DIABETES MELLITUS AND DIABETIC EYE DISEASE

Dr Russell J Watkins

Diabetes Mellitus

During a meal, insulin is released from the beta-cells of the pancreatic islet cells

Insulin is a key hormone that regulates metabolism of triglycerides & carbohydrates

Diabetes mellitus is a group of metabolic disorders characterised by chronic hyperglycaemia resulting from relative insulin deficiency, insulin resistance or both.

Usually primary but may be secondary to pancreatic disease, acromegaly, Cushing’s disease, effect of drugs.

Also, impaired glucose tolerance as an entity

Diabetes Mellitus

Insulin deficiency results in impaired metabolism of carbohydrate, fat, protein, water & electrolytes

Death may result from Acute metabolic decompensation Longstanding metabolic derangements -

diabetic complications

Diabetes Mellitus

Primary DM is classified as Type I (insulin dependent - IDDM)

• Always need insulin• Younger

Type II (non-insulin dependent NIDDM)• Diet &/or oral antihyperglycaemics usual• May need insulin• Older

Diabetes Mellitus

Epidemiology Worldwide distribution Incidence of both type I & type II DM

• Prevalence of both types varies in different parts of the world

UK prevalence is 1-2% of population• 50% of type II remain undetected• Ratio of type II:type I is ~7:3

Diabetes Mellitus

Uncertain aetiology Environmental factors interact with genetic

factors• Variable clinical syndrome• Variable timing of onset

Pattern of inheritance & environmental factors differ in type I & type II

Diabetes Mellitus

Genetics of type I DM Polygenic Strongest genetic association = HLA-DQ ~36% concordance with identical twin

Genetics of type II DM no HLA linkage genetic factors must be important

• ~95% concordance in identical twins• genetic factors not yet identified

Diabetes Mellitus

Environmental factors in DM Type I

• Viral aetiology may be important• Diet (?Early introduction of cow’s milk)• Autoimmune - association with other AI

disease, HLA linkage, insulin autoantibodies detectable

Diabetes Mellitus

Environmental factors in DM Type II

• “Western diet” & obesity

• Age• Pregnancy

Diabetes Mellitus

Principles of treatment To alleviate symptoms of hyperglycaemia To avoid hypoglycaemia To limit complications

Diabetes Mellitus Complications of diabetes

Vascular• Atherosclerosis

(macrovascular)• Microvascular

(retina, kidney, nerve sheath)

Infections and poor wound healing

• Impaired PMNL function

Diabetes Mellitus

The current cost of DM in the UK 30% reduction in life expectancy Commonest cause of blindness in 20-65 yr

age group 600 patients reach ESRF per year Lower limb amputation rate 25-fold Use of hospital beds 6-fold 5% of total NHS budget

Diabetes Mellitus

Diabetes Control & Complications Trial (1993 onwards - NEJM 1993;329:1796) Published in NEJM, JAMA et al Diabetic complications are preventable The aim of treatment should be ‘near-normal’

glycaemia whilst avoiding hypoglycaemic episodes in insulin-treated patients (3-fold in such episodes in tightly controlled patients)

Diabetes Mellitus

Early Treatment of Diabetic Retinopathy Study (ETDRS) Published in mid 1980’s 12 published papers Current practice based on ETDRS guidelines Diabetic maculopathy (Report 1) reference

Arch Ophthalmol 1985;103:1796)

Diabetes Mellitus

The spectrum of diabetic eye disease Corneal hypoaesthesia & RES Cataract Vitreous degeneration Cranial neuropathy Arteriosclerotic retinopathy Vascular retinopathy (accelerated atherosclerosis) Diabetic papillopathy Diabetic retinopathy Advanced diabetic eye disease including retinal

detachment and rubeosis iridis

Arteriosclerotic Retinopathy Usually associated with hypertension;

accelerated by DM Signs

AV nipping (Salus’ sign) Dilated vein distal to AV crossing (bonnet’s

sign) Tapering of vein either side of AV crossing

(gunn’s sign) Right angle deflection of vein

Arteriosclerotic Retinopathy Signs (cont.)

