Comprehensive review of Ophthalmic Manifestations of Systemic Disorders for undergraduate medical students and general practionaers. Lecture was taken by Associate Professor Dr. Zia ul Mazhry at Central Park Medical College Lahore Pakistan.

1. OPHTHALMIC
MANIFESTATIONS OF
SYSTEMIC DISORDERS
Dr. Zia-ul-Mazhry
F.R.C.S (Edinburgh)
F.R.C.S (Glasgow)
F.C.P.S (Pak)
Certified by International Council of Ophthalmology (UK)
Member American Academy of Ophthalmology
Member European society of Cataract and Refractive Surgery
Life Member Ophthalmological Society of Pakistan
Member Executive committee
Ophthalmological Society of Pakistan Lahore Branch
Gold Medalist OSP Lahore Branch
Gold Medalist OSP Hyderabad Branch
Asstt Professor
Central Park Medical College Lahore
Senior Eye Surgeon &
Head of Ophthalmology Department
Wapda Teaching Hospital
Complex
210-Feroz Pur Road
Lahore Pakistan

2. INTRODUCTION
• The eyes are frequently involved in diseases
affecting the rest of the body
• Ocular manifestations in certain multisystem
disorders may offer a diagnostic clue
• Sometime the eye involvement may be subtle
enough to avoid detection unless the
clinicians knows to look for it

3. Discussion Plan
• Part-1
– Overview
• Part-2
– Thyroid
ophthalmppathy
• Part-3
– Neurophthalmic
disorders
• Part-4
– Autoimmune
disorders
• Part-5
– Infectious disorders
and masqueraders
• Part-6
– Vascular disorders
• Part-7
– Vasculitis
• Part-8
– Phacomatosis

4. OVERVIEW

5. 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/Sy
stemic sclerosis
• Vasculitides (GCA)
• Sarcoidosis
• Behcet’s Disease
• Vogt Koyanagi Harada
syndrome
• Phakomatoses

6. THE CORNEA RELATED TO SYSTEMIC
DISEASES
• DISEASES OF THE SKIN AND MUCOUS
MEMBRANES
Atopic dermatitis, cicatricial pemphigoid,
epidermolysis bullosa, erythema multiforme
• DISORDERS OF COLLAGEN METABOLISM
Ehlers-Danlos syndrome, Marfan syndrome

7. THE CORNEA RELATED TO SYSTEMIC
DISEASES
• COLLAGEN DISEASES
Dermatomyositis, periarteritis nodosa,
rheumatoid arthritis, SLE
• METABOLIC DISEASES
Amyloidosis, cystinosis, glycogen storage
disease, gout, hyperlipidemia

8. CATARACT RELATED TO SYSTEMIC
DISEASES
• CHROMOSOMAL DISORDERS
Alport syndrome, Crouzon syndrome, myotonic
dystrophy,Trisomy 18, Turner syndrome
• DISEASES OF THE SKIN AND MUCOUS
MEMBRANES
Atopic dermatitis, pemphigus

9. CATARACT RELATED TO SYSTEMIC
DISEASES
• METABOLIC AND NUTRITION DISEASES
Aminoaciduria, diabetes mellitus,
galactosemia, hypoparathyroidism,
hypothyroidism, Wilson’s disease
• INFECTIOUS DISEASES
Congenital HSV, syphylis, CMV, rubella
• TOXIC SUBSTANCES

10. THE RETINA RELATED TO SYSTEMIC
DISEASES
CARDIOVASCULAR DISEASES
Aortic arch syndrome, hypertension and toxaemia
of pregnancy, occlusive vascular disease
COLLAGEN DISEASES
Dermatomyosistis, periarteritis nodosa, SLE, temporal
arteritis, Wegener granulomatosis
ENDOCRINE DISEASES
Diabetes mellitus, Cushing syndrome,
hyperthyroidism, hypothyroidism, hypoparathyroidism

11. THE RETINA RELATED TO SYSTEMIC
DISEASES
DISEASES OF THE SKIN AND MUCOUS MEMBRANES
Pseudoxanthoma elasticum
GASTROINTESTINAL AND NUTRITIONAL DISEASES
Regional enteritis, vitamin A deficiency
HEMATOLOGIC DISEASES
Anaemias, leukemias, sickle cell disease, thrombocytopenia
INFECTIOUS DISEASES
Candida retinitis, parasites, viral infections, tuberculosis, HIV, HSV,
HZV, CMV
PHAKOMATOSES
METABOLIC DISEASES

