SYMPATHETIC OPHTHALMIA

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SYMPATHETIC OPHTHALMIA 

• Dr.Rajesh Babu B
• MS, FMRF, MSc (CEH) DLSHTM, UK
• Consultant
• Uveitis Ocular Immunology
• Ocular Epidemiology Community Eye Health
• Narayana Nethralaya , Bangalore

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SYMPATHETIC OPHTHALMIA 

• Definition
• Epidemiology
• Theories of pathogenesis
• Clinical manifestations
• Symptoms
• Examination findings
• Complications
• Pathology
• Differential diagnosis
• Fluorescein angiography findings
• Treatment
• Prognosis

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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.

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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 gt 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. Surve
y Ophthalmology 1989 34 114. Kilmartin D,
Dick A, Forrester J. Prospective surveillance of
sympathetic ophthalmia in the UK and Republic of
Ireland . Br J Ophthalmology 2000 84 25963.
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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 lt 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
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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

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Role of Ocular Immune Privilege

• 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.ht
  m accessed 1 Feb 2010
• Streilein JW (ed) Immune Response and the Eye.
  Chem Immunol. Basel, Karger, 1999, vol 73.

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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.

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Clinical manifestations

• The traumatized eye in SO, either from an
  accidental penetrating injury or following
  intraocular surgery, characteristically exhibits
  a persistent granulomatous inflammatory reaction.

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• SYMPTOMS
• THE EARLIEST SYMPTOM MAY BE DECREASED
  ACCOMMODATION AND THE EARLIEST SIGN,
  RETROLENTICULAR FLARE AND CELLS IN THE FELLOW
  EYE.
•  
• 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.
•  

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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
  retinal-choroidal periphery.

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Complications

• Extensive anterior and posterior synechiae,
  pupillary membrane formation.
• Rubeosis, glaucoma, cataract
• Papillitis, optic atrophy
• Exudative retinal detachment,
• Chorioretinal scarring,
• Choroidal neovascularization,
• Phthisis.

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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.

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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
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• 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.

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Dalen-Fuch's nodules

• 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
  suppressor-cytotoxic subset
• THE CHORIOCAPILLARIS IS TYPICALLY SPARED.
• Eosinophils are a feature of sympathetic uveitis,
  especially in early cases.

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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

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• 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.
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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 
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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
200856237-9
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DIFFERENTIAL DIAGNOSIS

• Vogt-Koyanagi-Harada syndrome
• Phacoanaphylactic uveitis
• Sarcoidosis
• Chronic idiopathic uveitis
• Other granulomatous uveitis induced by
  mycobacteria or fungi

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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)
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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.

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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.

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Thank You
drrajeshbabu_at_yahoo.com