Systemic disease and
the eye
Deric De Wit
Aldrin Khan
Professor Lightman
Common systemic diseases
affecting the eye
Infectious
Toxoplasmosis
Toxocariasis
TB
Syphilis
Leprosy
HIV
CMV
Non-infectious
Endocrine – diabetes,
thyroid
Connective tissue
disease –
RA/SLE/Wegeners/PAN/
Systemic sclerosis
Vasculitides (GCA)
Sarcoidosis
Behcet’s Disease
Vogt Koyanagi Harada
syndrome
Phakomatoses
DIABETIC RETINOPATHY
1.
2.
3.
4.
Adverse risk factors
Pathogenesis
Background diabetic retinopathy
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
temporal to fovea
Hard exudates
frequently
arranged in clumps or
rings
Intraretinal dot and
blot haemorrhages
Retinal oedema seen as
thickening on biomicroscopy
Preproliferative diabetic retinopathy
Signs
• Cotton-wool spots
• Venous irregularities
• Dark blot haemorrhages
• 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
on contact lens magnification
•
Gentle intensity burn (0.10-0.05 sec)
Follow-up 4 to 8 weeks
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
Chemosis
Conjunctival hyperaemia
Superior limbic
keratoconjunctivitis
Signs of eyelid retraction
Occurs in about 50%
• Bilateral lid retraction
• No associated proptosis
• Bilateral lid retraction
• Bilateral proptosis
• Unilateral lid retraction
• Unilateral proptosis
• Lid lag in downgaze
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
compression at
orbital apex by enlarged recti
Often occurs in absence of significant
proptosis
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%)
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„
„
„
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%)
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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 preretinal
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 lymphadenopathy
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)
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•
•
•
Most common phacomatosis
Affects 1:4000 individuals
Presents in childhood
Gene localized to chromosome 17q11
Café-au-lait spots
Appear during first year of life
Increase in size and number throughout
childhood
Fibroma molluscum in NF-1
Appear at puberty
• Pedunculated, flabby nodules consisting of
neurofibromas or schwannomas
•
Increase in number
throughout life
• Frequently widely distributed
•
Plexiform neurofibroma in NF-1
•
•
Appear during childhood
Large and ill-defined
• May be associated with
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
left greater wing of sphenoid bone
invading hypothalamus
• Glioma may be unilateral or bilateral• Causes pulsating proptosis without bruit
Eyelid neurofibromas in NF-1
Nodular
May cause mechanical ptosis
Plexiform
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
tuberous sclerosis
and bilateral
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
•
•
Around nose and
cheeks
Appear after age 1
and slowly enlarge
Ash leaf spots
•
•
Hypopigmented skin patches
In infants best detected using
ultraviolet light (Wood’s lamp)
Shagreen patches
•
•
Diffuse thickening over
lumbar region
Present in 40%
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
dilatation and
Round orange-red massAssociated
tortuosity of feeder vessels
Systemic features of Sturge-Weber syndrome
Naevus flammeus
•
•
Congenital, does not blanche•
with pressure
Associated with ipsilateral •
glaucoma in 30% of cases
Meningeal haemangioma
CT scan showing left
parietal haemangioma
Complications - mental handicap,
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
ulceration similar to Mooren ulcer
Unlike Mooren ulcer sclera may also
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
„ Molluscum Contagiosum
„ Herpes Zoster
Ophthalmicus
„ Kaposi’s Sarcoma
„ Conjunctival Squamous
Cell Carcinoma
„ Trichomegaly
FRONT OF THE EYE
„ Dry Eye
„ Anterior Uveitis
BACK OF THE EYE
„ Retinal Microvasculopathy
„ CMV Retinitis
„ Acute Retinal Necrosis
„ Progressive Outer Retinal
Necrosis
„ Toxoplasmosis
Retinochoroiditis
„ Syphilis Retinitis
„ Candida albicans
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 nonpigmented 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
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„
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
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„
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
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„
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.
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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
enhancing lesion in the
midbrain
One week later, the lesion
showing ring enhancement
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.