SYMPATHETIC OPHTHALMIA
Dr.Rajesh Babu B
MS, FMRF, MSc (CEH) DLSHTM, UK
Consultant
Uveitis & Ocular Immunology
Ocular Epidemiology & Community Eye Health
Narayana Nethralaya , Bangalore
SYMPATHETIC OPHTHALMIA
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Definition
Epidemiology
Theories of pathogenesis
Clinical manifestations
Symptoms
Examination findings
Complications
Pathology
Differential diagnosis
Fluorescein angiography findings
Treatment
Prognosis
Definition
• Sympathetic ophthalmia is defined as a bilateral
granulomatous panuveitis that occurs after the
uvea of one eye is subjected to a penetrating
injury due to either accidental trauma or
surgery.
• The term “sympathetic ophthalmia” was coined
by Mackenzie in the first half of the 19th century.
Epidemiology
• Incidence:
– Prior to 1950 ~ 2% (16% during Civil War)
– Retrospective studies: 0.2 - 0.5% after penetrating
trauma and 0.01% after intraocular surgery.
– Prospective study: 0.03/100,000
• Inheritance: No proven role. Postulated
correlation of HLA DRB1, DQA1 reported in
Japanese and UK series
• Gender: M = F postsurgical; M > F traumatic
• No racial predisposition
• All ages, possibly increasing in the elderly
Albert D, Diaz-Rohena R. A historical review of sympathetic ophthalmia and its epidemiology. Survey Ophthalmology 1989; 34: 1–14.
Kilmartin D, Dick A, Forrester J. Prospective surveillance of sympathetic ophthalmia in the UK and Republic of Ireland . Br J Ophthalmology 2000; 84: 259–63.
Prevalence
• Difficult to measure because it has always
been a relatively rare disease; as a result of
improvements in modern surgical and medical
treatment, it has become even more
uncommon.
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Changing Trends in Sympathetic Ophthalmia
TREND
HISTORICAL
CURRENT
Cause
Post trauma
Post surgery (esp. vitreoretinal)
Patients
Males and children (reflecting trauma peaks)
No gender preference (reflects positive impact of
injury prevention programs) and increasingly elderly
patients (reflects impact of ocular surgery)
Incidence
Considered disappearing 30 years ago
Probably increasing (under-diagnosed?)
Onset
For 65%, within 2-8 weeks; for 90% < 1yr
Many delayed presentations as well
Presentation
Granulomatous panuveitis
Any clinical uveitis
Inciting Eye
Enucleation within 2 weeks of trauma for
prevention of SO
Enucleation solely for the prevention of SO is
questionable
Visual Prognosis
Poor
Reasonable due to modern
immunosuppression
Theories of pathogenesis
• It has long been thought that uveal pigment is somehow
released by trauma and incites an inflammatory reaction.
• Neurogenic (extension from one eye to the other through
the optic nerves or via the ciliary nerves)
• Infectious theory: tuberculosis, Actinomyces, Rickettsia,
virus
• Combined ciliary nerve and bacterial theories
• Allergic or Anaphylactic theory: Autoimmunity against
uveal melanin, uveal melanocytes, retinal pigment
epithelium, or retinal antigens (S & IRBP)
• Role of Ocular Immune Privilege
Role of Ocular Immune Privilege
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Not all cases of ocular injury progress to SO
Ocular immune privelege has a role to play
Antigen released by the trauma induces ACAID
An Immunosupressive Microenvironment
Evolutionary protective mechanism
Thwarts any process that endangers vision
•Streilein JW (ed):Ocular Immune Privilege-Protection that preserves sight. Karger Gazzete. The eye in focus. No.64
http://www.karger.ch/gazette/64/streilein/index.htm accessed 1 Feb 2010
•Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73.
Clinical manifestations
• The interval between ocular injury and the
onset of sympathetic ophthalmia has been
reported to be as short as 5 days or as long as
66 years.
• In general, 65% of sympathetic ophthalmia
cases occur 2 weeks to 2 months after injury
• 90% occur before 1 year.
Clinical manifestations
• The traumatized eye in SO, either from an
accidental penetrating injury or following
intraocular surgery, characteristically exhibits
a persistent granulomatous inflammatory
reaction.
• SYMPTOMS
• THE EARLIEST SYMPTOM MAY BE DECREASED ACCOMMODATION
AND THE EARLIEST SIGN, RETROLENTICULAR FLARE AND CELLS IN
THE FELLOW EYE.
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• Irritable red eye with or without decreased vision.
• Other symptoms include photophobia & transient hyperopia.
• Cutaneous and neurologic changes (alopecia, poliosis, vitiligo,
dysacousia, tinnitus, vertigo, and cells in the cerebrospinal fluid),
which are classically associated with Vogt-Koyanagi-Harada
syndrome, may rarely accompany SO.
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On examination
Bilateral granulomatous panuveitis:
• Mutton fat keratic precipitates,
• Cells and flare in the anterior chamber, vitreous
cells,
• Isolated or confluent patches of yellow-white
choroidal infiltrates.
• If undetected it eventually progresses to
panuveitis with exudative retinal detachment.
Dalen Fuch Nodules
• Although not
pathognomonic, are
quite suggestive of SO
and may indicate a more
severe stage of SO.
• Dalen-Fuchs nodules are
small, discrete,
yellowish infiltrates at
the level of the RPE that
are most often seen and
are largest in the retinalchoroidal periphery.
Complications
• Extensive anterior and posterior synechiae,
pupillary membrane formation.
• Rubeosis, glaucoma, cataract
• Papillitis, optic atrophy
• Exudative retinal detachment,
• Chorioretinal scarring,
• Choroidal neovascularization,
• Phthisis.
