Vasculaire geneeskunde meets

oogheelkunde:

arteriële en veneuze

problemen in het oog

Reinier Schlingemann

AMC

R.O.Schlingemann, Ocular Angiogenesis Group AMC

Hoornvlies

RetinaVitreous

Choroid

Sclera

Rods and cones

Anatomy of the retina

Retinal vasculatuer

Gezonde retina

Visual acuity and daily activities

0,5

0,1

0,16

0,05

Impact of retinal conditions on quality of life: time

trade-off values

Equivalent conditions

Mild AMD (0,5-1,0) 17% Symptomatic HIV

Moderate angina pectoris

Moderate AMD (0,1-

0,4)

30% Permanent kidney dialysis

Severe angina pectoris

Severe AMD(<0,05)

Total Blindness

35-65%

75%

Metastatic prostate cancer

with uncontrolled pain

Severe stroke with functional

loss

Ocular neovascularization

Pterygium

Cornea

CornealNeovascularization

Retina

RetinalNeovascularization

VitreoretinalNeovascularization

SubretinalNeovascularization

Iris

R.O.P

•Main cause of visual loss in the Western world

•Affects the lives of millions of people

B. Lafaut, 2000

Sub-retinal neovascularisation in AMD

Fluorescein angiogram

Vascular leakage in Diabetic Macular Oedema

Normal

retina

Diabetic

macular

oedema

OCT

Loss of capillaries causes

leakage and oedema

Fluorescein angiogram

Vaatgroei: Proliferatieve retinopathie

Littekenvorming

Ocular vascular occlusive

disorders

Ischemic optic neuropathy

Central retinal vein occlusion (CRVO)

Branch retinal vein occlusion (BRVO)

Central retinal artery occlusion (CRAO)

Branch retinal artery occlusion (BRAO)

Cilioretinal artery occlusion

Ocular Angiogenesis Group AMC Amsterdam

Vascular arcitecture in the optic

nerve head

R.O.Schlingemann, Ocular Angiogenesis Group AMC

Central retinal artery occlusion (CRAO)– Non-arteritic CRAO-67%

CRAO secondary to CRVO-<1%

– Non-arteritic CRAO with cilioretinal sparing-14%

– Arteritic CRAO with Giant cell arteritis-4.5%

– Transient CRAO-16%

Branch retinal artery occlusion (BRAO)– Permanent BRAO-61%

– Transient BRAO-6%

– Cilioretinal artery occlusion

Non-arteric-6%

Non-arteritic secondary to CRVO-19%

Arteritic with GCA-6%

Cotton-wool spots

Amaurosis fugax

ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

Ocular Angiogenesis Group AMC Amsterdam

Clinical presentation of acute arterial

occlusive disorders

sudden loss of vision in 1 eye

on initial ophthalmic evaluation retinal

opacity with cherry red spot

in eyes with transient CRAO, multiple

scattered patches of retinal opacity

“box-carring” (“cattle trucking”) of the

blood column in the retinal vessels

Ocular Angiogenesis Group AMC Amsterdam

Non-arteritic CRAO with cilioretinal

sparing

Ocular Angiogenesis Group AMC Amsterdam

Ocular Angiogenesis Group AMC Amsterdam

Causes of CRAO and BRAO

Systemic associations (OR 2-5)

– diabetes mellitus

– Renal disease

– arterial hypertension

– ischemic heart disease

– cerebrovascular accidents

– smoking

Ipsilateral internal carotid artery– >50% stenosis-30%

– Plaques-70%

Abnormal echocardiogram with an

embolic source-52/42%

Ocular Angiogenesis Group AMC Amsterdam

Causes of CRAO and BRAO

Direct cause in most cases

embolism

– Types of emboli

Cholesterol (Hollenhorst plaques)-74%

Calcific material-10.5%

Platelet-fibrin-15.5%

– Source

Carotid artery plaques

Heart

– Aortic and mitral valvular lesions

– Patent foramen ovale

– Left atrial myxoma

Ocular Angiogenesis Group AMC Amsterdam

Clinical outcome in CRAO and

BRAO

CRAO

– Visual acuity usually < 0.1

– Improvement in first week 22% non-arteritic CRAO

66% in non-arteritic CRAO with cilioretinal sparing

0% in arteritic CRAO with Giant cell arteritis

82% in transient CRAO

BRAO

– Visual field defects

– Final visual acuity > 0.5

89% in permanent BRAO

100% in transient BRAO

100% in non-arteritic cilioretinal artery occlusion

Ocular Angiogenesis Group AMC Amsterdam

Management of CRAO and BRAOHayreh: “a disease without any treatment has many treatments”.

