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Review Article

Update on Sympathetic Ophthalmia

J. Fernando Arevalo1,2, Reinaldo A. Garcia3, Hassan A. Al-Dhibi2, Juan G. Sanchez4, Luis Suarez-Tata3

ABSTRACT Access this article online

Website:
Sympathetic ophthalmia (SO) is a bilateral diffuse granulomatous intraocular inflammation www.meajo.org
that occurs in most cases within days or months after surgery or penetrating trauma to DOI:
one eye. The incidence of SO ranges from 0.2 to 0.5% after penetrating ocular injuries and 10.4103/0974-9233.92111
0.01% after intraocular surgery. Vitreoretinal surgery and cyclodestructive procedures are
Quick Response Code:
considered risk factors. The time from ocular injury to onset of SO varies greatly, ranging
from a few days to decades, with 80% of the cases occurring within 3 months after injury to
the exciting eye and 90% within 1 year. The diagnosis is based on clinical findings rather
than on serological testing or pathological studies. It presents as a bilateral diffuse uveitis.
Patients report an insidious onset of blurry vision, pain, epiphora, and photophobia in the
sympathizing, non-injured eye. Classically this is accompanied by conjunctival injection
and a granulomatous anterior chamber reaction with mutton-fat keratic precipitates (KPs)
on the corneal endothelium. In the posterior segment, the extent of inflammation can vary.
Systemic corticosteroids are the first line therapy for SO. If patients are non-responsive to
steroid therapy or have clinically significant side effects, cyclosporine, azathioprine or other
immunosuppressive agents can be used for long-term immunomodulatory therapy.

Key words: Dalen–Fuchs Nodules, Diffuse Granulomatous Intraocular Inflammation, Ocular

Autoimmune-Associated Disease, Ocular Trauma, Sympathetic Ophthalmia

INTRODUCTION classic model of an autoimmune- associated disease occurring

in humans. The reason for naming this disease sympathetic

S ympathetic ophthalmia (SO) is a bilateral diffuse

granulomatous intraocular inflammation that occurs in most
cases within days or months after either surgery or penetrating
trauma to one eye. The injured eye is known as the exciting eye
and the fellow eye, developing inflammation days to years later,
as the sympathizing eye. The sympathizing eye demonstrates
sings of the ocular inflammation without any apparent reason.
Although rare, SO remains an important public health problem
because it can cause bilateral blindness. The time from ocular
injury to onset of SO varies greatly, ranging from a few days to
decades, with 80% of the cases occurring within 3 months after
injury to the exciting eye and 90% within 1 year.1,2
This ocular disease is probably the best known and the most
ophthalmia remains obscure. One possible explanation is
that the sympathetic pathways (optic nerve and optic chiasm)
may be the pathway from the inciting eye to the sympathizing
eye.3 However, current evidence suggests a role for immune
dysregulation as a primary etiological mechanism. There appears
to be a cell-mediated immune response directed against ocular
self-antigens found on photoreceptors, the retinal pigment
epithelium (RPE) and/or choroidal melanocytes.
The condition was first recognized by Hippocrates, but was
first described and named by Mackenzie in the mid-1800s.3,4
Fuch’s provided the first histopathologic details in 1905.5 He
established it as a separate disease entity, distinct from other
ocular inflammatory disorders. Fuchs and Dalen independently

Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2The Vitreo-Retinal and
1

Uveitis Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia, 3The Clínica Oftalmológica El Viñedo, Valencia,
Venezuela, 4The Retina and Vitreous Service, Clínica Oftalmológica Centro Caracas, and the Arevalo-Coutinho Foundation for
Research in Ophthalmology, Caracas, Venezuela
Corresponding Author: Dr. J. Fernando Arevalo, Vitreoretinal Division, The King Khaled Eye Specialist Hospital, Al-Oruba Street, PO Box 7191,
Riyadh 11462, Kingdom of Saudi Arabia. E-mail: arevalojf@jhmi.edu

