Systemic disease and

the eye
Deric De Wit
Aldrin Khan
Professor Lightman
 Common systemic diseases
affecting the eye
Infectious Non-infectious
Endocrine – diabetes,
Toxoplasmosis thyroid
Toxocariasis Connective tissue
disease –
TB RA/SLE/Wegeners/PAN/
Syphilis Systemic sclerosis
Vasculitides (GCA)
Leprosy
Sarcoidosis
HIV Behcet’s Disease
CMV Vogt Koyanagi Harada
syndrome
Phakomatoses
 DIABETIC RETINOPATHY
1. Adverse risk factors
2. Pathogenesis
3. Background diabetic retinopathy
4. Diabetic maculopathies
• Focal
• Diffuse
• Ischaemic
5. Clinically significant macular oedema
6. Preproliferative diabetic retinopathy
7. Proliferative diabetic retinopathy
Adverse Risk Factors
1. Long duration of diabetes
2. Poor metabolic control
3. Pregnancy
4. Hypertension
5. Renal disease
6. Other
• Obesity
• Hyperlipidaemia
• Smoking
• Anaemia
Location of lesions in background
diabetic retinopathy
Signs of background diabetic retinopathy

Microaneurysms usually Intraretinal dot and

temporal to fovea blot haemorrhages

Hard exudates Retinal oedema seen as

frequently thickening on biomicroscopy
arranged in clumps or
rings
 Preproliferative diabetic retinopathy
Signs

• Cotton-wool spots • Dark blot haemorrhages

• Venous irregularities • Intraretinal microvascular
abnormalities (IRMA)

Treatment - not required but watch for proliferative disease

 Proliferative diabetic retinopathy
• Affects 5-10% of diabetics
• IDD at increased risk (60% after 30 years)
Neovascularization
• Flat or elevated
• Severity determined by comparing with area of disc

Neovascularization of disc = NVDNeovascularization elsewhere = NVE

 Laser panretinal photocoagulation

• Initial treatment is 2000-3000 burns• Area covered by complete PRP

• Spot size (200-500 µm) depends • Follow-up 4 to 8 weeks
on contact lens magnification
• Gentle intensity burn (0.10-0.05 sec)
 Retinal Vein Occlusion

Second most common cause of vascular-related visual loss.

Risk factors: hypertension, age, blood dyscrasias (OCP,HRT) and
vasculitis (Behcets,sarcoidosis,AIDS,SLE)
 Retinal Artery Occlusion

Risk factors: Carotid artery atherosclerosis (CRAO), carotid emboli

(BRAO), vasculitis (GCA,SLE,PAN), coagulopathy.

OCULAR EMERGENCY - Immediate referral to ophthalmologist

THYROID EYE DISEASE
1. Soft tissue involvement
• Periorbital and lid swelling
• Conjunctival hyperaemia
• Chemosis
• Superior limbic keratoconjunctivitis
2. Eyelid retraction
3. Proptosis
4. Optic neuropathy
5. Restrictive myopathy
 Soft tissue involvement
Periorbital and lid swelling Conjunctival hyperaemia

Superior limbic
Chemosis keratoconjunctivitis
 Signs of eyelid retraction
Occurs in about 50%

• Bilateral lid retraction • Bilateral lid retraction

• No associated proptosis • Bilateral proptosis

• Unilateral lid retraction • Lid lag in downgaze

• Unilateral proptosis
 Proptosis
• Occurs in about 50%
• Uninfluenced by treatment of hyperthyroidism

Axial and permanent in about 70% May be associated with choroidal folds
Treatment options
• Systemic steroids
• Radiotherapy
• Surgical decompression
 Optic neuropathy
• Occurs in about 5%
• Early defective colour vision
• Usually normal disc appearance

Caused by optic nerve Often occurs in absence of significant

compression at proptosis
orbital apex by enlarged recti
 Restrictive myopathy
• Occurs in about 40%
• Due to fibrotic contracture

