Diabetic Eye Disease

Diabetic Eye Disease

Diabetic Eye Disease

• Prevalence

• Symptoms

• Diagnostic techniques and signs

• Pathophysiology

• Associated conditions

• Management

Diabetic RetinopathyIntroduction

• 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 RetinopathyType 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 7th 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 RetinopathyDM 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 RetinopathyHistory & 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 RetinopathyHistory & 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 RetinopathyDiagnostic 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


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


Intra-retinal haemorrhages seen in moderate NPDR

Diabetic RetinopathyDiagnostic Techniques & SignsIntra-retinal lipid exudates seen in moderate NPDR


Intra-retinal lipid exudates

Drusen

In OPL and sharp-edged In Bruch’s membrane, poorly defined edges

Vascular disease No vascular disease

Near vascular lesions At posterior pole

Can re-absorb Do not re-absorb

Form streaks or circles Random patterns

Present at any age Rare before 45 years old

Affect VA if at fovea Little effect on VA until extensive foveal coverage


Cotton wool spots seen in moderate NPDR

Diabetic Retinopathy Diagnostic Techniques & Signs

• 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


Venous loop seen insevere 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


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 haemorrhageseen in PDR

Vitreous haemorrhageseen in PDR


Traction retinal detachment seen in PDR

Diabetic MaculopathyDiagnostic 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


Clinically Significant Macular Oedema

Diabetic Eye Disease Anterior SegmentDiagnostic 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

• IIIrd and VIth cranial nerve palsies– Esop and isolated SR palsy– Resolve in 2-6 months– No pupil involvement– Classic recent onset incommitant strabismus Sx


• 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


Rubeosis Iridis

Diabetes MellitusPathophysiology

• 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 RetinopathyPathophysiology

• 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 RetinopathyManagement

• 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 MellitusManagement

• 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 MellitusManagement

• 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


Minimal or Mild Background DR Low risk Background DR

Routine CareRecall 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 controlRenal diseaseHypertension

Early ReviewRecall and review every3 - 6 months

Unexplained drop in VA Hard exudates within 1DD of fovea Macular oedema Unexplained retinal findings Pre-proliferative or severe DR

ReferralOphthalmologist within 4 weeks

New vessels Pre-retinal and/or vitreous haemorrhage Rubeosis Iridis

Urgent ReferralOphthalmologist within 1 week

Sudden loss of vision Retinal detachment

Emergency ReferralOphthalmologist 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


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 MaculopathyManagement

• 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 MaculopathyManagement

Grid pattern photocoagulation at macula, just post-treatment

Diabetic Eye DiseaseManagement

• 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 DiseaseAssociated Conditions

• Primary open-angle glaucoma

• Secondary angle-closure glaucoma

• Vitreous haemorrhage

• Traction retinal detachment

• Rhegmatogenous retinal detachment

• Cataract

• Myopia

Diabetic Eye DiseaseAssociated Conditions

• Myocardial infarction• Transient ischaemic attacks• Reversible ischaemic neurological deficit• Stroke• Peripheral neuropathy• Foot ulceration• Gangrene• Nephropathy

Diabetic Eye DiseaseClinical 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

• The development of diabetic retinopathy is time-dependent

Health & Medicine

Diabetic Eye Disease