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

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

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Arevalo, et al.: Sympathetic Ophthalmia

a b

c d
Figure 1: Acute anterior uveitis with keratic precipitates, posterior synechiae and Figure 2: Clinical presentation of sympathetic ophthalmia after cyclophotocoagulation:
fibrin on the anterior lens capsule in the right eye of a 25-year-old male, who had (a) diffuse choroiditis with papillitis. (b) Late frame fluorescein angiogram
sustained a penetrating trauma to his left eye 3 months earlier (Reprinted with demonstrating optic disc and subretinal hyperfluorescence in the posterior pole.
permission from BenErza D25) (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 Figure 4: Fundal white dots in the macular region accompanied by retinal vasculitis
sympathizing eye demonstrating choroidal atrophy. (b) Multiple small Dalen–Fuchs were observed in the right eye of a 33-year-old male, who underwent multiple
nodules can be seen throughout the fundus in this sympathizing eye. Cell infiltrates intraocular surgeries in his left eye. The findings in the right eye were detected
were present in the vitreous. (c) This case was complicated by cataract and refractory 4 weeks after the last surgery in the left eye (Reprinted with permission from
glaucoma. The patient was treated by cataract extraction and trabeculectomy with BenErza D25)
mitomycin C initially followed by an Ahmed valve implant. (d) Exciting phthisical
left eye after trauma

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 can be found within the choroid, under the RPE or under the
what determines the fluorescence of these lesions. Blockage of neuroretina. Immunohistochemical identification of the cells in
choroidal fluorescence may occur when an intact dome of RPE Dalen–Fuchs nodules demonstrated cells originated mostly from
contains the cellular elements of the Dalen–Fuchs nodules. the reticuloendothelial system (histiocytes, lymphocytes, and de-
Gradual accumulation of fluorescein into Dalen–Fuchs nodules pigmented epithelial cells). The cellular compositions of Dalen–
may produce focal hyperfluorescence [Figure 6b]. However, Fuchs nodules in SO and in sarcoidosis are identical.35,38-40 The
degeneration of the RPE overlying the Dalen–Fuchs nodule RPE generally remains normal in appearance, but it may or
may allow fluorescein dye to permeate focally into the RPE and may not be intact anterior to these nodules. Reynard et al,29
gradually accumulate in the subretinal space.29 Late staining of reported an interesting morphological variation of Dalen–Fuchs
the optic nerve head is sometimes observed, even in the absence nodules in SO. They found three types of lesions at the level
of clinical papillitis or optic nerve head swelling. of the RPE.29 One type was a focal hyperplasia and aggregation
of retinal pigment epithelial cells. The second type, classically
As the disease process predominantly involves the choroid, referred to as Dalen–Fuchs nodules, consisted of epithelioid
ICG-V may be a useful adjunct to fluorescein angiography both cells and lymphocytes covered by an intact dome of RPE. The
for diagnosis and in evaluating the response to treatment. ICG-V third type of lesion was characterized by degeneration of the
studies show multifocal hypofluorescent spots that became more overlying RPE leading to disorganization of the Dalen–Fuchs
prominent as the study progresses. These lesions are thought nodules and possible release of their contents into subretinal
to be reflective of choroidal inflammatory cellular infiltration space. The spectrum of morphological changes occurring at the
and choroidal edema.30,31 level of the RPE is consistent with the Fuchs original hypothesis
that Dalen–Fuchs nodules undergo on evolutionary sequence of
Time domain optical coherence tomography has shown development. Jennings et al,41 suggest that the clinical appearance
disorganization and thinning of the inner retina, and pronounced of Dalen–Fuchs nodules appears to correlate with the severity
disintegration of the RPE and choriocapillaris.32 Fourier Domain of the disease.
OCT is also able to show choroidal and RPE thickening in SO
patients [Figure 6c–f]. ETIOLOGY
B-scan ultrasonography in SO demonstrates marked choroidal The etiology of SO is not clearly understood. Autoimmunity
thickening and retinal detachment in some difficult cases. and cell-mediated immune mechanisms are considered to
play a mediating role in the pathogenesis of SO. However, this
HISTOPATHOLOGY concept is not a new one, having been proposed by Elschnig
in 1910 with uveal pigment being considered a putative
The basic finding in the histopathological analysis of eyes with antigenic stimulus. Elschnig postulated that the injury to the
SO is granulomatous inflammation throughout the uveal tissue, exciting eye resulted in an absorption and dissemination of
except for the choriocapillaris and retinal vessels [Figures 7-9]. uveal pigment, which produced the hypersensitivity reaction
On histopathologic inspection, the yellowish-white choroidal in the injured eye. The continued absorption resulted in an
lesions seen clinically correspond to collections of lymphocytes, allergic reaction in the sensitized tissue of the sympathizing eye.
histiocytes, and de-pigmented RPE cells lying beneath Bruch’s Current evidence suggests that choroidal melanocytes alone as
membrane. Retinal infiltrates have been reported in 18% of an inciting target is considered insufficient to induce SO. The
SO cases.34 Specifically variable degrees of retinal involvement, cell-mediated immunity observed in SO could be directed
including perivasculitis, retinal detachment, and gliosis have been against some uveal antigen,42 a retinal antigen (such as Sag)37 or
described. The inflammatory cells involved in SO are primarily a surface antigen shared by photoreceptors, RPE, and choroidal
lymphocytes, epithelioid cells, and multinucleated giant cells, melanocytes.35 To date, no circulating antibodies directed against
all of which are components of classic granuloma. Occasionally, intraocular tissue have been found. No organism has ever been
eosinophils, neutrophils, and plasma cells may be present.34-36 consistently isolated from eyes with SO, and the disease has
never been incited in animal models following injection of an
Dalen–Fuchs nodules are found in approximately one-third infective agent. Nonetheless, through molecular mimicry of
of enucleated eyes thought to have SO [Figure 8].37 The an endogenous ocular antigen, a bacterial antigen, rather than
fundal white dots are the ophthalmoscopic counterpart of active proliferation of the organism, may be the inciting agent
the choroidal granulomata or Dalen–Fuchs nodules observed in the immune response.43
histologically. The localization of the Dalen–Fuchs nodules is
first and foremost within the choroid, as can be seen in the Albert et al,4 proposed a unified model to explain the pathogenesis
gross specimen of eyes with SO. However, histologic sections of SO. They proposed that since the choroid has no lymphatics,4
and immunostaining demonstrate that Dalen–Fuchs nodules the removal of intravitreal antigen by blood stream, or possibly,

