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1

Systemic Diseases with Ocular

Manifestations

Dr Nathan Kerr

NM Kerr 2008

Learning Objectives

1. To describe the ocular symptoms and

signs associated with common systemic

diseases

2. To be familiar with the non-ophthalmic

features of common systemic diseases

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Reading List

Required reading:

• Nil

Further reading:

• Chapter 20: Systemic

Diseases.Kanski, J.

Clinical Ophthalmology:

A Systematic Approach

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Introduction

"The Eyes Are The Windows To The Soul"

Nicole Buske 1995

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Introduction

Systemic diseases are diseases that involve

many organs or the whole body

Many of these diseases also affect the eye

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Significance

1. A patient with a known systemic condition

may present to you for an eye

examination; therefore, you need to know

what to look for

2. The presenting eye problem may be the

first sign of an underlying systemic

disease

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Classification of Systemic Diseases

• Autoimmune diseases

• Systemic infections

• Metabolic diseases

• Cardiovascular diseases

• Congenital disordersAutoimmune Diseases

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Rheumatoid Arthritis

• Affects 1-3% of the

population

• Prevalence increases

with age

• Most patients are

between 30 and 55

years of age

• Women are more

commonly affected

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Rheumatoid Arthritis

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Rheumatoid Arthritis

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Rheumatoid Arthritis

Common symptoms:

• Joint stiffness, pain,

warmth, and

deformity

• Fatigue

• Flu-like symptoms

• Rheumatoid nodules

or lumps of tissue

under the skin

25% of patients have ocular manifestations

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Rheumatoid Arthritis

Ocular manifestations:

• Keratoconjunctivitis

sicca

• Episcleritis

• Scleritis

• Keratitis

• Peripheral ulcerative

keratitis

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Rheumatoid Arthritis

Ocular manifestations:

• Keratoconjunctivitis

sicca

• Episcleritis

• Scleritis

• Keratitis

• Peripheral ulcerative

keratitis

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Episcleritis

Symptoms:

• Sudden onset

• Mild ache

• Photophobia

• No blurred vision

Signs:

• Normal visual acuity

• No tenderness on

palpation

• Episcleral injection

• Nodules

• Vessels moveable

and blanch with

phenylephrine

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Scleritis

Symptoms:

• Gradual onset

• Deep boring pain

which may wake

patient at night

• Photophobia

• Blurred vision

Signs:

• Decreased visual

acuity

• Tenderness on

palpation

• Bluish hue

• Scleromalacia

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Rheumatoid Arthritis

Ocular manifestations:

• Keratitis

• Peripheral ulcerative

keratitis

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Systemic Lupus Erythematosus

• Most patients

between 25-35 years

• 90% of patients are

women

• Maori and Pacific

Island people more

commonly affected

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Systemic Lupus Erythematosus

• Multisystem disease

with widespread

inflammation of blood

vessels (vasculitis)

and tissue damage

• Caused by numerous

autoantibodies and

circulating immune

complexes

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Systemic Lupus Erythematosus

• Skin: butterfly rash and

discoid rash

• Heart: inflammation of

the heart (myocarditis)

• Lungs: inflammation of

the lining of the lungs

(pleuritis) and collection

of fluid around the lungs

(pleural effusion)

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Systemic Lupus Erythematosus

• Blood vessels:

inflammation of blood

vessels (vasculitis)

leading to blockage

(arterial and venous

occlusions)

• Kidneys: inflammation of

the kidneys

(glomerulonephritis)

• Neurological: stroke and

nerve palsies20% of patients have ocular

manifestations

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Systemic Lupus Erythematosus

Ocular manifestations

• Common: kerato-

conjunctivitis sicca,

madarosis

• Uncommon:

peripheral ulcerative

keratopathy

• Rare: scleritis, optic

neuropathy, optic

neuritis, hemianopia,

cranial nerve palsies

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Systemic Lupus Erythematosus

Ocular manifestations

• Rare: retinal disease

(cotton wool spots,

retinal haemorrhages,

retinal vasculitis,

proliferative

retinopathy)