12. Peripheral corneal involvement in
rheumatoid arthritis
• Chronic and asymptomatic
• Circumferential thinning with intact
epithelium (‘contact lens cornea’)
• Acute and painful
• Circumferential ulceration and
infiltration
Treatment - systemic steroids and/or cytotoxic drugs
Without inflammation With inflammation

13. Peripheral corneal involvement in
Wegener granulomatosis and polyarteritis nodosa
Circumferential and central
ulceration similar to Mooren ulcer
Unlike Mooren ulcer sclera may also
become involved
Treatment - systemic steroids and cyclophosphamide

14. THYROID OPHTHALMOPATHY

15. THYROID EYE DISEASE (Graves’
ophthalmopathy)
The diagnosis may not be obvious, although it is quite
common!
The severity of the eye changes does not always relate to
the severity of the endocrine problem
It is not known why some patients with thyroid imbalance
have eye features and others do not
The link is immunological, though the details are unclear
Often the eye features develop out of phase with the
thyroid

16. 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
THYROID EYE DISEASE

17. FEATURES OF THYROID EYE DISEASE
Not all patients have all the
signs and symptoms!
Puffiness of lids and
conjunctiva, often worse in
the morning
Discomfort and redness
Watering
Upper lid
Retraction due to overaction
of Müller’s muscle
(Dalrymple’s sign)
Lag (Von Graefe’s sign)

18. FEATURES OF THYROID EYE DISEASE
Infiltrative ophthalmopathy
Enlargement of extraocular muscles
Proliferation of orbital fat and
connective tissue
Protrusion (with poor eyelid closure,
if severe corneal damage)
Double vision, often worse in the
morning
Visual failure from optic nerve
compression (rare, but needs urgent
treatment)!

19. PATHOGENESIS OF THYROID EYE
DISEASE
The disease is not completely understood
The existing knowledge suggests that the disease is likely to be
autoimmune in origin and linked to autoimmune thyroid disease
Cigarette smoking is commoner among patients with Graves’
disease and smokers have a more severe ophthalmopathy
Orbital fibroblasts synthesize more glycosaminoglycans when
cultured under hypoxic conditions.
Glycosaminoglycans attract water  swelling of extraocular
muscles
Infiltration of orbital tissue by immune cells ant their activation, with
subsequent cytokine release leads to local cell proliferation

20. Soft tissue involvement
Periorbital and lid swelling
Chemosis
Conjunctival hyperaemia
Superior limbic
keratoconjunctivitis

21. Signs of eyelid retraction
Occurs in about 50%
• Bilateral lid retraction
• No associated proptosis
• Bilateral lid retraction
• Bilateral proptosis
• Lid lag in downgaze• Unilateral lid retraction
• Unilateral proptosis

22. Proptosis
Treatment options
• Systemic steroids
• Radiotherapy
• Surgical decompression
• Occurs in about 50%
• Uninfluenced by treatment of hyperthyroidism
Axial and permanent in about 70%May be associated with choroidal fol

23. 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

24. • Occurs in about 40%
• Due to fibrotic contracture
Restrictive myopathy
Elevation defect - most common Abduction defect - less common
Depression defect - uncommon Adduction defect - rare

25. NEROOPHTHALMIC DISORDERS

26. OPHTHALMIC PROBLEMES IN
NEUROLOGICAL DISORDERS
• Multiple sclerosis
• Stroke
• Intracranial tumors
• Benign intracranial hypertension
• Facial palsy

27. MULTIPLE SCLEROSIS (demyelinisation)
Optic (ON) neuritis is the most
common manifestation (usually
unilateral, but may be bilateral)
and the presenting feature in
about 25% of MS patients
About 60% of patients in the 20-
40 years age group who
present with ON will
subsequently develop evidence
of systemic demyelinisation!

