Diabetic Eye Disease

Prevalence

Symptoms

Diagnostic techniques and signs

Pathophysiology

Associated conditions

Management

Diabetic Retinopathy Introduction

Chronic

Bilateral

Symmetrical

Capillary disease

Caused by systemic Diabetes Mellitus (DM)

Primary area of effect along with

Feet

Lower legs

Kidneys

Brain

Diabetic Retinopathy - Prevalence

The most common retinal vascular disease

Leading cause of preventable blindness in the working age population of the western world

Diabetes Mellitus

4% in the UK >40 age group

2% in the UK general population

10% of DM are Type 1

90% of DM are Type 2

Diabetic Retinopathy Type 1 vs Type 2

Type 1

Diagnosed before the age of 30

Also known as insulin dependent DM (IDDM)

Also known as juvenile onset DM

Autoimmune disease with HLA genetic associations

Onset principally between 10 and 14 years old

Type 2

Also known as non-insulin dependent DM (NIDDM)

Also known as adult onset DM

No HLA association

Incidence rises with age to 0.6% per year in 7 th decade

Diabetic Retinopathy - Prevalence

Diabetic retinopathy in 25% to 33% of DM patients

Sight threatening DR in 1 / 4 of juvenile onset type 1, 1 / 10 of later onset type 1 and 1 / 30 of type 2 diabetics

Nearly all (98%) of type 1 diabetics will have DR after 20 years duration of the DM

Duration of DM is the primary risk factor for the development of DR

The incidence of DR per year is lower, the earlier the age of diagnosis of DM

Diabetic Retinopathy DM Risk factors for Type 2

Afro-Caribbeans and Asians = relative risk factor 2-3x (Japanese have a relative risk factor <1)

Family history

Age

Hypertension

Obesity

Male

Smoking

History of DM during pregnancy

Diabetic Retinopathy –Morbidity Risk

Myocardial Infarction (heart attack) (2x)

Cerebral Vascular Accident (stroke) (2x)

Peripheral vascular disease

Diabetic Retinopathy History & Symptoms

Possible history of DM

Type 1 almost certainly

Type 2 possibly not

Mild systemic Sx

4-7 years suffering from condition prior to diagnosis

20% already have DR at diagnosis

Lethargy

Thirst (polydypsia)

Pee a lot (polyuria)

Weight loss

Increased appetite (polyphagia)

Reduced Visual Acuity

Diabetic Retinopathy History & Symptoms

In Type 1, 30% present with diabetic ketoacidosis

A hyperglycaemic episode

Sickly sweet breath smell (pear drops)

Signing respirations

Abdominal pain

Reduced consciousness or coma

Hypoglycaemia is a result of over treatment

Sweating

Shaking

Altered behaviour

Reduced consciousness levels

Seizure

Diabetic Retinopathy Diagnostic Techniques & Signs

Use the following tests in your eye examination:

Distance Visual Acuity (right and left)

Intraocular pressure measurement

Anterior segment examination with a slit-lamp biomicroscope

Dilated fundus examination with an indirect ophthalmoscopic method

Pupil assessment

The following tests are used by the GP for the diagnosis of type 2 DM:

Fasting blood glucose levels >7.8 mmol/l

Glycated haemoglobin (HbAC1) > 7%

Glucose tolerance test > 11.1 mmol/l 2 hrs after ingesting 75g of glucose

GTT >7.8 mmol/l suggests IGT, which often progresses to DM and carries the same cardiovascular risks as DM

The following stages of diabetic retinopathy have been described:

Mild non-proliferative diabetic retinopathy (NPDR)

Moderate non-proliferative retinopathy

Severe non-proliferative retinopathy

Proliferative diabetic retinopathy (PDR)

Diabetic maculopathy

In mild NPDR the only lesions seen in the fundus are microaneurysms (MA)

Outpouchings of capillary walls

Tiny, round, sharp-edged red dots

Most commonly seen in the temporal arcades

FFA shows them as white dots on a dark background

Located between the INL and the IPL

Very hard to differentiate from dot haemorrhages (MA are slightly smaller) without FFA

Diabetic Retinopathy Diagnostic Techniques & Signs MA seen in moderate NPDR

In moderate NPDR the same microaneurysms are seen plus any of:

Intra-retinal haemorrhages

Dot haemorrhages

Blot haemorrhages

Flame-shaped haemorrhages

Intra-retinal lipid exudates

Cotton wool spots

Diabetic Retinopathy Diagnostic Techniques & Signs Intra-retinal haemorrhages seen in moderate NPDR

