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Systemic diseases involving the orbit
Systemic Diseases Involving the Orbit Sally G. McKinnon and Lindell R. Gentry A variety of systemic pathological processes may involve the eye and the surrounding orbital adnexae. CT and MRI of the orbit have become useful clinical adjuvants, not only in establishment of the diagnosis, but also in suggesting the appropriate clinical treatment, sometimes preventing needless biopsy. Grave's disease, Wegener's granulomatosis, and sarcoidosis may all present initially with orbital disease before the onset of systemic manifestations. Idiopathic inflammatory disease of the orbit and lymphoproliferative disease of the orbit continue to remain radiological and clinical challenges. The article discusses the CT and MRI appearance of many of the common systemic diseases in adults with attention to features useful in clinical practice as well as in differential diagnosis.
ANY DIFFERENT systemic disorders can involve the orbit or its adnexa. Although the diagnosis may be clearly apparent from the orbital findings, often the initial presentation of systemic disease may be its orbital manifestations, which may require extensive study and testing to diagnose. Magnetic resonance imaging and computed tomography of the orbit have become important adjuncts in the diagnosis of systemic disease of the orbit.
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INFLAMMATORY DISEASES
Nongranulomatous Inflammatory Disease Idiopathic orbital inflammatory disease. Idiopathic orbital inflammatory disease (IO1D) or orbital pseudotumor is defined as a nonspecific idiopathic nongranulomatous inflammatory process for which there is no identifiable local or systemic cause. Histologically, the inflammation consists of a nonspecific inflammatory polymorphous cellular infiltrate, especially neutrophils, lymphocytes, plasma cells, and macrophages. No epithelioid or giant cells are observed. Depending on the chronicity, various amounts of fibrosis may be present. 1 The typical patient with idiopathic orbital inflammatory disease develops signs of unilateral orbital inflammation over a period of several weeks to months before presentation. No definite gender predilection has been observed. Although rare in the pediatric patient, the onset of symptoms is typically more sudden in the pediatric population, when compared with adults, and is more likely to be bilateral. 2 A variety of schemes have been proposed for
From the Department of Radiology, University of Wisconsin, Madison, WI. Address reprint requests to Lindell R. Gentry, Department of Radiology, E3/311 CSC, 600 HighlandAve., Madison, Wl53792. Copyright © 1998 by W.B. Saunders Company 0887-2171/98/1903-000658. 00/0 292
classification of IOID based on both the clinical presentation and the histopathology at the time of biopsy. Imaging (CT and MRI) has allowed an anatomic classification of the orbital inflammation that ranges from a diffuse form to localized forms affecting specific orbital tissue, including myositis, dacryoadenitis, periscleritis, and perineuritis. Each of these categories may be acute, subacute, acute recurrent, and chronic. It has been suggested that acute IOID can be clinically classified into six subsets3: (1) acute and subacute anterior inflammation, (2) acute or subacute diffuse inflammation, (3) acute and subacute myositic inflammation, (4) acute and subacute apical inflammation, (5) dacryoadenitis, and (6) perineuritis. The chronic form of IOID may be a sequela of acute recurrent orbital inflammation or may present insidiously as a subacute process. Although the inflammation is generally confined to the orbital soft tissues, rarely bone destruction or extraorbital extension can occur. 4 Patients with acute anterior IOID generally present with sudden onset of severe unilateral orbital pain with accompanying lid edema and sometimes erythema. Conjunctival chemosis, proptosis, uveitis, periscleritis, sclerotendonitis, papillitis, and exudative retinal detachment are other manifestations of acute IOID. 5 A sonographic " T " sign has been described which results from edema fluid present in Tenon's capsule and a widened appearance of the optic nerve secondary to edema or fluid entering the optic nerve sheath. 6 The sonographic "ring" sign results from edema in Tenon's capsule. Extraocular muscle involvement or dysfunction is uncommon. Both CT and MRI can demonstrate uveoscleral rim thickening and enhancement. The term "periscleritis" or °'posterior scleritis" has been used to describe inflammation that tends to occur around the posterior portions of the globe. Posterior scleritis in pseudotumor has been reported in isolation or with involvment of other
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orbital structures. The posterior scleritis of IOID has been reported to be more uniform in appearance than the posterior scleritis of metastatic disease or melanoma, which tend to be more focal v (Figs 1 and 2). Sclerotendonitis, inflammation at the site of the extraocular muscle tendon insertions on the sclera, is also common, and characteristically causes blurred vision and pain with ocular movements. Sclerotendonitis can also be associated with iritis and choroiditis. Posterior orbital inflammation may be associated with optic neuropathy, although early in the presentation, the visual fields and visual acuity are usually unaffected. The differential diagnosis of acute IOID includes orbital cellulitis, ruptured dermoid cyst, or the abrupt formation of a "chocolate" cyst as a result of hemorrhage into a lymphangioma. In children, rhabdomyosarcomas, metastatic neuroblastoma, or leukemic infiltration of the orbit can simulate nonspecific orbital inflammation. 6 The diffuse or tumefactive form of IOID presents with clinical features similar to acute and subacute anterior inflammation, but is often more severe in nature. In the diffuse form, presenting features include severe pain, proptosis, diplopia with extraocular muscle dysfunction, lid swelling, chemosis, papillitis, choroiditis, and optic neuropathy. 5 The diffuse form is characterized by the formation of dense collagenous connective tissue containing
Fig 1. Posterior scleritis in idiopathic orbital inflammatory disease (IOID). Axial CT section through the left orbit demonstrates uniform thickening of the uveoscleral rim and infiltration of the adjacent retrobulbar fat.
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Fig 2. Nodular posterior scleritis in IOID. Axial CT section through the orbits demonstrates nodular scleral thickening on the right. (Reprinted with permission from Johnson MH, DeFilipp G J, Zimmerman RA, Savino PJ: Scleral inflammatory disease. AJNR 8:861-865, 1987. 7)
hyaline. 8 The infiltrate can involve the whole orbit, including the entire intraconal and extraconal retrobulbar spaces. Typically, the infiltrate does not distort the boundaries of the globe, 3 (Fig 3). As the diffuse form becomes chronic, the response to steroid therapy diminishes. 6 A subset of the diffuse form of IOID is the sclerosing type of orbital pseudotumor. This process probably represents the chronic or endstage form of the disorder, although it has been reported to arise de novo. In sclerosing orbital pseudotumor, there is complete fixation of the intraorbital structures by formation of dense collagenous connective tissue which slowly mats together all of the intraorbital structures, decreasing their function as it progresses. Permanent extraocular muscle dysfunction and fixation of the globe leads to a fixed firm orbit and may result in blindness 6 (Fig 4). The chronic or sclerosing form of IOID is very difficult to treat, having a less dramatic response to steroids and radiation therapy. Radiation may be palliative for some steroid-resistant cases. 9 The differential diagnosis of the diffuse form of IOID includes primary tumors of the orbit, metastatic disease, and orbital lymphoid lesions. However, these conditions are not commonly associated with pain, erythema and extraocular muscle dysfunction, and have been noted to have a predilection for the superior orbit. 6 Neoplasms may not respect the boundaries of the eye, often indenting or invading the globe. Surface coil MR has been shown to he of use in differentiating orbital pseudo-
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Fig 3. Diffuse form of IOID. (A) Axial CT of the orbits reveals enlargement of the extraocular muscles, infiltration of the orbital fat, uveoscleral rim thickening, and infiltration of the medial eyelid on the right. The globe maintains a relatively normal shape. (B) Coronal CT reconstruction through the orbit confirms the enlargement of the extraocular muscles and enlargement of the optic nerve and sheath, and demonstrates infiltration of the orbital fat on the right.
tumor from other disease entities such as malignancy and hematoma. In a study by Atlas and Grossman et al, pseudotumor appeared hypointense to orbital fat (isointense to muscle) on Tl-weighted images and isointense or minimally hyperintense to orbital fat on T2-weighted images. Other benign inflammatory entities (infectious myosifts and sarcoid) had identical signal characteristics. This is in contradistinction to other diseases, including malignancy, which appeared markedly hyperintense to fat on T2-weighted images.
