DIS - Diseases of the Vasculature IV: Diabetes I

What is diabetes mellitus?

Sustained hyperglycaemia

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List the two types of diabetes and whether they are insulin dependent or independent.

Type 1 - insulin dependent
Type 2 - insulin independent

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What onset do type 1 and 2 diabetes typically have?

1 - juvenile
2 - adult

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Can non-insulin dependent diabetes develop into insulin dependent?

Yes

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What three things related to insulin can diabetes be due to?

Lack of endogenous insulin
Reduced efficacy of endogenous insulin
Both

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What is the typical random blood glucose level with diabetes? What about fasting?

Random - >11mmol/L
Fasting - >7mmol/L

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What does the glucose tolerance test measure?

Glucose clearance from the blood

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What is HbA1c with diabetes?

> 6.5%

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Describe how a glucose tolerance test is carried out and what the prerequisite is.

Prerequisite - eat/drink adequate carbohydrates for 3 days (150g/d)
Fast for 8h before the test
Take fasting blood glucose test
Ingest 75g of glucose (with 2L of fluid)
Blood glucose measured after 1 and 2h

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List three early systemic signs of diabetes. What is this related to?

Excessive thirst
Excessive urine production
Loss of appetite and weight
-all related to osmosis

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What is a late systemic sign of diabetes? Describe why it occurs.

Ketoacidosis
-insufficient insulin leads to the body burning fat for energy
-ketones accumulate in blood and urine

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Describe the association between insulin and nerves and what the evidence is like.

Some evidence suggests insulin is a neurotrophic factor
-neurons need insulin to sustain them

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What is the proportion of type 1 and 2 diabetes?

1 - 15%
2 - 85%

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List the two classifications of diabetic retinopathy and what they are characterised by (1, 2).

Non-proliferative
-microangiopathy
Proliferative
-formation of new vessels on the vitreo-retinal interface and in the vitreous
-proliferation of fibrovascular tissue on the retina/disc

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What two factors correlate strongest with the presence of diabetic retinopathy?

Duration of diabetes
Quality/degree of glycaemic control of diabetes

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What is thought to directly link to development and progression of diabetic retinopathy? What are the two major effects of this?

Altered glucose metabolism
-increased blood retinal barrier permeability - leakage
-alterations in retinal blood flow (hypoxia)

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Describe how hyperglycaemia can lead to changes in vessels (4). Explain what these changes are (2) and what it can lead to (2) and how (1).

Causes the production of advanced glycation end products and increased diacylglycerol levels
These activate protein kinase C and overexpression of VEGF
PKC activation lead to capillary leakage and neovascularisation
Capillary occlusion leads to increased expression of insulin-like growth factor (IGF-1)
This leads to the development of pre-retinal and iris neovascularisation

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What two things do all diabetics need?

Regular retinal examination
Dilated pupil exam

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Should newly diagnosed diabetics have a retinal exam?

Yes

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What happens to the basement membrane of retinal capillaries with diabetes? What is a consequence of this?

Thickens
-decreased O2

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What happens to pericytes and endothelial cells in retinal capillaries with diabetes? What are two consequences of this?

Loss of pericytes
Endothelial enlargement
-microaneurysm formation
-capillary leakage and eventual drop out

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What are three early signs of non-proliferative diabetic retinopathy?

Microaneurysms
Dot/blot haemorrhages
Lipid exudates

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What are five signs of more advanced non-proliferative diabetic retinopathy?

More of the three early signs plus
Cotton wool spots
Intraretinal microvascular abnormalities
Flame haemorrhages
Venous beading

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What are four signs of proliferative diabetic retinopathy?

Signs of non-proliferative DR (usually more advanced) plus
New vessels - NVI, NVE, NVD
Vitreous haemorrhage
Tractional retinal detachment

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How do microaneurysms appear? What about with angiography? Are they isolated or clustered?

Tiny red dots like dot haemorrhages Hyperfluorescent on FA Sometimes isolated, sometimes clustered

What retinal layer do dot/blot haemorrhages occur (non-specific)?

From middle retinal layers -from microaneurysms/deep capillaries

What colour and shape are intra-retinal lipids?

Yellow - often circinate - circular

What two things are generally used for staging diabetic retinopathy?

Number of microaneurysms and haemorrhages

What is a cotton wool spot?

Ischaemia of the RNFL

What is a flame haemorrhage?

Haemorrhage of the superficial capillary layer supplying the RNFL

What is venous beading? What can be seen on fluorescein angiography?

Sacular bulges, dilation Capillary dropout on both sides of the vein on angiography

What are intraretinal microvascular abnormalities? What do they bypass and what do they mimic? What are they often seen with?

Dilated abnormal capillaries Bypass capillaries Mimic new vessels Often with venous loops and cotton wool spots

Can capillary compromise/dropout be seen directly?

No, only with fluorescein angiography

What are venous loops often adjacent to?

Areas of ischaemia

What causes diabetic macular oedema? At what stage of DR can it develop?

Leakage from microaneurysms near the macula/fovea Can develop at any stage

Is diabetic macular oedema reversible?

Yes with timely treatment

What is the progression of diabetic macular oedema (2)?

VA drop from oedema affecting middleretinal layers Eventual destruction - atrophy -permanent vision loss

What is clinically significant macular a subset of?

Subset of diabetic macular oedema close to the fovea

How is clinically significant macular oedema defined (3)?

Retinal thickening within 500u of the centre of the fovea Lipid exudate within 500u of the centre of the fovea with adjacent retinal thickening Retinal thickening of >1,500u which is <1,500u from the centre of the fovea

What is 1,500u comparable to?

1DD

What consequence does diabetic macular oedema have on the blood retinal barrier?

