Case 5 -

Sympathetic Ophthalmia Sander R. Dubovy Bascom Palmer Eye Institute Miami, FL

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Clinical History This 84 year old male with a history of endophthalmitis in May, 2007 underwent pars plana vitrectomy and progressed to no light perception vision OD. The patient was lost to follow-up until the patient presented to BPEI on 9/14/07 with on week of decreased visual acuity, pain, and photophobia OS. Upon examination, the patient had a perforated corneal ulcer OD and multifocal exudative retinal detachments and disc edema OS. The patient's visual acuity was NLP OD and 20/200 OS. The patient now undergoes enucleation OD to rule out sympathetic ophthalmia. Case 5 - Figure 1 Case 5 - Figure 2 Case 5 - Figure 3 Case 5 - Figure 4 Case 5 - Figure 5 Case 5 - Figure 6 Case 5 - Figure 7 Case 5 - Figure 8 Case 5 - Figure 9 Case 5 - Figure 10 Case 5 - Figure 11 Case 5 - Figure 12 Introduction: William MacKenzie characterized and named the disease sympathetic ophthalmitis. Fuchs later described the histopathological findings of SO. Sympathetic ophthalmia is a rare disease with bilateral, diffuse, non-necrotizing granulomatous inflammation that typically occurs after penetrating ocular trauma or surgery. Although the pathogenesis is not completely understood, it is thought to be an autoimmune process that follows systemic exposure to sequestered uveal antigens. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Gross: Right eye of moderately firm consistency measuring 20 x 17 x 20 mm with 2 mm of attached optic nerve. The cornea is cloudy and measures 10.5 x 8 mm. The pupil is not well visualized. 360 degrees of corneal vasculariztion is present and extends to the central aspect of the cornea. A central area of central thinning is identified measuring 3.0 x 2.0 mm (descemetocele with ? perforation). Micro: Central area of ulceration and marked thinning. The epithelium is mostly intact. Bowman's later is largely replaced by superficial stromal scarring and vascularization. The cornea is markedly thinned centrally. A marked amount of scarring and vascularization is identified. A moderate primarily chronic inflammatory cell infiltrate is present within the corneal stroma. Descemet's membrane is variably gathered and multifocally discontinuous (presumed perforation). The endothelium is absent. Foci of PAS ositive lens capsule surrounding lenticular material are identified with surrounding necrosis and an acute inflammatory cell infiltrate. Foci of granulomatous inflammation are present in the area surrounding the necrotic portions of lens. The neural retina is poorly visualized. Foci of granulomatous inflammation are present within the uveal tissue. Pigment is variably present within the multinucleated giant cells which are present within the uveal tract. Chronic inflammatory cells including lymphocytes and plasma cells are also present in the uveal tract. An increased amount of eosinophilia is identified within the uveal tract. Differential Diagnoses: Vogt-Koyanagi-Harada (VKH) syndrome: Difficult to distinguish per pathological evaluation. Clinically VKH presents wtih alopecia, poliosis and vitiligo. No history of penetrating injury. More common in Asians and darkely pigmented individuals. VKH may be associated with signs of meningeal irritation and pleocytosis with increased protein in the CSF. Phacoanaphylaxis: Occurs in the setting of a ruptured or degenerative lens capsule and is characterized by a granulomatous antigenic reaction to lens protein. On histopathology is characterized by zonal granulomatous inflammation. Sarcoidosis: Sarcoidosis is an inflammatory multisystem granulomatous disease of unknown etiology. Up to 50% of patients have adnexal and ocular involvement. Granulomatous inflammation with Dalen Fuch's may be present. Final Diagnosis: Eye, Right: History of sympathetic ophthalmia Cornea: Ulcer with perforation Scarring and vascularization Lens: Zonal granulomatous inflammation suggestive of phacoanaphylaxis Choroid: Granulomatous inflammation consistent with sympathetic ophthalmia. Pigment laden macrophages Eosinophilia Case Discussion: Etiology: In the initial descriptions of sympathetic ophthalmia, the inciting factor was almost always a perforating wound with uveal tissue exposure. With the advent of vitreous surgery and other invasive