after enucleation, orbital exenteration or one of its modifications may be advisable.

Patients who have known systemic metastases, either before or after enucleation or other treatment, have a poor prognosis. In such a case, local resection, palliative irradiation, chemotherapy, or immunotherapy may be used. The aim of the ocular oncologist at present is to reach an accurate diagnosis and achieve local control of the tumor prior to its dissemination. However an ultimate cure for this dreadful disease will require collaboration between ophthalmologists and researchers in the basic sciences, immunology and medical oncology.

REFERENCES

Cohen VM, Carter MJ, Kemeny A, et al: Metastasis-free survival following treatment for uveal melanoma with either stereotactic radiosurgery or enucleation. Acta Ophthalmol Scand 81:383–388, 2003.

Cree IA, Di Nicolantonio F, Neale MH: Chemotherapy of uveal melanoma. In: Jager MJ, Niederkorn JY, Ksander BR, eds: Uveal melanoma: a model for exploring fundamental cancer biology. London, Taylor & Francis, 2004.

Damato BE: Local resection of uveal melanoma. Bull Soc Belge Ophthalmol 248:11–17, 1993.

Gragoudas ES, Lane AM, Regan S, et al: A randomized controlled trial of varying radiation doses in the treatment of choroidal melanoma. Arch Ophthalmol 118:773–778, 2000.

Oosterhuis JA, Journee-De Korver HG, Kakebeeke-Kemme HM, et al: Transpupillary thermotherapy in choroidal melanomas. Arch Ophthalmol 113:315–321, 1995.

Shields CL, Shields JA, Kiratli H, et al: Risk factors for growth and metastasis of small choroidal melanocytic lesions. Ophthalmology 102:1351– 1361, 1995.

Shields CL, Shields JA, Perez N, et al: Primary transpupillary thermotherapy for small choroidal melanoma in 256 consecutive cases: outcomes and limitations. Ophthalmology 109:225–234, 2002.

Singh AD, Rundle PA, Rennie IG: Uveal melanoma. In: Williams C, Chief ed: Evidence based oncology. London, BMJ, 2003.

175 SYMPATHETIC OPHTHALMIA

360.11

(Sympathetic Uveitis, Sympathetic

Ophthalmitis)

F. Hampton Roy, MD, FACS

Little Rock, Arkansas

Sympathetic ophthalmia, is a rare, bilateral, granulomatous panuveitis that occurs a few days to many years after accidental penetrating ocular injury or ocular surgery. Both the injured, eye and the fellow, or ‘sympathizing,’ eye are affected. In nearly all cases, injury to and incarceration of uveal tissues are characteristic features in the exciting eye. It is potentially blinding and is the most feared of all ocular complications in ophthalmology.

The interval from trauma to onset of inflammation may be as short as 5 days or as long as 66 years. Most cases occur within 1 year after the injury (90%). Inflammation often is present in the injured eye at the time of the insult, but the uninjured eye develops sympathetic inflammation at a later date. Patients present with pain, photophobia, and decreased vision in the sympathizing eye. The inflammation is granulomatous with mutton-fat precipitates, iris nodules, anterior segment cell and flare, and Dalen–Fuchs nodules, representing aggregates of epithelioid cells at the level of Bruch’s membrane. These Dalen– Fuchs nodules may be scattered throughout the fundus. Exudative retinal detachment, early optic disk edema, or late atrophy may be present. Occasionally, sympathetic ophthalmia may have systemic manifestations similar to those of Vogt– Koyanagi–Harada syndrome; these include cerebrospinal fluid pleocytosis; meningismus; skin manifestations such as alopecia, vitiligo, and poliosis; and dysacusis.

The cause of sympathetic ophthalmia is unknown. The common predisposing factor in the vast majority of cases is the presence of penetrating injury in which wound healing is complicated by incarceration of the iris, ciliary body or choroid. It is believed that a genetically predisposed host incites a cellmediated immune response against some unknown uveal antigen or antigens. Experimental studies have shown that patients with sympathetic ophthalmia have lymphocytes that are sensitized to some component or components of uvealretinal extracts. Retinal S-antigen, interphotoreceptor retinoidbinding protein, and retinal and choroidal melanocyte antigens have all been shown experimentally to produce uveitis similar to sympathetic ophthalmia in animal models. This immune response results in chronic granulomatous inflammation in both eyes.

The incidence of sympathetic ophthalmia is uncommon to rare, affecting 0.1% to 0.2% of patients with penetrating ocular injuries and 0.01% of patients who have undergone intraocular surgery. Sympathetic ophthalmia affects individuals of all ages. There is no race or gender predilection, although ocular trauma is much more common in men. Sympathetic ophthalmia can occur at any age, but cases tend to cluster in the first decade of life and in early adulthood, when trauma is more common, and in the sixth and seventh decades of life, when ocular surgical procedures become more common.

