Uveitis in systemic diseases

1. Uveitis in Systemic Diseases
Supervised by : Dr.Wafaa Al-Sakaji.
Presented by : Dr.Mohammad Dmour-PGY1
Ophthalmology Department- Islamic Hospital
February 9.2017.

9. Introduction
• The uvea consists of the middle, pigmented,
vascular layer of the eye and includes the iris,
ciliary body, and choroid.
• Uveitis is broadly defined as inflammation of the
uvea, and may be accompanied by involvement of
other ocular structures such as the retina, sclera,
cornea, vitreous, and optic nerve.

10. Introduction
• Because uveitis is frequently associated with
systemic disease, a careful, thorough history and
review of systems is an essential first step in
elucidating a cause.
• A comprehensive physical examination of the eye
and associated organ systems must be done to
characterize the type of inflammation present.

11. Outlines….
1. Anatomy of the Uveal Tract
2. Classification of Uveitis
3. Clinical Features
4. Principles of Diagnosis and Treatment
5. Uveitis in Spondyloarthropathies (HLA-B27
related)
6. Uveitis in Juvenile idiopathic arthritis (JIA)
7. Behçet disease
8. Sarcoidosis
9. Multiple sclerosis
10.Uveitis in Renal diseases

14. Classification

15. Classification

16. Classification

17. Classification

18. Classification

20. Clinical features

21. Clinical features

24. Clinical features- Anterior uveitis
1. Ciliary injection
2. Pupillary miosis
3. Inflammatory cells
4. Aqueous flare
5. Hypopyon
6. Keratic Precipitates
7. Fibrinous exudate
8. Iris nodules
9. Posterior synechiae (PS)
10.Band keratopathy

34. Posterior synechiae. (A) Adhesions in active acute anterior
uveitis; (B) extensive synechiae and pigment on the lens
following severe acute anterior uveitis.

35. Clinical features- Intermediate uveitis
1. Vitreal inflammatory cells.
2. Snowball opacities.
3. Exudates over the pars plana (snowbank).
4. Vitreal strands.

36. Vitreous inflammatory activity. (A) Mild; (B) severe
(A) (B)

37. Intermediate uveitis. (A)
Snowballs; (B) peripheral
periphlebitis and snowballs;
(C) inferior snowbanking and
snowballs.
(A)
(B)
(C)

38. Clinical features- Posterior uveitis
1. Retinal or choroidal inflammatory infiltrates.
2. Inflammatory sheathing of arteries or veins.
3. Exudative, tractional , or rhegmatogenous RD.
4. RPE hypertrophy or atrophy.
5. Atrophy or swelling of the retina, choroid, or
optic nerve head.
6. Preretinal or subretinal fibrosis.
7. Retinal or choroidal neovascularization.

39. Investigations
• Investigation is generally not indicated in the
following circumstances:
1. A single episode of unilateral mild/moderate non-
granulomatous AAU with no ocular or systemic
suggestion of underlying disease.
2. Typical clinical features of a specific entity for
which investigation is not usually indicated (e.g.
FUS).
3. A systemic diagnosis compatible with the clinical
features (e.g. sarcoidosis) has already been
confirmed.

42. Management of Uveitis

48. UVEITIS IN SPONDYLOARTHROPATHIES
• The Spondyloarthropathies are a group of
disorders featuring HLA-B27 positivity and
enthesitis as common factors.
• They are often referred to as seronegative
spondyloarthropathies, in that rheumatoid factor
is not present and the pathophysiological basis
differs.

52. Ankylosing spondylitis
• Ankylosing spondylitis (AS) is characterized by
inflammation, calcification and finally
ossification of ligaments and capsules of joints
with resultant bony ankylosis of the axial
skeleton.
• It more commonly affects males, of whom 90%
are HLA-B27-positive.

54. Ankylosing spondylitis
• Presentation is commonly in the third to fourth
decades with the insidious onset of pain and
stiffness in the lower back or buttocks.
• Spondyloarthritis causes progressive limitation
of spinal movements; eventually the spine may
become fixed in flexion.

55. Radiology of the sacroiliac joints shows juxta-articular osteoporosis in the early
stages, followed by sclerosis and bony obliteration of the joint . Calcification of spinal
ligaments gives rise to a ‘bamboo spine’.

56. Ocular features
• AAU is by far the most common ocular association,
and occurs in about 25% of patients with AS; 25% of
males with AAU will have AS.
• Either eye is frequently affected at different times
but bilateral simultaneous involvement is rare.
• There is often no correlation between the severity
and activity of eye and joint involvement. Chronicity
occurs in few patients.
• Other ocular features include scleritis, episcleritis,
keratitis and mechanical ptosis.

