Sympathetic ophthalmia (SO) is an uncommon, devastating disease which is difficult to treat once started. Ophthalmic surgeons, whether they have repaired a perforated globe or performed a pars plana vitrectomy, consider the development of this autoimmune uveitis a most serious sight threatening event. This is a disease in which a patient’s good eye became diseased because the patient’s other eye was penetrated or perforated and suffered uveal damage. SO is a bilateral disease. Its name was coined by Sir. William Mackenzie [1], a nineteenth century ophthalmologist who used history taking and keen powers of observation, aided by contact lenses in his examination of the eye. He did not use the Von Helmholtz ophthalmoscope which had just been invented. The pathology was described by Dalen in 1904 and Fuchs in 1905 [2]. Despite mankind’s march toward civilization, accidents, assaults and war are agents involved in the etiology of SO. However, intraocular surgery has replaced globe trauma as the number one cause of this disease, although this is debated in the literature.

A 5-year old boy presented to the ER of Brooklyn Eye and Ear Hospital in 1970 with complaints of pain, decreased vision, and light hurting his red left eye. As a second year ophthalmology resident, I was about to examine my first patient who had developed SO. The young boy exhibited all the findings of a granulomatous panuveitis. His right eye had been enucleated the year earlier, following a repair of a perforated globe secondary to a pencil injury. The right eye pathology slip in his chart stated perforated globe with heme and disruption of intraocular contents post-surgical repair. Our pathologist reviewed the slides and reversed the diagnosis to SO. We sent the slides to Dr. Lorenz Zimmerman at the AFIP who confirmed the diagnosis. Corticosteroids used locally and systemically brought the uveitis in his remaining eye to quiescence over several months [3]. We then tapered the steroid slowly over several more months. Our patient did quite well despite occasional flare-ups treated by reinstitution of steroid therapy. Additionally, no evidence of sarcoid, TB, toxoplasmosis, Vogt Koyanagi Harada (VKH) syndrome, herpetic disease, or syphilis was found.

Tempus fugit and the year is now 2015. I had become a 75-year old Jurassic park ophthalmologist about to retire from an academic position at The State University of New York—(SUNY) Downstate Medical Center. A 40-year old male from the Caribbean presented to our eye clinic at Kings County Hospital Center in Brooklyn, NY. Ocular exam revealed a bilateral granulomatous panuveitis. Our patient had been punched in his left eye (injured eye) some 4 weeks earlier, and had not sought medical attention until arriving in Brooklyn when his symptoms began. The exam of his OS revealed prolapsed uveal tissue under the conjunctiva anterior to the insertion of the superior rectus tendon. The anterior chamber was slightly deeper OS than OD. No hyphema was present. Phacodonesis was present. No cataract or lens capsule injury was apparent. A granulomatous panuveitis was present OU, more intense in the OD (the sympathizing eye) than in the OS (the injured inciting eye) [4]. No confirmatory findings of Vogt–Koyanagi–Harada (VKH), sarcoid, TB, herpes, toxoplasmosis, or syphilis were found. A diagnosis of SO was made and steroid treatment commenced.

The ophthalmologist must be fastidious in evaluating the proptotic ecchymotic patient with subconjunctival heme. In addition to orbital fracture, occult rupture of the globe must be ruled out. Careful globe exploration surgery should be done when there is a suspicion of globe rupture, especially in the presence of low intraocular pressure, lid laceration and/or intraocular heme on the injured side.

The question of who should repair an orbital fracture is important. While ENT and oral maxillary surgeons [5] may know how to repair an orbital fracture, are they able to identify a globe penetration or perforation? If this surgery is done by other than an oculoplastic surgeon, should careful ophthalmic evaluation be done before our colleagues in another specialty perform the repair?

Sympathetic ophthalmia SO is a bilateral granulomatous panuveitis secondary to traumatic or surgically induced uveal damage. The disease may present as early as 5 days or as late as 66 years post injury [6]. An autoimmune etiology is suggested by the lymphocyte, macrophage, and giant cell response in the uveal tract [7]. Genetic makeup [8] (i.e. HLA-DR4, HLA-DQw3, and HLA-DRw53) may increase the susceptibility to developing SO.