Fig 4. Sclerosing form of IOID. Coronal Tl-weighted MR image demonstrates sclerosing pseudotumor. Note the thick band of tissue superior to the globe on the right.
Orbital myositis is a subtype of nonspecific orbital inflammation that is characterized by infiltration of one or more of the extraocular muscles by an inflammatory process (Fig 5). Acute, subacute, and recurrent forms have been described. In the acute form, the extraocular muscle limitation is often directly related to the action of the muscle. In
Fig 5. Myositic form of IOID. Coronal CT section through the orbits demonstrates isolated enlargement of the left superior rectus muscle. Note also minimal infiltration of the orbital fat on the left.
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the subacute form, however, the deficit may be identical to that noted in thyroid ophthalmopathy with restriction of gaze in the opposite field of action of the involved muscle secondary to chronic fibrosis. 6 Myositis often affects more than a single muscle and is not uncommonly bilateral, m MRI and CT may show enlargement of one or more extraocular muscles, which extends anteriorly to involve the inserting tendon. However, this sign may or may not be present. Its absence does not exclude the diagnosis of the myositic form of pseudotumor. Orbital thyroid ophthalmopathy, enlargement of the extraocular muscles with carotid cavernous fistula or cavernous dural AVM, and neoplastic/metastatic infiltration of the extraocular muscles can mimic the myositic form of pseudotumot. 6 Orbital apicitis may result from IOID involving the orbital apex. CT and MRI can show infiltrative tissue at the orbital apex extending anteriorly along the optic nerve or extraocular muscles. Typically, the anatomic boundaries of the extraocular muscles and optic nerve are obscured at the orbital apex (Figs 3 and 6). Symptoms may include painful ophthalmoplegia, extraocular muscle dysfunction and/or restriction, optic neuropathy, diplopia, and mild proptosis.5 A variant of pseudotumor is TolosaHunt syndrome, which can also involve the orbital apex, including the superior orbital fissure, as well
Fig 6. Orbital apicitis in IOID. Axial CT of the orbits shows the diffuse form of IOID with obliteration of the anatomic boundaries of the extraocular muscles and the optic nerve at the orbital apex (arrowheads),
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as the cavernous sinus. In Tolosa-Hunt syndrome, the ophthalmoplegia consists of palsies of the third, fourth, and sixth cranial nerves as well as the ophthalmic division of the trigeminal nerve. Most cases of Tolosa-Hunt syndrome are generally unilateral. 11 (See the article by Mark in this same issue.) Perineuritis, an unusual type of nonspecific orbital inflammation, can present with orbital pain, decreased visual acuity, and disc edema. There is often pain with eye movement and ballottement of the globe. This is in distinction to optic neuritis, which rarely presents with pain with ballottement of the globe and eye movements. MRI and CT show enlargement and enhancement of the optic nerve sheath, often with a ragged border6 (Figs 7A, B). The anterior segment is usually normal. Nonspecific inflammation involving the lacrimal gland is present in idiopathic dacryoadenitis. Tenderness is usually present in the upper outer quadrant of the orbit at the level of the lacrimal gland. Mild erythema, conjunctival chemosis, and an "S"-shaped appearance to the upper lid are common clinical features. CT and MRI characteristically show an enhancing mass in the lacrimal region, often with edema extending into Tenon's capsule. Viral dacryoadenitis can pose a similar appearance, but can often be distinguished by the presence of peripheral adenopathy and lymphocytosis (especially in mononucleosis). Chronic idiopathic dacryoadenitis can be a more difficult clinical distinction. Pain is often a feature of malignant tumors arising in the lacrimal gland. Bone destruction may be present in these cases, which is rare in idiopathic chronic dacryoadenitis. Biopsy or fine needle aspiration may be necessary.22 Nonspecific or idiopathic orbital inflammatory disease has been observed in individuals who have systemic diseases such as sarcoidosis, Wegener's granulomatosis, thyroid disease, and Langerhan's histiocytosis among others. Interestingly, orbital pseudotumor has also been observed in patients with retroperitoneal fibrosis (multifocal fibrosclerosis). Multifocal fibrosclerosis 13 defnes a constellation of pathologically similar syndromes. The most common of these include mediastinal fibrosis, retroperitoneal fibrosis, orbital pseudotumor, Reidel's thyroiditis, and sclerosing thyroiditis. Other manifestations can include Peyronie's disease, Dupuytren's contractures, vasculitis, subcutaneous fibrosis, idiopathic hypertrophic pachymeningitis, and testicular fibrosis. The disorder can be familial
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Fig 7. Perineuritis in IOID (pseudotumor). (A) Sagittal fat-suppressed contrast-enhanced T1 MR section which reveals enhancement of the anterior one half of the optic nerve sheath and enhancement of both the optic nerve and nerve sheath posteriorly. (B) Axial fat-suppressed contrast-enhanced T1 MR image demonstrates perineural infiltration of the orbital fat as well as enhancement of the optic nerve sheath,
or sporadic and has no known etiology. The clinical course of the disorder is highly variable, with the illness following a prolonged course in many individuals. Rapid deterioration has also been reported. This syndrome should be considered in patients who show intracranial extension of orbital pseudotumor, and indicates the potential for future complications of systemic disease in patients who initially present with IOID. The diversity of diseases associated with IOID and the number of disorders that can mimic IOID of the orbit is extensive. It is no surprise that IOID remains a diagnosis of exclusion, based on the results of laboratory tests, clinical history, response to therapy, and often biopsy.