58. Reactive arthritis
• Reactive arthritis (Reiter syndrome) is
characterized by a triad of non-specific
urethritis, conjunctivitis and arthritis.
• Around 75% of patients are positive for
HLA-B27.

59. Reactive arthritis
• A range of infective agents can trigger the
syndrome, which develops in 1–3% of men after
non-specific urethritis, and around 4% of
individuals after enteric infections caused by a
range of organisms including Shigella,
Salmonella and Campylobacter.
• Chlamydia pneumoniae respiratory infection
and others may also precede ReA.

60. Reactive arthritis
• Presentation is with the acute onset of malaise, with
fever and dysuria 1–4 weeks after a linked infection in
a patient aged between 20 and 40, with arthritis that
may be preceded by conjunctivitis.
1. Peripheral oligoarthritis
2. Spondyloarthritis
3. Enthesitis
4. Mucocutaneous lesions include painless mouth
ulceration, circinate balanitis and keratoderma
blennorrhagica.
5. Genitourinary involvement includes cervicitis,
prostatitis and epididymitis.
6. Aortitis occurs in 1–2%.

61. Keratoderma blennorrhagica in reactive arthritis (Reiter syndrome)

62. Ocular features
• The eye is involved in 50% of cases with a
urogenital inciting infection and 75% of enteric
ReA syndrome.
• Conjunctivitis is very common; it classically
follows urethritis but precedes arthritis.
• AAU occurs in 20%.
• Episcleritis sometimes occurs.

63. Early onset complete posterior synechiae in iridocyclitis with Reiter's disease

64. Psoriatic arthritis

65. Psoriasis. (A) Skin plaques; (B) arthritis and severe nail dystrophy
(A) (B)

66. Ocular features
• AAU occurs in approximately 7%.
• Conjunctivitis
• Marginal corneal infiltrates
• Secondary Sjogren syndrome

68. UVEITIS IN BOWEL DISEASE Ulcerative colitis
• Ulcerative colitis (UC) is an idiopathic chronic
relapsing inflammatory disease, involving the
rectum and extending proximally to involve part
or all of the large intestine.
• The disease is characterized by contiguous
surface ulceration of the bowel mucosa with the
development of crypt abscesses and
pseudopolyps.

69. Ocular features
• AAU occurs in about 5% and may coincide with
exacerbations of colitis. As expected, uveitis is
more common in patients with associated
arthritis, AS and HLA-B27 positivity.
• Other ocular features: conjunctivitis, episcleritis
and scleritis may all be more common than in
the general population.

70. Ulcerative colitis. (A) Barium enema shows pseudopolyposis, lack of
haustral markings and straightening of the ascending colon; (B) pyoderma
gangrenosum

71. Crohn disease
• Crohn disease (CD) is an idiopathic chronic relapsing
disease characterized by multifocal full-thickness
granulomatous inflammation of the intestinal wall.
• It most frequently involves the terminal ileum and
colon but in contrast to UC any area of the
gastrointestinal tract, including the mouth, may be
affected.
• AAU occurs in about 3%; dry eye, conjunctivitis
and scleritis may be more common than in the
general population.

72. UVEITIS IN JUVENILE IDIOPATHIC ARTHRITIS
• Juvenile idiopathic arthritis (JIA) is by far the
most common systemic disease associated with
childhood anterior uveitis; the prevalence is
about 1 : 1000.
• It is defined as arthritis of unknown aetiology
that begins before the age of 16 years and persists
for at least 6 weeks; up to 50% of children
affected have persistently active disease after 10
years.

73. Juvenile idiopathic arthritis (JIA)
1. Oligoarticular is the most common form.
2. Polyarticular (rheumatoid factor negative):
Uveitis occurs in 5–10% of cases.
3. Systemic (Still’s disease): The disease occurs
with equal frequency in boys and girls and may
occur at any age throughout childhood. The
majority are negative for ANA, and uveitis is
rare.

74. Juvenile idiopathic arthritis (JIA)
• Anterior uveitis is a key cause of morbidity in
JIA. It is particularly common in oligoarticular
JIA, and relatively frequent in several other
types.
• Progression to blindness has been high in
historical data but shows a declining trend in
recent years associated with improved
screening and management.