28. SYMPTOMS OF OPTIC NEURITIS
Decreased visual acuity
Afferent pupillary defect (if
unilateral or asymmetric)
Impairment of color vision
Pain with eye movements
or pressure on the globe
Central or ceco-central
visual field defect

29. STROKE
Homonymous hemianopia is the commonest finding
Often not recognized by the patient
Lesion within the optic path behind the chiasm
(usually in the radiation passing through temporal
and parietal areas to the occipital cortex)
Occlusion of the vertebrobasilar circulation may cause
bilateral cortical lesions and marked visual disability
Many patients have reading difficulties

31. INTRACRANIAL TUMORS
A tumor close to the optic nerve, chiasm or radiation
may affect visual acuity or visual field
Check both visual field and visual acuity in patients
with vague, but persistent and progressive complaints
Headache is not always present!
Look for papilloedema or atrophy of one or both optic
nerve heads

32. PAPILLOEDEMA
Is caused by impairment of
axonic flow in the optic nerve
Does not impair visual acuity
but increases the size of the
blind spot
Optic atrophy implies death
of nerve fibers and is
associated with impairment
of visual acuity, field or color
vision

33. BENIGN INTRACRANIAL
HYPERTENSION
Papilloedema
Raised intracranial pressure
No tumor
Syndrome found in plump young women with
persistent headache and menstrual irregularities
Cause unknown
Therapy: diuretics
Long-term monitoring by a specialist

34. FACIAL PALSY
Weakness of eye closure
Patients at risk of corneal
ulceration
Depending on severity of
malfunction therapy consists of
topical antibiotics (for
lubrication and prevention of
secondary infections), taping
or temporary suturing of the
eyelids

35. AUTOIMMUNE DISORDERS

36. EYE PROBLEMS IN JOINT DISORDERS
Some patients with joint disorders have inflammation of
the coats of the eye (e.g. episcleritis, scleritis), other
condition are associated with internal inflammation (iritis),
some are a cause of dryness of the eye (sicca)
Rheumatoid arthritis
Ankylosing spondylitis
Reiter syndrome
Sjögren syndrome
Juvenile arthritis

37. RHEUMATOID ARTHRITIS
Dry eye (discomfort, burning
sensation)
Scleritis (necrosis of the
sclera may occur)
Refer urgently the
rheumatoid arthritis patient
with a painful eye even if it is
not particularly red!

38. EYE PROBLEMS IN JOINT DISORDERS
ANKYLOSING SPONDYLITIS
Occurs in younger patients with HLA B27 positivity,
causes sacroiliitis
Patients have recurrent anterior uveitis
REITER’S SYNDROME
Ocular inflammation with oligoarticular arthritis and
urethritis
Chlamydia, Yersinia, Salmonella may be the
causative agent

39. SJÖGREN’S SYNDROME
Typically affects
conjunctiva and oral
mucosa
The ophthalmologist is
frequently the first doctor
to see the patient
DRY EYE!

40. JUVENILE IDIOPATHIC ARTHRITIS
Low grade iritis, that may lead
to blindness, if not recognized
and treated
Children with inflammatory
arthritis under 12 years of age
are at risk
Screening!
COMPLICATIONS:
•Cataract
•Glaucoma
•Band keratopathy
•Phthisis bulbi

41. EYE PROBLEMS IN SKIN DISORDERS
ALLERGIC REACTIONS
Acute allergic reaction in atopic
patients
Cell-mediated allergy (e.g.
topical treatment)
SEBORRHOEIC DERMATITIS
Blepharitis

42. EYE PROBLEMS IN SKIN DISORDERS
ROSACEA
BLEPHARITIS
Severe corneal changes
PSORIASIS
Iritis in some patients

43. BLISTERING DISORDERS
• STEVENS-JOHNSON SYNDROME
• PEMPHIGOID
• EPIDERMOLYSIS BULLOSA

44. STEVENS-JOHNSON SYNDROME
Acute hypersensitivity vesiculobullous
reaction of the skin and mucous
membranes
Immune complex deposition incited
by medications or infectious agents
Corneal ulceration and severe
pseudomembranous conjunctivitis
Symblepharon, entropion,
ectropion, trichiasis, dry eye,
persistent conjunctival
inflammation, corneal opacification

