Download Orbital and Adnexal Sarcoidosis

CLINICAL SCIENCES
Orbital and Adnexal Sarcoidosis
Venkatesh C. Prabhakaran, MS, MRCOphth; Perooz Saeed, MD; Bita Esmaeli, MD; Timothy J. Sullivan, FRANZCO;
Alan McNab, MD, FRANZCO; Garry Davis, FRANZCO; Alejandra Valenzuela, MD; Igal Leibovitch, MD;
Anat Kesler, MD; Jennifer Sivak-Callcott, MD; Erika Hoyama, MD; Dinesh Selva, FRANZCO
Objective: To present the clinical features and man-
agement in a series of patients with orbital and adnexal
sarcoidosis.
Methods: This multicenter retrospective study in-
cluded patients with biopsy-proven noncaseating granuloma involving the orbit or adnexa and evidence of systemic sarcoidosis. Clinical records were reviewed for initial
examination findings, radiological findings, treatment modalities, and outcome.
Results: The study included 26 patients (19 female, 7
male; mean age, 52 years). The most common feature at
the first examination was a palpable periocular mass followed by discomfort, proptosis, ptosis, dry eye, diplopia, and decreased vision. The disease affected the lacrimal gland (42.3%), orbit (38.5%), eyelid (11.5%), and
Author Affiliations: South
Australian Institute of
Ophthalmology and
Department of Ophthalmology
and Visual Sciences, University
of Adelaide, Adelaide, Australia
(Drs Prabhakaran, Davis,
Hoyama, and Selva); Academic
Medical Center, University of
Amsterdam, Amsterdam,
Netherlands (Dr Saeed); Section
of Ophthalmology, M. D.
Anderson Cancer Center,
Houston, Texas (Dr Esmaeli);
Department of Ophthalmology,
Royal Brisbane Hospital,
Brisbane, Australia (Mr Sullivan
and Dr Valenzuela); Royal
Victoria Eye and Ear Hospital,
Melbourne, Australia
(Dr McNab); Department of
Ophthalmology, Tel Aviv
Medical Center, University of
Tel Aviv, Tel Aviv, Israel
(Drs Leibovitch and Kesler);
and Department of
Ophthalmology, West Virginia
University School of Medicine,
Morgantown
(Dr Sivak-Callcott).
lacrimal sac (7.7%). Among orbital lesions, the anteroinferior quadrant was preferentially involved. Treatment modalities included steroids, surgical debulking,
and methotrexate. During a mean follow-up of 18.75
months, 84.6% of patients showed a complete response
to the treatment, but 19.2% of patients developed further signs of sarcoidosis.
Conclusions: Orbital soft tissue involvement is more
common in patients older than 50 years and in women.
The anterior inferior quadrants of the orbits appear to
be preferentially affected. Although a good response to
treatment with oral steroids is seen, long-term follow-up is recommended because active systemic disease can develop months to years later.
Arch Ophthalmol. 2007;125(12):1657-1662
S
ARCOIDOSIS IS A MULTISYS tem disease of unknown
cause that is characterized
histologically by the presence of granulomas in the affected organs.1 The diagnosis of sarcoidosis is based on a positive biopsy
(demonstrating noncaseating granulomas), a constellation of typical clinical features (such as restrictive lung disease, erythema nodosum/lupus pernio, and uveitis),
and positive chest radiography (hilar
lymphadenopathy and/or parenchymal infiltrates) in the absence of any condition
that can cause similar clinico-radiological and pathological changes.
Ocular involvement varies with race
and sex and is seen in approximately 25%
of patients with sarcoidosis.1 Uveitis is the
most common ocular manifestation, but
sarcoidosis may involve any part of the eye,
orbit, or lacrimal system.2 Orbital and adnexal manifestations of sarcoid (to distinguish from asymptomatic involvement) are
uncommon with few series in the literature,3-5 and there is a tendency in the ophthalmic literature to confuse isolated orbital granulomatous disease with
sarcoidosis. We report on a large series of
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patients with orbital and adnexal sarcoidosis, all of whom had evidence of systemic involvement. We also review the literature on this subject to better define the
clinical features and management of orbital-adnexal sarcoidosis.
