Sympathetic ophthalmia

Sympathetic ophthalmia (SO) is a granulomatous uveitis (a kind of inflammation) of both eyes following trauma to one eye. It can leave the patient completely blind. Symptoms may develop from days to several years after a penetrating eye injury. See also the reviews by Damico et al. (2005), Chu and Foster (2002), and Friedlaender et al. (2001).

History
The descriptions of sympathetic ophthalmia can be found in Greek texts (Albert and Diaz-Rohena, 1989), modern understanding of SO derives from the works of William MacKenzie, who characterized and named the disease sympathetic ophthalmitis. At that time, oral mercury and leeches applied to the conjunctiva were the treatments of choice for SO (MacKenzie, 1954).

It is thought that Louis Braille, who injured his left eye as a child, lost vision in his right eye due to SO (Kaden 1977). James Thurber's adult blindness was also diagnosed as sympathetic ophthalmia deriving from the loss of an eye when he was six years old.

Clinical features
Floating spots and loss of accommodation are among the earliest symptoms. The disease may progress to severe iridocyclitis with pain and photophobia. Commonly the eye remains relatively painless while the inflammatory disease spreads through the uvea. The retina, however, usually remains uninvolved, although perivascular cuffing of the retinal vessels with inflammatory cells may occur. Papilledema, secondary glaucoma, vitiligo, and poliosis of the eyelashes may accompany SO.

In approximately 80% of cases, the uveitis appears within 2-12 weeks after injury, and 90% occur within 1 year from the time of injury. However, isolated cases as early as 1 week (2003) or as late as 66 years after initial injury have been reported (Zaharia et al., 1984).

Epidemiology
Sympathetic ophthalmia is rare, affecting 0.2% to 0.5% of non-surgical eye wounds, and less than 0.1% of surgical penetrating eye wounds. There are no gender or racial differences in incidence of SO.

Pathophysiology
Sympathetic ophthalmia is currently thought to be an autoimmune inflammatory response toward ocular antigens, specifically a delayed hypersensitivity to melanin-containing structures from the outer segments of the photoreceptor layer of the retina. The immune system, which normally is not exposed to ocular antigens, is introduced to the contents of the eye following traumatic injury. Once exposed, it senses these antigens as foreign, and begins attacking them. The onset of this process can be from days to years after the inciting traumatic event.

Diagnosis
Diagnosis is clinical, seeking a history of eye injury. An important differential diagnosis is Vogt-Koyanagi-Harada syndrome (VKH), which is thought to have the same pathogenesis, without a history of surgery or penetrating eye injury.

Still experimental, skin tests with soluble extracts of human or bovine uveal tissue are said to elicit delayed hypersensitivity responses in these patients. Additionally, circulating antibodies to uveal antigens have been found in patients with SO and VKH, as well as those with long-standing uveitis, making this a less than specific assay for SO and VKH.

Prevention and treatment
Definitive prevention of SO requires prompt (within the first 7 to 10 days following injury) enucleation of the injured eye. Evisceration—the removal of the contents of the globe while leaving the sclera and extraocular muscles intact--is easier to perform, offers long-term orbital stability, and is more aesthetically pleasing. There is concern, however, that evisceration may lead to a higher incidence of SO compared to enucleation (reviewed by Migliori, 2002). Several retrospective studies involving over 3000 eviscerations, however, have failed to identify a single case of SO.

Because SO is so rarely encountered following eye injury, even when the injured eye is retained, the first choice of treatment may not be enucleation or evisceration, especially if there is a chance that the injured eye may regain some function (Gurdal et al., 2002). Additionally, with current advanced surgical techniques, many eyes once considered nonviable now have a fair prognosis.

Immunosuppressive therapy is the mainstay of treatment for SO. When initiated promptly following injury, it is effective in controlling the inflammation and improving the prognosis. Mild cases may be treated with local application of corticosteroids and pupillary dilators. More severe or progressive cases require high-dose systemic corticosteroids for months to years. Patients who become resistant to corticosteroids or develop side effects of long-term corticosteroid therapy (osteoporosis and pathologic fractures, mental status changes, etc.), may be candidates for therapy with chlorambucil, cyclophosphamide, or ciclosporin.

Associated conditions

 * Vogt-Koyanagi-Harada syndrome