Sympathetic Ophthalmia
Sympathetic ophthalmia (SO) is a rare, bilateral, diffuse, granulomatous, nonnecrotizing panuveitis that may develop after either surgical or accidental trauma to 1 eye (called the exciting eye), followed by a latent period and the appearance of uveitis in the uninjured fellow eye (the sympathizing eye). Although the precise incidence of SO is difficult to ascertain because of its rarity, significant improvements in the management of ocular trauma have led to an overall decrease. Earlier estimates of the incidence of SO ranged from 0.01% after intraocular surgery to 0.5% in eyes with nonsurgical trauma. Although the most recent minimum incidence estimate is low (0.03/100,000), SO remains a disease with a persistent and potentially devastating presence.
Accidental penetrating ocular trauma was once the most common precipitating event for SO. Ocular surgery—particularly vitreoretinal surgery—has emerged as the main risk for the development of SO. In the early 1980s, the prevalence of SO in patients who had undergone pars plana vitrectomy was reported to be 0.01%, increasing to 0.06% when the procedure was performed in the context of other penetrating ocular injuries. More recent studies suggest that the risk of developing SO following pars plana vitrectomy is more than twice this figure and may be significantly higher than the risk of infectious endophthalmitis after vitrectomy. Improved access to emergency surgical care following penetrating ocular trauma and improved microsurgical technique have undoubtedly influenced this etiologic shift from penetrating injury to surgical trauma.
Similarly, the demographic of SO has changed from earlier reports, in which there was higher prevalence among men, children, and older patients (due to their presumed increased risk of accidental trauma), to more recent studies, which show no sex predominance and a lower risk in children (resulting in part from a reduced incidence of pediatric ocular injuries), as well as an increased risk in older patients (likely stemming from an increased frequency of ocular surgery and retinal detachment in this population).
In addition, although SO has traditionally been reported to develop in 80% of patients within 3 months of injury and in 90% within 1 year, these time intervals may actually be longer than previously thought. In a recent series, only one-third of patients developed SO within 3 months, and less than one-half did so within 1 year of injury.
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Chu XK, Chan CC. Sympathetic ophthalmia: to the twenty-first century and beyond. J Ophthalmic Inflamm Infect. 2013;3(1):49.
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Galor A, Davis JL, Flynn HW Jr, et al. Sympathetic ophthalmia: incidence of ocular complications and vision loss in the sympathizing eye. Am J Ophthalmol. 2009;148(5):704–710.
Manifestations
Patients with SO typically present with asymmetric bilateral panuveitis, in which the exciting eye exhibits more severe inflammation than the sympathizing eye, at least initially. Signs and symptoms vary in their severity and onset. Anterior segment findings include mutton-fat KPs, thickening of the iris from lymphocytic infiltration, and posterior synechiae formation. Intraocular pressure (IOP) may be elevated, due to trabeculitis, or low as a result of ciliary body shutdown.
Posterior segment findings include moderate to severe vitritis with characteristic yellowish white, midperipheral choroidal lesions (Dalen-Fuchs nodules) that may become confluent. Peripapillary choroidal lesions and exudative retinal detachment may also develop (Fig 9-48). Structural complications of SO include cataract, chronic macular edema, peripapillary and macular CNV, and optic atrophy. In a recent study, complications in the sympathizing eye at presentation were frequent (up to 47%); cataract and optic nerve abnormalities were most often associated with decreased vision and the further development of new complications, which occurred at a rate of 40% per person-year. Furthermore, a history of traumatic injury, the presence of active intraocular inflammation, and exudative retinal detachment correlated with poorer vision in the sympathizing eye. Extraocular findings similar to those observed with VKH syndrome, including cerebral spinal fluid pleocytosis, sensory neural hearing disturbance, alopecia, poliosis, and vitiligo, may be noted, although they are uncommon.
