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

2. SYMPATHETIC OPHTHALMIA
Definition
Epidemiology
Theories of pathogenesis
Clinical manifestations
Symptoms
Examination findings
Complications
Pathology
Differential diagnosis
Fluorescein angiography findings
Treatment
Prognosis

3. 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.

4. Epidemiology Incidence:
Prior to 1950 ~ 2% (16% during Civil War)
Retrospective studies: % 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.

5. 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.

6. Changing Trends in Sympathetic Ophthalmia
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

7. 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

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

9. 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.

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

11. 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.  

12. 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.

13. 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.

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

15. 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.

16. CASELLA, Antônio Marcelo Barbante et al
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  ], pp  

17. 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.

18. 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.

19. 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

20. 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.

21. 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  ], pp  

22. Disc hyperfluorescence with blurring of margins in late phase
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

23. DIFFERENTIAL DIAGNOSIS
Vogt-Koyanagi-Harada syndrome
Phacoanaphylactic uveitis
Sarcoidosis
Chronic idiopathic uveitis
Other granulomatous uveitis induced by mycobacteria or fungi

24. 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
Common (75%)
Retinal serous detachment
Frequently seen
Choriocapillaris involvement
Usually absent
CSF findings
Usually normal
Pleocytosis (84%)

25. 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.

26. 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.

27. Thank You