Granulomatous Disease Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various etiologies with a common histopathological substrate. Infection by various bacterial pathogens (mycobacterium tuberculosis, histoplasma capsulatum, mycobacterium leprae, treponema pallidum) and variety of suspected immune-mediated diseases (Wegener's granulomatosis, sarcoidosis, Langerhan's cell histiocytosis, Sj6gren's syndrome, Erdheim-Chester disease, xanthogranulomatous disease) cause a granulomatous inflammatory response within the orbit. Granulomatous disease that primarily affects the gastrointestinal system such as Crohn's disease, ulcerative
colitis, and Whipple's disease rarely may also affect the orbit. Wegener's granulomatosis. Wegener's disease is characterized by necrotizing granulomatous vasculitis and can involve multiple organ systems including the respiratory tract, kidneys, and the eyes. The disease is twice as common in men as in women, with the peak incidence in the fifth decade of life. Although the etiology is unknown, the disease may result from hypersensitivity to an unidentified antigen. Immune-related complexes have been found in biopsy specimens of involved tissues. 14 Before the introduction of immunosuppressive therapy, Wegener's disease was typically fatal, usually from the sequela of renal failure. 15 The orbit can be involved as a part of disseminated Wegener's disease or as a localized abnormality. 16 Isolated orbital involvement may be the initial sign of the disease. The most common ocular features are progressive marginal ulcerative keratitis, scleritis, episcleritis, and conjunctival inflammation. Posterior segment involvement includes retinitis with venous congestion, uveitis, and optic neuropathy. MRI or CT findings are nonspecific and most commonly demonstrate the orbital adnexal involvement or sinus inflammation (Fig 8). Patients may develop a "saddle nose" deformity from destruction of the nasal cartilages. Unilateral or bilateral orbital masses may be present 17 (Fig 9). The nasolacrimal ducts may be obstructed and the lacrimal glands enlarged. Occasionally, lid nodules
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Fig 8. Wegner's granulomatosis. (A) Thickened, enhancing scleral characteristic of posterior scleritis is apparent along with enhancement of the optic nerve sheath. (B) Enhancement of the superior rectus muscle is apparent.
(granulomas), dacryoadenitis, and lid swelling are present. 18Bilateral orbital involvement is common. A chronically progressive orbital apex syndrome has also been associated with Wegener's granulomatosis. 15,19The orbital manifestations of Wegener's disease should be differentiated from metastatic disease, idiopathic orbital inflammatory disease (pseudotumor), and lymphoproliferafive disease of the orbit, 2° usually by biopsy. Sarcoidosis. Sarcoidosis, an idiopathic systemic granulomatous disorder, primarily occurs in the third and fourth decades of life. The disease seems to represent an immune response to an unknown antigen. Because of the high frequency of pulmonary and hilar manifestations at the time of presentation, many researchers believe the antigen is airborne. Antigen-stimulated T-helper cells that
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secrete lymphokines, which activate monocytes to differentiate into epithelioid and multinucleated giant cells, mediate the granulomatous response. Although the disease can involve multiple systems, the lungs, skin, and eyes are most often affected. Sarcoidosis is 10 to 20 times more common in the African-American population than in Caucasians. The visual system is affected in approximately one fourth of cases and may be the initial presentation of the disease (19% in o n e s e r i e s ) . 22 Anterior granulomatous uveitis is the most common ocular manifestation of sarcoidosis. 21 Nodules develop on the iris at the pupillary margin (Koeppe's nodules) or in the superficial stroma (Busacca's nodules) as a result of granuloma formation. Uveitis can be associated with facial nerve palsy and fever (Heerfordt's syndrome). Circulating immune complexes are the etiology of Lofgren's syndrome (acute iritis, erythema nodosum, malaise, bilateral hilar lymphadenopathy, arthralgias) which generally has a good prognosis. The posterior segment is involved in about one quarter of patients with ocular sarcoid, and such involvement correlates with a high incidence of central nervous system involvement? 1,22 The optic nerve is occasionally affected, often with the central nervous systemY Several mechanisms have been proposed by which the optic nerve may be affected, including optic disk papillitis due to intraocular inflammation, papilledema secondary to increased intracranial pressure, optic atrophy, and primary infiltration of the optic nerves and nerve sheaths. On gadoliniumenhanced MRI, the optic nerves may demonstrate perineural enhancement, enlargement, or atrophy (Fig 10). Chiasmatic involvement can be present. Optic nerve enlargement in sarcoidosis may resemble a primary neoplasm of the optic nerve or nerve sheath. 24 A trial of corticosteroids can help differentiate optic nerve involvement by sarcoid from optic nerve sheath meningioma, preventing unnecessary optic nerve biopsy. Granulomatous lesions of the optic nerve usually show a decrease in size and contrast enhancement on MRI after steroid treatment. Meningiomas do not typically respond to steroids? 3 Differentiation from optic neuritis associated with demyelinating disease, particularly multiple sclerosis, may be difficult. Evaluation of the brain parenchyma is often helpful, revealing a pattern of demyelination consistent with multiple sclerosis. Leptomeningeal enhancement is strong supporting evidence of neurosarcoid-
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Fig 9. Wegener's granulomatosis. (A) Axial CT section the orbits reveals diffuse infiltration of the orbital contents leading to a "frozen" orbit, The globe maintains its normal contour (B) Coronal and axial {C) CT section demonstrates the diffuse pronounced bony thickening and sclerosis of the walls of the maxillary sinuses. The septal erosion and perforation may lead to the "saddle nose" deformity in Wegener's granulomatosis.
osis provided that other causes, such as tuberculosis, fungal disease, and neoplasm, have also been excluded. In the absence of CNS involvement, laboratory studies may be helpful. Peripheral seventh nerve palsy is a common finding with neurosarcoidosis, but not in multiple sclerosis. The lacrimal gland is often involved in orbital sarcoidosis, presenting as a chronic dacryoadenitis (Fig 11). Extensive involvement of the lacrimal glands and salivary glands may result in xerostomia and tear hyposecretion (Mikulicz syndrome). Metastatic disease and lymphoma involving the lacrimal gland usually shows high signal intensity on T2weighted MR images in contrast to sarcoidosis and orbital pseudotumor. Infiltrating retrobulbar orbital
masses resulting in proptosis or myositis may occur in sarcoidosis 19 and are indistinguishable from pseudotumor o n M R [ . 23,25 Erdheim-Chester. Erdheim-Chester disease is a rare form of systemic xanthogranulomatous disease that occurs in adults. The disease uncommonly involves the orbit. However, orbital involvement, when present, mimics orbital pseudotumor and is most often bilateral. Patients typically demonstrate bilateral exophthalmos that can lead to ophthalmoplegia and visual loss as a result of compression from infiltration of the orbital fatty reticulum. 26 At biopsy, fibrosing xanthogranulomas, xanthogranulomatous histiocytes, and occasional Touton giant cells are present. Radiological findings include soft
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Fig 10. Sarcoidosis. (A) An inversion recovery MR image reveals abnormal high signal intensity present along the right optic nerve and optic nerve sheath extending intracranially (arrow). (B) Coronal MR image shows abnormal high signal involving the right optic nerve and nerve sheath. A similar appearance may be observed with optic neuritis associated with multiple sclerosis, or neoplasms such as meningioma, or optic glioma.
tissue infiltration of the orbital fat and enlarged extraocular muscles and lacrimal gland. 27 Systemic manifestations include infiltration of the lungs, kidneys, heart, bones, and retroperitoneum. Neerobiotic xanthogranuloma. Necrobiotic xanthogranuloma is a disease characterized by multiple waxy, yellow, indurated or inflamed subcutaneous nodules or plaques. The disease has a predilection for the periorbital regions, especially the eyelids and
occasionally the anterior orbit. The disease is associated with paraproteinemia and hematologic proliferative disorders, especially multiple myeloma. It has also been reported in leukemia patients. Typically, the subcutaneous lesions exhibit prominent tracts of necrobiosis surrounded by palisading histiocytes and Touton giant cells. Chemotherapy has been found to be the most efficacious treatment although response to steroids has been observed. 19
Inflammatory Bowel Disease
Fig 11. Sarcoidosis. Axial T1 MR image shows mild, bilateral enlargement lacrimal glands, The lacrimal glands remain low in signal intensity.