Arteriolar “silver wiring” Ischaemic choroidal infarcts (elschnig bodies) Retinal arterial macroaneurysm Ischaemic optic neuropathy

Diabetic Retinopathy Prevalence of retinopathy at time of diagnosis:

1.5% age 20-40yrs 7% age 50-60yrs 10% age 60+

Diabetic retinopathy develops after >~8yrs duration of DM 79% of diabetics have retinopathy after 20yrs

Diabetic Retinopathy DR is the most common cause of blind & partial

sight registration in 30-60yr age group Blind diabetics

50% are dead within 3-4 yrs of registration Only 20% survive for 10 yrs

Diabetic Retinopathy Possible pathogenic mechanisms

Thickening of capillary basement membrane Capillary endothelial cell damage (aldose

reductase) Impaired RBC function O2 transport Stickiness & aggregation of platelets Loss of vascular pericytes (aldose reductase)

Diabetic Retinopathy Classification

Background Pre-proliferative Proliferative Maculopathy (can occur at any stage) Advanced

Background Retinopathy Signs of background diabetic retinopathy

Microaneurysms• First clinically detectable sign• INL

Hard exudates• OPL & INL

Haemorrhages• Flame shaped• Dot & blot

Pre-proliferative Retinopathy Pre-proliferative retinopathy

Cotton wool spots Venous dilatation & beading Arteriolar narrowing Large blot haemorrhages IRMA Capillary closure on FFA

Pre-proliferative Retinopathy

Risk of progression to proliferative retinopathy as predicted by ETDRS• Venous beading - >4x• Haemorrhages/microaneurysms - 4x• IRMA - 4x• CWS - 2x

Management is controversial - some would photocoagulate; others would monitor closely & treat NV

Proliferative Retinopathy Proliferative retinopathy

Overall Incidence of Proliferative Change Is 10-20% of Diabetics

Type I>type II Neovascularisation Is Pathognomonic of

Proliferative DR NVD & NVE Fibrovascular Epiretinal Membrane; Initially

Transparent, Becomes Opaque Vitreous traction with RD

Proliferative Retinopathy Results from

• Extensive capillary closure• Angiogenic factor causes friable NV at

watersheds• Endothelial buds from the venous end of

capillaries• Fibrovascular network adherent to vitreous

face• PVD may elevate vessels

Proliferative Retinopathy Management

• Photocoagulation• Good glycaemic control (DCCT)• Stop smoking & heavy alcohol intake• Treat systemic hypertension• Avoid physical exertion• Avoid direct trauma

Proliferative Retinopathy Risk of severe

visual loss in 2yrs Risk if treated

NVD + VH

40%

20%

NVD - VH

25%

5%

NVE + VH

30%

7%

NVE - VH

7%

7%

Diabetic Maculopathy Diabetic maculopathy

Retinopathy in the macula area Most common cause of visual loss in DM Type ii>type I Treatment based on ETDRS guidelines Classified as

• Exudative/focal• Oedematous/diffuse• Ischaemic• Mixed

Diabetic Maculopathy Exudative

Exudates in the macula area circinate Photocoagulation may be beneficial when

VA>6/60 Rx to centre of circinate ring or site of leakage

Oedematous Macular oedema (ECF in Henle’s layer) Rx with grid laser when VA>6/18

Diabetic Maculopathy Ischaemic

FFA reveals capillary non-perfusion No proven Rx 30% proceed to proliferative DR within 2yrs so

eventually require PRP

Mixed Exudates, oedema, ischaemia Laser may be of benefit

Diabetic Maculopathy ETDRS guidelines (CSME)

Thickening of retina at or within 500m of the fovea

Exudates at or within 500m of the fovea, if thickening of adjacent retina

A zone or zones of retinal thickening 1 disc area or larger, any part of which is within 1 disc diameter of the fovea

Advanced Diabetic Eye Disease Persistent vitreous haemorrhage Tractional retinal detachment Posterior hyaloid membrane Neovascular glaucoma with rubeosis iridis Patients will usually require vitrectomy, cutting

of traction membranes, epiretinal membrane peeling