It breaks down

What 6 overlapping vascular, inflammatory, and neuronal changes occur as a result of diabetic macular oedema?

Proinflammatory cytokines Increased VEGF production Endothelial tight junction dysfunction Involvement of leucocytes Microglial activation Muller cell dysfunction

What happens to the retinal inner layers as a result of diabetic macular oedema? what is this called?

DRIL - disorganisation of retinal inner layers -loss of boundaries

Can there be recovery from DRIL?

What is neovascularisation indicative of in diabetic retinopathy (2)? What is it associated with?

Proliferative DR Significant oedema Associated with capillary dropout/non-perfusion

Where does neovascularisation first occur, growing through what layer? What is a vitreous scaffold?

Originate in retina, grow through ILM Vitreous scaffold - on or above retina

With neovvascularisation in diabetic retinopathy, where does it often occur in the periphery and what appearance does it have (2)?

Often along vascular vessels -cartwheel appearance -fine wispy vessels

Define NVE, NVD, NVI.

New vessels elsewhere New vessels on disc New vessels on iris

What is often the reason for blindness in diabetes?

Uncontrolled neovascularisation

What three things does neovascularisation in diabetic retinopathy give significant risk of?

Pre-retinal/vitreous haemorrhage Fibrosis with subsequent shrinkage Neovascular glaucoma

Distinguish between intra-retinal microvascular abnormalities and neovascularisation in diabetic retinopathy.

Neovascularisation - vessels grow on the retinal surface and into the vitreous IRMA - intra-retinal

What is tractional retinal detachment in proliferative diabetic retinopathy the end result of (2)?

Vitrous haemorrhage and fibrosis on the retinal surface Contraction of fibrous membrane on the retinal surface

What should you beware in patients with longstanding diabetes and apparently mild DR?

May have a silent problem -slow peripheral capillary dropout -very subtle neovascularisation

What is a differential diagnosis for non-proliverative DR? Give nine examples.

Any retinal vascular change associated with ischaemia -hypertension -CRVO (non-ischaemic) -radiation retinopathy -sickle cell disease -macroaneurysm -haemoglobinopathies -carotid artery disease -vaculitis -HIV retinopathy

What is a differential diagnosis for diabetic macular oedema?

Any exudation from capillaries at/near the macula

What is a differential diagnosis for proliferative DR?

Any retinal vascular change associated with ischaemia, elevated VEGF, and vitreos haemorrhage

Describe what you would expect to see with mild non-proliferative DR (1).

Microaneurysms only

Describe what you would expect to see with moderate non-proliferative DR (1).

More microaneurysms, but less than severe NPDR

Describe what you would expect to see with severe non-proliferative DR (3).

Any of the following: >20 haemorrhages in each of the four quadrants Venous beading in 2 or more quadrants Prominent IRMA in one or more quadrant

The presence of what defines proliferative retinopathy (2)?

Neovascularisation and/or vitreous/pre-retinal haemorrage

Describe mild, moderate, and severe diabetic macular oedema.

Mild - some exudate/thickening but not close to the fovea Moderate - some exudate/thickening, close to, but not involving the macula Severe - exudate or thickening involving the macula

List 5 practitioners that can be involved in the management of diabetes.

GP Ophthalmologist Endocrinologist Optometrist Podiatrist

How often should a type 2 diabetic patient be screened for DR? What about if theyre at high risk of DR

Every 2 years at least High risk - every year

How often should a type 2 diabetic patient with NPDR have a retinal exam?

Every 3-6 months depending on severity

How often should pregnant patients with gestational diabetes have an eye exam for DR screening?

No need unless it persists

How often should pregnant patients have an eye exam for DR screening? What about if they have DR

Examine during the first trimester Any DR - follow through pregnancy

Is pan-retinal photocoagulation a viable treatment option for DR? List 4 side effects

It is effective in preventing vision loss -pain -loss of visual field and some night vision -increased risk of diabetic macular oedema -some may still need vitrectomy later

does the evidence suggest it is justifiable to treat diabetics with panretinal photocoagulation to prevent proliferative DR?

Yes

Is anti-VEGF a viable treatment option for PDR?

Yes -standard of care for DMO

Can anti-VEGF slow down NPDR progression or does it have no effect?

Can slow down all forms of progression, including NPDR to PDR

Can anti-VEGF result in regression of PDR to NPDR or is PDR permanent?

It can cause regression

What is a disadvantage of anti-VEGF when used for DR?

Drug effect lost quickly, repeated injections needed

In what three cases would you refer to an ophthalmologist with suspected DR?

Unexplained VA loss Suspicion of macular oedema or PDR

What stages of DR should you refer (2)?

All except mild NPDR -includes CSMO, vitreous haemorrhaging etc

When is vitrectomy indicated for DR (3).

Vitreous haemorrhage Tractional RD Neovascular glaucoma

When is focal and grid photocoagulation used for diabetic macular oedema?

Focal - to treat focal CSMO -directed at microaneurysms Grid - to treat diffuse CSMO

Can ranimizumab improve macular oedema and vision?

Yes

Are anti-VEGF and ranimizumab superior to laser for DR?

Yes, both

Aside from anti-VEGF, what is the treatment for DMO?

Corticosteroid injection

List four mechanisms behind how photocoagulation can treat PDR.

Increased oxygenation of inner retinal layers may decrease stimulus for VEGF production May directly damage or destroy cells that produce angiogenic cytokines Direct closure of leaky aneurysms Effects on RPE function

When is the optimum time for cataract surgery with DR (3)?

If DR advanced, surgery may push retinopathy to disastrous level Moderate - may cause vision threatening exacerbation Mild - should be safe

DIS - Diseases of the Vasculature IV: Diabetes I - Week 11 Flashcards