Whipple's disease. Whipple's disease is a rare multisystem chronic noncaseating granulomatous bacterial infectious disease. Propionibacterium acnes has been cultured from involved lymph nodes. The gastrointestinal system is predominately affected, often resulting in steatorrhea in advanced disease. The cardiovascular, respiratory, central nervous, and musculoskeletal systems are also frequently involved. Orbital manifestations are often found early in the disease and consist of ophthalmoplegia, nystagmus, gaze palsy, ptosis, and papilledema. Ocular findings may include kerafitis uveitis, inflammatory vitreous opacities, vitreous hemorrhage, retinal hemorrhage, and vasculitis involving the retinal and choroidal vessels. 28,29 The ocular disease is often secondary to
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central nervous system involvement. CT and MRI findings are nonspecific. Crohn's disease and ulcerative colitis. Ocular complications are observed in approximately 10% of patients with Crohn's disease and less frequently in ulcerative colitis. The orbital disease can be divided into primary, secondary, and coincidental complications. 3° Primary complications occur during periods of active disease in the gut and respond to treatment of the gut. Episcleritis, uveitis, and keratopathy are seen most commonly as primary manifestations of Crohn's disease. However, orbital pseudotumor and optic neuropathy can also occur.31,32 Episcleritis is not a manifestation of ulcerative colitis. A specific sign of Crohn's disease on ophthalmic examination is multiple gray densities that occur in the anterior cornea. 33 Secondary complications occur usually as a result of malnutrition, particularly vitamin A deficiency as a result of malabsorption. Kimura's disease. Kimura's disease or angiolymphoid hyperplasia with eosinophilia is an idiopathic inflammation of the skin that involves the head and neck region, usually in the fourth or fifth decade of life. A slight male preponderance has been observed. Orbital findings simulate orbital pseudotumor and can involve the orbit and the orbital adnexa, most commonly unilaterally, although bilateral involvement has been reported. 34 Grossly, the lesions are well-circumscribed, firm, reddish brown masses with increased vascularity. These lesions pathologically consist of a central area of proliferation of blood vessels surrounded by an infiltrate containing scattered numerous eosinophils and lymphocytes.3s Systemic findings include peripheral blood eosinophilia, multiple nodular, macular skin lesions, and lymphadenopathy. The disease is thought to represent a benign inflammatory process rather than a true neoplasm.
ENDOCRINE DISEASE
Several common endocrine systemic diseases often present with striking orbital manifestations. The two endocrine diseases that most commonly present with orbital complications include Graves' disease and diabetes mellitus. However, acromegaly may also present with orbital findings.
Grave's Disease
Graves' disease, or thyroid ophthalmopathy, is an autoimmune inflammatory condition of orbital tissues, particularly the extraocular muscles and orbital fat. The inflammatory reaction has both humeral and cell-mediated components. The lacrimal gland may also show inflammatory change, although it is usually not as severe. The histology of the inflammatory infiltrate is primarily lymphocytes, plasma cells, and occasional mast cells. A fibroblast reaction is present with production of mucopolysaccharides, especially hyaluronic acid. In the adult population, hyperthyroidism is more prevalent in women than men (4:1 ratio). It is relatively uncommon in children. Orbital symptoms include lid retraction, lagophthalmos, conjuncrival and periorbital edema, restrictive extraocular myopathy, and proptosis. Enlarged episcleral vessels over the rectus muscle insertions, diplopia, and glaucoma can occur owing to enlargement, restriction, and vascular engorgement of the rectus muscles. Long-standing inflammation leads to fibrosis of the muscles. 36 Most clinicians consider thyroid ophthalmopathy to be a component of Graves' disease. A recent Japanese study of 21 patients with untreated Graves' disease and no clinical manifestations of thyroid eye disease showed that 7 1% of these patients did have extraocular muscle enlargement when imaged with MRI. 37 However, thyroid eye disease may present before, coincident with, or after the onset of the systemic disease, causing some investigators to believe that they are separate diseases. 38,39 Nevertheless, the diagnosis is usually established by clinical means, most commonly, laboratory tests. CT and MRI characteristically show enlargement of the extraocular muscles. The sparing of the tendons of the affected rectus muscles is typical and can be helpful in distinguishing thyroid ophthalmopathy from IOID of the orbit. The inferior rectus muscle is the most frequently affected followed by the medial rectus and the superior rectus-levator complex4°,41 (Fig 12). With gadolinium-enhanced MRI, the muscle bellies show marked enhancement (Fig 13). This is in contradistinction to other skeletal muscles, which usually reveal little contrast enhancement. The margins of the muscles are generally well-defined. The lateral rectus muscle
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Thyroid ophthalmopathy should be distinguished from other causes of extraocular muscle enlargement including IOID, metastatic disease, lymphoid diseases, acromegaly, amyloidosis, and vascular malformations with subsequent rectus muscle enlargement. HEMATOLOGIC AND HEMATOPOIETIC DISEASES
Some hematologic and hematopoietic diseases may exhibit relatively specific orbital manifestations, whereas in other cases the orbital changes may be only incidental to the disease. This topic is
Fig 12. Thyroid ophthalmopathy. Coronal T1 MR image demonstrates the extraocular muscle enlargement in thyroid eye disease. Note the normal size of the lateral rectus muscle, whereas the inferior, medial, and superior rectus muscles are enlarged.
may also show enlargement, but it is generally in conjunction with enlargement of other muscles. If the rectus muscle enlargement is severe, extrinsic pressure on the optic nerve, especially at the orbital apex, can result in vision loss and visual field deficits42 (Fig 14). Coronal imaging is superior to axial imaging in the evaluation of the rectus muscles. The orbital fat volume is also frequently expanded and should be suspected in patients with severe exophthalmos. The optic nerve often becomes stretched. The orbital septum bulges anteriorly (Fig 15). The orbital fat has a somewhat "dirty" appearance on CT as a result of increased densities within the fat which have been proven to represent lymphocytic infiltrations. Rarely, the optic nerve can appear slightly enlarged. Bone changes can also occur in conjunction with thyroid ophthalmopathy. This is usually observed when there is extreme enlargement of the medial recti, which causes medial bowing of the lamina papyracea. This appearance has been called the "soda bottle" contour.43 Short tan inversion recovery (STIR) MR imaging has recently shown increased signal within the muscles during active periods of the orbital disease. 44 Cine MR can show the extraocular muscle restriction and reduced elasticity with eye movement from the disease in its "burnt out" phase. Reduced elasticity is manifest by failure of the extraocular muscle to stretch with eye movement44 (Fig 16). These MR findings can be an adjunct to therapeutic planning. 44
Fig 13. Thyroid ophthalmopathy. Axial pre {A) and post (B) contrast images show enlargement and enhancement of the medial and lateral rectus muscles in thyroid ophthalmopathy.