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Arevalo, et al.: Sympathetic Ophthalmia
described the inflammatory nodular aggregates termed “Dalen–
Fuchs nodules.”6
EPIDEMIOLOGY
Given its rare occurrence, the true incidence of SO is difficult to
establish and literature reports are variable, likely owing to the
fact that the diagnosis of SO is based on clinical findings rather
than on serological testing or histopathology. The true incidence
is unknown because of lack of pathologic proof, the difficulty in
studying sufficiently large cases series and the fact that most data
are from the dated literature that often confused SO with other
forms of uveitis.7 In 1982, Gass reported the prevalence of SO at
0.01% following pars plana vitrectomy, and a 0.06% after other
penetrating ocular trauma.8 Epidemiological estimates have
shown the incidence to be 0.2% to 0.5% after penetrating ocular
injuries and 0.01% after intraocular surgery.9,10 According to
Gomi et al,11 SO accounted for approximately 0.3% of the uveitis
and the one-year incidence was calculated to be a minimum of
0.03/100,000 population.12
There is no racial or age predisposition. The incidence of SO
is equal in males and females after surgery; the disease occurs
more frequently in males after trauma. This likely reflects the
difference in the frequency of ocular injury between genders.
SO occurs more often after non-surgical trauma.13,14 However,
SO has been reported after various intraocular procedures such
as, trans-scleral neodymium: YAG cyclodestruction, cataract
extraction, evisceration, paracentesis, iridectomy, pars plana
vitrectomy, and retinal detachment repair.15-18 SO has also been
reported after perforated corneal ulcer, radiation for choroidal
melanoma and external beam radiation.19-21 Vitreoretinal surgery
and cyclodestructive procedures are considered risk factors
for SO.15,17-18 Recently, SO has been described after 23-gauge
vitrectomy.18 Although some recent reviews consider ocular
surgery, particularly vitreoretinal surgery, as the main risk for
SO, our experience is that SO is still more frequent after non-
surgical trauma (unpublished data).
SO has been associated with particular major histocompatibility
antigen (MHC) haplotypes. This finding suggests a role for
immune dysregulation, increased susceptibility, and increased
severity associated with pathogenesis. Patients with SO are more
likely to express human leukocyte antigen DR4 (HLA-DR4,
and closely related HLADQw3 and HLA-DRw53) phenotype.22
These phenotypes are also found more frequently in patients
with Vogt-Koyanagi-Harada (VKH) disease. HLA-DRB1*04
and HLA-DQA1*03 haplotypes have been considered markers
of increased SO susceptibility and severity in British and
Irish patients.23 Therefore, select patients may have a genetic
predisposition to developing SO following accidental or surgical
ocular trauma.
14 Middle East African Journal of Ophthalmology, Volume 19, Number 1, January - March 2012
CLINICAL FEATURES
Onset occurs within 1 month in approximately 17% of cases;
within 3 months in 50%; within 6 months in 65%, and within the
first year after injury in 90%. After the inciting event, traumatic
or surgical, bilateral intraocular inflammation has been reported
between 1 week and 66 years.24
Sympathetic ophthalmia presents as a bilateral diffuse uveitis.
Patients report insidious onset of blurry vision, pain, epiphora,
and photophobia in the sympathizing, non-injured eye.
Classically this is accompanied by conjunctival injection and a
granulomatous anterior chamber reaction with mutton-fat KPs
on the corneal endothelium; however, the anterior chamber
reaction can be relatively mild, and the inflammation can be
non-granulomatous. The inflammation can be so mild that the
term “sympathetic irritation” is used. The iris may thicken from
lymphocytic infiltration; the severe inflammation may lead to
formation of posterior synechiae [Figure 1]. Intraocular pressure
may be elevated secondary to inflammatory cell blockage of
the trabecular meshwork, or it may lower as a result of ciliary
body shutdown.
In the posterior segment, the extent of inflammation can
vary. Patients may have vitritis, retinal vasculitis, choroiditis,
and papillitis. The extent of inflammation may sometimes
be represented by serous retinal detachment and optic nerve
swelling in affected patients. Indirect ophthalmoscopy is
helpful for following the course of the disease [Figure 2].10,26
White-yellowish lesions at the choroidal are more common
in the peripheral fundus of patients with SO (Dalen–Fuchs
nodules) [Figures 3 and 4]. Dalen–Fuchs nodules were initially
characterized in eyes with SO. However, other granulomatous
inflammatory eye diseases may also present with Dalen–Fuchs
nodules including Vogt-Koyanagi-Harada disease and sarcoidosis.
The sequelae of inflammation noted in SO are quite variable,
depending on the severity of the ocular inflammation and
whether therapy has been initiated. Secondary glaucoma as
well as cataract can be present. In addition, retinal and optic
atrophy may occur in association with retinal detachment,
subretinal fibrosis, and underlying choroidal atrophy.27 Choroidal
neovascularization and phthisis bulbi are rare and are usually
related to delayed diagnosis and inappropriate treatment.
BenErza documented various factors that contribute to the
development of clinically apparent SO [Table 1].25
DIAGNOSIS
The diagnosis of sympathetic ophthalmia is based on history
and clinical examination. There are no specific laboratory
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Arevalo, et al.: Sympathetic Ophthalmia