45. OCULAR CICATRICIAL PEMPHIGOID
Slowly progressive, chronic
cicatrizing conjunctivitis
Idiopathic, possibly a type II
hypersensitivity reaction
Presents in women over 60 with
recurrent attacks of nonspecific
conjunctival inflammation
There may be associated oral,
pharyngeal or urethral mucosal
lesions

46. INFECTIOUS DISORDERS

47. INFECTIONS OF THE SKIN INVOLVING THE
EYE
• HERPES ZOSTER
– Often involves the eyelid
– Cornea and uvea may be involved (secondary glaucoma)
• VARICELLA
– Lid and corneal lesions
• IMPETIGO
• WARTS
• MOLLUSCUM CONTAGIOSUM
• PUBIC LICE

48. HERPES ZOSTER (HZ)
Incidence: between 40
and 70 years
Healthy and immuno-
compromized patients are
affected
HZ ophthalmicus
represents 10 - 15% of
cases

49. HERPES ZOSTER
Any branch of the Vth cranial
nerve may be affected
Ocular complications are
related to infection of the naso-
ciliary nerve
Eyelid cicatrization
Symblepharon
Keratitis
ANTERIOR UVEITIS WITH
SECONDARY GLAUCOMA!

50. AIDS
TWENTY MILLION CASES WORLDWIDE IN
2000!
Retrovirus (HIV) which infects immunocompetent
CD4+ cells
RESULTS IN CELLULAR IMMUNODEFICIENCY
(T-CELL AND MACROPHAGE DEFICIT)
Complications due
1) to the virus itself
2) to superinfection by opportunistic pathogens

51. OCULAR INVOLVEMENT IN AIDS
Ocular manifestations have been reported in up to 70% of
individuals infected with HIV
Ocular manifestations almost invariably reflect systemic
disease and may be the first sign of disseminated systemic
infection
The most common ocular finding is HIV retinopathy,
occurring in about 50%-70% of cases
HIV has been isolated from human retina, and its antigen
has been detected in retinal endothelial cells
Endothelial infection may be responsible for the vascular
alterations

52. INFECTIOUS AGENTS THAT AFFECT THE
EYE IN AIDS
Cytomegalovirus (CMV) - retinitis
Herpes Zoster - retinal necrosis
Toxoplasma gondii - retinochoroiditis
Mycobacterium tuberculosis - multifocal choroiditis
Cryptococcus neoformans - multifocal choroiditis
Pneumocystis carinii- choroiditis
These agents can infect the ocular adnexa, anterior or
posterior segment
Multifocal choroiditis is an alarming sign, since it
frequently represents disseminated infection!

53. OCULAR MANIFESTATIONS OF AIDS
Clinically 75% of patients have
ocular signs or symptoms
ANTERIOR SEGMENT
COMPLICATIONS
Conjunctival teleangiectasia, giant
molluscum,
High grade malignant
lymphoma/Burkitt lymphoma
Kaposi sarcoma
Keratitis, keratoconjunctivitis (HZ)

54. OCULAR MANIFESTATIONS OF AIDS
POSTERIOR SEGMENT
COMPLICATIONS
Vasculitis (direct effect of the virus)
VIRUS INFECTIONS (MULTIPLE)
CMV retinitis
HSV acute retinal necrosis
MYCOTIC AND PARASITIC INFECTIONS
Pneumocystis carinii

55. 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

57. 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

58. 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

59. 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.

61. 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.

63. 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

65. 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

66. 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

67. 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, Cytomegalovirus,
Toxoplasma gondii, Syphilis

68. Rifabutin induced anterior uveitis

69. 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

70. Cotton Wool Spots

71. 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 Active Antiretroviral Therapy

72. 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.
– Intravitreal implants release the drug over a six-month period, achieving prolonged
high intravitreal levelsof drug.

73. CMV Retinitis

74. 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.

75. Acute Retinal Necrosis

76. 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”.

78. MASQUERADERS

79. 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.

80. 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.

81. MRI T1 showing an uniformly
enhancing lesion in the midbrain
One week later, the lesion showing
ring enhancement

82. Immunocompetent Immunocompromised

83. 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.

