Diabetic Retinopathy

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Succinct notes to superpower your revision
Diabetic eye disease\: includes diabetic retinopathy (DR), cataracts, cranial nerve palsies, retinal artery/vein occlusions.
Diabetic retinopathy\: damage to microvasculature of the retina due to chronic hyperglycaemia, leading to progressive
vision loss and potential blindness.
Epidemiology\: most common cause of blindness in working-age UK population; nearly all type 1 diabetics have
retinopathy within 20 years; many type 2 diabetics have signs at diagnosis.
Aetiology\: high blood glucose weakens/ruptures retinal vessels, leading to microaneurysms, haemorrhages, hard
exudates, neovascularization, vitreous haemorrhage, retinal detachment.
Risk factors\: duration of diabetes, hypertension, ethnicity, renal disease, pregnancy, rapid blood sugar improvement,
hyperlipidaemia.
Clinical features\: often asymptomatic early; symptoms include
vision loss, blindness.
Classi
Non-proliferative\: background (microaneurysms) and pre-proliferative (multiple microaneurysms, haemorrhages, exudates,
venous beading, IRMAs).
Proliferative\: neovascularization, vitreous haemorrhage, tractional retinal detachment.
Diabetic macular oedema (DMO)\: focal/di
(CSMO).
Investigations\: HbA1c, optical coherence tomography (OCT),
Management\:
Medical\: glycaemic control (HbA1c 48-58mmol/mol), blood pressure control (\<140/80mmHg), lifestyle modi
Photocoagulation\: focal/grid or pan-retinal photocoagulation (PRP).
Intravitreal injections\: anti-VEGF (e.g. a
Vitrectomy\: for persistent vitreous haemorrhage or tractional retinal detachment.
Screening\: annual NHS eye screening for diabetic patients over 12 years old.
Complications\: neovascular glaucoma, retinal detachment, vitreous haemorrhage.
Prognosis\: untreated proliferative DR leads to signi
treatment reduces risk of severe vision loss by 50%.
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A comprehensive topic overview

Introduction

Diabetes can manifest itself through several ophthalmic conditions, grouped under the term diabetic eye disease.
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Diabetic retinopathy (DR) is the most prevalent of these and is characterised by damage to the microvasculature
supplying the eye due to chronically high glucose levels. The resulting insult to retinal cells can lead to a progressive
deterioration in vision through various mechanisms and can lead to blindness.
Cataracts and cranial nerve palsies are examples of other ophthalmic complications associated with diabetes. Diabetic
individuals are also at an increased risk of retinal artery/vein occlusions.Epidemiology
DR is the most common cause of blindness in the working-age demographic of the UK.
There are approximately 3.5 million people diagnosed with diabetes in the UK.
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Almost all patients with type 1 diabetes will have some degree of retinopathy within 20 years of diagnosis.
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Many patients with type 2 diabetes may already have some signs of retinopathy at diagnosis, after going through an
asymptomatic period of hyperglycaemia.

Aetiology

Diabetes is characterised by high blood glucose levels because of the body’s inability to produce insulin and/or resistance
of the body to insulin.
Chronic hyperglycaemia causes blood vessels, including those supplying the retina, to weaken and rupture; the vessel
walls may dilate resulting in microaneurysms or small haemorrhages.
The damaged pericytes and erythrocytes increase vascular permeability. Lipoproteins, lipids and other products carried
by blood are therefore able to leak out and cluster onto the retina as hard exudates.
As blood
stimulate the release of mediators such as vascular endothelial growth factor (VEGF) which promotes
neovascularization. However, these new vessels are poorly formed and easily rupture resulting in bleeding.
Neovascularization into the vitreous humour may culminate in widespread vitreous haemorrhage causing sudden and
complete visual loss. Fibrovascular bundles can lead to
detachment and recurrent vitreous haemorrhage.