Elevation defect - most common Abduction defect - less common

Depression defect - uncommon Adduction defect - rare

 SARCOIDOSIS
Idiopathic multisystem disorder
Characterised by non-caseating
granulomata
More common in women 20-50 yrs
More common in blacks and Asians
? Related to mycobacteria
 SARCOIDOSIS
Systemic Involvement
Lung lesions – 95%
Thoracic lymph nodes
– 50%
Skin lesions – 30% →
Eyes – 30%
 SARCOIDOSIS
Ocular Involvement
Anterior segment
lesions (30%)
„ Conjunctival granuloma
„ Lacrimal gland
involvement/dry eye
„ Acute or chronic uveitis
→
„ KPs described as
‘mutton fat’ because they
are large and greasy
 SARCOIDOSIS
Ocular Involvement
Posterior segment
lesions (20%)
„ Patchy venous sheathing
„ Cellular infiltrate around
vessels
„ Chorioretinal
granulonmas
„ Vasculitis including
occlusive causing:-
„ Neovascularisation
„ Infiltrate in vitreous
(vitritis) including cell
clumps (snowballs)
 SARCOIDOSIS
Ocular Involvement
Sheathing of the
retinal veins

Fluorescein
angiography showing
leakage and staining
at sites of sheathing
 SARCOIDOSIS
Granuloma in Fundus
Retinal and pre-
retinal

Choroidal
 SARCOIDOSIS
Granuloma in Fundus
Optic nerve head
granuloma

Normal optic nerve

head
 SARCOIDOSIS
Systemic Signs
Lupus pernio affecting
the nose – a chronic
progressive
cutaneous sarcoid
that most commonly
affects face and ears
 SARCOIDOSIS
Systemic signs
Facial palsy

Salivary gland
enlargement
 SARCOIDOSIS
Systemic signs
Hilar adenopathy on
chest x-ray
Lung infiltrate

Erythema nodosum

Arthritis
 SARCOIDOSIS
Investigations (1)
CXR – to detect
pulmonary signs
Bilateral hilar lymph-
adenopathy

Pulmonary mottling
 SARCOIDOSIS
Investigations (2)

Serum angiotensin-converting enzyme

(ACE) – elevated in active sarcoidosis
Mantoux test – caution in patients who
have had BCG vaccination. Test may be
negative
Lung function tests
 SARCOIDOSIS
Investigations (3)
Gallium scan showing
increased uptake in
the lacrimal and
parotid glands and
pulmonary regions in
a patient with active
sarcoidosis
 SARCOIDOSIS
Treatment

Systemic steroids may be necessary in

patients with posterior segment disease
where vision is threatened, especially if
optic nerve is involved
 PHACOMATOSES

1. Neurofibromatosis
• Type I (NF-1) - von Recklinghausen disease
• Type II (NF-2) - bilateral acoustic neuromas

2. Tuberous sclerosis (Bourneville disease)

3. von-Hippel-Lindau syndrome

4. Sturge-Weber syndrome
 Neurofibromatosis type-1 - (NF-1)
• Most common phacomatosis
• Affects 1:4000 individuals
• Presents in childhood
• Gene localized to chromosome 17q11
Café-au-lait spots

Increase in size and number throughout

Appear during first year of life childhood
 Fibroma molluscum in NF-1

• Appear at puberty • Increase in number

• Pedunculated, flabby nodules consisting of
throughout life
neurofibromas or schwannomas • Frequently widely distributed
 Plexiform neurofibroma in NF-1

• Appear during childhood • May be associated with

• Large and ill-defined overgrowth of overlying skin
 Skeletal defects in NF-1

• Facial hemiatrophy • Mild head enlargement - uncommon

• Other - scoliosis, short stature, thinning of
long bones
 Orbital lesions in NF-1
Optic nerve glioma in about 15% Spheno-orbital encephalocele

• Axial CT scan of congenital absence of

• Sagittal MRI scan of optic nerve glioma
invading hypothalamus left greater wing of sphenoid bone
• Glioma may be unilateral or bilateral• Causes pulsating proptosis without bruit
 Eyelid neurofibromas in NF-1

Nodular Plexiform

May cause mechanical ptosis May be associated with glaucoma

 Intraocular lesions in NF-1
Lisch nodules Congenital ectropion uveae

Very common - eventually present

Uncommon - may be associated
in 95% of cases with glaucoma
Choroidal naevi Retinal astrocytomas

Common - may be multifocal Rare - identical to those seen in

and bilateral tuberous sclerosis
 Ocular features of NF-2

Very common p- resenile cataract Common - combined hamartomas of RPE

and retina
 Tuberous sclerosis (Bourneville disease)
• Autosomal dominant
• Triad - mental handicap, epilepsy, adenoma sebaceum
Adenoma sebaceum Ash leaf spots Shagreen patches

• Around nose and • Hypopigmented skin patches • Diffuse thickening over

cheeks • In infants best detected using lumbar region
• Appear after age 1 ultraviolet light (Wood’s lamp) • Present in 40%
and slowly enlarge
Systemic hamartomas in tuberous sclerosis
Astrocytic cerebral hamartomas Visceral and subungual hamartomas