85. 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

86. SARCOIDOSIS
Systemic Involvement
• Lung lesions – 95%
• Thoracic lymph nodes –
50%
• Skin lesions – 30% 
• Eyes – 30%

87. 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

88. 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)

89. SARCOIDOSIS
Ocular Involvement
• Sheathing of the retinal
veins
• Fluorescein angiography
showing leakage and
staining at sites of
sheathing

90. SARCOIDOSIS
Granuloma in Fundus
• Retinal and pre-retinal
• Choroidal

91. SARCOIDOSIS
Granuloma in Fundus
• Optic nerve head
granuloma
• Normal optic nerve head

92. SARCOIDOSIS
Systemic Signs
Lupus pernio affecting
the nose – a chronic
progressive cutaneous
sarcoid that most
commonly affects face
and ears

93. SARCOIDOSIS
Systemic signs
• Facial palsy
• Salivary gland
enlargement

94. SARCOIDOSIS
Systemic signs
• Hilar adenopathy on
chest x-ray
• Lung infiltrate
• Erythema nodosum
• Arthritis

95. SARCOIDOSIS
Investigations (1)
CXR – to detect
pulmonary signs
• Bilateral hilar lymph-
adenopathy
• Pulmonary mottling

96. 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

97. SARCOIDOSIS
Investigations (3)
Gallium scan showing
increased uptake in the
lacrimal and parotid
glands and pulmonary
regions in a patient with
active sarcoidosis

98. SARCOIDOSIS
Treatment
Systemic steroids may be necessary in
patients with posterior segment disease
where vision is threatened, especially if optic
nerve is involved

99. FUNGAL DISORDERS

100. 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

101. Candida albicans endophthalmitis

102. 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.

103. VASCULAR DISORDERS

104. EYE PROBLEMS IN VASCULAR
DISORDERS
• Hypertension
• Diabetes mellitus
• Hyperlipidaemia
• Hematological disorders
• Vasculitis
• Ischaemic optic nerve disease
• Retinal vascular occlusions

105. RETINAL FEATURES OF
HYPERTENSION
Vessels (especially arterioles)
Narrowing
Thickening with silvering or
tortuosity
Arteriovenous crossing change
(nipping in of the vein)

106. RETINAL FEATURES OF
HYPERTENSION
Hemorrhages
Cotton wool spots
(microinfarcts)
Retinal edema and disc
swelling
Hard exudates (lipid)
Macroaneurysms

107. DIABETIC RETINOPATHY
A sight-threatening chronic process based primarily
on damage to the retinal capillaries (microangiopathy)
Later the process involves larger vessels: venules,
arterioles and arteries
A certain degree of retinopathy develops in virtually
every diabetic patient

108. DIABETIC RETINOPATHY
• In type -1 (insulin-dependent) diabetes the first
ophthalmologic examination should be performed 3
to 5 years after the diagnosis
• In type -2 diabetes (NIDDM) the beginning of the
disease is usually not known, ophthalmologic
examination is mandatory, as retinopathy or
macular edema may already be present at
diagnosis!

109. DIABETIC RETINOPATHY (pathogenic
mechanisms)
• Capillary hypertension
• Systemic hypertension
• Insulin resistance
• Increased vascular permeability
• Endothelial dysfunction
• Hyperglycemic pseudohypoxia
• Non-enzymatic glycosylation

110. Capillary damage
Pericyte necrosis
(capillaries and veins)
Endothelial damage
Capillary non-perfusion
Retinal ischaemia
Vasoactive factors
Hyperperfusion
Abnormal autoregulation
Hypertension
New vesselsGrowth factors
Hyperglycemia

111. NON-PROLIFERATIVE DIABETIC
RETINOPATHY
MICROANEURYSMS and
blot-and-dot hemorrhages
INCREASED VASCULAR
PERMEABILITY (hard
exudates)
ISCHAEMIA (cotton-wool
spots: damage to axoplasmic
flow in the nerve fiber layer)

112. NON-PROLIFERATIVE DIABETIC
RETINOPATHY
Venous “beading”
IRMA (intraretinal
microvascular anomalies)
Extensive capillary
occlusion and ischaemia

113. PROLIFERATIVE DIABETIC
RETINOPATHY
IS CHARACTERIZED BY
NEWLY FORMED VESSELS
(neovascularisation) which
originate from vessels of the
optic nerve or from the surface
of the retina
Newly formed vessels are
abnormal, extremely fragile
vessels!