Risk factors

Risk factors for diabetic retinopathy include\:
Length of exposure to hyperglycaemia\: the more time a patient’s eye has been exposed to high blood sugars, the
greater the severity of DR.
Duration since diabetes diagnosis\: patients who have had diabetes for a greater length of time are more likely to develop
DR.
Hypertension\: uncontrolled blood pressure can increase the risk of DR and its progression.
Ethnicity\: individuals with type 2 diabetes belonging to ethnic minority groups are more susceptible to developing DR
compared to those of Caucasian background.
Renal disease\: diabetic nephropathy is another microvascular complication of diabetes, characterised by proteinuria. If
present, it is a strong indicator that the patient will also have diabetic retinopathy.
Pregnancy\: has been shown to increase the rate at which DR progresses in several scenarios, including in severe
baseline DR or concurrent hypertension (whether this is pre-existing or pregnancy-induced).
Rapid improvement of blood sugar levels\: rapidly lowering blood sugar levels (decrease of HbA1c >30mmol/mol or 3%)
can increase the progression of DR.
Hyperlipidaemia/hypercholesterolaemia

Clinical features

History
Many patients will remain asymptomatic, even in the presence of proliferative disease. Unfortunately, a lot of these
patients will only present after developing clinically signi
haemorrhage.
Early disease may be incidentally picked up during regular eye tests.
In cases where patients develop symptoms, typical symptoms of diabetic retinopathy may include\:Floaters\: the result of small haemorrhages obscuring areas of vision and usually self-resolving.
Blurred vision and distortion\: central vision may be blurred if the macula is a
Decreased visual acuity\: gradual, painless reduction in the quality of vision.
Loss of vision\: a severe haemorrhage can result in a sudden complete and painless loss of vision.
Blindness\: a culmination of the disease if left untreated and uncontrolled.
Clinical examination
Visual acuity (VA)\:
Currently, the Baily-Lovie chart (LogMAR chart) is most commonly used to test VA (Snellen chart has also been widely
used previously).
See our visual assessment guide for more details.
Fundoscopy\:
The fundus needs to be visualised to examine and monitor any changes that may occur as a result of retinopathy.
The gold-standard for examination is with a slit lamp or through fundus photography.
See our fundoscopy guide for more details.
Classi
DR is classi
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Diabetic retinopathy can be split into three classes\:
Non-proliferative
Proliferative
Diabetic macular oedema
Non-proliferative diabetic retinopathy
Non-proliferative DR can be further subdivided into background retinopathy and pre-proliferative retinopathy.
Background retinopathy\:
The presence of at least one microaneurysm.
Pre-proliferative retinopathy\:
The presence of multiple microaneurysms with or without haemorrhages and hard exudates.
Evidence of retinal ischaemia, for example, venous beading, arteriolar narrowing and intraretinal microvascular
abnormalities (IRMAs).
The severity of this stage depends on the number and size of clinical signs, and on how many quadrants of the retina are
a
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The 4-2-1 rule of severe pre-proliferative diabetic retinopathy
Blot haemorrhages in 4 quadrants
Venous beading in 2 quadrants
IRMA in 1 quadrantFigure 1. Background retinopathy. Microaneurysms with dot and blot haemorrhages.
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Table 1. Signs of diabetic retinopathy.
Sign Description
Microaneurysms
“Out-pouching” results from weakened capillary walls.
The earliest visible clinical sign of diabetic retinopathy.
Dot and blot
haemorrhages
Damaged vessels may rupture and leak blood.
Hard exudates
Cotton wool spots
Venous beading
IRMAs
Deposits of lipids that have leaked onto the retina
through damaged vessels.
Microinfarction of the retinal nerve
chronic ischaemia.
Venous changes are a reliable indicator of
generalised ischaemia.
Intraretinal microvascular abnormalities are irregular
formations of dilated capillary beds.
Proliferative diabetic retinopathy
Proliferative diabetic retinopathy is characterised by new vessels on the disc (NVD) and/or new vessels elsewhere (NVE).
It can also present as neovascular glaucoma, pre-retinal Figure 3.Proliferative retinopathy\: widespread neovascularization.
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Table 2. Signs associated with proliferative diabetic retinopathy.
Sign Description
Growth factors stimulate the formation of weak, leaky
Neovascularization
blood vessels because of chronic hypoxia.
Newly formed leaky vessels can extend into the vitreous
humour which can then start to haemorrhage.
Vitreous
haemorrhage
Retinal
detachment
Typically tractional in aetiology.
Diabetic macular oedema (DMO)
DMO is characterised by oedematous changes in or around the macula. As the macula is responsible for central vision,
a
the commonest cause of visual loss in patients with diabetes.
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DMO can be subcategorised into\:
Focal/di
more widespread and poorly demarcated in nature (di
Ischaemic maculopathy\: patients will be symptomatic with defects in visual acuity due to ischaemia at the site of the
macula. These areas are best visualised with
Clinically signi
as hard exudates and retinal thickening, found within a certain distance to the fovea or greater than a certain size.