75. Juvenile idiopathic arthritis (JIA)
• The uveitis of JIA is particularly dangerous
because it is invariably asymptomatic .
• Even during acute exacerbations with +4
aqueous cells, it is rare for patients to complain,
although a few report an increase in vitreous
floaters.
• Often uveitis may not be suspected until the
parents recognize complications such as
strabismus, or an abnormal appearance of the
eyeball due to band keratopathy or cataract.

76. JIA
• Injection is usually absent even in the presence of severe uveitis
• Both eyes are affected in 70%; when bilateral, the severity of
inflammation is usually symmetrical.
• During acute exacerbations, the entire endothelium shows
‘dusting’ by many hundreds of cells, but hypopyon is absent.
• Posterior synechiae are common in long-standing undetected
cases.
• Band keratopathy and cataract are extremely common in severe
cases.
• Other serious complications include glaucoma, amblyopia,
maculopathy (CME, epiretinal membrane), cyclitic membrane
and phthisis.

77. Band keratopathy, posterior synechiae and mature cataract in
chronic anterior uveitis associated with JIA.

78. Prognosis
• In about 10% the uveitis is mild, with never
more than +1 aqueous cells, and persists for less
than 12 months.
• About 15% of patients have one attack lasting
less than 4 months, the severity of inflammation
varying from +2 to +4 aqueous cells.
• In 50% of cases, the uveitis is moderate to severe
and persists for more than 4 months, and in
25%, the uveitis is very severe, lasts for several
years and responds poorly to treatment.

79. Lab tests
• Antinuclear antibody (ANA): Positivity denotes an
increased risk of uveitis.
• HLA-B27 testing is useful in differential diagnosis and if
present may indicate an increased risk of uveitis.
• Rheumatoid factor: is also useful in differential diagnosis.
• Screening. There has been a shift in recommendation
towards long-term 3–4 monthly review intervals in all
higher-risk categories. Review should continue in most
cases until the age of 12 years.
• Initial examination within 6 weeks of first diagnosis of
JIA.

80. Treatment
• Topical steroids are effective in most cases (80%);
acute exacerbations require very frequent
instillation.
• Mydriatic agents may be required for exacerbations
to prevent synechiae formation.
• Periocular steroids.
• Oral steroids.
• (NSAIDs).
• Systemic immunosuppressive agents will be required
in resistant cases (e.g. methotrexate, infliximab,
adalimumab, ciclosporin). Doses required are often
low.

81. Behçet Disease
• BD probably has an autoimmune basis, and may
be precipitated by exposure to an infectious agent
with subsequent cross-reaction.
• It is strongly associated with HLA-B51.
• Mortality is around 5% at 5–10 years, typically
due to cardiovascular or CNS complications.
• The peak age of onset is the third decade;
reported gender prevalence varies with ethnicity.

83. Systemic features
• Vascular lesions : Aneurysms, venous
thrombosis/thrombophlebitis.
• Arthritis occurs in 30%, though arthralgia is
more common.
• Dermatographia.
• Neurological manifestations (5%) such as
meningoencephalitis of the brainstem, dural
sinus thrombosis and cerebral aneurysms.

84. Behçet disease. (A) Major aphthous ulceration; (B) superficial thrombophlebitis; (C)
dermatographia (Courtesy of MA Mir, from Atlas of Clinical Diagnosis, Saunders
2003)

85. Ocular features
• Ocular inflammation occurs in about 70%, and
tends to be more severe in men; it is the
presenting manifestation in about 10%.
• Relapsing/remitting acute onset panuveitis with
retinal vasculitis and often spontaneous
resolution even without treatment is the classical
pattern of eye involvement.
• Retinal vascular disease (vasculitis and occlusion)
is the main cause of visual impairment.

86. Behçet Disease
• AAU, often bilateral, is typical. It is not
granulomatous. A transient mobile hypopyon in
a relatively white eye is characteristic.
• Vitritis may be severe; it is universal in eyes
with active posterior segment disease.
• Retinitis: Transient superficial white
infiltrates that heal without scarring may be
seen during acute systemic disease.

87. Ocular lesions in Behçet disease. (A) Hypopyon in a white eye; (B) retinal infiltrates;
(C) occlusive vasculitis; (D) end-stage disease
(A) (B)
(C) (D)

88. Behçet Disease
• Retinal Vasculitis, arteritis as well as phlebitis, in
contrast to pure venous involvement in sarcoidosis
• Vascular leakage may give rise to diffuse retinal
oedema and CMO.
• Optic disc hyperaemia and oedema.
• Disc and retinal neovascularization
• Uncommon manifestations include conjunctivitis,
conjunctival ulcers, episcleritis, scleritis and
ophthalmoplegia from neurological involvement.

