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Sympathetic ophthalmia (SO) is a rare, diffuse, bilateral, and granulomatous nonnecrotizing panuveitis that may follow intraocular penetrating trauma. Our aim is to report a rare case of SO following orbital exenteration. Orbital exenteration was performed on a 48-year-old african female due to conjunctival keratinizing squamous cell carcinoma with intraocular involvement of the left eye. Five days after the uneventful procedure, the patient presented signs and symptoms compatible with SO. Key differential diagnoses were excluded, and prompt and aggressive immunosuppression was started with a favourable but slow clinical response. This case highlights the fact that SO can also be induced by a neoplasm with intraocular invasion or by aggressive nonpenetrating surgery. While the underlying pathogenesis of SO is still not fully elucidated, we hereby contribute with a novel potential mechanism leading to its development.
Sympathetic ophthalmia (SO) is a rare, diffuse, bilateral and granulomatous nonnecrotizing panuveitis that follows intraocular penetrating trauma.[1,2,3,4,5] The injured eye is the first to show signs of uveitis, whereas the fellow eye is called the “sympathizing” eye.[1,3,4] The latent period between ocular injury and SO development is described to be between 5 days and 50 years.[3,4] It is proposed that the penetrating injury may allow drainage of uveal antigens from the eye to the lymphatics, triggering the immunopathologic process. If left untreated, SO has a chronic course with exacerbations, eventually leading to complete the loss of vision.[1,4]
A 48-year-old african female with an unremarkable medical history other than tobacco smoking was referred due to an irregular, leukoplakic, nonulcerated, and nonmobile mass in the left nasal conjunctiva and cornea. It was present for 7 months and was 3 cm × 3 cm in size. Magnetic resonance imaging (MRI) [Fig. 1] showed neoplastic invasion of the left orbit and eye, involving the medial rectus insertion, orbital fat, ciliary body, and also causing cornea ulceration. Due to its extensive spread, the multidisciplinary team decided to proceed to the left orbital exenteration. Before surgery, fellow eye examination revealed best-corrected visual acuity (BVCA) of 20/20, intraocular pressure (IOP) of 14 mmHg, unremarkable biomicroscopy, and fundoscopy. The surgery was uneventful, and the surgical specimen is shown in Fig. 2a. Pathology from the excised tumor revealed a conjunctival keratinizing squamous cell carcinoma [Fig. 2b] that had originated in the bulbar conjunctiva with subsequent invasion of the cornea, ciliary body, and choroid (causing a breach in these structures), along with perivascular infiltration. Surgical margins were negative for neoplastic tissue. Five days after the procedure, the patient presented with acute-onset photophobia, pain, and reduced visual acuity of the right eye. BVCA was 20/20 in the right eye, and the IOP was 16 mmHg. Biomicroscopy revealed anterior chamber cells (2+) and flare (0.5+), as well as vitreous cells (2+). On dilated fundus examination, multiple small yellow-white subretinal spots (Dalen-Fuchs nodules) and multifocal areas of serous retinal detachment were observed [Fig. 3a].
Right macular optical coherence tomography (OCT) confirmed multiple serous retinal detachments [Fig. 4] and increased choroidal thickness [Fig. 5]. Fluorescein angiography [Fig. 3b] revealed a delayed and irregular pattern of choroidal perfusion and multiple hyperfluorescent spots in the early phase with late leakage. Laboratory investigations showed neutrophilic leukocytosis with elevated C-reactive protein levels and erythrocyte sedimentation rate.
Our differential included Vogt–Koyanagi–Harada (VKH) disease, SO, sarcoidosis, syphilis and tuberculosis. Ancillary tests, including chest X-ray, tuberculin skin test, rapid plasma reagin, angiotensin-converting enzyme, and serum calcium levels were normal. Complete VKH disease was not considered because the patient did not have any neurological symptoms or integumentary involvement. However, probable VKH disease (isolated ocular disease), according to the revised diagnostic criteria, could not be completely excluded as clinical and laboratory findings are very similar.
A presumptive diagnosis of SO was made, and the patient was immediately started on pulsed steroid therapy (1 g intravenous methylprednisolone for 3 days), followed by oral prednisone 80 mg qds. Oral cyclosporine A (CsA) 150 mg twice a day was later added as a steroid-sparing agent, and the oral prednisone dose was slowly tapered. CsA was chosen based on its mechanism of action which is thought to counteract the underlying pathogenesis of SO,[4,7] its documented efficacy in posterior uveitis and previous experience in our department. The patient had a subsequently favorable but slow clinical course. Serial OCT [Fig. 4] showed a gradual reduction in the size of the neuroretinal detachments. At her most recent follow-up consultation, one and half year after the onset of SO, the patient was on cyclosporine 300 mg once per day and right BVCA had stabilized at 20/40.
Although the eye is considered immunologically privileged due to its unique barriers and lack of a fully developed lymphatic drainage system, one should be aware of this immune-mediated condition. SO is a rare panuveitis that typically follows intraocular penetrating trauma.[1,2,3,4,5] However, anecdotal clinical reports in the literature describe SO occurring after self-sealing, occult globe rupture, or radiation exposure.[5,9] The mechanism believed to trigger SO in those rare contexts is retinal manipulation and a breakdown of the blood-retinal barrier (BRB), with release of retinal and uveal antigens.[2,9] It is believed to represent an autoimmune T-cell response.[1,3] The patient developed SO after several months of intraocular spread of a conjunctival malignant tumor and 5 days after orbital exenteration. The main finding of this report is that SO occurred in the absence of surgical or accidental ocular penetrating trauma.
We believe that this case was possibly triggered by a conjugation of two factors. The least probable mechanism is that neoplastic intraocular invasion of the ciliary body and cornea by tumor spreading (documented by MRI and pathology) may have caused exposure of uveal antigens. A more reasonable mechanism is that orbital exenteration elicited SO as it occurred several days after surgery. Due to the aggressive surgical maneuvers required for orbital exenteration before removal of the intact eye, retinal, and uveal manipulation may have occurred, with consequent disruption of tight junctions between endothelial and retinal pigment epithelial cells, which form the inner and outer BRB, respectively.[2,3,9] The subsequent antigens' release and exposure may have triggered the development of SO. Considering the history of surgical intervention, SO is more likely than probable VKH disease (isolated ocular disease). This case highlights that SO may occur following circumstances, in which there is no documented penetrating ocular injury or intraocular surgery. We should emphasize that there are no reported cases in the literature of SO occurring after orbital exenteration.
There are no conflicts of interest.
The authors would like to thank Dr. Colin Chu, University of Bristol, for English corrections and careful manuscript revision and Dr. Mónica Cardoso, Hospital de Santa Maria, for providing histopathology images.