Pathology
• The inflammatory changes in the exciting and
sympathizing eyes are the same, except for features of
trauma in the exciting eye.
• Granulomatous Uveitis –
• The minimal and classic changes for the
histopathologic diagnosis of sympathetic ophthalmia
are diffuse lymphocytic infiltration of the uveal tract
with epithelioid cell nests, pigment phagocytosis by
the epithelioid cells, absence of necrosis, and sparing
of the retina and choriocapillaris by the
granulomatous process.
CASELLA, Antônio Marcelo Barbante et al. Sympathetic ophthalmia - histopathological correlation with
fluorescein and indocyanine green angiography: case report. Arq. Bras. Oftalmol. [online]. 2008, vol.71, n.6
[cited 2010-01-31], pp. 886-889 http://www.scielo.br/img/revistas/abo/v71n6/a25fig02.jpg
• The uveal tract is usually diffusely thickened
(massively in some) by an infiltration of
lymphocytes in which various numbers of
nests of epithelioid cells displaying pigment
phagocytosis are present.
Dalen-Fuch's nodules
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Small, deep-yellow white lesions
called Dalen-Fuch's nodules in the
choroid. These nodules occur
mostly in the periphery and consist
of epithelioid cells located just
internal to Bruch's membrane.
Histopathologically they are nodular
aggregations of lymphocytes and
epitheloid cells with proliferation of
retinal pigment epithelium.
Dalen-Fuchs nodules are composed
of a mixture of histiocytes,
depigmented retinal pigment
epithelial cells with lipofuscin and
desmosomes, and small numbers of
T lymphocytes of the suppressorcytotoxic subset
THE CHORIOCAPILLARIS IS
TYPICALLY SPARED.
Eosinophils are a feature of
sympathetic uveitis, especially in
early cases.
ATYPICAL PATHOLOGIC FEATURES
– Focal nongranulomatous to diffuse nonnecrotizing
granulomatous infiltrate
– Focal choriocapillary involvement
– Chorioretinal adhesions
– Retinal detachment
– Optic atrophy
– Retinal perivasculitis
– Mild inflammatory involvement of the meninges
– Preferential anterior segment inflammation
• Multiple areas of Early
Hyperfluorescence and
leakage at the level of the
RPE (Dalen-Fuchs
nodules) and the choroid
(choroidal granuloma) in
most cases, very similar
to those seen in Harada's
disease.
• These sites (“window
defects”) correspond to
the Dalen-Fuchs nodules
observed clinically.
Presumably the hyperfluorescent or hypofluorescent nature in the early phase is determined
by whether the Dalen-Fuchs nodules have an intact or a disrupted overlying RPE.
FLUORESCEIN ANGIOGRAPHY
If there is a serous retinal
detachment, pooling of dye in the
late frames of the angiogram can be
observed.
The FFA of the eye with inactive S.O
will characteristically have scattered
multiple window defects.
CASELLA, Antônio Marcelo Barbante et al. Sympathetic ophthalmia - histopathological
correlation with fluorescein and indocyanine green angiography: case report. Arq. Bras.
Oftalmol. [online]. 2008, vol.71, n.6 [cited 2010-01-31], pp. 886-889
Hyperemic disc with blurred disc margins
and tortuous dilated vessels
Disc hyperfluorescence with
blurring of margins in late phase
(C and D) FFA showing multiple areas (encircled) of pinhead-sized leaks (arrow)
Sampangi R, Venkatesh P, Mandal S, Garg SP. Recurrent neovascularization of the disc in sympathetic ophthalmia. Indian J
Ophthalmol 2008;56:237-9
DIFFERENTIAL DIAGNOSIS
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Vogt-Koyanagi-Harada syndrome
Phacoanaphylactic uveitis
Sarcoidosis
Chronic idiopathic uveitis
Other granulomatous uveitis induced by
mycobacteria or fungi
Differences between SO & VKH
Sympathetic Ophthalmia
Vogt-Koyanagi-Harada Syndrome
Age
All ages
20-50 years of age
Racial predisposition
None
Asian and Black
Penetrating trauma
Almost always present
Absent
Skin changes
Uncommon or unrelated
Common (60-90%)
CNS findings
Uncommon
Common (85%)
Hearing dysfunction
Uncommon
Common (75%)
Retinal serous detachment
Uncommon
Frequently seen
Choriocapillaris
involvement
Usually absent
Frequently seen
CSF findings
Usually normal
Pleocytosis (84%)
Treatment
• Role of Enucleation of the Inciting Eye
– Conventionally said to prevent SO if within 2 weeks of
inciting event
– Controversial whether enucleation is of benefit once SO
develops
• Pharmacological Therapy
– Current:
• Corticosteroids - oral, periocular, intraocular, topical
• Steroid-sparing agents - Imuran, Cellcept, Cyclosporine A
• Prophylactic steroids do not prevent sympathetic uveitis but can
improve the visual outcome and can alter the histopathologic
features.
Prognosis
• The relapsing nature of SO and the potential toxicity of
treatment modalities warrant a careful long-term follow up
of patients with this disease.
• Spontaneous improvement rarely occurs and if left
untreated, SO leads to loss of vision and phthisis bulbi.
• The use of corticosteroid and other immunosuppressive
agents together with the advancements in microsurgical
techniques for wound repair have improved the prognosis
of SO,
• 50% of patients achieving a final visual acuity of 20/40 or
better in at least 1 eye.
• Cataract, secondary glaucoma, and chronic maculopathy
are the major causes of visual loss.
Thank You
drrajeshbabu@yahoo.com