Investigations

Laboratory investigations
HbA1c\: to assess how well or poorly a patient’s diabetes is being controlled.
Optical coherence tomography (OCT)
OCT imaging provides a cross-sectional view of the retina.
It is more typically used when examining diabetic macular oedema to help quantify levels of oedema and retinal
thickness in and around the macula.Fluorescein angiography (FA)
FA is the gold-standard technique for visualising the vasculature of the retina.
It is used in DR for clearer identi
ischaemia and identifying microvasculature). FA can also highlight other retinal features such as microaneurysms and
dot/blot haemorrhages.

Management

Many patients with DR will have little/no symptoms with DR and therefore require minimal intervention.
As with managing any medical condition, a bene
methods attempted before considering more invasive options.
Medical management
Glycaemic control\: ensuring blood sugar levels are well controlled will delay the progression of DR. Patients with diabetes
should aim for a HbA1c between 48-58mmol/mol.
Blood pressure control\: diabetic patients should aim to stabilise their blood pressure \< 140/80mmHg to help prevent the
progression of DR. Where the condition is already severe, patients should aim to keep their systolic \< 130 mmHg.
Diet, exercise and smoking cessation\: as part of managing diabetes, the patient should aim to make general lifestyle
modi
Photocoagulation
Photocoagulation is the primary intervention in the management of proliferative DR and, in some cases, severe non-
proliferative DR (especially if the patient is at high risk of progression e.g. pregnancy, frequent
cataract surgery etc).
Photocoagulation involves using a laser is used to create numerous burns in the retina, thus destroying photoreceptors.
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With fewer photoreceptors, oxygen demand in the retina decreases and endothelial cells express fewer growth
mediators (e.g. VEGF). Ultimately, the progression of DR is delayed.
There are two di
Focal photocoagulation (FP)
In focal photocoagulation, a speci
photocoagulation targets more di
Complications of photocoagulation include the decreased quality of central vision and/or formation of a paracentral
scotoma. In a minority of patients, DMO may worsen because of FP.
Pan-retinal photocoagulation (PRP)
The periphery of the retina is targeted with the aim of achieving a global reduction in oxygen demand. More commonly
used than FP, approximately 1200-1500 burns can be made to the retina using this technique.
Complications of PRP include a restricted peripheral vision, reduced quality of night vision, ocular pain and, as with FP,
there may be a worsening of macular oedema.Figure 4.Pan-retinal photocoagulation. Each yellow dot represents a burn on the retina.
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Intravitreal anti-VEGF/corticosteroid injections
Anti-VEGF injections focus on minimising neovascularization and thus are used in proliferative diabetic retinopathy.
A
Although the mechanism of action is not completely understood, trials have shown intravitreal corticosteroids can also be
e
Corticosteroids may be used either as an adjunct to other management options or as primary therapy. Usually, patients will
experience the full bene
Complications include cataract formation and increased intraocular pressure.
Anti-VEGF is contraindicated in patients who have su
Vitrectomy
A potential complication of proliferative DR is bleeding into the vitreous humour, which further increases the risk of retinal
detachment. In many cases, waiting for the haemorrhage to settle can allow su
However, in persistent haemorrhage or in central, sight-threatening tractional retinal detachment a vitrectomy may be
performed. This allows for the removal of the vitreous and repair of any scarring/detachment of the retina.
Photocoagulation may be used intra-operatively to reduce the risk of further neovascularization post-operatively.
Screening
diabetes.
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In the United Kingdom, the NHS provides an annual eye screening programme for any individual over the age of 12 with
The screening programme aims to promptly identify and manage any changes associated with diabetic retinopathy.

Complications

Neovascular glaucoma13
Diabetic retinopathy is one of several causes of neovascular glaucoma, a type of secondary glaucoma.
Neovascularization can occur within the iris and its trabecular meshwork (rubeosis) causing a narrowing and closure of
the drainage angle and therefore increased intraocular pressure.The typical presentation may include a patient complaining of an acutely painful, red eye. The patient may also complain
of vision loss.
As well as managing underlying diabetes and associated retinopathy, neovascular glaucoma may also be directly managed
medically, with laser therapy or surgically.
Other complications
Retinal detachment and vitreous haemorrhage are other complications of diabetic retinopathy, as discussed earlier.
Prognosis
If left untreated, approximately 50% of patients with proliferative DR will lose their vision in 2 years.
Around 90% of a
Those with proliferative DR that undergo treatment can reduce their risk of severe vision loss by 50%.

Reviewer

Mr George Moussa
Source\: geekymedics.com