METHODS
This is a multicenter retrospective study of all
patients with orbital and adnexal sarcoidosis
who were seen in 7 orbital units: Royal Adelaide Hospital, Adelaide, Australia, January
2000 to June 2007 (5 cases); Royal Brisbane
Hospital, Brisbane, Australia, January 1996 to
October 2006 (5 cases); Royal Victoria Eye and
Ear Hospital, Melbourne, Australia, January
1990 to June 2007 (3 cases); Academic Medical Center at the University of Amsterdam, Amsterdam, the Netherlands, January 1998 to October 2006 (8 cases); M. D. Anderson Cancer
Center, Houston, Texas, September 2004 to October 2006 (3 cases); West Virginia University, Morgantown, January 2006 to June 2007
(1 case); and Tel Aviv Medical Center, Tel Aviv,
Israel, January 2006 to October 2006 (1 case).
The inclusion criteria for the study were biopsy-proven noncaseating epithelioid granuloma in the lacrimal gland, orbit, eyelids, or lacrimal sac together with 1 or more of the
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A
Table 1. Signs and Symptoms at Initial Examination of
Patients With Orbital and Adnexal Sarcoidosis
Signs and Symptoms at Initial
Examination
Cases, No. (%)
Mass/swelling
Proptosis/globe displacement
Discomfort
Ptosis
Restricted ocular motility
Dry eye
Diplopia
Decreased vision
23 (88.5)
11 (42.3)
8 (30.8)
7 (26.9)
6 (23.1)
5 (19.2)
4 (15.4)
3 (11.5)
following: hilar lymphadenopathy on chest imaging, biopsyproven noncaseating epithelioid granuloma in another extrapulmonary organ or unexplained raised serum angiotensin converting enzyme (ACE) values. An epithelioid granuloma was
diagnosed on the basis of characteristic histopathological features: a discrete collection of epithelioid cells intermixed with
giant cells and lymphocytes. Special stains for fungi and mycobacteria were used to exclude infective causes. The chest xrays were read by experienced radiologists and disease activity, if present, was staged according to standard criteria. The
medical records were reviewed for the following data: age, sex,
ethnicity, duration of signs and symptoms, clinical signs at the
initial examination, site involved, imaging findings on chest
x-ray, computed tomography and/or magnetic resonance
imaging (MRI), biopsy findings, results of other investigations including gallium scanning and positron emission tomography (PET), results of serological tests including serum
ACE, treatment modalities, and outcome. Response to treatment was graded as good (improvement of more than 80% in
symptoms and signs), average (improvement of 50%-80%), poor
(less than 50%), or progressive disease. Institutional review board
and ethics committee approval was obtained at those institutions where required for this retrospective case review.
RESULTS
Our study included 26 patients (19 female, 7 male) with
a mean age of 52 years (median, 50 years; range, 28-83
years). Nineteen cases were unilateral and 7 bilateral.
There were 16 white patients, 7 African American patients, 2 Indian patients, and 1 Japanese patient. The mean
duration from initial clinical signs and symptoms to diagnosis was 8.2 months (median, 4 months; range, 1
month to 5 years).
Seven patients had been previously diagnosed with sarcoidosis (4 pulmonary, 2 pulmonary and cutaneous, and
1 cutaneous). Additional medical history included diabetes mellitus (3 patients), hypertension (5), large cell
lymphoma of the inguinal area (1), psoriatic arthritis (1),
and breast cancer (1). None of the patients had a prior
history of tuberculosis or occupational lung diseases. The
ophthalmic history was noncontributory except for 1 patient who had a history of granulomatous uveitis. The
signs and symptoms of all patients at their first examinations are summarized in Table 1.