• Slow-growing periventricular tumours • Usually asymptomatic and

• May cause hydrocephalus, epilepsy and innocuous
• Kidneys (angiomyolipoma), heart
mental retardation
(rhabdomyoma)
Retinal astrocytomas in tuberous scleritis
• Innocuous tumour present in 50% of patients
• May be multiple and bilateral
Early

Semitranslucent nodule White plaque

Advanced

Dense white tumour Mulberry-like tumour

Systemic features of v-H-L syndrome
Autosomal dominant
CNS Haemangioblastoma Visceral tumours

MRI of spinal cord tumour

• Tumours - renal
carcinoma and
phaeochromocytoma
• Cysts - kidneys, liver,
pancreas, epididymis,
ovary and lungs

Angiogram of cerebellar• Polycythaemia

tumour
Retinal capillary haemangioma
in v-H-L syndrome
• Vision-threatening tumour present in 50% of patients
• May be multiple and bilateral
Early

Tiny lesion between Small red nodule

arteriole and venuole
Advanced

Round orange-red massAssociated dilatation and

tortuosity of feeder vessels
Systemic features of Sturge-Weber syndrome
Naevus flammeus Meningeal haemangioma

• Congenital, does not blanche• CT scan showing left

with pressure parietal haemangioma
• Associated with ipsilateral • Complications - mental handicap,
glaucoma in 30% of cases epilepsy and hemiparesis
Ocular features of Sturge-Weber syndrome
Glaucoma

Buphthalmos in 60% May be associated with

episcleral haemangioma
Diffuse choroidal haemangioma

Normal eye Affected eye

 Peripheral corneal involvement in
rheumatoid arthritis
Without inflammation With inflammation

• Chronic and asymptomatic • Acute and painful

• Circumferential thinning with intact • Circumferential ulceration and
epithelium (‘contact lens cornea’) infiltration

Treatment - systemic steroids and/or cytotoxic drugs

 Peripheral corneal involvement in
Wegener granulomatosis and polyarteritis nodos

Circumferential and central Unlike Mooren ulcer sclera may also

ulceration similar to Mooren ulcer become involved

Treatment - systemic steroids and cyclophosphamide

 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
 GIANT CELL ARTERITIS
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
 GIANT CELL ARTERITIS
Management
ESR if suspected
Start high dose steroids immediately to
prevent stroke or second eye involvement
Temporal artery biopsy within a week of
starting steroids
 GIANT CELL ARTERITIS
Temporal Artery Biopsy
Arteries have skip
lesions
ultrasound/Doppler may
help identify involved
areas
If positive, confirms
diagnosis – helpful in
management of future
disease
If negative, doesn’t
exclude diagnosis, but
need to think about an
alternative diagnosis
 GIANT CELL ARTERITIS
Histopathology
Granulomatous cell
infiltration
Giant cells
Disruption of internal
elastic lamina
Proliferation of intima
Occlusion of lumen
 GIANT CELL ARTERITIS
Treatment

Intravenous and oral steroids – prolonged

course of steroids often necessary
Ocular manifestations of
HIV infection
 Introduction

AIDS is an infectious disease caused by the gradual

decrease in CD4+ T lymphocytes causing
subsequent opportunistic infections and neoplasia. It
is a blood borne and sexually transmitted infection
caused by the HIV (Human Immunodeficiency Virus)
Approximately 36 million persons around the world
are infected. Up to 70% of patients infected with HIV
will develop some form of ocular involvement, ie:
direct infection by HIV,opportunistic infections and
neoplasia.
HIV infection progresses though different phases
Ophthalmic Manifestations of HIV Infection

AROUND THE EYE BACK OF THE EYE

„ Molluscum Contagiosum „ Retinal Microvasculopathy

„ Herpes Zoster „ CMV Retinitis

Ophthalmicus „ Acute Retinal Necrosis

„ Kaposi’s Sarcoma „ Progressive Outer Retinal

„ Conjunctival Squamous Necrosis

Cell Carcinoma „ Toxoplasmosis

„ Trichomegaly Retinochoroiditis
FRONT OF THE EYE „ Syphilis Retinitis

„ Dry Eye „ Candida albicans

„ Anterior Uveitis endophthalmitis

NEURO-OPHTHALMIC
 Molluscum Contagiosum

Molluscum contagiosum is a
viral infection of the skin.
Affects up to 20% of
symptomatic HIV infected
patients.
Clinically appears like painless,
small, umbilicated nodules,
which produce a waxy
discharge when pressured.
Treatment consists on excision
of the lesion, curettage or
cryotherapy
 Herpes Zoster Ophthalmicus