a b

Figure 1: Acute anterior uveitis with keratic precipitates, posterior synechiae and
fibrin on the anterior lens capsule in the right eye of a 25-year-old male, who had
sustained a penetrating trauma to his left eye 3 months earlier (Reprinted with
permission from BenErza D25)
c d
Figure 2: Clinical presentation of sympathetic ophthalmia after cyclophotocoagulation:
(a) diffuse choroiditis with papillitis. (b) Late frame fluorescein angiogram
demonstrating optic disc and subretinal hyperfluorescence in the posterior pole.
(c) B-scan ultrasound shows exudative retinal detachment OD. (d) Optical coherence
tomography OD demonstrates elevation of the retinal layers with subretinal
hyporeflectivity corresponding with subretinal fluid

a b

c d
Figure 3: Sympathetic ophthalmia after trauma: (a) Posterior pole of the right
sympathizing eye demonstrating choroidal atrophy. (b) Multiple small Dalen–Fuchs
nodules can be seen throughout the fundus in this sympathizing eye. Cell infiltrates
were present in the vitreous. (c) This case was complicated by cataract and refractory
glaucoma. The patient was treated by cataract extraction and trabeculectomy with
mitomycin C initially followed by an Ahmed valve implant. (d) Exciting phthisical
left eye after trauma
Figure 4: Fundal white dots in the macular region accompanied by retinal vasculitis
were observed in the right eye of a 33-year-old male, who underwent multiple
intraocular surgeries in his left eye. The findings in the right eye were detected
4 weeks after the last surgery in the left eye (Reprinted with permission from
BenErza D25)

Table 1: Factors that contribute to the development of clinically with a similar clinical picture. Fluorescein angiography (FA)
apparent sympathetic ophthalmia* and indocyanine green video-angiography (ICG-V) are useful
Factor Characteristic adjuncts in establishing the extent and severity of SO.
Type of trauma Penetrating trauma
Surgery Surgical repair 48 h more after initial injury In the acute phase of SO, FA typically demonstrates multiple
Treatment with Use local and systemic for more than a
corticosteroids week after initial injury hyperfluorescent leakage sites at the RPE during the venous phase
Site of penetrating injury Ciliary body that persist into the late frames of the study [Figures 5 and 6].
Ocular inflammation Intensity in the inciting eye There may be spreading of the dye from these areas and, in
Size of wound Larger than 5 mm
Age of patients First decade of life severe cases, pools of the exudates coalesce into large areas of
*Sympathetic ophthalmia. (Reprinted with permission from BenErza D27) exudative retinal detachment.10 The less common appearance
of SO in FA is that of early hypofluorescent lesions and late
studies to establish the diagnosis of SO; however, focused staining similarly to that seen in acute multifocal posterior
clinical testing can be used to rule out other disease entities placoid pigment epitheliopathy.28 The status of the RPE overlying