The most common complaint was that of a slowly progressing mass (88.5%), and although discomfort was present in 30.8% of patients, significant pain was not a feature. Although dry eye symptoms were elicited in 5
B
Figure 1. Lacrimal gland sarcoidosis. A, Clinical photograph of a 39-year-old
woman who had a 3-month history of left upper eyelid swelling. B, Axial
computed tomographic scan shows an enlarged left lacrimal gland (arrow).
patients (19.2%) (4 with lacrimal gland involvement and
1 with orbital involvement), only 1 had objective evidence of dry eye on Schirmer test. Decreased vision was
an initial sign in 3 patients and was secondary to anterior uveitis in 2 cases and cataract in the other.
Computed tomographic data were available for 22 patients and MRI data for 9 patients. Those with lacrimal
gland involvement showed well-defined homogenous enlargement of the gland, but the cases with orbital involvement tended to manifest as a more diffuse process.
The lacrimal gland was involved in 11 cases (42.3%) (7
unilateral and 4 bilateral and 1 case with associated lateral rectus involvement) (Figure 1). Orbital involvement was present in 10 patients (38.5%) and could be
categorized as discrete (Figure 2) or diffuse (affecting
more than 2 quadrants) (Figure 3). Three patients had
diffuse orbital disease, and, interestingly, all 3 suffered
from active systemic sarcoidosis. In all patients with discrete lesions, the anterior orbit was involved, and of the
7 cases, 6 involved the inferior orbital quadrants and 1
the superior orbit. Extension into the eyelid from the anterior orbital process was noted in 5 of the 7 cases. Extraocular muscles were involved in 6 cases (in conjunction with orbital soft tissue in 5 cases and lacrimal gland
in 1 case). One patient with discrete orbital involvement also demonstrated irregular thickening of the left
optic nerve sheath on computed tomography (Figure 2).
Three patients (13.5%) (all female) had solitary eyelid involvement. In 2, the lower lid was affected and this
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A
A
B
B
Figure 3. Diffuse orbital sarcoidosis. A, Clinical photograph of a 63-year-old
male patient with a 5-week history of lid swelling in the right eye. B,
Magnetic resonance imaging scan demonstrates a diffuse soft tissue mass
involving the superior and medial quadrants and enveloping the globe.
C
Figure 2. Discrete orbital sarcoidosis. A, Clinical photograph of an
83-year-old female patient with a 2-month history of puffiness around left
eye. Note the superior displacement of the left eye. B, Magnetic resonance
imaging scan shows a localized soft tissue mass in the left anterior inferior
orbit (arrow). C, Axial computed tomographic scan of the same patient
shows thickening around the left optic nerve (arrow).
was the initial manifestation of the disease. The third patient, who had a history of sarcoidosis, developed sarcoidal granulomas over the medial canthi, both sides being
affected at different times. The lacrimal sac and nasolacrimal duct was involved in 2 patients (7.7%) (both female).
A biopsy of the orbital or adnexal lesion was performed in all cases and in each case showed granulomatous inflammation with epithelioid histiocytes, giant cells,
and lymphocytes (Figure 4). None demonstrated caseating necrosis, and special stains for fungal and tuberculous infection showed negative results. Polarization was
Figure 4. Photomicrograph showing a characteristic sarcoidal granuloma
embedded in orbital fat. The granuloma is composed predominantly of
epithelioid histiocytes with scattered giant cells (arrow). The granuloma is
not surrounded by lymphocytes (so-called naked granuloma, typical of
sarcoidosis).
performed to rule out the presence of foreign material.
Chest x-ray was performed in all 26 cases and findings suggestive of sarcoidosis (hilar lymphadenopathy
with or without parenchymal involvement) were present in 17 (65.4%). Positive chest x-rays were seen in 6
of the 11 cases with lacrimal gland involvement and 11
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Table 2. Summary of Demographic and Clinical Data According to Anatomical Location of Orbital-Adnexal Sarcoidosis
Characteristic
Mean age, y (range)
F/M ratio
Ethnicity
Prior history of sarcoidosis, No.
