Ocular Immunology and Inflammation

ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: http://www.tandfonline.com/loi/ioii20

Sympathetic Ophthalmia

Emmett T. Cunningham Jr., Dara Kilmartin, Mamta Agarwal & Manfred

Zierhut

To cite this article: Emmett T. Cunningham Jr., Dara Kilmartin, Mamta Agarwal & Manfred Zierhut
(2017) Sympathetic Ophthalmia, Ocular Immunology and Inflammation, 25:2, 149-151, DOI:
10.1080/09273948.2017.1305727

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Published online: 17 Apr 2017.

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Ocular Immunology & Inflammation, 2017; 25(2): 149–151
© Taylor & Francis Group, LLC
ISSN: 0927-3948 print / 1744-5078 online
DOI: 10.1080/09273948.2017.1305727

EDITORIAL

Sympathetic Ophthalmia
Emmett T. Cunningham, Jr., MD, PHD, MPH1,2,3, Dara Kilmartin, MSC, FRCSI, FRCOPHTH, FEBO4,
Mamta Agarwal, MD5, and Manfred Zierhut, MD6

1
Department of Ophthalmology, California Pacific Medical Center, San Francisco, California, USA, 2The
Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, USA, 3The
Francis I. Proctor Foundation, UCSF School of Medicine, San Francisco, California, USA, 4Research
Foundation, Royal Victoria Eye & Ear Hospital, Dublin, Ireland, 5Uveitis Services, Medical Research
Foundation, Sankara Nethralaya, Chennai, India, and 6Centre for Ophthalmology, University Tuebingen,
Elfriede-Aulhorn-Str, Tuebingen, Germany
Sympathetic Ophthalmia (SO) is a rare, but serious, bilat- vitrectomies. While the total sample size was small, results
eral uveitis that occurs after either eye surgery or penetrat- from a retrospective study by Rishi et al.29 suggested that
ing or perforating eye trauma.1–11 The eye with a history SO following both trauma and therapeutic vitrectomy (n =
of injury or surgery is referred to as the “inciting” or 7) tended to occur sooner (1.5 vs 8.0 months) and was
“exciting” eye, whereas the contralateral eye is said to be more likely to be accompanied by SRD at presentation
“sympathizing”. This distinction may be unclear, how- (100% vs 30%) than eyes that developed SO with no
ever, in patients who have undergone or experienced history of trauma (n = 10). Although the pathogenesis of
bilateral procedures or injury. Moreover, SO has been SO is incompletely understood, most evidence supports
reported following intravitreal injection,12 after some variant of Elschnig’s original, 1910 suggestion30 that
infectious13,14 or chemical keratitis,15 and in association the immune system is somehow sensitized to self when
with non-penetrating procedures, including irradiation otherwise sequestered ocular antigens are presented to the
for ocular melanoma16–20 and laser- and cryo- extraocular immune system,1 a notion supported by an
cyclodestructive procedures to lower intraocular association between SO and both specific class II human
pressure.21–26 The time from surgery or trauma to onset leukocyte antigens31 and interleukin-10 gene
of SO varies from days to decades, with the vast majority polymorphisms.32 Histological examination of eyes with
of cases occurring within 12 months. The protective role of SO is said to show granulomatous inflammation with
primary enucleation or evisceration is unproven and such relative sparing of the choriocapillaris, although recent
procedures are generally discouraged unless surgical studies suggest that both a mixed inflammatory infiltrate
reconstruction of the eye is deemed impossible at the and involvement of the choriocapillaris are common.33
time of injury.27,28 Castiblanco and Adelman7 reviewed Treatment of SO involves initial control of the uveitis
the world literature on SO through 2008 – a total of 86 with systemic and regional corticosteroids in virtually all
patients, 60 of whom had a description of clinical findings patients, followed by long-term use of corticosteroid-
at presentation and 46 of whom had prior surgery. The sparing immunosuppressive agents in the vast
most commonly reported clinical features at presentation majority.2,34 A comprehensive review35 and two original
included the presence of active inflammation (83.3%), articles36,37 in this issue of Ocular Immunology &
nummular, depigmented, chorioretinitis spots known as Inflammation address important aspects of the pathogen-
Dalen-Fuchs nodules (33.3%), optic disc swelling (20.0%), esis, diagnosis, and management of SO.
serous retinal detachment (SRD; 11.7%), and choroiditis Mahajan et al.35 systematically reviewed the use of
(8.3%). Anterior uveitis (55.0%) was slightly more com- multimodal imaging in SO. The authors reminded us of
mon than vitritis (47.0%), with many eyes having both. the importance of history supported by suggestive poster-
Cataract surgery and vitrectomy were the most frequently ior segment findings, particularly SRD in the acute phase
performed antecedent surgical procedures at 18 (30%) and Dalen-Fuchs nodules both early and late. Fluorescein
each, but given that cataract surgery is performed vastly angiography (FA) is most relevant when such changes are
more often than vitrectomy, posterior segment surgery present, particularly early in the course of disease when
would appear to confer the greatest risk, with an SO multiple and progressive pinpoint leaks through the ret-
event rate estimated by Kilmartin et al.10 to be 1 in 800 inal pigment epithelium (RPE) lead to late filling of the

Correspondence: Emmett T. Cunningham, Jr., MD, PhD, MPH, West Coast Retina Medical Group; 1445 Bush Street, San Francisco, CA 94109,
USA. E-mail: emmett_cunningham@yahoo.com