COURSE/PROGNOSIS

Untreated sympathetic ophthalmia runs a long, variable, and complicated course, with episodes of acute inflammation followed by long periods of quiescence lasting from several months to years. However, recurrent inflammation occurs in as many as 60% of patients with sympathetic ophthalmia. This chronic recurrent inflammation can lead to irreversible ocular damage and phthisis bulbi. With aggressive systemic corticosteroid or immunosuppressive therapy, or both, the prognosis improves, with more than 50% of eyes maintaining visual acuity of 20/60 or better.

cells, and occasional giant cells. Pigment often is found within the epithelioid and giant cells. Nodular clusters of these epithelioid cells may be found between the retinal pigment epithelium and Bruch’s membrane; these appear yellow-white clinically and are called Dalen–Fuchs nodules. In the majority of cases, the inflammation spares the choriocapillaris and retina. Necrosis of the inflamed tissues is characteristically absent.

Clinical signs and symptoms

●History of penetrating eye injury.

●Granulomatous panuveitis.

●Mutton-fat precipitates.

●Inflammatory iris nodules (Koeppe and Busacca).

●Vitritis.

●Dalen–Fuchs nodules in choroid (especially inferiorly).

●Creamy yellow-white lesions below the retinal pigment epithelium.

●Later may become punched-out chorioretinal lesions of onefourth to one-half disk diameter.

●Exudative retinal detachments: shifting subretinal fluid.

●Early disk edema: late optic atrophy.

Laboratory findings

●Fluorescein angiography.

●Multiple pinpoint areas of choroidal hyperfluorescence in the posterior pole.

●Enlarge over time.

●Leak and coalesce late in subretinal fluid if there is exudative retinal detachment.

●Late disk leakage.

●Ophthalmic ultrasonography.

●Medium to high internal reflectivity thickening of choroid of posterior pole.

●Exudative retinal detachments with subretinal fluid.

●Laboratory testing.

●None.

●HLA: DR4/DQw3 associated but not helpful in diagnosis.

TREATMENT

Aggressive systemic corticosteroid therapy is the cornerstone of the treatment of sympathetic ophthalmia.

Systemic

●Corticosteroids (mainstay of therapy for sympathetic ophthalmia).

●Prednisone 1 to 2.5 mg/kg/day with slow tapering over 6 months.

●Supplement with topical and periocular corticosteroids.

●Immunosuppressive therapy (if corticosteroids cannot be tolerated or fail).

●Cyclosporin A 5 mg/kg/day PO.

●Azathioprine 1 to 2.5 mg/kg/day PO.

●Methotrexate (low dose) 5 to 30 mg/week PO.

●Cyclophosphamide 1 to 2 mg/kg/day PO.

Local

Local therapy supplements systemic therapy.

●Topical therapy:

●Prednisolone 1% (intensive; hourly, if necessary);

●Mydriatics: cyclopentolate, homatropine, or atropine.

●Periocular therapy: corticosteroids.

●Triamcinolone 40 mg. Repeat up to four times in first 4 to 8 weeks for severe inflammation. Supplements systemic therapy;

●Intravitreal steroid injection.

Surgical

●Enucleation of injured eye.

●Within 2 weeks after penetrating injury.

●If severely injured, unsalvageable eye with poor vision.

●May be helpful in the prevention of sympathetic ophthalmia.

●Enucleation of exciting eye after the onset of inflammation in the sympathizing eye probably not beneficial.

PROPHYLAXIS

Early enucleation of the severely injured eye with poor vision is the best way to prevent the onset of sympathetic ophthalmia. The decision to enucleate an eye that has been severely and irreversibly injured and has severe visual loss is an easy decision to make; however, in cases in which the eye has useful vision, has had minimal injury, and can be salvaged, most ophthalmologists do not advocate enucleation because of the extremely low incidence of sympathetic ophthalmia. It has been suggested by many that enucleation, if it is to be done, should be performed within 2 weeks of the injury. Once sympathetic ophthalmia begins, there does not appear to be a visual benefit to enucleation of the injured eye. In some cases, the exciting eye eventually provides better visual acuity, so enucleation could deprive the patient of visual potential.

REFERENCES

Buller AJ, Doris JP, Bonshek R, et al: Sympathetic ophthalmia following severe fungal keratitis. Eye 12:261, 2006.

Chan CC: Relationship between sympathetic ophthalmia, phacoanaphylactic endophthalmitis, and Vogt-Koyanagi-Harada disease. Ophthalmology 95:619–624, 1988.

Chan CC, Roberge FG, Whitcup SM, Nussenblatt RB: 32 cases of sympathetic ophthalmia: a retrospective study at the National Eye Institute, Bethesda, Md, from 1982–1992. Arch Ophthalmol 113:597–600, 1995.

Chan RV, Seiff BD, Lincoff HA, et al: Rapid recovery of sympathetic ophthalmia with treatment augmented by intravitreal steroids. Retina 26:243–247, 2006.

Freidlin J, Pak J, Tessler, HH, et al: Sympathetic ophthalmia after injury in the Iraq war. Ophthal Plast Reconstr Surg 22:133–134, 2006

Jonas JB, Back W, Sauder G, et al: Sympathetic ophthalmia in vater association combined with persisting hyperplastic primary vitreous after cyclodestructive procedure. Eur J Ophthalmol 16:171–172, 2006.