Positive chest x-ray, No. (%)
Elevated serum ACE, No. (%)
Treatment
Observation
Surgical debulking
Oral steroid
Methotrexate
Intralesional steroid injection
Response
Complete
Partial
Progression
Lacrimal Gland
(n = 11)
Extralacrimal Orbit
(n = 10)
Eyelid
(n = 3)
Lacrimal Sac
(n = 2)
46.1 (28-66)
6:5
6W, 2AA, 2I, 1J
3
6 (54.5)
9 (81.8) b
59.3 (38-83)
8:2
6W, 4AA
1
9 (90) a
3 (30)
54.3 (33-79)
3:0
3W
1
0
3 (100)
44.5 (40-49)
2:0
1W, 1AA
2
2 (100)
0
1
3
10
2
0
0
2
8
2
1
0
3
0
0
0
0
2
1
0
0
10
1
0
8
1
1
2
0
1
2
0
0
Abbreviations: AA, African American/African; ACE, angiotensin converting enzyme; CSF, cerebrospinal fluid; I, Asian Indian; J, Japanese;
PET, positron emission tomography; W, white.
a Including 1 patient in whom hilar uptake was demonstrated by PET.
b Including 1 patient in whom CSF ACE was elevated.
of the 15 cases with extralacrimal gland involvement
(Table 2). In 1 patient with a negative chest x-ray, a PET
scan demonstrated hilar uptake.
Serum ACE estimation was performed in 24 cases and
was found to be elevated (in comparison with the referral laboratory range) in 15 (62.5%). The serum ACE was
elevated in 8 of the 11 cases with lacrimal gland involvement and 6 of the 13 extralacrimal cases in which it was
estimated (Table 2). In 1 patient with bilateral lacrimal
gland enlargement and seventh nerve palsy, serum ACE
was normal but the cerebrospinal fluid ACE was elevated.
Additional systemic investigations performed included gallium scintigraphy (5 patients, all with lacrimal gland involvement; positive in 4), serum lysozyme
(8 patients; elevated levels in 2), serum calcium (13 patients; elevated levels in 1), liver function tests (19 patients; abnormal results in 3), pulmonary function tests
(16 patients; abnormal results in 7), tuberculin test (9
patients; anergy in 1 case), mediastinal lymph node biopsy (2 patients, both positive), liver biopsy (2 patients;
positive in 1), and a nasal mucosa biopsy that showed
granulomatous inflammation in 1 patient with lacrimal
sac involvement.
Three patients (11.5%) had pulmonary symptoms and
signs at the initial examination (previously undiagnosed sarcoid), and 1 of them also had sinus, parotid,
and epididymal involvement at the initial examination.
Four patients had active anterior uveitis at diagnosis or
in the follow-up period, and residual signs of old uveitis
were present in 2 patients. Cutaneous involvement (lupus pernio) was present in 3 patients. Other extrapulmonary manifestations of sarcoidosis (uveitis, optic disc
swelling, seventh nerve palsy, epididymal mass, miliary
liver lesions) occurred in 5 patients (19.2%) during the
follow-up period (within 1 year of initial ophthalmic
symptoms in all except in 1 patient who developed mili-
ary liver and lung lesions 5 years following orbital involvement). The patient who developed a right-sided facial palsy (4 weeks into the follow-up period) also had
bilateral granulomatous anterior uveitis, vitritis, and left
optic disc edema (suggestive of Heerfordt syndrome).
None of the patients with neurological symptoms had evidence of central nervous system involvement on neuroimaging.
Management modalities included steroids (oral prednisolone: 19 patients, 73.1%; intraorbital steroid injection: 1 patient, 3.8%), surgical debulking (10 patients,
38.5%), and methotrexate (4 patients, 15.4%). Five patients (2 each with orbital and eyelid disease and 1 with
lacrimal sac involvement) had only surgical debulking.
One patient with lacrimal gland involvement did not elect
to have any further treatment. The steroid dose ranged
from 25 mg to 80 mg and was tapered on an individual
basis. The duration of treatment ranged from 2 to 36
months (mean, 6.9 months; median, 3 months). Intraorbital steroid injections (3 injections of triamcinolone
acetonide, total 100 mg, over 2 months) were used in 1
patient who was not tolerant to oral steroids. Four patients required additional treatment with methotrexate
(in 2 patients as a steroid-sparing agent, in 1 patient for
active systemic disease, and in 1 patient in whom steroids were ineffective in controlling ophthalmic disease).
