Definition

Patients with poorly managed diabetes mellitus can develop vascular occlusion and leakage of capillaries that supply the retina (the bit of the eye that sends information to the brain, letting someone see). This can cause retinal ischaemia, new vessel formation, and if not managed, loss of sight. Diabetic retinopathy is the most common cause of blindness in adults aged 35-65.(1,2)

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Types

Diabetic retinopathy can be broadly classified as either non-proliferative diabetic retinopathy or proliferative diabetic retinopathy.

Non-proliferative diabetic retinopathy (NPDR)
NPDR is cause by diabetic microvascular abnormalities that cause ischaemia.

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Proliferative diabetic retinopathy (PDR)

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PDR is characterised by new vessels on the disc and/or new vessels anywhere else in the eye, which occurs due to severe ischaemia. These new vessels will be weak and prone to leak. If these vessels go into the vitreous humour, it can lead to vitreous haemorrhage. The neovascularisation process is really bad for the eye, and ultimately leads to poor blood flow to the retina and production of VEGF.(4)

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Maculopathy

Diabetic maculopathy is macular oedema caused by vessels that are close to the macula leaking. The macula is responsible for central vision, and thus patients normally complain about difficulty with recognising faces or blurred vision when reading. This is an emergency as it can cause blindness.(5)

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Physiology and pathology

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Diabetes is characterised by high blood glucose levels (hyperglycaemia) due to the body being unable to produce and/or being resistant to insulin. Long term, hyperglycaemia can cause blood vessels (including those that supply the retina), to become weak and thus rupture. The vessel walls can also dilate causing microaneurysms (small haemorrhages).

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Damaged pericytes (vascular cells) and erythrocytes (red blood cells) lead to an increased vascular permeability which allows lipids, lipoproteins, and other cells to leak out and form hard exudates on the retina.(6)

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When blood flow is compromised, parts of the retina will become hypoxic due to the lack of oxygen. This stimulates vascular endothelial growth factor (VEGF), thus causing neovascularisation (the formation of new blood vessels). These blood vessels are poorly formed, and so are weak, leaky, and easily rupture.(6)

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Neovascularisation in one part of the eye can lead to widespread vitreous haemorrhage, which will cause sudden and complete loss of vision. Retinal detachment can also occur if fibrovascular bundles cause fibrosis and thus retinal traction.(7)

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Presentation (6)

• Generally asymptomatic initially

• Acutely painful red eye
• Changes to vision including:

• Floaters

• Blurred vision (if central, think diabetic maculopathy!)

• Distortion

• Progressive visual acuity loss

• Blindness

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Risk factors (6, 8)

• Length of exposure to hyperglycaemia

• Duration since diabetes diagnosis: patients who have had diabetes for a longer time are more

  likely to develop diabetic retinopathy

• Hypertension

• Ethnicity: those with T2DM from ethnic minority groups are more likely to develop diabetic

  retinopathy than those with a Caucasian background

• Pregnancy

• Rapid improvement of blood sugar levels

• Hyperlipidiaemia
• Hypercholesterolaemia

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Investigations and clinical examination

Visual acuity assessment using the LogMAR chart
Fundoscopy: the gold-standard is with a slit lamp or through fundus photography (could show micro-aneurysms, dot blot haemorrhages, hard exudates, cotton wool spots, and/or venous bleeding) (6, 9)

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HbA1c to monitor how well/poorly the diabetes is being controlled (6)

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OCT imaging will show a cross-section of the retina. It is used when examining diabetic macular oedema to quantify oedema thickening and retinal thickness in and around the macula.

The gold standard technique for visualising the vasculature of the retina is using fluorescein angiography (FA). (6, 9)

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More on fundoscopy findings (3, 6)

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Management

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All patients should have (3, 6):

• Optimised glycemic control (aim for an HbA1c between 48-58mmol/mol)

• Blood pressure control (aim for <140/80mmHg)
• Hyperlipidaemia under control
• General lifestyle advice regarding diet, exercise, and smoking cessation • Regular reviews by ophthalmology

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Maculopathy specific:
• Following changes to vision, intravitreal vascular endothelial growth factor (VEGF) inhibitors

should be given

Non-proliferative retinopathy specific:
• regular observation
• If severe or very severe then panretinal laser photocoagulation

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Proliferative retinopathy specific:
• Pan-retinal laser photocoagulation
• Intra-vitreal VEGF inhibitors to decrease bleeding
• Vitro-retinal surgery if severe or if vitreous haemorrhage present

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Complications

• Neovascular glaucoma is a type of secondary glaucoma caused when neovascularisation

  causes a narrowing and closure of the draining angle causing raised intraocular pressures. The

  typical presentation is with an acutely painful and red eye. (10)

• Retinal detachment

• Vitreous haemorrhage

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Summary of key points:

• Diabetic retinopathy is retinal damage caused by diabetes

• Poorly controlled diabetes leads to chronically raised glucose levels which causes damage to

  the microvasculature supplying the retina

• This is a sight-threatening condition and the leading cause of blindness in young adults

• It can be broadly characterised as non-proliferative or proliferative

• Many patients remain asymptomatic initially

• Photocoagulation is the main active treatment, with anti-VEGF injections helping to manage

  proliferative diabetic retinopathy

• Complications include blindness, neovascular glaucoma, retinal detachment, and vitreous

  haemorrhage