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Arevalo, et al.: Sympathetic Ophthalmia

a b

c d

e f
Figure 5: Fluorescein angiography of the acute phase of sympathetic ophthalmia Figure 6: Sympathetic ophthalmia in the left eye after trauma to the right eye. (a) The
showing multiple hyperfluorescent dots in the mid-periphery with some confluence color fundus photograph demonstrates optic disc edema and hypopigmented round
anteriorly (Reprinted with permission from Damico FM et al.,26) 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 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 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
Figure 9: Sympathetic ophthalmia. The choroid is infiltrated by lymphocytes and
macrophages separated by groups of multinucleated cells and epithelioid cells
attack.35 This type of lymphocyte likely recognizes cell surface
(Reprinted with permission from Evans M33) 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 performed. If necessary, a vitreous sample must be obtained for
the proliferative response of primed T-helper lymphocytes to diagnostic purposes. Tuberculosis, sarcoidosis, and syphilis are
antigen present on conventional antigen-presenting cells, as well usually accompanied by constitutional signs and symptoms of
as their subsequent interleukin-2-dependent expansion. The the underlying systemic disease. These features, combined with
damage inflicted by the T cells on the uvea is for the most part appropriate testing for tuberculosis (PPD skin testing and chest
focal and slow, and is rarely accompanied by fulminant necrosis. radiograph), sarcoidosis (serum angiotensin-converting enzyme
Histiocytes and epithelioid cells also enter the immunoreactive and lysozyme, and chest radiograph), and syphilis (RPR and
sites adjacent to the uvea and become part of the Dalen–Fuchs FTA-ABS) can distinguish these systemic infections from SO.
nodules. In the same manner, the RPE cells proliferate and
change to become incorporated in the nodules. In cases where It is important to rule out potentially devastating fungal and
T-cells are able to bypass the RPE and enter the retina, retinal bacterial infections, which may evolve rapidly from uveitis to
inflammation and damage may ensue.4 severe endophthalmitis. Post-traumatic iridocyclitis may also
cause an inflammatory reaction. However, neither infection nor
DIFFERENTIAL DIAGNOSIS iridocyclitis involves the fellow eye.