149
150 E. T. Cunningham et al.
detachment spaces. Mild to moderate late leakage from
the optic disc is also common. Irregular filling of the
choroid may be present, and in some patients may be
dramatic and resemble acute posterior multifocal placoid
pigment epitheliopathy, with early hypofluorescence fol-
lowed by late hyperfluorescence of involved areas. Over
time, FA shows the location and extent of chorioretinal
scarring and, when present, can reflect or reveal the pre-
sence of subretinal fibrosis and/or choroidal neovascular-
ization. These acute and chronic FA findings are
indistinguishable from those seen in many patients with
Vogt–Koyanagi–Harada (VKH) disease and, with a his-
tory of penetrating trauma or surgery, are virtually
pathognomonic of SO. Choroidal imaging is largely sup-
portive in the acute phase, although assumes increasing
importance to monitor disease activity and response to
therapy once the RPE leaks and SRDs have resolved.
When active, indocyanine green angiography shows mul-
tiple hypocyanescent spots believed to represent focal,
choroidal, inflammatory infiltrates. Spectral domain-
optical coherence tomography (SD-OCT), including
enhanced depth imaging of the choroid, provides what
is perhaps the most diagnostically and therapeutically
relevant information after FA, including the presence of
shallow SRDs not appreciated clinically or on FA, and
infiltrative thickening of the choroid producing both
undulations in the normally curvilinear and concave
RPE line and loss of the vascular lacunae normally present
in Sattler’s and Haller’s layers. Acutely, Dalen-Fuchs
nodules imaged on SD-OCT appear as small, irregular,
hyperreflective pigment epithelial detachments, often
with disruption of the overlying RPE and extension of
the hyperreflective, presumed inflammatory, material
into the outer retina. More chronically they appear as
focal chorioretinal scars, with circumscribed loss or dis-
ruption of the outer retina and inner choroid. B-scan ultra-
sonography can also be used to reveal thickening of the
posterior eye wall, as well as medium-to-large SRDs, par-
ticularly when direct visualization of the posterior seg-
ment is limited, as is often the case in the inciting eye.
While non-invasive, fundus autofluorescence is generally
less useful in that it tends to reflect the location and extent
of RPE disruption seen on FA. The authors concluded that
FA and SD-OCT provide the most valuable diagnostic
information early and that SD-OCT alone can often be
used to monitor for disease activity.
Payal and Foster36 studied responses to therapy and
outcomes in 19 patients with SO seen over an 8-year
period (2005–2013) at a uveitis referral center in Boston,
USA. Patient age ranged from 16 to 95 years (median 58
years). All patients were followed up for at least 24
months and roughly half were treated for the entire period
of the study (median follow-up, 7.1 years). A total of 10
patients (52.6%) were female. Most patients (11; 57.9%)
developed SO following non-surgical trauma. Of the six
patients who developed SO following surgery, four
(66.6%) had prior retinal detachment repair. While the
authors described their general approach to the
management of severe uveitis of the sort seen in SO, and
stated that inflammation was ultimately controlled in all
subjects, specifics regarding initial and subsequent treat-
ments used in the 19 patients were not provided. Tabular
summaries of agents used at last visit for those unable to
discontinue all medications suggested judicious use of
regional and systemic corticosteroids, together with both
conventional and biologic immunosuppressive agents. Of
note, while long-term drug-free remission has been
reported previously following treatment with chlorambu-
cil, and the authors themselves describe a similarly treated
patient who went into prolonged remission following 10
months of treatment with this agent, they claim to be the
first to report sustained drug-free remission in two
patients following 29 and 36 months of therapy with
conventional immunosuppressive agents. Two patients
in the cohort received chlorambucil for 10 and 24 months,
respectively, but without experiencing remission. The
potential dangers of alkylating agent immunosuppressive
therapy38 were highlighted by the death of a
chlorambucil-treated patient following the development
of acute myeloid leukemia. Best-corrected vision at last
visit was 20/40 or better in 11 patients (57.9%) and 20/200
or worse in 3 (15.8%), figures generally in line with pre-
vious clinic-based cohorts.7 The authors concluded that
SO can be controlled in virtually all patients with an
aggressive, step-wise approach to corticosteroid-sparing
immunosuppressive therapy, and that prolonged drug-
free remission can be achieved in a minority of patients.
Goudot et al.37 studied nine patients with SO seen over
a 9-year period (2007–2015) at a uveitis referral center in
Paris, France, for evidence at presentation of lymphocytic
meningitis, which they defined as more than 10
leucocytes/mm3 in the cerebral spinal fluid (CSF).
Pleocytosis was identified in 5 of 9 subjects (55.6%) – two
of whom had symptoms of meningeal irritation (head-
aches). Other extraocular symptoms at presentation
included hypoacusis in three subjects, and vitiligo, ver-
tigo, and tinnitus in one patient each. Demographic and
clinical features of the cohort were otherwise similar to
those reported in earlier series.7 The authors cited pre-
vious reports of both CSF pleocytosis and meningeal
symptoms in patients with SO and reminded us that
such findings may be more common than generally
appreciated. They also pointed out that the presence or
absence of CSF pleocytosis and meningeal symptoms
should not be used to distinguish between SO from
VKH disease. Further work remains to be done to deter-
mine whether CSF lymphocyte immunotyping and/or
cytokine profile analyses might be clinically useful.
Together, these studies highlight important issues
related to the diagnosis and management of SO.
Particularly noteworthy are the utility of multimodal
imaging to diagnosis and management of the condi-
tion, and the power of prompt and aggressive corti-
costeroid followed by corticosteroid-sparing
immunosuppressive therapy to both control inflamma-
tion and limit vision loss.
Ocular Immunology & Inflammation

DECLARATION OF INTEREST
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of the
article.
FUNDING
Supported in part by The Pacific Vision Foundation
(ETC) and The San Francisco Retina Foundation (ETC).
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