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Arevalo, et al.: Sympathetic Ophthalmia
Dalen–Fuchs nodules or the integrity of the choriocapillaris is
what determines the fluorescence of these lesions. Blockage of
choroidal fluorescence may occur when an intact dome of RPE
contains the cellular elements of the Dalen–Fuchs nodules.
Gradual accumulation of fluorescein into Dalen–Fuchs nodules
may produce focal hyperfluorescence [Figure 6b]. However,
degeneration of the RPE overlying the Dalen–Fuchs nodule
may allow fluorescein dye to permeate focally into the RPE and
gradually accumulate in the subretinal space.29 Late staining of
the optic nerve head is sometimes observed, even in the absence
of clinical papillitis or optic nerve head swelling.
As the disease process predominantly involves the choroid,
ICG-V may be a useful adjunct to fluorescein angiography both
for diagnosis and in evaluating the response to treatment. ICG-V
studies show multifocal hypofluorescent spots that became more
prominent as the study progresses. These lesions are thought
to be reflective of choroidal inflammatory cellular infiltration
and choroidal edema.30,31
Time domain optical coherence tomography has shown
disorganization and thinning of the inner retina, and pronounced
disintegration of the RPE and choriocapillaris.32 Fourier Domain
OCT is also able to show choroidal and RPE thickening in SO
patients [Figure 6c–f].
B-scan ultrasonography in SO demonstrates marked choroidal
thickening and retinal detachment in some difficult cases.
HISTOPATHOLOGY
The basic finding in the histopathological analysis of eyes with
SO is granulomatous inflammation throughout the uveal tissue,
except for the choriocapillaris and retinal vessels [Figures 7-9].
On histopathologic inspection, the yellowish-white choroidal
lesions seen clinically correspond to collections of lymphocytes,
histiocytes, and de-pigmented RPE cells lying beneath Bruch’s
membrane. Retinal infiltrates have been reported in 18% of
SO cases.34 Specifically variable degrees of retinal involvement,
including perivasculitis, retinal detachment, and gliosis have been
described. The inflammatory cells involved in SO are primarily
lymphocytes, epithelioid cells, and multinucleated giant cells,
all of which are components of classic granuloma. Occasionally,
eosinophils, neutrophils, and plasma cells may be present.34-36
Dalen–Fuchs nodules are found in approximately one-third
of enucleated eyes thought to have SO [Figure 8].37 The
fundal white dots are the ophthalmoscopic counterpart of
the choroidal granulomata or Dalen–Fuchs nodules observed
histologically. The localization of the Dalen–Fuchs nodules is
first and foremost within the choroid, as can be seen in the
gross specimen of eyes with SO. However, histologic sections
and immunostaining demonstrate that Dalen–Fuchs nodules
16 Middle East African Journal of Ophthalmology, Volume 19, Number 1, January - March 2012
can be found within the choroid, under the RPE or under the
neuroretina. Immunohistochemical identification of the cells in
Dalen–Fuchs nodules demonstrated cells originated mostly from
the reticuloendothelial system (histiocytes, lymphocytes, and de-
pigmented epithelial cells). The cellular compositions of Dalen–
Fuchs nodules in SO and in sarcoidosis are identical.35,38-40 The
RPE generally remains normal in appearance, but it may or
may not be intact anterior to these nodules. Reynard et al,29
reported an interesting morphological variation of Dalen–Fuchs
nodules in SO. They found three types of lesions at the level
of the RPE.29 One type was a focal hyperplasia and aggregation
of retinal pigment epithelial cells. The second type, classically
referred to as Dalen–Fuchs nodules, consisted of epithelioid
cells and lymphocytes covered by an intact dome of RPE. The
third type of lesion was characterized by degeneration of the
overlying RPE leading to disorganization of the Dalen–Fuchs
nodules and possible release of their contents into subretinal
space. The spectrum of morphological changes occurring at the