114. PROLIFERATIVE DIABETIC
RETINOPATHY
Vascular buds grow into the
vitreous cortex through the
damaged internal limiting
membrane of the retina
Shrinkage and retraction of
the vitreous is complicated
by vitreous hemorrhage
and/or retinal detachment

115. ANTERIOR SEGMENT COMPLICATIONS OF
DIABETES
Recurrent, non-healing
corneal epithelial defects
Neovascular glaucoma
(related to rubeosis iridis
ang anterior chamber angle
neovascularization)

116. HYPERLIPIDAEMIA
OCULAR SYMPTOMS
Corneal arc
Eruptive xanthoma

117. VASCULITIS

118. VASCULITIS
PERIARTERITIS
NODOSA
WEGENER
GRANULOMATOSIS

119. VASCULITIS
ARTERITIS TEMPORALIS
(GIANT CELL ARTERITIS)
Arteritic ischemic optic
neuropathy
Painless visual loss with
altitudinal visual field defect
Age more than 55 years!
Elevated ESR!

120. 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

121. GIANT CELL ARTERITIS
Presentation
• Headache
• Scalp tenderness
• Thickened temporal
arteries
• Jaw claudication
• Acute visual loss
• Weight loss, anorexia,
fever, night sweats,
malaise & depression

122. 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

123. 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

124. 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

125. GIANT CELL ARTERITIS
Histopathology
• Granulomatous cell
infiltration
• Giant cells
• Disruption of internal
elastic lamina
• Proliferation of intima
• Occlusion of lumen

126. GIANT CELL ARTERITIS
Treatment
• Intravenous and oral steroids – prolonged
course of steroids often necessary

127. PHACOMATOSIS

128. PHAKOMATOSES
• Phakomatoses or neurocutaneous syndromes are a group of
disorders featuring multiple discrete lesions of one or a few
histologic types that are found in two or more organ
systems, including skin or central nervous system or both.
• Eye involvement is frequent, and may constitute an
important source of morbidity or provide information critical
to diagnosis
• Neurofibromatosis (von Recklinghausen disease)
• Tuberous sclerosis (Bourneville disease)
• Angiomatosis of retina and cerebellum (von Hippel-Lindau)
• Encephalotrigeminal angiomatosis (Sturge-Weber
syndrome)

129. PHACOMATOSES
1. Neurofibromatosis
2. Tuberous sclerosis (Bourneville disease)
3. von-Hippel-Lindau syndrome
4. Sturge-Weber syndrome
• Type I (NF-1) - von Recklinghausen disease
• Type II (NF-2) - bilateral acoustic neuromas

130. NEUROFIBROMATOSIS
• Two genetically distinct form are recognized
• NF-1, one of the commonest autosomal dominant
disorders. Variation in the spectrum and severity of
expression are prominent features.
• NF-1 gene is a tumor suppressor gene
(chromosome 17q12)
• Diagnostic features
– Café au lait spots
– Skin neurofibromas
– Lisch nodules

131. NEUROFIBROMATOSIS 1 (NF-1)
• Associated ocular features
–Neurofibroma of eyelid and orbit
–Uveal melanocytic nevi
–Retinal glial hamartoma
–Congenital glaucoma
–Optic nerve glioma

132. NEUROFIBROMATOSIS 2 (NF-2)
The gene maps to chromosome 22
Diagnostic features
Schwannoma of VIII cranial nerve
Meningioma
Spinal nerve root tumors
Cutaneous neurofibroma (relatively rare)
Associated ocular features
Lens opacities - posterior capsular cataract
developing during adolescence or young adulthood

133. Neurofibromatosis type-1 - (NF-1)
Appear during first year of life
Café-au-lait spots
• Most common phacomatosis
Increase in size and number throughout
childhood
• Affects 1:4000 individuals
• Presents in childhood
• Gene localized to chromosome 17q11

134. Fibroma molluscum in NF-1
• Appear at puberty
• Pedunculated, flabby nodules consisting of
neurofibromas or schwannomas
• Increase in number
throughout life
• Frequently widely distributed

135. Plexiform neurofibroma in NF-1
• May be associated with
overgrowth of overlying skin
• Appear during childhood
• Large and ill-defined