The mean follow-up period was 18.75 months (median, 9 months; range, 3-60 months). In 22 patients
(84.6%), the response to treatment was graded as good
with significant decrease in the size of the lesion and symptom resolution. Two patients who were treated with oral
steroids had a partial decrease in the size of the lesion
but were symptomatically better. Progression was noted
in 2 patients: 1 patient with orbital disease who developed new orbital lesions while on prednisolone and
methotrexate and 1 patient with eyelid involvement,
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treated only with surgical debulking, who developed bilateral lacrimal gland enlargement and swollen optic discs
3 months into the follow-up period. During the follow-up period, no patient developed recurrence.
COMMENT
We present a series of biopsy-proven orbital and adnexal sarcoidosis, including treatment details and outcomes. Our study highlights the clinical features of extralacrimal orbital sarcoidosis, an uncommon condition
that may be the initial feature of systemic sarcoidosis. We
found that orbital involvement is more commonly seen
in the fifth to seventh decades and is more frequent in
women. It appears to occur in 2 forms, diffuse and discrete: diffuse involvement that may occur more commonly in patients with active systemic sarcoidosis and
discrete lesions that appear to have a predilection for the
anterior inferior quadrants of the orbit.
Ophthalmic involvement in systemic sarcoidosis is common (25%-60% of patients)6 with anterior uveitis being
the most common manifestation. However, involvement
of the orbit and adnexal structures is much less common
with conflicting data on incidence due to the differing diagnostic criteria for sarcoidosis employed in the various
studies. Most cases reported as solitary orbital sarcoid may
represent idiopathic granulomatous orbital inflammation. This entity was reviewed by Mombaerts and coworkers,7 who found that it affected men more commonly, that
it was usually seen in the fourth decade, and that 50% of
cases affected the lacrimal glands. We agree with Mombaerts and colleagues7 that the term orbital sarcoid should
not be used in the absence of any evidence of systemic disease because this may hamper a more rigorous investigation into the causes of a solitary orbital granulomatous lesion. Also, the distinction between solitary orbital sarcoid
and granulomatous pseudotumor (idiopathic inflammation) is probably academic because both are diagnoses of
exclusion and are moreover etymological cousins (sarcoid deriving from sarcoma-like; in other words, a pseudotumor). It should be emphasized that all the patients
in our series had evidence of systemic involvement with
sarcoidosis.
Within the orbit, sarcoidosis can involve the lacrimal
gland, soft tissues of the orbit, and the optic nerve. The
lacrimal gland is said to be commonly affected in sarcoidosis,2 and 2 large studies found incidence rates of
15.8%3 and 7%.5 It should be noted, however, that biopsy confirmation was obtained only in a minority of cases
in both studies and that the diagnosis of lacrimal gland
involvement was based on clinically evident enlargement of the gland or on the presence of dry eye symptoms. It is interesting to note that in our series, with biopsy confirmation of lacrimal gland involvement, only
5 patients had dry eye symptoms and only 1 patient had
objective evidence of aqueous deficiency. In our series,
there were almost equal numbers of patients with lacrimal and extralacrimal orbital disease: this may reflect a
referral bias in that most patients with systemic sarcoidosis and lacrimal gland enlargement may not be referred to an orbital center.
Orbital soft tissue involvement is a distinctly uncommon manifestation of sarcoidosis. The first case was reported by King8 in 1939, and since then scattered case reports9-16 and 1 case series4 have appeared in the literature.
In 3 large series on ophthalmic manifestations of sarcoidosis, orbital involvement was seen in 2 of 202 patients (1%)
in 1 series3 and in none of the patients in the other 2 series.5,17 As previously discussed, analysis of the literature
on orbital sarcoidosis is complicated by the tendency of some
authors to report solitary orbital granulomas with no evidence of systemic disease under the rubric of sarcoidosis.