89. Behçet Disease
• End-stage disease is characterized by optic
atrophy, retinal atrophy and gliosis, and
sheathing, attenuation and ghosting of affected
vessels ; the vitreous tends to clear.
• Other complications include posterior synechiae,
cataract, glaucoma and, uncommonly, retinal
detachment and phthisis.

90. Investigations
1. HLA-B51
2. Pathergy test
3. Inflammatory markers (e.g. ESR, CRP, WBCs)
4. Thrombophilia screening.
5. FA delineates ischaemic areas
6. Laser flare photometry of the anterior chamber
correlates well with FA in determining the level of
inflammatory activity.
7. Superficial lesion biopsy, synovial fluid aspiration
and lumbar puncture may be used to help rule out
alternative diagnoses.
8. brain MRI/ (MRA), CT/ (CTA) and conventional
angiography to identify ischaemia.

91. Treatment
• Immunosuppressant are the mainstay of
treatment.
• Topical steroids alone may be adequate if (rarely)
there is no trace of posterior segment
involvement.
• Systemic steroids and azathioprine (2.5
mg/kg/day) in combination are recommended
for the initial management of posterior uveitis.

92. Treatment
• Ciclosporin (2–5 mg/kg/day) or infliximab, in
combination with azathioprine and systemic
steroids, is recommended by for severe eye
disease (> 2 lines reduction in visual acuity
and/or retinal vasculitis or macular
involvement).
• Infliximab or adalimumab should be considered
early for vision-threatening Behçet disease
(American Uveitis Society recommendation).

93. Treatment
• Interferon-Alfa (6 million IU per day
subcutaneously initially, gradually tapered) with
or without steroids is a EULAR-recommended
alternative to the ciclosporin/
infliximab/azathioprine/steroid regimen above
for severe disease.
• Anticoagulants are not recommended.

94. SARCOIDOSIS
• Sarcoidosis is a chronic multisystemic
granulomatous disorder of unknown etiology
thought to result from an exaggerated cellular
immune response to a variety of self antigens or
non-self antigens that is characterized by its
pathological hallmark, the noncaseating
granuloma.
• It more frequently (10 : 1) affects patients of
black than white ethnicity but is more common
in colder climates.

95. (A) Bilateral hilar lymphadenopathy; (B) erythema nodosum; (C) lupus pernio
(Courtesy of MA Mir, from Atlas of Clinical Diagnosis, Saunders 2003 – fig. C)

96. SARCOIDOSIS
• Ocular inflammation occurs in 25–70% of sarcoid
patients depending on ethnicity; granulomatous
anterior uveitis is the most common
manifestation.
• Blindness can occur if not adequately managed.
• AAU typically affects patients with acute-onset
sarcoidosis.
• CAU, typically granulomatous, tends to affect
older patients with chronic pulmonary disease.

98. SARCOIDOSIS
• The International Workshop on Ocular Sarcoidosis
(IWOS), reporting in 2009, identified seven key signs in
the diagnosis of intraocular sarcoidosis:
1. Mutton fat’ KPs and/or small granulomatous KPs
and/or iris nodules (Koeppe and/or Busacca).
2. Trabecular meshwork (TM) nodules
3. Vitreous opacities: snowballs and/or ‘strings of pearls’.
4. Multiple chorioretinal peripheral lesions (active and/or
atrophic).
5. Nodular and/or segmental periphlebitis (± ‘candle wax
drippings’) and/or retinal macroaneurysm in an
inflamed eye.
6. Optic disc nodule(s)/granuloma and/or solitary
choroidal nodule.
7. Bilaterality.

99. Ocular sarcoidosis. (A) Very large granulomatous ‘mutton fat’ keratic precipitates; (B) large
iris nodules; (C) nodular involvement of the trabecular meshwork; (D) snowballs

100. Choroidal and retinal involvement in sarcoidosis.
(A) Small choroidal granulomata; (B) same eye as (A) showing lesion with a punched-out
appearance; (C) confluent choroidal infiltration; (D) multifocal choroiditis; (E) multiple small
retinal granulomata.
(A)
(B) (C) (D)
(E)

101. Periphlebitis in sarcoidosis. (A) ‘Candle wax drippings’; (B) occlusive periphlebitis
and disc oedema (Courtesy of P Morse – fig. A; C Pavesio – fig. B)

102. Involvement of the optic nerve head in sarcoidosis – granulomata and periphlebitis
(Courtesy of J Donald M Gass, from Stereoscopic Atlas of Macular Diseases,
Mosby 1997).

