholesterol, are associated with the progression and severity of diabetic retinopathy.
• Genetic factors: some individuals with diabetes mellitus are more genetically predisposed to developing diabetic retinopathy than others. The specific genes linked to the susceptibility of diabetic retinopathy are under investigation.
• Diabetic nephropathy: the presence of diabetic nephropathy, another microvascular complication of diabetes, is strongly associated with the risk and progression of diabetic retinopathy.

Clinical features

Non-proliferative diabetic retinopathy