No proven treatment for the eye

– Advocated treatments in CRAO ocular massage

a reduction of intraocular pressure

vasodilation of the CRA by sublingual isosorbide dinitrate,

rebreathing of expired CO2 in a bag, breathing Carbogen etc.

antiplatelet therapy or heparin therapy

Intra-arterial fibrinolysis

Prevention of CRAO/BRAO in the other eye

– Detect and treat source of emboli

– Anti-coagulants indicated

Ocular Angiogenesis Group AMC Amsterdam

GIANT CELL ARTERITIS(Temporal or Cranial Arteritis)

Idiopathic vasculitis

– Same disease spectrum as

polymyalgia rheumatica

– Mainly women 65-80 years old

– Medium and large arteries in

head & neck involved

Presentation– Headache

– Scalp tenderness

– Thickened temporal arteries

– Jaw claudication

– Acute visual loss

– Weight loss, anorexia, fever, night sweats, malaise & depression

GIANT CELL ARTERITIS

Ocular Complications

Transient monocular visual loss (amaurosis fugax)

Visual loss due to– Central retinal

artery occlusion (CRAO) or

– Anterior ischaemic optic neuropathy (AION)

Visual field defects

Ischemic optic

neuropathy

Types

– Anterior (AION)– Arteritic

– Non-arteritic

– Posterior (PION)

Pathogenesis of NA-AION

– Acute ischemia of the optic nerve head

– Systemic and local risk factors

– Nocturnal hypotension

Treatment

– Aspirin not useful

– Early systemic steroids may be useful

Ocular Angiogenesis Group AMC Amsterdam

Branch vein occlusion

Central Vein occlusion

Retinal vein occlusions

Ischemic Non-ischemic

Central retinal vein occlusion Prevalence 0.1-0.4%

Most patients 60-70, any age possible,

10% <50 years

Ocular risk factors

– Glaucoma and ocular hypertension-30-70%

– Trauma-14%

Systemic risk factors

– Cardiovascular >50 years-OR 3-5

– Thrombophilia <50 years?

Hyperhomocysteinuria

Anti-phospholipid syndrome

– No clear association with hereditary

thrombophilic syndromes or other risk

factors for DVT

Cause of CRVO

– Steep venous pressure gradient

– Atherosclerosis

– Local hemodynamic factors

– Secundary EC proliferation and thrombosis

Ocular Angiogenesis Group AMC Amsterdam

Pathogenesis of CRVO

R.O.Schlingemann, Ocular Angiogenesis Group AMC

BRVO Prevalence 0.6-1.1%

Ocular risk factors

– Not glaucoma and ocular hypertension

Systemic risk factors– Systemic hypertension

Causes of BRVO

– Atherosclerosis

– Venous obstruction at arteriovenous crossing

– Secondary EC proliferation and thrombosis

Subtypes

– Major BRVO

– Macular BRVO

Ocular Angiogenesis Group AMC Amsterdam

CRVO and BRVO Collaterals

Blood-retinal barrier loss and macular edema in BRVO

Anti-VEGF in macular edema secondary to

retinal vein occlusions

Copernicus Study: Aflibercept in CRVOE

TD

RS

lett

ers

Week *P < 0.001

vs. Sham

LOCF; full analysis set; sham n=73; 2q4 n=114;

VEGF-AProperties

– Glycoprotein dimer

– 4 isoforms: 121, 165, 189, 206 amino acids

– Secretion upregulated under hypoxic conditions

– Functions: survival, permeability and angiogenesis

In vitro effects:

– Mitogenic

– Tube formation

– Upregulation of

-urokinase and tpa

-urokinase PA-receptor

-integrins v3 and v5

-VEGFR1 and -2

Normal Embryo

Embryo w knockout of

VEGF gene - lethal

VEGF-A induced iris neovascularization in the monkey eye

VEGF-A PBS

CD31

Vascular occlusive disorders-

Take home messages Artery occlusions

– Retinal infarction caused by embolism

– Anticoagulants useful

– Beware of GCA

Ischemic optic neuropathy

– Optic nerve head infarction caused by vascular insufficiency

– Anticoagulants not useful

– Beware of GCA

Vein occlusions

– CRVO caused by atherosclerosis and local hemodynamic factors

Strong association with high intra-ocular pressure

Retinal thrombosis is misnomer

Anticoagulants not useful

Thrombophilia may contribute if <50 years

– BRVO caused by atherosclerosis

Strong association with systemic hypertension

– Anti-VEGF very effective in secondary macular edema

Ocular Angiogenesis Group AMC Amsterdam