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Sjögren Syndrome

• Autoimmune destruction of

the lacrimal and salivary

glands

• Onset between 30 and 50

years of age

• 90% of patients are female

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Sjögren Syndrome

Primary

• Occurs in isolation

Secondary

• Associated with other

diseases such as

rheumatoid arthritis

and systemic lupus

erythematosus

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Sjögren Syndrome

Symptoms:

• Dry mouth

• Dry eye

• Enlargement of the

parotid glands

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Sjögren Syndrome

Ocular manifestations:

• Keratoconjunctivitis

sicca

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Behçet Disease

• Recurrent oral/genital

ulceration

• More common in men

than women

• Associated with

Eastern

Mediterranean and

Japan ethnicity and

HLA-B51

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Behçet Disease

• Recurrent oral/genital

ulceration

• Skin lesions

• Cutaneous

hypersensitivity

(dermatographism)

90% of men and 70% of women

have ocular manifestations

Behçet Disease

Common ocular manifestations:

• Recurrent anterior uveitis

(often with hypopyon)

• Retinal infiltrates

• Retinal vasculitis

• Retinal oedema

• Vitritis

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Behçet Disease

Rare ocular manifestations:

• Conjunctivitis

• Conjunctival ulcers

• Episcleritis

• Sclertis

• Ophthalmoplegia

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Sarcoidosis

Multi-system

granulomatous disorder

A granuloma is a mass or

nodule of chronically inflamed

tissue

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Sarcoidosis

• Peak incidence in

early adult life

• More common in

women than men

• More common and

severe in Maori and

Pacific Island people

• Uncommon in AsiansSarcoidosis most commonly

affects the lungs and skin

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Sarcoidosis

Clinical presentation:

• Common: acute

onset, fever,

shortness of breath,

skin rash, joint pain

• Less common:

insidious onset in

later life, fatigue,

shortness of breath,

joint pain

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Sarcoidosis

Clinical features:

• Lungs: enlarged lymph nodes, scarring (fibrosis) of the lungs

• Skin: rash (erythemanodosum)

• Other: enlarged parotid glands

• Blood tests: elevated calcium, elevated angiotensin converting enzyme (ACE)

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Sarcoidosis

Ocular manifestations:

• Involvement of

lacrimal gland

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Sarcoidosis

Ocular manifestations:

• Acute anterior uveitis

• Chronic anterior

uveitis

(granulomatous)

• Intermediate uveitis

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Sarcoidosis

Ocular manifestations:

• Periphlebitis

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Sarcoidosis

Ocular manifestations:

• Choroidal infiltrates

• Multifocal choroiditis

• Retinal granulomas

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Sarcoidosis

Ocular manifestations:

• Optic nerve

involvement

• Intracranial

granulomas

• Meningeal infiltration

• Cranial nerve palsies

(especially facial)

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Graves’ Disease

• Most common cause

of an over active

thyroid gland

(hyperthyroidism)

• Presents between 30

and 60 years of age

• 90% of patients are

female

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Graves’ Disease

Caused by

autoantibodies that

stimulate the thyroid

gland

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Graves’ Disease

Symptoms:

• Enlargement of the

thyroid (goitre)

• Heat intolerance

• Anxiety

• Tremor

25-50% of patients with Graves’

have eye involvement

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Graves’ Disease

Ocular manifestations:

• Thyroid eye disease

– soft tissue

involvement

– lid retraction

– proptosis

– optic neuropathy

– restrictive myopathy

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Graves’ Disease

Ocular manifestations:

• Thyroid eye disease

– soft tissue

involvement

– lid retraction

– proptosis

– optic neuropathy

– restrictive myopathy

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Graves’ Disease

Ocular manifestations:

• Thyroid eye disease

– soft tissue

involvement

– lid retraction

– proptosis

– optic neuropathy

– restrictive myopathy

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Graves’ Disease

Ocular manifestations:

• Thyroid eye disease

– soft tissue

involvement

– lid retraction

– proptosis

– optic neuropathy

– restrictive myopathy

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Multiple Sclerosis

Multiple sclerosis is an

autoimmune disorder

where patches of

inflammation damage

the myelin sheath of

neurons in the central

nervous system (brain

and spinal cord) but

not the peripheral

nervous system

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Multiple Sclerosis

• Peak age of onset is

20-40 years of age

• 67% of patients are

female

• Common in

temperate zones; rare

in the tropics

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Multiple Sclerosis

Clinical features:

• Brain: euphoria, confusion, dementia, slurred speech, weakness, unsteady walking

• Brain stem: diplopia, sensory loss on the face (CN V), facial weakness (CN VII)

• Spinal cord: weakness, sensory loss

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Multiple Sclerosis

Ocular manifestations:

• Input (afferent): optic

neuritis

• Output (efferent):

internuclear

ophthalmoplegia,

nystagmus, cranial

nerve palsies

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Giant Cell Arteritis

• Granulomatous

necrotising arteritis

• Predilection for large

and medium-sized

arteries (termporal,

ophthalmic, posterior

ciliary, and proximal

vertebral)

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Giant Cell Arteritis

Common symptoms:

• Headache

• Temporal tenderness

• Jaw claudication

• Proximal muscle

stiffness

• Fatigue

• Night sweats

• Weight loss

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Giant Cell Arteritis

Ocular manifestations:

• Common: arteritic

anterior ischaemic

optic neuropathy

• Uncommon:

amaurosis fugax,

cotton wool spots,

central retinal artery

occlusion, cilioretinal

artery occlusion,

cranial nerve palsies

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Systemic Diseases with Ocular

Manifestations: Part II

Dr Nathan Kerr

Systemic Infections

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Acquired Immunodeficiency Syndrome

• Acquired

immunodeficiency

syndrome (AIDS) is

caused by the human

immunodeficiency

virus (HIV)

• Global pandemic

• Predominately affects

young adults and

children

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Acquired Immunodeficiency Syndrome

• HIV targets CD4 cells

which are vital to the

initiation of an

immune response to

pathogens

• A steady decline in

CD4 cells occurs

leading to progressive

immunodeficiency

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Acquired Immunodeficiency Syndrome

Common symptoms:

• Acute seroconversion

illness: sore throat,

fever, malaise, sore

joints, rash

• Asymptomatic infection:

no symptoms

• Symptomatic infection:

opportunistic infections

Ocular complications occur in 75% of

AIDS patients

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Acquired Immunodeficiency Syndrome

Ocular manifestations:

• Orbit: orbital cellulitisfrom sinus infection

• Lids: Kaposi sarcoma, molluscumcontagiosum, herpes zoster ophthalmicus

• Conjunctiva: Kaposi sarcoma, squamouscell carcinoma

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Acquired Immunodeficiency Syndrome

Ocular manifestations:

• Anterior segment:

keratitis due to

keratoconjunctivitis

sicca, herpes simplex

virus, and herpes

zoster; anterior uveitis

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Acquired Immunodeficiency Syndrome

Ocular manifestations:

• Posterior segment:

cotton wool spots

(HIV retinopathy),

cytomegalovirus

retinitis, progressive

outer retinal necrosis,

chorioretinitis,

choroiditis, B-cell

intraocular lymphoma

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Acquired Syphilis

Treponema pallidum

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Acquired Syphilis

Primary

• Painless ulcer

Secondary

• Enlarged lymph glands

• Rash on trunk and hands

• Mucous patches in the mouth

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Acquired Syphilis

Latent

• Can only be detected by serological (blood) tests

Tertiary

• Cardiovascular: inflammation of aorta

• Neurosyphilis: general paralysis of the insane, gummata

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Acquired Syphilis

Investigations

• VDRL

• FTA-ABS

Management

• Penicillin

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Acquired Syphilis

Ophthalmic manifestations

• Common: Madarosis and keratitis

• Uncommon: Anterior uveitis, chorioretinitis,

periarteritis, and neuroretinitis

• Rare: Optic neuritis and Argyll Robertson pupils

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Congenital Syphilis

Early Signs

• Rhinitis (runny nose)