The differential diagnosis of SO includes all diseases that can TREATMENT

present as panuveitis. However, patient history will reveal
previous penetrating ocular injury or intraocular surgery The treatment of SO is primarily medical. The mainstay of
[Table 2]. Occasionally, it may be difficult to distinguish SO from treatment is systemic immunomodulatory therapy. Systemic
VKH disease. However, patients with VKH have no history of corticosteroids are the first-line therapy for SO. They may
surgery or trauma and VKH presents as bilateral granulomatous be given topically, by sub-tenon or transseptal injection, and
panuveitis with prominent choroidal involvement. Typically, systemically. Oral prednisone is most frequently employed in
patients with VKH have serous retinal detachment and optic the treatment of SO. Treatment is initiated with high dosage oral
nerve involvement, not seen in SO. In addition, VKH is also prednisone (1.0 to 2.0 mg/kg/day) and tapered slowly over 3
more prevalent in certain racial and ethnic groups, and they to 4 months. In severe cases, intravenous pulse steroid therapy
may have skin and hair changes, such as vitiligo, alopecia, or can be employed (methylprednisolone 1.0 g/day for 3 days).
poliosis, or neurological symptoms such as tinnitus, headache, Adjunctive topical corticosteroids and cycloplegics are used to
or mental status change. If it is necessary to differentiate from prevent synechia formation from the anterior chamber reaction.
VKH, the cerebral spinal fluid of patients with VKH may reveal The clinical criterion for response to therapy incorporates an
pleocytosis in 84% of cases. VKH and SO are autoimmune appraisal of the inflammatory response, such as the degree of
disorders targeting melanin-bearing cells. Both diseases are choroiditis and papillitis. If there is a significant decrease in
characterized by immunologic dysregulation. Al-Halafi et al,44 inflammation, a slow taper of the oral corticosteroid may be
found a statistically significant association of systemic disorders initiated. The minimum dosing schedule required to control
and malignancy with VKH compared to SO. This finding suggests inflammation is at least a year in most cases. However, steroid use
that the two disorders have different etiology with similar ocular is associated with the development of cataracts and glaucoma.
and systemic manifestations. Regional injection of steroids in the peribulbar space can result
in scarring of orbital tissue and glaucoma.
Lymphoma, syphilis, tuberculosis, and sarcoidosis have to be
ruled out as these diseases demonstrate multiple small foci of Steroid-sparing immunomodulation may be more advantageous
choroiditis with vitreal cells. If lymphoma is suspected, careful in patients with SO. If patients are steroid-resistant or have
systemic workup, including neurological evaluation, should be intolerable side effects, cyclosporine can be used as a long-term

Table 2: Differential diagnosis of Sympathetic Ophthalmia

Sympathetic ophthalmia VKH‡ syndrome Sarcoidosis Posterior Syphilis
Age All ages 20–50 years 20–40 years All ages
Racial predisposition None Asian and blacks US: blacks None
Europe: whites
Penetrating trauma Always present Absent Absent Absent
Skin changes Uncommon Common 9 –37% patients Secondary
CNS* findings Uncommon Common 25–30 % patients Uncommon
Retinal serous detachment Rare Frequently seen Present not common Localized
Choriocapillaris involvement Usually absent Frequently seen Usually absent Usually absent
CSF† findings Usually normal Pleocytosis Usually normal Positive results
*CNS: Central nervous system, †CSF: Cerebrospinal fluid, ‡VKH: Voght–Koyanagi–Harada