ocular procedures, sympathetic ophthalmia is no longer solely associated with penetrating ocular trauma. In addition, recent case reports have documented sympathetic ophthalmia in patients with non- penetrating ocular procedures such as ocular contusion, cyclotherapy, laser iridectomy and proton beam irradiation and helium ion therapy for choroidal melanoma. The exact pathogenesis of sympathetic ophthalmia has not yet been clearly identified. Initially, MacKenzie postulated that the inflammatory process spreads from one eye to another via the optic nerve. Later it was postulated that an infectious agent initiated the inflammatory response but no organism has been consistently isolated from SO eyes. Currently, it is strongly thought to be that the penetrating injury exposes ocular self-antigens found on ocular melanocytes triggering an autoimmune inflammatory response. Incidence: The incidence of SO is variable since it does not depend on serological or pathological studies rather on clinical findings. The increased awareness of the disease entity, the advances diagnostic imaging and timely enucleation of the injured eye have all contributed to the significant decrease in incidence of SO. More recent studies report that the incidence of SO post penetrating ocular injury is between 0.2- 0.5% after penetrating ocular injuries and 0.01% after intraocular surgery. Clinical Features: As sympathetic ophthalmia is a clinical diagnosis that is confirmed by pathology, a through clinical examination is essential. High clinical suspicion should be present as one can potentially present as early as 5 days or as long as 42 years after the insult. Patients present with signs and symptoms of uveitis including: photophobia, pain with eye movement, decrease in vision in the sympathezing eye and worsening of vision in the traumatized eye, ciliary flush, aqueous humor cells, flare, keratic precipitates on the corneal surface. In complicated cases peripheral anterior synechiae, rubeosis iridis, cataract and occlusion and seclusion of the pupil may ensue. The optic nerve may be swollen secondary to inflammatory infiltration. Fluorescein angiography is a useful imaging modality that can delineate multifocal areas of leakage at the level of the RPE. Histopathology: In sympathetic ophthalmia the histopathological changes are similar in both the exciting and the sympathizing eye. In literature SO features and categorized by typical and atypical changes. Typical changes include: diffuse lymphocytic infiltration of the uveal tract with epithiloid cell nests, pigment phagocytosis sparing of retina and choirocapillaris. Uveal tract diffusely thickened, epithiloid cells engulfing pigment, eosinophils, Dalen –Fuchs nodules located internal to Bruch's memebrane. Although present in approximately one-third of patients with SO, Dalen-Fuchs nodules are not pathognomonic as they could be present in Sarcoidosis and other inflammatory diseases. Atypical changes include: Retinal perivasculitis, retinitis, retinal detachment, gliosis as well as focal involvement of the choriocapillaris. Review of the Literature/Treatment Options (if applicable): (Treatment: The mainstay of treatment is prevention by enucleation of the injured eye within 14 days of insult. If the patient developed SO then corticosteroids and immunosuppressive therapy cyclosporin). Enucleation of the exciting eye after SO has developed for at least 2 months will not be beneficial to the course of the disease. Patient will maintain Conclusion(s): Sympathetic ophthalmia is a rare bilateral uveitis with an insidious onset and a progressive course. It almost invariably results secondary to a penetrating ocular injury exposing ocular antigens in the exciting eye, initiating a systemic immune response. Enucleation of the exciting eye is indicated within 14 days of injury, otherwise, the patient carries the risk of developing a diffuse granulomatous lymphocytic infiltration of the uveal tract that is potentially blinding in both the exciting and sympathezing eye. If SO develops then treated medically with corticosteroids and immunosuppressive therapy (e.g. cyclosporine). References: Sympathetic ophthalmia. Damico FM, Kiss S, Young LH. Semin Ophthalmol. 2005 Jul-Sep;20(3):191-7. Sympathetic ophthalmia. Chu DS, Foster CS. Int Ophthalmol Clin. 2002 Summer;42(3):179-85. Review.