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regarding this entity, which comprises a diverse group of lesions ranging from benign lymphoid hyperplasia to malignant lymphoma. Clinical evaluation, imaging, and pathological tissue analysis are problematic in these related disorders.45 Lymphoid proliferations may occur anywhere in the orbit and mimic many different orbital diseases. There are no absolute clinical, imaging, or laboratory criteria that can facilitate a distinction among the benign and malignant lesions. It has been suggested that the periocular lymphoproliferative diseases be classified into three groups based on their histological and cytological features. These include pseudolymphoma (including reactive lymphoid hyperplasia), atypical lymphoid hyperplasia, and malignant lymphoma.46,47 Other investigators believe that the various lymphoid proliferations are more properly classified as a continuum from benign to malignant disease. Accurate classification of lymphoid proliferative disease requires histopathological analysis as well as imrnunophenotypic and molecular genetic analysis. In general, a pleomorphic cellular infiltrate is correlated with more benign biological activity than an infiltrate with a more uniform cellular appearance.48 These lesions have overlapping histology, and malignant transformation of a benign process is not uncommon. Therefore, all patients presenting
Fig 14. Thyroid ophthalmopathy. (A) Oblique sagittal T1 MR image through the left orbit demonstrates optic nerve compression as a result of enlargement of the superior rectus-levator muscle complex. The mid portion of the optic nerve is displaced inferiorly. (B) Coronal T1 MR image demonstrates bilateral EOM involvement.
so extensive that the discussion here will be limited to only lymphoproliferative disease of the orbit and amyloidosis with anecdotal mention of sickle cell anemia.
Lymphoproliferative Disease of the Orbit Lymphoproliferative disease of the orbit is one of the most common disease entities found in orbital pathology. Much controversy still exists
Fig 15. Thyroid ophthalmopathy. Axial T1 MR image demonstrates expansion of the intraorbital fat with associated proptosis. Very subtle high signal can be seen in the rectus muscles suggesting early fatty infiltration, commonly observed in association with atrophy of the muscle in chronic thyroid eye disease.
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Fig 16. Thyroid ophthalmopathy. (A) Axial T1 MR image with gaze directed to the left (medial). Notice the normal medial rectus muscle tendon and the enlarged medial rectus muscle belly. The lateral rectus muscle, relatively unaffected in this patient, has stretched to allow rotation of the eye medially. The lateral rectus muscle belly is thin (closed arrow). (B) Axial T1 MR image in the same patient with gaze directed to the right (lateral). Note the restriction of lateral gaze as a result of reduced elasticity of the medial rectus muscle. The medial rectus muscle belly remains thickened. Contrast this to the lateral rectus muscle, which stretches with medial gaze and thickens with lateral gaze (open arrow).
with orbital lesions should have a noninvasive systemic evaluation including chest CT, abdominal CT, and bone scan. Other laboratory tests and a bone marrow aspirate should also be performed. Systemic disease is present in approximately 30% of cases of orbital lymphoid disease. However, of all patients with orbital lymphoma, 75% have or will have systemic disease. 48 The MRI and CT features of lymphoproliferative disease are nonspecific, and it may be impossible to differentiate lymphoma from orbital pseudotumor, lacrimal gland tumors, Graves' ophthalmopathy, and other primary orbital tumors. Clinical signs and symptoms may be helpful. The typical patient with lymphoproliferative disease of the orbit is usually older than 50 and presents with slowly progressive ocular displacement or mass formation, accompanied by minimal injection or pain. Because the majority of lymphoproliferative disease tends to occur in the superior orbit, proptosis often is associated with downward displacement of the globe (Fig 17). On MRI or CT, the mass tends to be homogeneous and circumscribed. 49 Anterior lesions may show a mass with an irregular contour that may appear to mold around the globe or to be in contiguity with the lacrimal gland (Fig 18). Posterior lesions may also mold around the globe, and linear densities may project from the edge of the lesion in a perpendicular or angular fashion as a
result of infiltration into potential spaces defined by facial planes. 5°,51 The optic nerve may be deviated. When the lesion extends along the extraconal space, the margins of the adjacent rectus muscles (often the medial or lateral rectus muscle) are often obliterated (Fig 19). Rarely, the lymphoid infiltration can be confined to an extraocular muscle. Lymphomatous infiltrates can also be scattered throughout the orbit and observed as multiple ill-defined lesions. A large diffuse homogenous mass obliterating the orbital contents can also be present. Lid lesions are not uncommonly associated with systemic lymphoma and can be observed as a mass arising anterior to the globe. Conjunctival lesions may be visible clinically as orange- or "salmon"-colored patches. Lid and conjunctival lesions may be impossible to distinguish on CT or MRI (Fig 20). Bone destruction is distinctly uncommon in lymphoproliferative disease of the orbit. The proliferation is usually confined to the orbit or orbital adnexa, although extension through the orbital fissures does occur. There is usually little enhancement following iodinated contrast administration for CT. However, with gadoliniumenhanced MRI, there is usually moderate to marked enhancement. The tumor or infiltrate is usually of low signal intensity on Tl-weighted images and variable on T2-weighted images.
Fig 17. Lymphoma. (A, B) Coronal T1 MR images demonstrates a large mass in the anterior superior orbit, which conforms to the shape of the globe and slightly displaces the globe inferiorly. (C) Coronal contrast-enhanced T1 MR image reveals marked enhancement of the tumor.
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Fig 18. Lymphoma. Axial CT sections: (A) Soft tissue w i n d o w setting and (B) bone w i n d o w setting reveal an infiltrating preseptal soft tissue mass which conforms to the shape of the globe and osseous structures without evidence of bone destruction or erosion.
Amyloidosis Amyloidosis encompasses a diverse collection of diseases characterized by the presence of extracellular deposits of insoluble fibrillar, proteinaceous material with a beta-pleated sheet ultrastructure. Clinically, amyloidosis can be categorized into two forms: systemic and localized. Systemic amyloidosis is a serious and often fatal disease that can be further divided into three subsets: (1)
idiopathic or primary amyloidosis (associated with B cell or plasma cell dyscrasias and monoclonal light chain fragments); (2) reactive or secondary amyloidosis (associated with acute phase lipoprotein serum amyloid A); and (3) familial amyloidosis. Familial amyloidosis is present in less than 2% of amyloidosis cases. Focal amyloidosis frequently involves the head and neck and carries a better prognosis than the systemic disease. Common sites
Fig 19. Lymphoma. (A) Four contiguous coronal T1 MR sections show a mass arising from the medial rectus muscle. Note the lesion causes only minimal deviation of the globe and tends to conform to the shape of the globe and optic nerve. (B) Four contiguous axial contrast enhanced T1 MR sections revealing an enhancing mass arising form the medial rectus muscle, deviating the optic nerve laterally. The medial rectus muscle is obliterated with both intraconal and extraconal extension.