level of the RPE is consistent with the Fuchs original hypothesis
that Dalen–Fuchs nodules undergo on evolutionary sequence of
development. Jennings et al,41 suggest that the clinical appearance
of Dalen–Fuchs nodules appears to correlate with the severity
of the disease.
ETIOLOGY
The etiology of SO is not clearly understood. Autoimmunity
and cell-mediated immune mechanisms are considered to
play a mediating role in the pathogenesis of SO. However, this
concept is not a new one, having been proposed by Elschnig
in 1910 with uveal pigment being considered a putative
antigenic stimulus. Elschnig postulated that the injury to the
exciting eye resulted in an absorption and dissemination of
uveal pigment, which produced the hypersensitivity reaction
in the injured eye. The continued absorption resulted in an
allergic reaction in the sensitized tissue of the sympathizing eye.
Current evidence suggests that choroidal melanocytes alone as
an inciting target is considered insufficient to induce SO. The
cell-mediated immunity observed in SO could be directed
against some uveal antigen,42 a retinal antigen (such as Sag)37 or
a surface antigen shared by photoreceptors, RPE, and choroidal
melanocytes.35 To date, no circulating antibodies directed against
intraocular tissue have been found. No organism has ever been
consistently isolated from eyes with SO, and the disease has
never been incited in animal models following injection of an
infective agent. Nonetheless, through molecular mimicry of
an endogenous ocular antigen, a bacterial antigen, rather than
active proliferation of the organism, may be the inciting agent
in the immune response.43
Albert et al,4 proposed a unified model to explain the pathogenesis
of SO. They proposed that since the choroid has no lymphatics,4
the removal of intravitreal antigen by blood stream, or possibly,
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Arevalo, et al.: Sympathetic Ophthalmia
Figure 5: Fluorescein angiography of the acute phase of sympathetic ophthalmia
showing multiple hyperfluorescent dots in the mid-periphery with some confluence
anteriorly (Reprinted with permission from Damico FM et al.,26)
Figure 7: Enucleated specimen of a patient with a ruptured globe by penetrating
ocular trauma, who developed sympathetic ophthalmia two weeks after the
event. The cornea demonstrates a scar at the trauma site. Note exudative retinal
detachment and choroidal thickening more prominent posteriorly (Reprinted with
permission from Evans M33)
Figure 9: Sympathetic ophthalmia. The choroid is infiltrated by lymphocytes and
macrophages separated by groups of multinucleated cells and epithelioid cells
(Reprinted with permission from Evans M33)
Middle East African Journal of Ophthalmology, Volume 19, Number 1, January - March 2012 17
a b
c d
e f
Figure 6: Sympathetic ophthalmia in the left eye after trauma to the right eye. (a) The
color fundus photograph demonstrates optic disc edema and hypopigmented round
100-200 µ in size lesions in the posterior pole (Dalen–Fuchs nodules; white arrows).
(b) Fluorescein angiogram shows that the lesions are hyper and hypofluorescent,
and accompanied by choroidal folds inferotemporally. (c–f) Optical coherence
tomography (horizontal scans) characterize the Dalen–Fuchs nodules as fusiform
hypereflective lesions of the RPE (white arrows). Note the hyporeflective outer retina
associated with optic disc edema
Figure 8: Photomicrograph shows Dalen–Fuchs nodule in a patient with sympathetic
uveitis. Note, the collection of mononuclear cells and RPE cells beneath the RPE
and Bruch’s membrane (Reprinted with permission from Evans M33)
conveyance of suppression signals by intravitreal immunoreactive
cells to bloodstream and spleen results in immunologic tolerance.
In penetrating injuries followed by uveal prolapse, there is access
of uveal tissue to the conjunctival lymphatics, resulting in a
removal of the antigen or suppression signals to the regional
lymph nodes. In the latter sites, there is a sensitizing reaction to
the uveoretinal antigens, or some inhibiting signal. The antigenic