During the acute stage of the disease, FA reveals multiple hyperfluorescent sites of leakage during the early phase, which persists into the late phase of the study (Fig 9-49). Pooling of dye is observed in areas of exudative neurosensory retinal detachment. Multiple chorioretinal lesions may be present and appear hypofluorescent in early phases, simulating the pattern seen in APMPPE, or hyperfluorescent with late staining. Indocyanine green angiography reveals numerous hypocyanescent foci, which are best visualized during the intermediate phase of the angiogram; some of these foci may become less visible in the late stage of the study (Fig 9-50). Optical coherence tomography may demonstrate a shallow, serous retinal detachment and/or intraretinal edema, and monitoring these findings can help determine the efficacy of treatment (Fig 9-51). B-scan ultrasonography frequently reveals choroidal thickening.
The histologic features of SO are similar for both the exciting and sympathizing eyes. Findings include diffuse, granulomatous, nonnecrotizing infiltration of the choroid that classically spares the choriocapillaris in the early stage. Dalen-Fuchs nodules, which are clusters of epithelioid cells located between the RPE and Bruch membrane, are present in about one-third of patients. The nodules are not specific to SO and can also be found in VKH syndrome and sarcoidosis (see BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors).
Diagnosis
The precise etiology of SO is unknown; however, in the overwhelming majority of patients, there is a history of surgery or penetrating ocular injury complicated by incarceration of uveal tissue. The disorder may result from altered T-lymphocyte responses to previously sequestered ocular antigens derived from the RPE or choroid. The penetrating wound itself may facilitate exposure of uveoretinal antigens to conjunctival lymphatic channels and thereby initiate this immunopathologic response. Furthermore, there may be a genetic predisposition to the development of the disease, as patients with SO are more likely to express HLA-DR4, -DRw53, and -DQw3 haplotypes. It should be noted that the immunogenetics of SO and VKH syndrome are virtually identical, as the same associations have been found in both diseases.
The diagnosis of SO is clinical, and the disorder should be suspected in the presence of bilateral uveitis following any ocular trauma or surgery. Differential diagnosis includes other causes of panuveitis, including TB, sarcoidosis, syphilis, and fungal infections, as well as traumatic or postoperative endophthalmitis. Lens-associated uveitis has been reported with SO in up to 25% of cases and may present with a similar clinical picture. The clinical presentations of SO and VKH syndrome may be strikingly similar; however, a history of prior ocular injury is by definition absent in patients with VKH syndrome.
Treatment
The course of SO is chronic, with frequent exacerbations; however, it is a treatable condition, and in cases with penetrating trauma, every attempt should be made to salvage eyes with a reasonable prognosis for useful vision. Enucleation within 2 weeks of injury to prevent the development of SO should be considered in patients with grossly disorganized globes and no discernible visual potential. Although controversial, enucleation may still be preferred to evisceration as the operation of choice for the removal of ocular contents in severely injured eyes, because it eliminates the possibility of residual uveal tissue, which may predispose to the development of sympathetic disease. BCSC Section 7, Oculofacial Plastic and Orbital Surgery, discusses the advantages and disadvantages of enucleation and evisceration in greater detail. Regardless of visual potential, once SO has developed, enucleation of the exciting eye has not been shown to be beneficial in altering the disease course of the sympathizing eye. In fact, the exciting eye may eventually become the better-seeing eye.
The initial treatment of SO involves systemic corticosteroids, with the frequent addition of corticosteroid-sparing drugs such as azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, chlorambucil, and cyclophosphamide, as chronic therapy is anticipated in most patients. Topical corticosteroids are essential in the treatment of the acute anterior uveitis associated with SO. Periocular and intravitreal corticosteroids, including the intravitreal fluocinolone acetonide implant, are options for patients intolerant of systemic corticosteroid therapy. With prompt and aggressive systemic therapy, the visual prognosis of SO is good; 60% of patients achieve a final visual acuity of 20/40, although up to 25% may decline to 20/200 or worse in the sympathizing eye.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.