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immunomodulatory agent. Cyclosporine is initiated at a dose their51 series only two patients (0.3%) developed SO and had
of 5 mg/kg/day and increased until the ocular inflammatory maintained good vision in the sympathizing eye. Savar et al,51
reaction is controlled. Once the disease is in remission for at used Bellan hypothetical calculations51 to find that between
least 3 months, a slow taper (0.5 mg/kg/day every 1–2 months) 908 (assuming a sympathetic ophthalmia rate of 3.1%) and
of cyclosporine can be initiated and progressively substituted 9999 (assuming a SO rate of 0.28%) prophylactic enucleations
by low doses of corticosteroid. Nussenblatt et al,45 reported following open globe injury would need to be performed to
successful use of cyclosporin A in conjunction with prednisone. prevent one case of legal blindness from SO. We recommend
that primary anatomical reconstruction should be performed
Other immunosuppressive agents including chlorambucil, and that should be followed by discussion with the patient and
cyclophosphamide, or azathioprine may also be utilized if family members regarding whether to retain or remove eye.
the inflammatory reaction cannot be adequately controlled
with corticosteroids or cyclosporine. Jennings and Tessler46 Controversy remains with respect to enucleation of the exciting
described favorable results with various combinations of eye after development of SO development for the management
cyclophosphamide, azathioprine, and chlorambucil with or of this condition. Kilmartin et al,12 found that once SO develops,
without steroids. Mycophenolate has also been recommended secondary enucleation of the exciting eye to reduce inflammation
for the treatment of refractory panuveitis or posterior uveitis in the sympathizing eye does not necessarily lead to a better
unresponsive to high-dose maintenance steroids (>15 mg/day) visual outcome or to a reduced need for medical therapy.
or other immunosuppressive agents or where toxicity concerns Unfortunately, the time frame necessary to perform prophylactic
exist.47 Dosage is 2 g orally and blood count monitoring is secondary enucleation remains uncertain, as SO has been
necessary. Tacrolimus has also been shown to be effective; reported with secondary enucleation performed as early as
however, renal dysfunction and glucose intolerance should be five days following a penetrating ocular injury.16 In addition, in
monitored.48 Given the more powerful nature and less favorable certain cases the exciting eye may become the better seeing eye
side-effect profile of these agents, collaborative management after chronic or severe SO. However, the pre-existing lack of
with experienced immunology specialists is advisable. vision in previously injured eyes changes the context in which a
subsequent penetrating ocular injury is managed. In this setting,
Atan et al,49 studied whether polymorphisms in the cytokine repairing the injury in order to assess for visual potential is futile,
genes are important markers for disease severity and outcome and primary enucleation may offer the best prophylaxis against
in patients with SO. Their49 results show that cytokine gene SO.16,52,53 Although it would appear that evisceration after severe
polymorphisms are markers for the severity of disease in SO and ocular trauma is a safe option with a very low risk of developing
were found to be associated with recurrence of previously stable SO, it is known that SO may occur due to uveal tissue remaining
disease and with the level of maintenance steroid treatment behind in scleral emissary channels. We suggest the surgeons
required to control inflammation. pay particular attention to the theoretically increased risk of SO
after evisceration versus enucleation.
Recently, Mahajan et al,50 proposed that fluocinolone acetonide
implant provides inflammator y control and reduces the SUMMARY
dependence on systemic immunosuppression in patients with
SO. Sympathetic ophthalmia is a rare and potentially visually
devastating bilateral panuveitis, typically following surgery
PREVENTION or non-surgical penetrating injury to one eye. High index of
suspicion is vital to ensure early diagnosis and initiation of
Surgery prior to disease onset appears to play an important role treatment, thereby allowing good final visual acuity in most
in the prevention of SO. In general, the time frame required for patients. Diverse clinical presentations are possible in SO and
this approach is believed to be within 10 days to 2 weeks from any bilateral uveitis following vitreoretinal surgery should alert
the penetrating injury.1,4 The problem with this approach is the surgeon to the possibility of SO.
that with current advanced surgical techniques, many eyes once
considered nonviable may now have a fair prognosis. Therefore, Although there is no consensus regarding optimal treatment,
current opinion sustains that SO is extremely rare and can be most experts concur that SO requires prompt attention and
effectively treated in most cases. Recently, Savar et al,51 reported treatment. Prompt and effective management with systemic
their experience with enucleation after open globe trauma at immunosuppressive agents may allow control the disease and
the Massachusetts Eye and Ear Infirmary center. Among 660 retention of good visual acuity in the remaining eye. Modern
open globe injuries, 55 had undergone enucleation, 11 primary, immunosuppressive therapy with systemic steroids and steroid-
and 44 secondary cases were documented.51 The most common sparing agents such as cyclosporin A and azathioprine have
reason for secondary enucleation was a blind, painful eye.51 In improved the prognosis of SO. However, informed consent for

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Arevalo, et al.: Sympathetic Ophthalmia

vitreoretinal surgery (especially in re-operations) should now of sympathetic ophthalmia in British and Irish patients. Br J
Ophthalmol 2001;85:281-6.
include the risk of SO (approximately 1 in 800).
24. Zaharia MA, Lamarche J, Laurin M. Sympathetic uveitis 66 years
after injury. Can J Ophthalmol 1984;19:240-3.
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1. Lubin JR, Albert DM, Weinstein M. Sixty-five years of Dunitz Ltd; 1999. p. 377-92.
sympathetic ophthalmia: A clinicopathologic review of 105 26. Damico FM, Kiss S, Young LH. Sympathetic ophthalmia. Semin
cases (1913-1978). Ophthalmology 1980;87:109-21. Ophthalmol 2005;20:191-7.
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Source of Support: Nil, Conflict of Interest: None declared.
49. Atan D, Turner SJ, Kilmartin DJ, Forrester JV, Bidwell J,

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