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tion from infection. MRI has also recently been shown to be of value in separating these processes. MRI can show hemorrhage and edema within the marrow, findings that are suggestive of infarction. Hemorrhage is distinctly unusual with inflammation related to infection in sickle cell disease patients. 53 DISORDERS OF CONNECTIVE TISSUE AND JOINTS
Fig 20. Lymphoma. Axial CT section revealing nodular thickening of the anterior sclera/conjunctiva. The lesion also conforms or " m o l d s " to the shape of the globe.
of focal involvement include the larynx and oropharynx. The orbital masses have been occasionally reported in a few cases of familial amyloidosis. These lesions have usually shown calcification on CT scans but little or no enhancement after contrast administration. Amyloid deposits have been shown to have a MR signal intensity that follows that of skeletal muscle on all pulse sequences. This is a helpful diagnostic feature because most neoplasms have a more fluid-like structure than amyloid and thus tend to be high in signal intensity on T2weighted images: 2 Clinical features include blepharoptosis caused by infiltration of the upper eyelid levator muscle and oculomotor palsies resulting from infiltration of multiple extraocular muscles. When deposits occur in the lacrimal gland, the disease can mimic lacrimal gland neoplasms. Sickle Cell Anemia Sickle cell disease has been noted to involve all ocular and orbital structures, including the conjunctiva, iris, vitreous, retina, and orbital apex. Bone infarction is a well-known complication of sickle cell disease. Bone infarction can also involve the orbit and adjacent sinuses, where it may mimic periorbital cellulitis, including the presence of a fluid collection beneath the periorbita. In the case of infection, the subperiosteal fluid collection is composed of inflammatory cells, whereas in cases of infarction, inflammatory cells or hemorrhage may be present. Tc-99m bone scans have been used in the past with some success to distinguish infarc-
Ocular lesions owing to connective tissue diseases and the arthritides are rarely imaged by the radiologist. However, because of the significant number of patients with these disorders, recognition of the MRI and CT appearance of manifestations within the orbit may prevent unnecessary biopsy and undue clinical concern for such lesions. SjOgren' s Syndrome Sj6gren's syndrome is commonly associated with connective tissue disease (rheumatoid arthritis, systemic lupus erythematosus, vasculitis, scleroderma) and is characterized by xerostomia and keratoconjuctivitis sicca (lacrimal deficiency). It may also occur in the absence of any systemic disease and is a multisystem autoimmune disorder primarily involving the lacrimal glands, salivary glands, and mucous-secreting gland of the GI and respiratory tracts. The lacrimal and salivary glands become infiltrated by periductal lymphocytes that eventually cause destruction of the acini with subsequent atrophy and fibrosis. The disease is commonly bilateral and can be similar in appearance to Wegener's granulomatosis and lymphoproliferative disease of the orbit. Sj6gren's syndrome is observed in about 25% of patients with rheumatoid arthritis, whereas a full 60% of patients with Sj6gren's syndrome have an associated connective tissue disease. Rheumatoid Arthritis Pseudorheumatoid nodules usually occur in association with juvenile rheumatoid arthritis and present as focal masses in the dermis of children. They are thought to represent sites of previous trauma and consist of zonular granulomas surrounding areas of necrobiosis. The lesions may appear histologically similar to necrobiotic xanthogranulomas
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o f adults, d i f f e r i n g o n l y in the p a u c i t y o f g i a n t cells. The disease may involve the periorbital region, and t h e l e s i o n s are easily m a n a g e d b y excision.19,2° A h i g h i n c i d e n c e o f p o s t e r i o r scleritis h a s b e e n r e p o r t e d i n p a t i e n t s w i t h c o n n e c t i v e t i s s u e disease,
p a r t i c u l a r l y r h e u m a t o i d arthritis. 54 T h e p o s t e r i o r scleritis in t h e s e cases m a y b e diffuse or nodular. I n r h e u m a t o i d arthritis, t h e h i s t o l o g y o f t h e l e s i o n s is s i m i l a r to t h e s u b c u t a n e o u s n o d u l e s also o b s e r v e d in t h e disease.
REFERENCES 1. Flanders AE, Mafee MF, Rao VM, et al: CT characteristics of orbital pseudotumors and other orbital inflammatory processes. J Comput Assist Tomogr 13:40-47, 1989 2. Mottow LS, Jakobiec FA: Idiopathic inflammatory orbital pseudotumor in childhood. Arch Ophthalmol 96:1410-1417, 1978 3. Mafee MF, Som PM, Curtin HD (eds): Head and Neck Imaging, 3rd ed. St. Louis, MO, Mosby, 1995, pp 1096-1099 4. Frohman LP, Kupersmith MJ, Lang J, et al: Intracranial extension and bone destruction in orbital pseudotumor. Arch Ophthalmol 104:380-384, 1986 5. Rootman J, Nugent R: The classification and management of acute orbital pseudotumors. Ophthalmology 89:1040-2048, 1982 6. Kennerdell JS, Dresner SC: The nonspecific orbital inflammatory syndromes. Surv Ophthalmo129:93-103, 1984 7. Johnson MH, DeFilipp GJ, Zimmerman RA, Savino PJ: Scleral inflammatory disease. AJNR 8:861-865, 1987 8. Blodi FC, Gass JDM: Inflammatory pseudotumor of the orbit. Br J Ophthalmo152:79-93, 1963 9. Sergott RC, Glaser JS, Charyulu K: Radiotherapy for idiopathic inflammatory orbital pseudotumor. Arch Ophthalmol 99:853-856, 1981 10. Slavin ML, Glaser JS: Idiopathic orbital myositis. A report of six cases. Arch Ophthalmol 100:1261-1265, 1982 11. Hunt W: Tolosa-Hunt syndrome: One cause of painful ophthalmoplegia. J Neurosurg 44:544-549, 1976 12. Hershey BL, Roth TC: Orbital infections. Semin Ultrasound CT MRI 18:448-459, 1997 13. Berger JR, Snodgrass S, Glaser