The clinical exam of the SO patient may reveal mutton fat keratic precipitates (KPT), anterior chamber flare and cells, posterior synechiae, cyclitis with decreased accommodation, vitritis, choroiditis with various degrees of choroidal thickening, Dalen-Fuchs Nodules, papillitis, serous detachments of the retina, occasional areas of choroidal and retinal vasculitis, cataracts, and glaucoma. The Dalen-Fuchs Nodules can be found in some 25% of SO patients. The nodule is not specific for SO, as it can be found in VKH and sarcoid patients as well. The Dalen-Fuchs Nodules [9] appear as yellow white spots 60–70 um in diameter. They are located near the equator mostly. Histologically, these nodules are made up of histiocytes and pigment epithelial cells. While inflammation of the choriocapillaris is not the usual finding, it is sometimes found. Several other panuveitis diseases must be considered in the differential diagnosis of SO including VKH, sarcoid, tuberculosis, toxoplasmosis, syphilis, herpes simplex and zoster, Behcet’s disease, and intraocular lymphoma. The history of no accidental or surgical trauma antecedent to the “uveitis” developing is usually the case in these entities.

The VKH patient may have headache, meningismus, and dysacousia accompanying or preceding the uveitis. Such is not usually the case in SO. As time goes on, the VKH patient may develop poliosis, alopecia, and vitiligo. Asian, Middle Eastern, Native American, and Hispanic people are the patient populations mostly involved. The VKH patient is more likely to have bilateral exudative retinal detachments than is the SO patient. The VKH patient is more likely to demonstrate involvement of the choriocapillaris than is the SO patient.

The sarcoid patent may present with enlarged lacrimal, parotid and/or salivary glands. A fever may be present. Enlarged parotid glands and fever is known as Heerfordt’s syndrome. Erythema nodosum is sometimes present as is lupus pernio on occasion. Hilar lymphadenopathy on chest X-ray and other pulmonary findings are often seen. Noncaseating granulomas of the conjunctiva can appear as chalazia. The sarcoid granuloma may even be present in the bundle of His and cause bradycardia. An elevated angiotensin-converting enzyme level is sometimes found. The ocular exam will sometimes reveal granulomatous panuveitis with a multifocal choroiditis. Candle wax drippings near the veins will outline periphlebitis.

The patient with tuberculosis may have active tuberculosis or TB in the past. A PPD test would be positive (usually) and might even have incited the uveitis. An interferon gold test would be positive. Evidence of pulmonary infiltration, and scarring, particularly in the upper lobes, might be present. Acid fast bacilli may be present in the sputum. A solitary choroidal granuloma or a multifocal choroiditis can be present. Periphlebitis of the retinal veins is another feature.

The toxoplasmosis patient may have a history of exposure to cats. The mother of the patient may have been exposed to cats as well. The eating of undercooked meats and unclean vegetables are also etiological factors. The chorioretinitis is sometimes bilateral as can be an anterior uveitis. An old pigmented chorioretinal scar may be near a new yellow chorioretinal lesion seen hazily through the dense fog of a vitritis (headlight in the fog).

Syphilis, the great masquerader can present with nongranulomatous as well as granulomatous uveitis. Ocular disease is usually seen during the secondary stage, but it can be seen in all three stages. When the diagnosis of ocular syphilis is made, HIV should be ruled out and vice versa as there may be overlapping risk factors. The patient with secondary syphilis presents with a generalized maculopapular rash that involves the palms and soles. A positive VDRL (earlier) and a positive FTA-ABS test (later) will be present. Many diseases including Lyme can give false positive tests for syphilis. If one performs an anterior chamber tap on a patient with iritis who has secondary syphilis, one may demonstrate by dark field microscopy the presence of Treponema pallidum. A neuroretinitis might accompany the anterior uveitis. Retinal artery and vein occlusions are sometimes seen. The treatment must be treatment for neurosyphilis.

The patient with herpes zoster (HZV) involving the eye will demonstrate the typical painful vesicular rash, usually unilateral. A panuveitis might accompany the dermatologic findings. An optic neuritis and/or an extraocular muscle problem can be present. The cornea may show dendrites (without the terminal bulbs). There is hyposensitivity of the cornea and an acute retinal necrosis occasionally can be present. The patient usually develops HZV only once. Herpes simplex types one and two can cause an iridocyclitis. The latter can be accompanied by a panuveitis occasionally. If the uveitis has not been preceded by a keratitis, the correct diagnosis of the recurrent herpetic uveitis might not be made until much later in the course of the disease. Typically, the herpes simplex patient presents with a dendritic keratitis (dendrite with terminal bulbs) and the corneal sensitivity is diminished. The anterior uveitis may be accompanied by elevated intraocular pressure. A panuveitis is occasionally accompanied by acute retinal necrosis. Viral studies of corneal scraping smears, culture, and even polymerase chain reaction testing can be confirmatory.