load may affect the histopathologic picture. The findings of
Rao et al,37 suggest that a high dose of antigen early in the
course of the disease may induce a transitory antigen–antibody
reaction. Furthermore, there is a key role for activated helper-T
lymphocytes to affect and perpetuate the ultimate immunologic
attack.35 This type of lymphocyte likely recognizes cell surface
antigens shared by the membranes of photoreceptor and RPE
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Arevalo, et al.: Sympathetic Ophthalmia
cells. In the retina, the Müeller cells may profoundly suppress
the proliferative response of primed T-helper lymphocytes to
antigen present on conventional antigen-presenting cells, as well
as their subsequent interleukin-2-dependent expansion. The
damage inflicted by the T cells on the uvea is for the most part
focal and slow, and is rarely accompanied by fulminant necrosis.
Histiocytes and epithelioid cells also enter the immunoreactive
sites adjacent to the uvea and become part of the Dalen–Fuchs
nodules. In the same manner, the RPE cells proliferate and
change to become incorporated in the nodules. In cases where
T-cells are able to bypass the RPE and enter the retina, retinal
inflammation and damage may ensue.4
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of SO includes all diseases that can
present as panuveitis. However, patient history will reveal
previous penetrating ocular injury or intraocular surgery
[Table 2]. Occasionally, it may be difficult to distinguish SO from
VKH disease. However, patients with VKH have no history of
surgery or trauma and VKH presents as bilateral granulomatous
panuveitis with prominent choroidal involvement. Typically,
patients with VKH have serous retinal detachment and optic
nerve involvement, not seen in SO. In addition, VKH is also
more prevalent in certain racial and ethnic groups, and they
may have skin and hair changes, such as vitiligo, alopecia, or
poliosis, or neurological symptoms such as tinnitus, headache,
or mental status change. If it is necessary to differentiate from
VKH, the cerebral spinal fluid of patients with VKH may reveal
pleocytosis in 84% of cases. VKH and SO are autoimmune
disorders targeting melanin-bearing cells. Both diseases are
characterized by immunologic dysregulation. Al-Halafi et al,44
found a statistically significant association of systemic disorders
and malignancy with VKH compared to SO. This finding suggests
that the two disorders have different etiology with similar ocular
and systemic manifestations.
Lymphoma, syphilis, tuberculosis, and sarcoidosis have to be
ruled out as these diseases demonstrate multiple small foci of
choroiditis with vitreal cells. If lymphoma is suspected, careful
systemic workup, including neurological evaluation, should be
Table 2: Differential diagnosis of Sympathetic Ophthalmia
Sympathetic ophthalmia VKH‡ syndrome
Age All ages 20–50 years
Racial predisposition None Asian and blacks
Penetrating trauma Always present Absent
Skin changes Uncommon Common
CNS* findings Uncommon Common
Retinal serous detachment Rare Frequently seen
Choriocapillaris involvement Usually absent Frequently seen
CSF† findings Usually normal Pleocytosis
*CNS: Central nervous system, †CSF: Cerebrospinal fluid, ‡VKH: Voght–Koyanagi–Harada
18 Middle East African Journal of Ophthalmology, Volume 19, Number 1, January - March 2012
performed. If necessary, a vitreous sample must be obtained for
diagnostic purposes. Tuberculosis, sarcoidosis, and syphilis are
usually accompanied by constitutional signs and symptoms of
the underlying systemic disease. These features, combined with
appropriate testing for tuberculosis (PPD skin testing and chest
radiograph), sarcoidosis (serum angiotensin-converting enzyme
and lysozyme, and chest radiograph), and syphilis (RPR and
FTA-ABS) can distinguish these systemic infections from SO.
It is important to rule out potentially devastating fungal and
bacterial infections, which may evolve rapidly from uveitis to
severe endophthalmitis. Post-traumatic iridocyclitis may also
cause an inflammatory reaction. However, neither infection nor