Diabetic Retinopathy Diagnostic Techniques & Signs Intra-retinal lipid exudates seen in moderate NPDR

Diabetic Retinopathy Diagnostic Techniques & Signs Little effect on VA until extensive foveal coverage Affect VA if at fovea Rare before 45 years old Present at any age Random patterns Form streaks or circles Do not re-absorb Can re-absorb At posterior pole Near vascular lesions No vascular disease Vascular disease In Bruch’s membrane, poorly defined edges In OPL and sharp-edged Drusen Intra-retinal lipid exudates

Diabetic Retinopathy Diagnostic Techniques & Signs Cotton wool spots seen in moderate NPDR

In severe NPDR extensive spread of the same features as mild NPDR are seen plus any of:

Intra-retinal microvascular abnormalities (IRMA)

Venous beading/loops/segmentation

The 4-2-1 rule

Diabetic Retinopathy Diagnostic Techniques & Signs Venous loop seen in severe NPDR Venous beading and IRMA seen in severe NPDR

Proliferative Diabetic Retinopathy

A sight-threatening retinopathy

Characterised by the growth of new blood vessels on the retina

New vessels within 1DD of the disc (NVD)

Or elsewhere (NVE)

Filamentous loops, from a single vein, form a seafan

Grow internal to the ILM and cover retinal vessels

Diabetic Retinopathy Diagnostic Techniques & Signs NVD seen in PDR NVE seen in PDR

New vessels

Very leaky

Release substances that create a fibrous skeleton

Fibrous contraction pulls on the vessel

Rupture causes pre-retinal or vitreous haemorrhage

Further contraction causes traction retinal detachment or retinal tears and rhegmatogenous retinal detachment

Diabetic Retinopathy Diagnostic Techniques & Signs Pre-retinal haemorrhage seen in PDR Vitreous haemorrhage seen in PDR

Diabetic Retinopathy Diagnostic Techniques & Signs Traction retinal detachment seen in PDR

Diabetic Maculopathy Diagnostic Techniques & Signs

The most common cause of blindness in DM

Prevalence 30% after 20 years in both type 1 and type 2 DM

More prevalent in type 2

Classified as:

Focal

Diffuse

Ischaemic

Diabetic Maculopathy Diagnostic Techniques & Signs Focal Maculopathy

Diffuse maculopathy

No obvious site of vascular leakage

Causes macular oedema

Causes loss of the foveal light reflex

Detectable only with stereoscopic viewing or FFA

Ischaemic maculopathy

Extensive ischaemia and vascular leakage

Resulting from capillary closure

Multiple intra-retinal haemorrhages

Multiple cotton wool spots

IRMA

Venous abnormalities

Diabetic Maculopathy Diagnostic Techniques & Signs Clinically Significant Macular Oedema

Diabetic Eye Disease Anterior Segment Diagnostic Techniques & Signs

Manifest refractive changes

1.5x more likely to be myopic

Investigate in adult-onset myopia

Cataract formation

More commonly cortical cataract

Predictive of mortality

III rd and VI th cranial nerve palsies

Esop and isolated SR palsy

Resolve in 2-6 months

No pupil involvement

Classic recent onset incommitant strabismus Sx

Diabetic Eye Disease Anterior Segment Diagnostic Techniques & Signs

Recurrent corneal epithelial erosions and reduced corneal sensitivity

Trauma

CL fitting

Conjunctival hyperaemia and MA

Blepharitis, styes and chalazion

Rubeosis Iridis

Sign of advanced diabetic eye disease

Growth starts at pupil margin

Leads to acute ACG

Diabetic Eye Disease Anterior Segment Diagnostic Techniques & Signs Rubeosis Iridis

Diabetes Mellitus Pathophysiology

Failure in glucose metabolism

Hyperglycaemia, following food intake

Aetiology is different between type 1 and 2

Insulin deficiency or insulin receptor resistance are the causes

Insulin

Created in the pancreas (beta cells)

Promotes cellular glucose uptake

Promotes conversion of glucose to glycogen

Promotes conversion of glucose to lipids

Glucagon

Created in the pancreas (alpha cells)

Opposite action to insulin

Type 1 diabetes

Beta cells are destroyed by an inappropriate immune response to an antigen

Complete absence of insulin production

Cow’s milk additives in infant feeds and viruses implicated as possible antigens

Many associated HLA genes on chromosome 6

Environment and heredity important – 30% concordance in identical twins

Type 2 diabetes

Beta cells are less effective at secreting insulin

Insulin receptors in the body’s cells are less stimulated by a given amount of insulin