• Failure to thrive

• Rash

• Fissures around lips and anus

• Pneumonia

• Enlarged liver

• Jaundice

Late signs

• Sensorineuraldeafness

• Various deformities

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Congenital Syphilis

Ocular manifestations:

• Common: anterior

uveitis and interstitial

keratitis

• Uncommon:

pigmentary

retinopathy

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Tuberculosis

Tuberculosis is a

chronic

granulomatous

infection caused by

Mycobacterium

tuberculosis

A granuloma is a mass or

nodule of chronically inflamed

tissue

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Tuberculosis

• Tuberculosis is

common worldwide

• Asians and Pacific

Island people have

the highest rates of

tuberculosis

• Spread by close

contact with an

infected person

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Tuberculosis

• Mycobacterium

tuberculosis settles in

the lungs and causes

inflammation which

heals with scarring

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Tuberculosis

Symptoms:

• No symptoms when

first exposed

• Chronic cough

• Night sweats

• Malaise

• Loss of appetite

• Weight loss

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Tuberculosis

Investigations:

• Sputum

• Chest xray

• Mantoux test

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Tuberculosis

Ocular manifestations:

• Uncommon:

granulomatous

anterior uveitis, multi-

focal choroiditis,

retinal periphlebitis

• Rare: solitary

granulomas

Metabolic Diseases

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Diabetes Mellitus

Common metabolic disorder characterised

by elevated blood sugars

Diabetes Mellitus

Type I

• Onset between 10 and 20

• Polydipsia (drinking a lot)

• Polyuria (passing large

amount of urine)

• Weight loss

• Caused by autoimmune

destruction of the cells in

the pancreas that make

insulin

Type II

• Onset between 50 and 70

• Often discovered by

chance

• Caused by obesity which

leads to insulin resistance

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Diabetes Mellitus

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Diabetes Mellitus

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Diabetes Mellitus

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Diabetes Mellitus

Diabetes Mellitus

Monitoring

• Blood glucose

• HbA1c

• Urine testing

• Foot sensation

Treatment

• Type I: insulin

• Type II: oral

hypoglycaemics and then

insulin

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Diabetes Mellitus

Ocular manifestations:

• Retinopathy

• Cataract

• Pupil-sparing third

nerve palsy

• Papillitis

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Cardiovascular Diseases

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Hypertension

• Defined as blood

pressure greater than

140/90

• Usually presents in

fifth and sixth

decades

• Asymptomatic

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Hypertension

Complications

• Stroke

• Enlarged heart

• Heart attack

• Kidney damage

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Hypertension

Ocular manifestations:

• Retinal arteriosclerosis

• Hypertensive retinopathy

• Retinal artery occlusion

• Retinal artery macroaneurysm

• Anterior ischaemicoptic neuropathy

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Carotid Stenosis

• Narrowing of the

carotid artery

• Usually caused by

atherosclerosis

(hardening of the

arteries)

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Carotid Stenosis

Ocular manifestations:

• Amaurosis fugax

• Retinal emboli

• Retinal artery

occlusion

• Ocular ischaemic

syndrome

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Carotid Stenosis

Investigations:

• Carotid duplex

ultrasound

• Angiography

Management:

• Stop smoking

• Aspirin

• Warfarin

• Surgery

Congenital Disorders

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Neurofibromatosis

• Neurofibromatosis is

a genetic disorder of

the nervous system

• It affects how nerve

cells form and grow

• It causes tumors to

grow on nerves

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Neurofibromatosis

Symptoms/signs:

• Neurofibromas

• Cafe-au-lait spots

• Freckles in armpits

• Malignancies

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Neurofibromatosis

Ocular manifestations:

• Eyelid neurofibromas

• Lisch nodules

• Optic nerve glioma

• Other neural orbital

tumours

Conclusion

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Key Points

• Systemic diseases may have ocular

manifestations

• Always take a medical history from every

patient and look specifically for ocular

manifestations of their disease

• Remember that an eye condition may be

the first sign of a systemic disease