103. Lacrimal gland enlargement in sarcoidosis

104. A. Conjunctival nodules B. Biopsy of a conjunctival nodules demonstrating giant cell
and noncaseating granuloma C. Enlarged prolapsable lacrimal gland D. medium and
small keratic precipitates, anterior chamber reaction, and posterior
synechiae. E. Peripheral so called candlewax dripping in sarcoid uveitis F. Solitary
choroidal granuloma.

105. Investigations…
1. Negative tuberculin skin test in a BCG-vaccinated
patient or in a patient having had a positive
tuberculin skin test previously.
2. Elevated serum ACE levels.
3. Chest X-ray showing bilateral hilar
lymphadenopathy (BHL). Chest radiography is
abnormal in 90%.
4. Abnormal liver enzyme tests.
5. High-resolution Chest CT scan in patients with a
negative chest X-ray result.

106. Investigations…
• Fibreoptic bronchoscopy with biopsy.
• Thoracic endosonography (endobronchial or
oesophageal) with needle aspiration has been shown
in a large trial to be a more sensitive technique than
bronchoscopic biopsy.
• Miscellaneous biopsy sites include superficial lymph
nodes or skin lesions, conjunctival nodules and
lacrimal glands. If the eye is involved, vitreous biopsy
is very useful (e.g. CD4/CD8 ratio).
• Other imaging modalities include MRI cardiac and
CNS imaging, PET scanning and occasionally whole-
body gallium scanning.

107. Investigations…
• Calcium and vitamin D levels may be abnormal
depending on disease pattern and level of
activity.
• Hypercalciuria is common.
• Pulmonary function testing.
• Bronchoalveolar lavage fluid (BALF) shows
characteristic changes; CD4/CD8 T cell ratios
are a key indicator.

108. Treatment…
• Corticosteroids have conventionally been the major
treatment modality in ocular and systemic
sarcoidosis.
• Treatment should be initiated aggressively to
prevent sight-threatening complications.
• Treatment of anterior and intermediate uveitis is
approached in a stepwise fashion as for idiopathic
inflammation.
• Posterior uveitis generally requires systemic steroids
and occasionally immunosuppressive agents such as
methotrexate, azathioprine, ciclosporin and tumour
necrosis factor (TNF) inhibitors (e.g. adalimumab).

109. Treatment…
• Peripheral retinal neovascularization can be
treated with scatter photocoagulation to
ischaemic areas demonstrated by FA.
• Cystoid macular oedema may respond to a
topical NSAID.
• Cataract and glaucoma may require treatment;
inflammation should be suppressed prior to
surgery, preferably for at least 3 months in the
case of cataract surgery.

110. Multiple Sclerosis
• Uveitis is 10 times more common in MS patients than in
the general population.
• The frequency of uveitis in patients with MS is reported to
be as high as 30%, and the onset of uveitis may precede the
diagnosis of MS in up to 25% of patients and by 5–10
years.
• MS usually affects white women 20–50 years of age, and
intermediate uveitis is the most common manifestation of
MS-associated uveitis. Up to 95% of cases are bilateral.
• Up to 15% of patients with pars planitis may eventually
develop MS. Intermediate uveitis appears to be of milder
severity in MS than in idiopathic cases.

111. Multiple Sclerosis
• Most patients develop mild vitritis with
periphlebitis. Periphlebitis in MS is not clearly
related to optic neuritis, systemic exacerbations,
or disease severity.
• HLA-DR15 appears to be associated with the
combination of MS and uveitis.
• It is unclear whether treatment of MS with
interferon has any effect on intermediate uveitis;
however, reports of macular edema associated
with fingolimod therapy for MS are of interest.

112. Tubulointerstitial nephritis
• Tubulointerstitial nephritis and uveitis (TINU) is an
uncommon disorder of immune origin characterized by a
combination of acute tubulointerstitial nephritis and
uveitis.
• It typically occurs in adolescent girls; renal disease usually
precedes uveitis.
• Bilateral non-granulomatous (occasionally
granulomatous) anterior uveitis that usually responds well
to topical steroids.
• Disc and macular oedema may occur. Many cases are
relapsing and some require systemic steroids or
immunosuppressive therapy. Intermediate, posterior or
panuveitis may occur.

113. IgA nephropathy
• IgA nephropathy (Berger disease) is a relatively
common kidney disease in which
immunoglobulin A is deposited in the
glomerular mesangium.
• Presentation is usually at age 16–35 with
recurrent haematuria, often associated with an
upper respiratory tract infection, but may be
asymptomatic.
• AAU and other ocular inflammatory
phenomena may occur but are uncommon.