Analysis of only reported cases with systemic involvement8-16 demonstrates that orbital sarcoidosis predominantly occurs in older persons (mean age, 55.9 years, range,
27-85 years) and is more common in women (ratio, 4:3).
A racial predilection was not evident from the cases reviewed. A prior history of sarcoidosis is rare, but the chest
x-ray usually reveals hilar lymphadenopathy. In cases with
a normal chest x-ray but a high suspicion of sarcoidosis,
high-resolution computed tomography of the chest may
be more sensitive. In cases where information regarding
the location was available, the inferior orbit was involved
in 60%. Further systemic involvement was diagnosed in 2
patients 1 year following the diagnosis of orbital disease
(lung parenchymal involvement in 1 patient12 and positive liver biopsy in another11). In cases where details of treatment were reported, the orbital lesion was uniformly responsive to oral steroids. These data are similar to the
findings in our study. It may be noted here that extraocular muscle involvement may be seen in association with orbital lesions (especially in cases of diffuse involvement),
as was the case in our patients, but solitary muscle enlargement secondary to sarcoidosis is a rare event with only a
few cases reported, and these have been reviewed in a report by Cornblath and colleagues.18
Involvement of the skin of the eyelids with cutaneous
sarcoidosis may be seen (in the form of millet-seed nodules or rarely destructive skin lesions),11,19-21 but sarcoidal
granulomas within the eyelid appears to be an uncommon finding.5,11,22,23 In our series, all 3 patients with eyelid
involvement were female, the lower lid was involved in 2
cases, and in both this feature was the initial feature of systemic disease. All 3 cases were treated successfully with surgical excision. Eyelid sarcoidosis appears to be much more
common in women, may have a predilection for the lower
lid, and may often be the first feature of sarcoidosis.
Sarcoidosis of the lacrimal sac and nasolacrimal duct
is also an uncommon event. Harris and coworkers24 reviewed the literature on sarcoidosis of the lacrimal sac
and found that it usually occurs in association with nasal mucosa involvement. Patients with sarcoidosis of the
nasolacrimal system are also at increased risk of failure
following dacryocystorhinostomy.24 Both our patients with
lacrimal sac sarcoidosis had recurrence of epiphora following dacryocystorhinostomy.
Management of orbital and adnexal sarcoidosis depends on the extent and site of disease, degree of functional impairment, and presence or absence of active systemic disease. Although up to two-thirds of cases of
systemic sarcoidosis show spontaneous remission,25 there
are insufficient data on the natural history of orbital and
adnexal disease to recommend observation as a plan of
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management. Oral steroids have been the mainstay of
treatment in these patients, and most reported cases (including those in this study) show a good response. In cases
without active systemic disease, a short course of oral prednisolone (starting at 1 mg per kilogram of body weight
and tapering over 3 months) may be considered as initial therapy. In those who fail to respond or are steroidintolerant, cytotoxic agents such as methotrexate may be
used. In localized orbital disease, periocular steroids (1-mL
injection of triamcinolone acetonide 40 mg/mL) may be
considered,26 and this was effective in 1 of our patients
who was unable to tolerate steroids. Surgical debulking
or excision appears to be an effective treatment and may
be considered for localized orbital disease and especially for eyelid disease.
A long-term follow-up of these patients by a pulmonary specialist is recommended because they can develop systemic disease months to years later and also because steroid-responsive cases of systemic sarcoidosis are
at increased risk for relapses.25 Patients should also be
counseled regarding the multisystem nature of sarcoidosis and the possibility of developing active systemic disease in the future. One of the limitations of our study is
the short period of follow-up in most cases; thus we are
unable to comment on the long-term risk of recurrence
or of developing active systemic disease in this subset of
patients with extrapulmonary sarcoidosis.
Submitted for Publication: April 8, 2007; final revision
received September 5, 2007; accepted September 6, 2007.
Correspondence: Venkatesh Prabhakaran, MS,
MRCOphth, Oculoplastic and Orbital Division, Department of Ophthalmology and Visual Sciences, Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia, Australia ([email protected]).