iridocyclitis involves the fellow eye.
TREATMENT
The treatment of SO is primarily medical. The mainstay of
treatment is systemic immunomodulatory therapy. Systemic
corticosteroids are the first-line therapy for SO. They may
be given topically, by sub-tenon or transseptal injection, and
systemically. Oral prednisone is most frequently employed in
the treatment of SO. Treatment is initiated with high dosage oral
prednisone (1.0 to 2.0 mg/kg/day) and tapered slowly over 3
to 4 months. In severe cases, intravenous pulse steroid therapy
can be employed (methylprednisolone 1.0 g/day for 3 days).
Adjunctive topical corticosteroids and cycloplegics are used to
prevent synechia formation from the anterior chamber reaction.
The clinical criterion for response to therapy incorporates an
appraisal of the inflammatory response, such as the degree of
choroiditis and papillitis. If there is a significant decrease in
inflammation, a slow taper of the oral corticosteroid may be
initiated. The minimum dosing schedule required to control
inflammation is at least a year in most cases. However, steroid use
is associated with the development of cataracts and glaucoma.
Regional injection of steroids in the peribulbar space can result
in scarring of orbital tissue and glaucoma.
Steroid-sparing immunomodulation may be more advantageous
in patients with SO. If patients are steroid-resistant or have
intolerable side effects, cyclosporine can be used as a long-term
Sarcoidosis Posterior Syphilis
20–40 years All ages
US: blacks None
Europe: whites
Absent Absent
9 –37% patients Secondary
25–30 % patients Uncommon
Present not common Localized
Usually absent Usually absent
Usually normal Positive results
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Arevalo, et al.: Sympathetic Ophthalmia
immunomodulatory agent. Cyclosporine is initiated at a dose
of 5 mg/kg/day and increased until the ocular inflammatory
reaction is controlled. Once the disease is in remission for at
least 3 months, a slow taper (0.5 mg/kg/day every 1–2 months)
of cyclosporine can be initiated and progressively substituted
by low doses of corticosteroid. Nussenblatt et al,45 reported
successful use of cyclosporin A in conjunction with prednisone.
Other immunosuppressive agents including chlorambucil,
cyclophosphamide, or azathioprine may also be utilized if
the inflammatory reaction cannot be adequately controlled
with corticosteroids or cyclosporine. Jennings and Tessler46
described favorable results with various combinations of
cyclophosphamide, azathioprine, and chlorambucil with or
without steroids. Mycophenolate has also been recommended
for the treatment of refractory panuveitis or posterior uveitis
unresponsive to high-dose maintenance steroids (>15 mg/day)
or other immunosuppressive agents or where toxicity concerns
exist.47 Dosage is 2 g orally and blood count monitoring is
necessary. Tacrolimus has also been shown to be effective;
however, renal dysfunction and glucose intolerance should be
monitored.48 Given the more powerful nature and less favorable
side-effect profile of these agents, collaborative management
with experienced immunology specialists is advisable.
Atan et al,49 studied whether polymorphisms in the cytokine
genes are important markers for disease severity and outcome
in patients with SO. Their49 results show that cytokine gene
polymorphisms are markers for the severity of disease in SO and
were found to be associated with recurrence of previously stable
disease and with the level of maintenance steroid treatment
required to control inflammation.
Recently, Mahajan et al,50 proposed that fluocinolone acetonide
implant provides inflammator y control and reduces the
dependence on systemic immunosuppression in patients with
SO.
PREVENTION
Surgery prior to disease onset appears to play an important role
in the prevention of SO. In general, the time frame required for
this approach is believed to be within 10 days to 2 weeks from
the penetrating injury.1,4 The problem with this approach is
that with current advanced surgical techniques, many eyes once
