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

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

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

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

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

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

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

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

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

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

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

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 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  )

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

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

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

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

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

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   O 2 transport  Stickiness & aggregation of platelets Loss of vascular pericytes (aldose reductase)

Possible pathogenic mechanisms

Thickening of capillary basement membrane

Capillary endothelial cell damage (aldose reductase)

Impaired RBC function   O 2 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

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

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

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

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

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

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

Management

Photocoagulation

Good glycaemic control (DCCT)

Stop smoking &  heavy alcohol intake

Treat systemic hypertension

Avoid physical exertion

Avoid direct trauma

Proliferative Retinopathy

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

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

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

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 500  m of the fovea Exudates at or within 500  m 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

ETDRS guidelines (CSME)

Thickening of retina at or within 500  m of the fovea

Exudates at or within 500  m 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

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