136. Skeletal defects in NF-1
• Mild head enlargement - uncommon
• Other - scoliosis, short stature, thinning of
long bones
• Facial hemiatrophy

137. Orbital lesions in NF-1
Spheno-orbital encephaloceleOptic nerve glioma in about 15%
• Sagittal MRI scan of optic nerve glioma
invading hypothalamus
• Glioma may be unilateral or bilateral
• Axial CT scan of congenital absence of
left greater wing of sphenoid bone
• Causes pulsating proptosis without bruit

138. Eyelid neurofibromas in NF-1
Nodular Plexiform
May cause mechanical ptosis May be associated with glaucoma

139. Intraocular lesions in NF-1
Lisch nodules
Very common - eventually present
in 95% of cases
Congenital ectropion uveae
Uncommon - may be associated
with glaucoma
Retinal astrocytomas
Rare - identical to those seen in
tuberous sclerosis
Choroidal naevi
Common - may be multifocal
and bilateral

140. Ocular features of NF-2
Common - combined hamartomas of RPE
and retina
Very common - presenile cataract

141. TUBEROUS SCLEROSIS
Autosomal dominant trait, the responsible
gene maps to chromosome 9q34
Skin lesions
Angiofibroma (adenoma sebaceum)
Seizures
Mental retardation in 50% of cases
Eye lesions
Astrocytic hamartoma (composed of nerve
fibers and glial cells) may be flat or
mulberry-like

142. Tuberous sclerosis (Bourneville disease)
• Diffuse thickening over
lumbar region
• Present in 40%
Shagreen patches
• 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)

143. Systemic hamartomas in tuberous sclerosis
Astrocytic cerebral hamartomas
• Slow-growing periventricular tumours
• May cause hydrocephalus, epilepsy and
mental retardation
• Usually asymptomatic and
innocuous
• Kidneys (angiomyolipoma), heart
(rhabdomyoma)
Visceral and subungual hamartomas

144. Retinal astrocytomas in tuberous scleritis
Dense white tumour Mulberry-like tumour
Early
• Innocuous tumour present in 50% of patients
• May be multiple and bilateral
Semitranslucent nodule White plaque
Advanced

145. VON HIPPEL-LINDAU DISEASE
Autosomal dominant disease, maps to
chromosome 3p25
Diagnostic features
Retinal angioma supplied by
dilated tortuous arteriole and
venule, may be multiple
Cerebellar angioma
Associated ocular conditions
Retinal exudates,
hemorrhage, retinal
detachment
Associated general
conditions
Kidney tumors (renal
carcinoma)
Pheochromocytoma
Cysts in different
organs

146. Systemic features of v-H-L syndrome
Autosomal dominant
• Tumours - renal
carcinoma and
phaeochromocytoma
• Cysts - kidneys, liver,
pancreas, epididymis,
ovary and lungs
• Polycythaemia
CNS Haemangioblastoma
MRI of spinal cord tumour
Angiogram of cerebellar
tumour
Visceral tumours

147. Retinal capillary haemangioma
in v-H-L syndrome
Round orange-red mass
Early
• Vision-threatening tumour present in 50% of patients
• May be multiple and bilateral
Tiny lesion between
arteriole and venuole
Small red nodule
Associated dilatation and
tortuosity of feeder vessels
Advanced

148. STURGE-WEBER SYNDROME
Is not genetically transmitted
Diagnostic features
Facial cutaneous angioma
(consists of excessively
numerous dilated capillaries
in the dermis)
Cerebral calcification
Seizures

149. STURGE-WEBER SYNDROME
OCULAR FEATURES
Choroidal involvement -
increased number of
choroidal vessels
Glaucoma is the most
serious complication seen
in children with SWS

150. Systemic features of Sturge-Weber syndrome
• Congenital, does not blanche
with pressure
• Associated with ipsilateral
glaucoma in 30% of cases
Naevus flammeus
• CT scan showing left
parietal haemangioma
• Complications - mental handicap,
epilepsy and hemiparesis
Meningeal haemangioma

151. Ocular features of Sturge-Weber syndrome
Normal eye
Buphthalmos in 60% May be associated with
episcleral haemangioma
Affected eye
Diffuse choroidal haemangioma
Glaucoma

152. THANK YOU