considered nonviable may now have a fair prognosis. Therefore,
current opinion sustains that SO is extremely rare and can be
effectively treated in most cases. Recently, Savar et al,51 reported
their experience with enucleation after open globe trauma at
the Massachusetts Eye and Ear Infirmary center. Among 660
open globe injuries, 55 had undergone enucleation, 11 primary,
and 44 secondary cases were documented.51 The most common
reason for secondary enucleation was a blind, painful eye.51 In
Middle East African Journal of Ophthalmology, Volume 19, Number 1, January - March 2012 19
their51 series only two patients (0.3%) developed SO and had
maintained good vision in the sympathizing eye. Savar et al,51
used Bellan hypothetical calculations51 to find that between
908 (assuming a sympathetic ophthalmia rate of 3.1%) and
9999 (assuming a SO rate of 0.28%) prophylactic enucleations
following open globe injury would need to be performed to
prevent one case of legal blindness from SO. We recommend
that primary anatomical reconstruction should be performed
and that should be followed by discussion with the patient and
family members regarding whether to retain or remove eye.
Controversy remains with respect to enucleation of the exciting
eye after development of SO development for the management
of this condition. Kilmartin et al,12 found that once SO develops,
secondary enucleation of the exciting eye to reduce inflammation
in the sympathizing eye does not necessarily lead to a better
visual outcome or to a reduced need for medical therapy.
Unfortunately, the time frame necessary to perform prophylactic
secondary enucleation remains uncertain, as SO has been
reported with secondary enucleation performed as early as
five days following a penetrating ocular injury.16 In addition, in
certain cases the exciting eye may become the better seeing eye
after chronic or severe SO. However, the pre-existing lack of
vision in previously injured eyes changes the context in which a
subsequent penetrating ocular injury is managed. In this setting,
repairing the injury in order to assess for visual potential is futile,
and primary enucleation may offer the best prophylaxis against
SO.16,52,53 Although it would appear that evisceration after severe
ocular trauma is a safe option with a very low risk of developing
SO, it is known that SO may occur due to uveal tissue remaining
behind in scleral emissary channels. We suggest the surgeons
pay particular attention to the theoretically increased risk of SO
after evisceration versus enucleation.
SUMMARY
Sympathetic ophthalmia is a rare and potentially visually
devastating bilateral panuveitis, typically following surgery
or non-surgical penetrating injury to one eye. High index of
suspicion is vital to ensure early diagnosis and initiation of
treatment, thereby allowing good final visual acuity in most
patients. Diverse clinical presentations are possible in SO and
any bilateral uveitis following vitreoretinal surgery should alert
the surgeon to the possibility of SO.
Although there is no consensus regarding optimal treatment,
most experts concur that SO requires prompt attention and
treatment. Prompt and effective management with systemic
immunosuppressive agents may allow control the disease and
retention of good visual acuity in the remaining eye. Modern
immunosuppressive therapy with systemic steroids and steroid-
sparing agents such as cyclosporin A and azathioprine have
improved the prognosis of SO. However, informed consent for
[Downloaded free from http://www.meajo.org on Wednesday, May 30, 2018, IP: 202.80.214.226]
Arevalo, et al.: Sympathetic Ophthalmia
vitreoretinal surgery (especially in re-operations) should now
include the risk of SO (approximately 1 in 800).
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Cite this article as: Arevalo JF, Garcia RA, Al-Dhibi HA, Sanchez JG,
Suarez-Tata L. Update on sympathetic Ophthalmia. Middle East Afr J
Ophthalmol 2012;19:13-21.
Source of Support: Nil, Conflict of Interest: None declared.

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