J, et al: Multifocal fibrosclerosis with hypertrophic intracranial pachymeningitis. Neurology 39:1345-1349, 1989 14. FauciAS, Haynes BE Katz P: The spectrum of vasculitis: clinical, pathological, immunologic, and therapeutic considerations Part I. Ann Intern Med 89:660, 1978 15. Rootman J (ed): Diseases of the Orbit. Philadelphia, PA, JB Lippincott, 1988 16. Coutu R, Klein M, Lessell S, et al: Limited form of Wegener's granulomatosis: Eye involvement as a major sign. JAMA 233:868-871, 1975 17. Koornneef L, Melief C, Peterse H, et al: Wegener's granulomatosis of the orbit. Orbit 2:1-10, 1983 18. Grove AS Jr., in Gold DH, Weingcist TA (eds): The Eye in Systemic Disease. Philadelphia, PA, JB Lippincott, 1990, pp 74-76 19. Satorre J, Antle CM, O'Sullivan R, et al: Orbital lesions with grannlomatous inflammation. Can J Ophthalmol 6:179181, 1991 20. Shields JA (ed): Diagnosis and Management of Orbital Tumors. Philadelphia, PA, WB Sannders, 1989 21. Jabs DA, Johns CJ: Ocular involvement in chronic sarcoidosis. Am J Ophthalmol 102:302-307, 1986
22. Obenauf CD, Shaw HE, Sydnor CR, et al: Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 86:648655, 1978 23. Carmody RF, Mafee MF, Goodwin JA, et al: Orbital and optic pathway sarcoidosis: MR findings. AJNR 15:775-783, 1994 24. Ing EB, Garrity JA, Cross SA, et al: Sarcoid masquerading as optic nerve sheath meningioma. Mayo Clin Proc 72:3843, 1997 25. Atlas SW, Grossman RI, Savino PJ, et al: Surface coil MR of orbital pseudotumor. AJNR 8:141 - 146, 1987 26. Alper MG, Zimmemlan LE, LaPiena FG: Orbital manifestations of Erdheim Chester disease. Trans Am Ophthalmol Soc 81:64, 1983 27. Tien RD, Brasch RC, Jackson DE, et al: Cerebral Erdheim-Chester disease: Persistent enhancement with GdDTPA on MR images. Radiology 172:791-792, 1989 28. Selsky EJ, Knox DL, Maumenee AE, et al: Ocular involvement in Whipple's disease. Retina 4:103-106, 1984 29. Leland TM, Chambers JK: Ocular findings in Whipple's Disease. Southern Med J 71:335-338, 1978 30. Knox DL, Schachat AP, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn's disease. Ophthalmology 91:163-173, 1984 31. Weinstein JM, Koch K, Lane S: Orbital pseudotumor in Crohn's Colitis. Ann Ophthalmol 16:275-278, 1984 32. Sedwick LA, Klingele TG, Burde RM, et al: Optic neuritis in inflammatory bowel disease. J Clin Neuro-ophthalmol 4:3-6, 1984 33. Knox DL, Snip RC, Stark WJ: The keratopathy of Crohn's disease. Am J Ophthalmo190:862-865, 1980 34. Hidayat AA, Cameron JD, Font RL, et al: Angiolymphoid hyperplasia with cosinophilia (Kimura's disease) of the orbit and ocular adenexac. Am J Ophthalmol 96:176-189, 1983 35. Motto-Lippa L, Jakobiec FA, Smith M: Idiopathic inflammatory orbital pseudotumor in childhood. II. Results of diagnostic tests and biopsies. Ophthalmology 88:565-574, 1981 36. Fries PD, Devron HC, Gold DH, Weingeist TA (eds): The Eye in Systemic Disease. Philadelphia, PA, Lippincott, 1990, pp 86-88 37. Villadolid MC, Yokoyama N, Izumi M, et al: Untreated Graves' disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle enlargement by magnetic resonance. J Clin Endocrinol Metabol 80:2830-2832, 1995 38. Char DH: Thyroid Eye Disease, 2nd ed. New York, NY, Churchill Livingstone, 1989 39. Gorman CA: Temporal relationship between the onset of Graves' ophthalmopathy and diagnosis of thyrotoxicosis. Mayo Clin Proc 58:515, 1983 40. Trokel SL, Jakobiec FA: Correlation of CT scanning and
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pathologic features of ophthalmic Graves' disease. Ophthalmology 88:553-554, 1981 41. Enzemann D, Marshall WH, Rosenthal AR: Computed tomography in Graves ophthalmopathy. Arch Ophthalmol 100: 1266-1269, 1982 42. Barrett L, Glatt HJ, Burde RM, et al: Optic nerve dysfunction in thyroid eye disease. Radiology 167:503-507, 1988 43. Casper DS, Chi TL, Trokel SL: Orbital Disease, Imaging and Analysis. New York, NY, Thieme, 1993, pp 149-164 44. Bailey CC, Kabala J, Laitt R, et al: Magnetic resonance imaging in thyroid eye disease. Eye 10:617-619, 1996 45. Knowles DM, Jakobiec FA, McNally L, et al: Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit conjunctiva, and eyelids). A prospective mukiparametric analysis of 108 cases during 1977 to 1987. Hum Pathol 21:959-973, 1990 46. Knowles DM, Jakobiec FA: Orbital lymphoid neoplasms: A clinicopathologic study of 60 patients. Cancer 46:576589, 1980 47. Medeiros LJ, Harris NL: Lymphoid infiltrates of the orbit
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and conjunctiva: A morphologic and immunophenotypic study of 99 cases. Am J Surg Pathol 13:459-471, 1989 48. Flanders AE, Espinosa GA, Marklewicz DA, et al: Orbital lymphoma: Radiol Clin North Am 25:601-612, 1987 49. Mauriello 2 Jr., Flanagan J: Management of orbital inflammatory disease. A protocol. Surv Ophthalmo129:104-116, 1984 50. Weber AL, Dallow RL, Oot RF: CT evaluation of lymphoproliferative diseases of the orbit in fifty patients. Acta Radiol Suppl 369, 1987 51. Yeo JH, Jakobied FA, Abbott GF, et al: Combined clinical and computed tomographic diagnosis of orbital lymphoid tumors. Am J Ophthalmo194:235-245, 1982 52. Gean-Marton AD, Kitsch CF, Vezina LG, et al: Focal amyloidosis of the head and neck: Evaluation with CT and MR imaging. Radiology 181:521-525, 1991 53. Rebsamen SL, Bilaniuk LT, Granet D, et al: Orbital wall infarction in sickle cell disease: MR evaluation. AJNR 14:777779, 1993 54. Watson PG, Hayreh SS: Scleritis and episcleritis. Br J Ophthalmo160:163-191, 1976
ANY DIFFERENT systemic disorders can involve the orbit or its adnexa. Although the diagnosis may be clearly apparent from the orbital findings, often the initial presentation of systemic disease may be its orbital manifestations, which may require extensive study and testing to diagnose. Magnetic resonance imaging and computed tomography of the orbit have become important adjuncts in the diagnosis of systemic disease of the orbit.