Due to the reactivation of a latent infection by Varicella

Zoster Virus in the dorsal root of trigeminal nerve
ganglion.
It manifests with a maculo-papulo-vesicular rash which
often is preceded by pain. Usually involves the upper lid
and does not cross the midline
Treatment consists on oral Aciclovir 800mg 5 times
/day. In immunocompromised patients Aciclovir is given
intravenously for two weeks. Ocular manifestations
such as anterior uveitis, are treated with topical steroids
and mydriatics.
 Kaposi’s Sarcoma

Kaposi’s sarcoma is a vascular neoplasm which is almost

exclusively seen in patients with AIDS.
KS is the commonest anterior segment lesion seen in AIDS;
appears as a violaceous non-tender nodule on the eyelid or
conjunctiva.
Typically KS involves only the skin but when there is a
reduced CD4 count it can progress rapidly to other sites
such as the gastrointestinal tract and CNS
Treatment of ocular adnexal KS may be necessary for
cosmesis and to relieve functional difficulties. The mainstay
of treatment is radiotherapy. Other options include
cryotherapy or chemotherapy.
 Conjunctival Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is the third most

common neoplasm associated to HIV infection. This may
be due to an interaction between HIV, sunlight and
Human Papilloma Virus infection.
SCC appears as a pink, gelatinous growth, usually in the
interpalpebral area. Often an engorged blood vessel
feeding the tumour is seen. It may extend onto the
cornea, but deep invasion and metastasis are rare.
The treatment of choice is local excision and cryotherapy
but the presence of orbital invasion is an indication of
exenteration
 Trichomegaly

Trichomegaly or
hypertrichosis is an
exaggerated growth of
the eye lashes found in
the later stages of the
disease
The cause is not known
When symptomatic or for
cosmetic reasons the
eyelashes can be
trimmed or plucked
 Dry Eye
Sicca syndrome is
frequent among
patients with HIV
infection
Patients complain of
burning uncomfortable
red eyes.
There are several
causes of dry eye in
HIV infection from
blepharitis to
destruction of the
lacrimal glands.
Treatment is with tear
supplements
 Anterior Uveitis
HIV related anterior uveitis can
be:
„ Direct manifestation of the

human immunodeficiency
virus infection
„ autoimmnune in origin

„ drug induced ie: rifabutin,

secondary to direct toxic

effect upon the non-
pigmented epithelium of the
ciliary body
„ Any of the different infections

associated with AIDS, ie:

Herpes Zoster Virus, Herpes
Simplex Virus,
Rifabutin induced anterior uveitis
 Retinal microvasculitis

Retinal microvasculopathy occurs in more than half of the

patients with HIV
It is seen as transient cotton wool spots (CWS), intra-retinal
haemorrhages and microaneurysm, which occurs in 50-70% of
patients. It is usually asymptomatic.
It has an unclear pathogenesis, but it is thought to be HIV
infection of retinal vascular cells.
In an otherwise healthy individual the presence of CWS, should
be differentiated from other forms of retinopathy, such as
diabetic or hypertensive retinopathy. Serological test for HIV will
confirm the diagnosis
Treatment is based in delaying the progression of the disease
associated with HIV
Cotton Wool Spots
 CMV Retinitis
Introduction
„ CMV Retinitis is the commonest intraocular ocular opportunistic infection
seen in patients with AIDS
„ Antibodies are found in almost 95% of adults, causing a trivial illness in
immunocompetent adults, however severe immunosuppression causes
viral reactivation and tissue invasive disease
Pathogenesis
„ Reactivation from extraocular sites leads to seeding in other sites such
as the retina
Epidemiology
„ The number of newly diagnosed cases of CMVR has decreased since
the introduction of the HAART

Highly
HighlyActive
ActiveAntiretroviral
AntiretroviralTherapy
Therapy
 CMV Retinitis
Clinical manifestations
„ Patients may complain of minor visual symptoms such as floaters,
flashing lights or mild blurred vision, or be totally asymptomatic.
„ It presents with a wide range of clinical appearances. From cotton wool
spots which may look like HIV Retinopathy to confluent areas of full
thickness retinal necrosis and vasculitis. CMVR can progress in a
“brushfire” pattern from the active edge of an active lesion. The retinal
vessels in an affected area show attenuation, becoming ghost vessels
eventually.
Treatment
„ The treatment of CMVR in patients with AIDS requires the use of specific
antiviral agents, ganciclovir, foscarnet or cidovir in conjunction with
HAART.
„ These treatments can be administered orally, intravenously or
intravitreally. Systemic treatment has the advantage of treating infection
elsewhere in the body as well as the other eye but has the
disadvantages of systemic side effects.
I i li l l h d i h i d hi i
CMV Retinitis
 Acute Retinal Necrosis