Financial Disclosure: None reported.
REFERENCES
1. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336(17):12241234.
2. Bradley D, Baughman RP, Raymond L, Kaufman AH. Ocular manifestations of
sarcoidosis. Semin Respir Crit Care Med. 2002;23(6):543-548.
3. Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol. 1978;86(5):648-655.
4. Collison JMT, Miller NR, Green WR. Involvement of orbital tissues by sarcoid.
Am J Ophthalmol. 1986;102(3):302-307.
5. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol.
1986;102(3):297-301.
6. Hunter DG, Foster CS. Ocular manifestations of sarcoidosis. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia, PA: WB
Saunders; 1994:443-450.
7. Mombaerts I, Schlingemann RO, Goldschmeding R, Koornneef L. Idiopathic granulomatous orbital inflammation. Ophthalmology. 1996;103(12):2135-2141.
8. King MJ. Ocular lesions of Boeck’s sarcoid. Trans Am Ophthalmol Soc. 1939;37:
422-458.
9. Kaplan M. Boeck’s sarcoid: report of a case with an unusual precipitating factor.
Am J Ophthalmol. 1948;31:83-85.
10. Bodian M, Lasky MA. Sarcoidosis of the orbit. Am J Ophthalmol. 1950;33:343353.
11. Henkind P. Sarcoidosis: an expanding ophthalmic horizon. J R Soc Med. 1982;
75(3):153-159.
12. Leino M, Tuovinen E, Romppanen T. Orbital sarcoidosis: a case report. Acta Ophthalmol (Copenh). 1982;60(5):809-814.
13. Imes RK, Reifschneider JS, O’Connor LE. Systemic sarcoidosis presenting initially with bilateral orbital and upper lid masses. Ann Ophthalmol. 1988;20
(12):466-469.
14. Faller M, Purohit A, Kennel N, et al. Systemic sarcoidosis initially presenting as
an orbital tumor. Eur Respir J. 1995;8(3):474-476.
15. Peterson E, Hymas D, Pratt D, et al. Sarcoidosis with orbital tumor outside the
lacrimal gland: initial manifestation in 2 elderly white women. Arch Ophthalmol.
1998;116(6):804-806.
16. Biswas J, Krishnakumar S, Raghavendran R, Mahesh L. Lid swelling and diplopia as presenting features of orbital sarcoid. Indian J Ophthalmol. 2000;48
(3):231-233.
17. Karma A. Ophthalmic changes in sarcoidosis. Acta Ophthalmol (Copenh). 1979;
(5)141:1-94.
18. Cornblath WT, Elner V, Rolfe M. Extraocular muscle involvement in sarcoidosis.
Ophthalmology. 1993;100(4):501-505.
19. Brownstein S, Liszauer AD, Carey WD, Nicolle DA. Sarcoidosis of the eyelid skin.
Can J Ophthalmol. 1990;25(5):256-259.
20. Hall JG, Cohen KL. Sarcoidosis of the eyelid skin. Am J Ophthalmol. 1995;119(1):
100-101.
21. Moin M, Kersten RC, Bernardini F, Kulwin DR. Destructive eyelid lesions in
sarcoidosis. Ophthal Plast Reconstr Surg. 2001;17(2):123-125.
22. Cacciatori M, McLaren KM, Kearns PP. Sarcoidosis presenting as a cutaneous
eyelid mass. Br J Ophthalmol. 1997;81(4):329-330.
23. Evans M, Sharma O, LaBree L, Smith RE, Rao NA. Differences in clinical findings between Caucasians and African Americans with biopsy proven sarcoidosis.
Ophthalmology. 2007;114(2):325-333.
24. Harris GJ, Williams GA, Clarke GP. Sarcoidosis of the lacrimal sac. Arch Ophthalmol.
1981;99(7):1198-1201.
25. American Thoracic Society. Statement on sarcoidosis. Am J Respir Crit Care Med.
1999;160(2):736-755.
26. Goldberg RA. Orbital steroid injections. Br J Ophthalmol. 2004;88(11):1359-1360.
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