No HLA associated genetic component

Heredity very important – 100% concordance in identical twins

Diabetic Retinopathy Pathophysiology

A disease of the retinal microvasculature causing capillary leakage and occlusion

Larger retinal vessels are located in the NFL and GCL

Smaller retinal capillaries are located as deep as the INL

The RPE and the retinal vasculature form the Blood-Retinal barrier

Tight junctions

No fenestrations

Pericytes to control growth and provide support

Basement membrane

Abnormal changes to the microvasculature

Thickening of the basement membrane

Loss of pericytes

Endothelial cell changes

Basement membrane effect is accelerated ageing

75% pericyte loss removes support and allows bulging of the vessel wall (saccular MA)

Extra growth of endothelial cells, forming tight loop MAs

Loss of tight junctions breaks down the blood-retinal barrier

Intra-retinal lipid exudates

From leakage of plasma proteins and lipo-proteins

Located in OPL and form streaks or circles around areas of leakage

Leakage at macula leads to visible oedema (focal and diffuse)

Further leakage causes:

Intra-retinal haemorrhages

Flame-shaped haemorrhages when from superficial capillary bed

Dot and blot haemorrhages when from deep capillary bed.

Capillary blockage due to:

Thickening of basement membrane

Sticky endothelial cell

Increased blood viscosity as platelets aggregate and red blood cells change

Causes local retinal hypoxia and nerve cell death

Metabolic debris accumulates in the nerve fibres as axoplasmic transport fails

This material is located at the edges of ischaemic retina and appears as cotton wool spots

The retinal hypoxic response

Vascular endothelial growth factor is released from veins in areas of retinal hypoperfusion

Initial response is limited to the capillary bed, in the dilation of pre-existing arterio-venous connections (IRMA)

Later, outgrowths from the veins begin to grow through the ILM and across the face of the posterior vitreous forming new vessels (PDR)

New vessels

Immature, without normal pericytes numbers or tight junctions, but with fenestrations

Prone to bleeding and leakage

Accompanied by fibroblasts, forming fibrous attachments between vessels and vitreous

Fibrous contraction causes:

Bleeding

Retinal detachment

Retinal tears

Rhegmatogenous retinal detachment

VEGF leads to new vessel formation on the iris (rubeosis iridis)

The link between impaired glucose metabolism and microvascular pathophysiology is through the sorbitol pathway

In the presence of hyperglycaemia, aldose reductase catalyses the conversion of glucose into sorbitol

Osmotic changes cause the lens pathology

Toxic sorbitol destroys the capillary pericytes causing the microvascular changes

Diabetic Retinopathy Management

Two-fold approach:

Prevention through management of DM

Screening and direct treatment with laser photocoagulation when appropriate

Control of DM is through good control of blood glucose levels and reduction of risk factors through lifestyle changes:

Reduce lipid intake

Reduce sugar intake

Reduce obesity

Increase exercise

Reduce tobacco and ETOH intake

Diabetes Mellitus Management

Type 1:

Self-administered sub-cutaneous insulin injections

Blood glucose monitoring

Type 2:

Lifestyle modification for 3 months

Patient urine glucose checks, GP blood glucose checks

HbAC1 blood tests

If control is insufficient use medical therapy

Diabetes Mellitus Management

Type 2 medical therapy:

Sulphonylureas

Glibenclamide

Gliclazide

Tolbutamide

Biguadine

Metformin (for obese, but not renal dysfunction)

Intestinal glucosidase inhibitor

Acarbose

Thiazolidinediones

Pioglitazone

Prandial glucose regulators

Repaglinide

10% end up using insulin

NICE guideline for detecting DR:

Test requirement:

> 80% sensitivity

> 95% specificity

< 5% technical failure

Suggested tests:

Retinal photography

Indirect ophthalmoscopy with Volk lens and SLE by trained personnel

Suggested procedure:

Dilation with 1% tropicamide prior to application of test

NICE guideline for screening protocol in DR:

Recall system for annual review in type 2 DM

Appropriate and acceptable screening test to be applied to all type 2 diabetics

Participation in opportunistic screening is not an adequate substitute for formal screening and should be used only where formal screening is impossible

Diabetics can reduce the risk of DR by:

Controlling BP and blood glucose levels

Losing/managing weight

Maintaining good levels of physical activity

Reduce cholesterol intake

Stopping/reducing smoking and alcohol intake

Important especially for:

Men

Asians and Afro-Caribbeans

Older people

Diabetic Retinopathy Management Minimal or Mild Background DR Low risk Background DR Routine Care Recall for annual review

Occurrence/worsening of lesions since previous assessment

Scattered exudates >1DD from fovea

People at high risk of progression

Sudden improvement in glycaemic control

Renal disease

Hypertension

Early Review Recall and review every 3 - 6 months Unexplained drop in VA Hard exudates within 1DD of fovea Macular oedema Unexplained retinal findings Pre-proliferative or severe DR Referral Ophthalmologist within 4 weeks New vessels Pre-retinal and/or vitreous haemorrhage Rubeosis Iridis Urgent Referral Ophthalmologist within 1 week Sudden loss of vision Retinal detachment Emergency Referral Ophthalmologist same day Condition Action

Laser photocoagulation:

Argon laser, with a contact or Volk lens at a SL

Targeting laser and foot control

Topical anaesthesia

Light of 514nm

500 μm, 200mW, 0.1 secs exposure

Energy absorbed by blood and retinal pigment causes local heating

Burning kills retinal cells and seals blood vessels

The effect of the burn:

Reduced local and global retinal oxygen demand

Enhanced transmission of oxygen from choroid

Breaks the metabolic chain of events leading to advanced diabetic eye disease

When to use Laser photocoagulation:

No advantage to Tx at severe NPDR stage

Monitor every 4/12 and instigate Tx immediately PDR appears

Tx earlier if:

One-eyed

Hx of fellow-eye PDR

Local circumstances prevent 4/12 follow-up

NVD > ¼ disc area

NVD with pre-retinal/vitreous haemorrhage

NVE with pre-retinal/vitreous haemorrhage

Rubeosis Iridis

Extensive retinal hypoxia on FFA

How to use Laser photocoagulation:

Usually pan-retinal photocoagulation (PRP)

1200-1600 (sometimes many more) individual burns

500 μm spacing

Outside temporal arcades

500 μm beyond nasal margin of disc

2 or more visits

Limited NVE may use more localised treatment

Diabetic Retinopathy Management Pan-retinal photocoagulation

PRP – The good:

Reduces rate of severe visual loss to 50% of what it would be untreated

Causes regression of new vessels after 2-3 weeks

Returns venous circulation to normal

Can be re-applied

PRP – The bad:

Destroys retina

Causes extensive visual field loss

Causes loss of night vision

May cause reduction in VA if burns are too close to the fovea

May cause arcuate scotomata if burn energy is too high

Diabetic Maculopathy Management

More photocoagulation

Less intense and smaller burns than PRP

Within the temporal arcades

Over area of retinal ischaemia and leakage in focal maculopathy

Tx area often surrounded by circinate exudates

Grid pattern for CSMO in diffuse maculopathy, with 100-150 burns in macular area

No Tx is useful for ischaemic maculopathy. 30% develop PDR within 2 years

Avoid the area within 375 μm of the fovea

Tx, if possible, reduces moderate visual loss to 40% of untreated condition

Diabetic Maculopathy Management Grid pattern photocoagulation at macula, just post-treatment

Diabetic Eye Disease Management

Vitrectomy:

Removal of blood, vascular and fibrous material and vitreous from the vitreous

Replacement with clear fluid (silicone oil or saline)

Use when:

Non-clearing vitreous haemorrhage (6/12)

Traction retinal detachment involving macula

Combined traction/rhegmatogenous retinal detachment

Monitored using ultrasonography

Type 1 diabetics have the greater risk without Tx

Detachment and tear repair

Diabetic Eye Disease Associated Conditions

Primary open-angle glaucoma

Secondary angle-closure glaucoma

Vitreous haemorrhage

Traction retinal detachment

Rhegmatogenous retinal detachment

Cataract

Myopia

Diabetic Eye Disease Associated Conditions

Myocardial infarction

Transient ischaemic attacks

Reversible ischaemic neurological deficit

Stroke

Peripheral neuropathy

Foot ulceration

Gangrene

Nephropathy

Diabetic Eye Disease Clinical Pearls

Maculopathy is the commonest cause of blindness in diabetes mellitus

Clinically significant macular oedema is unrelated to visual acuity and can exist in the presence of ‘normal’ 6/6 vision. It can only be identified through observation using stereoscopic indirect biomicroscopy

FFA is only used for treatment , it is not a tool for diagnosis. Angiography is not required for treating proliferative disease since PRP does not require precise aiming of the laser