ARN is a confluent peripheral whitening of the retina with

marked vitritis and blood vessel closure. Optic neuritis
and retinal detachment are frequent complications.
ARN is usually due to Varicella-Zoster infection, but it can
also be caused by Herpes Simplex virus or
Cytomegalovirus.
Initially described in the immunocompetent, it has also
been described in the immunosuppressed.
The diagnosis is mainly clinical and is confirmed by PCR
assays on vitreous samples.
Patients are treated with high doses of intravenous
aciclovir or famciclovir, combined with laser treatment to
prevent retinal detachment.
Acute Retinal Necrosis
 Progressive Outer Retinal
Necrosis
(Varicella-Zoster Retinitis)
PORN is a devastating viral retinitis caused by Varicella-Zoster
virus, without vitritis or retinal vasculitis.
The retinitis can be located anywhere but it is common for the
lesions to coalesce and spread posteriorly in a rapid fashion.
The main symptom is rapid loss of vision.The retina shows
typically a white lesion with no haemorrhages or exudates.
Treatment is often unsatisfactory and usually requires
combination of Ganciclovir and Aciclovir. The prognosis is very
poor and retinal detachment is common. Resolution may leave
a white plaque with the appearance of “cracked mud”.
 Toxoplasma Retinochoroiditis

Toxoplasmosis retinochoroiditis is an uncommon

infection of the eye in AIDS. Ocular toxoplasmosis in HIV
positive patients is different in appearance from
immunocompetent patients. Unlike in immunocompetent
patients, HIV infected patients often have bilateral and
multifocal disease associated with anterior uveitis and
vitritis but unlike immunocompetent patients, in HIV
infected patients often have with no pigmented scars
adjacent to the areas of retinal necrosis. Toxoplasmosis
in immunocompromised patients is not self-limiting as it
is in imunocompetent patients.
 Toxoplasma Retinochoroiditis

When testing patients for antibodies to toxoplasmosis

both IgG and IgM levels may be raised, but in
immunocompromised patients these tests may be
negative.
Treatment in immunocompromised patients consists in
the association of sulphadiazine or clindamycin,
pyrimethamine and folinic acid (triple therapy).
Long term maintenance treatment may be needed in
order to prevent relapses.
Often associated with toxoplasma lesions in the Central
Nervous System.
MRI T1 showing an uniformly One week later, the lesion
enhancing lesion in the showing ring enhancement
midbrain
Immunocompetent Immunocompromised
 Syphilis Retinitis

There is a strong association between syphilis and

HIV infection.
It can manifest as a retinitis with dense vitritis,
retinal vasculitis, serous retinal detachment or
neuroretinitis, as well as other types of ocular
involvement such as, conjunctivitis, anterior uveitis,
cranial nerve palsies and optic neuritis.
Treatment consists in high dose of intravenous
Penicillin for 2 weeks.
 Candida albicans
endophthalmitis

Infection with candida albicans is rare. Candida albicans

is the commonest cause of fungal endophthalmitis
Affected patients usually have a history of drug abuse
or indwelling central lines
In the initial stages, floaters are the main symptom. As
the condition progresses, whitish “puff-balls” and
vitreous strands develop. Later, similar infiltrates appear
in the choroid and retina
The treatment depends on the severity of the ocular
involvement and systemic disease. The original foci
should be removed. The drugs of choice are
Amphotericine B and Fluconazol
Candida albicans
endophthalmitis
 Glossary
CD4: Director of the immune response. When activated it
releases cytokines which in turn will activate the immune
system
Cotton Wool Spots: Light-coloured deposits in the retina
secondary to infarcts of the nerve fibre layer
HAART: Highly Active Antiretroviral Therapy
Immunoblogulin: Protein in charge of fighting foreign
substances in our body. IgG is the commonest type of
immunoglobulin and IgM is the earliest class
of immunoglobulin.
PCR: Polymerase Chain Reaction is a technique used to make
numerous copies of an specific portion of DNA
VDRL: Venereal Disease Research Laboratory. The test
becomes negative after successful treatment of the disease.