M
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Nongranulomatous Inflammatory Disease Idiopathic orbital inflammatory disease. Idiopathic orbital inflammatory disease (IO1D) or orbital pseudotumor is defined as a nonspecific idiopathic nongranulomatous inflammatory process for which there is no identifiable local or systemic cause. Histologically, the inflammation consists of a nonspecific inflammatory polymorphous cellular infiltrate, especially neutrophils, lymphocytes, plasma cells, and macrophages. No epithelioid or giant cells are observed. Depending on the chronicity, various amounts of fibrosis may be present. 1 The typical patient with idiopathic orbital inflammatory disease develops signs of unilateral orbital inflammation over a period of several weeks to months before presentation. No definite gender predilection has been observed. Although rare in the pediatric patient, the onset of symptoms is typically more sudden in the pediatric population, when compared with adults, and is more likely to be bilateral. 2 A variety of schemes have been proposed for
From the Department of Radiology, University of Wisconsin, Madison, WI. Address reprint requests to Lindell R. Gentry, Department of Radiology, E3/311 CSC, 600 HighlandAve., Madison, Wl53792. Copyright © 1998 by W.B. Saunders Company 0887-2171/98/1903-000658. 00/0 292
classification of IOID based on both the clinical presentation and the histopathology at the time of biopsy. Imaging (CT and MRI) has allowed an anatomic classification of the orbital inflammation that ranges from a diffuse form to localized forms affecting specific orbital tissue, including myositis, dacryoadenitis, periscleritis, and perineuritis. Each of these categories may be acute, subacute, acute recurrent, and chronic. It has been suggested that acute IOID can be clinically classified into six subsets3: (1) acute and subacute anterior inflammation, (2) acute or subacute diffuse inflammation, (3) acute and subacute myositic inflammation, (4) acute and subacute apical inflammation, (5) dacryoadenitis, and (6) perineuritis. The chronic form of IOID may be a sequela of acute recurrent orbital inflammation or may present insidiously as a subacute process. Although the inflammation is generally confined to the orbital soft tissues, rarely bone destruction or extraorbital extension can occur. 4 Patients with acute anterior IOID generally present with sudden onset of severe unilateral orbital pain with accompanying lid edema and sometimes erythema. Conjunctival chemosis, proptosis, uveitis, periscleritis, sclerotendonitis, papillitis, and exudative retinal detachment are other manifestations of acute IOID. 5 A sonographic " T " sign has been described which results from edema fluid present in Tenon's capsule and a widened appearance of the optic nerve secondary to edema or fluid entering the optic nerve sheath. 6 The sonographic "ring" sign results from edema in Tenon's capsule. Extraocular muscle involvement or dysfunction is uncommon. Both CT and MRI can demonstrate uveoscleral rim thickening and enhancement. The term "periscleritis" or °'posterior scleritis" has been used to describe inflammation that tends to occur around the posterior portions of the globe. Posterior scleritis in pseudotumor has been reported in isolation or with involvment of other
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orbital structures. The posterior scleritis of IOID has been reported to be more uniform in appearance than the posterior scleritis of metastatic disease or melanoma, which tend to be more focal v (Figs 1 and 2). Sclerotendonitis, inflammation at the site of the extraocular muscle tendon insertions on the sclera, is also common, and characteristically causes blurred vision and pain with ocular movements. Sclerotendonitis can also be associated with iritis and choroiditis. Posterior orbital inflammation may be associated with optic neuropathy, although early in the presentation, the visual fields and visual acuity are usually unaffected. The differential diagnosis of acute IOID includes orbital cellulitis, ruptured dermoid cyst, or the abrupt formation of a "chocolate" cyst as a result of hemorrhage into a lymphangioma. In children, rhabdomyosarcomas, metastatic neuroblastoma, or leukemic infiltration of the orbit can simulate nonspecific orbital inflammation. 6 The diffuse or tumefactive form of IOID presents with clinical features similar to acute and subacute anterior inflammation, but is often more severe in nature. In the diffuse form, presenting features include severe pain, proptosis, diplopia with extraocular muscle dysfunction, lid swelling, chemosis, papillitis, choroiditis, and optic neuropathy. 5 The diffuse form is characterized by the formation of dense collagenous connective tissue containing
Fig 1. Posterior scleritis in idiopathic orbital inflammatory disease (IOID). Axial CT section through the left orbit demonstrates uniform thickening of the uveoscleral rim and infiltration of the adjacent retrobulbar fat.
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Fig 2. Nodular posterior scleritis in IOID. Axial CT section through the orbits demonstrates nodular scleral thickening on the right. (Reprinted with permission from Johnson MH, DeFilipp G J, Zimmerman RA, Savino PJ: Scleral inflammatory disease. AJNR 8:861-865, 1987. 7)
hyaline. 8 The infiltrate can involve the whole orbit, including the entire intraconal and extraconal retrobulbar spaces. Typically, the infiltrate does not distort the boundaries of the globe, 3 (Fig 3). As the diffuse form becomes chronic, the response to steroid therapy diminishes. 6 A subset of the diffuse form of IOID is the sclerosing type of orbital pseudotumor. This process probably represents the chronic or endstage form of the disorder, although it has been reported to arise de novo. In sclerosing orbital pseudotumor, there is complete fixation of the intraorbital structures by formation of dense collagenous connective tissue which slowly mats together all of the intraorbital structures, decreasing their function as it progresses. Permanent extraocular muscle dysfunction and fixation of the globe leads to a fixed firm orbit and may result in blindness 6 (Fig 4). The chronic or sclerosing form of IOID is very difficult to treat, having a less dramatic response to steroids and radiation therapy. Radiation may be palliative for some steroid-resistant cases. 9 The differential diagnosis of the diffuse form of IOID includes primary tumors of the orbit, metastatic disease, and orbital lymphoid lesions. However, these conditions are not commonly associated with pain, erythema and extraocular muscle dysfunction, and have been noted to have a predilection for the superior orbit. 6 Neoplasms may not respect the boundaries of the eye, often indenting or invading the globe. Surface coil MR has been shown to he of use in differentiating orbital pseudo-
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Fig 3. Diffuse form of IOID. (A) Axial CT of the orbits reveals enlargement of the extraocular muscles, infiltration of the orbital fat, uveoscleral rim thickening, and infiltration of the medial eyelid on the right. The globe maintains a relatively normal shape. (B) Coronal CT reconstruction through the orbit confirms the enlargement of the extraocular muscles and enlargement of the optic nerve and sheath, and demonstrates infiltration of the orbital fat on the right.
tumor from other disease entities such as malignancy and hematoma. In a study by Atlas and Grossman et al, pseudotumor appeared hypointense to orbital fat (isointense to muscle) on Tl-weighted images and isointense or minimally hyperintense to orbital fat on T2-weighted images. Other benign inflammatory entities (infectious myosifts and sarcoid) had identical signal characteristics. This is in contradistinction to other diseases, including malignancy, which appeared markedly hyperintense to fat on T2-weighted images.
Fig 4. Sclerosing form of IOID. Coronal Tl-weighted MR image demonstrates sclerosing pseudotumor. Note the thick band of tissue superior to the globe on the right.
Orbital myositis is a subtype of nonspecific orbital inflammation that is characterized by infiltration of one or more of the extraocular muscles by an inflammatory process (Fig 5). Acute, subacute, and recurrent forms have been described. In the acute form, the extraocular muscle limitation is often directly related to the action of the muscle. In
Fig 5. Myositic form of IOID. Coronal CT section through the orbits demonstrates isolated enlargement of the left superior rectus muscle. Note also minimal infiltration of the orbital fat on the left.
SYSTEMIC DISEASES OF THE ORBIT
the subacute form, however, the deficit may be identical to that noted in thyroid ophthalmopathy with restriction of gaze in the opposite field of action of the involved muscle secondary to chronic fibrosis. 6 Myositis often affects more than a single muscle and is not uncommonly bilateral, m MRI and CT may show enlargement of one or more extraocular muscles, which extends anteriorly to involve the inserting tendon. However, this sign may or may not be present. Its absence does not exclude the diagnosis of the myositic form of pseudotumor. Orbital thyroid ophthalmopathy, enlargement of the extraocular muscles with carotid cavernous fistula or cavernous dural AVM, and neoplastic/metastatic infiltration of the extraocular muscles can mimic the myositic form of pseudotumot. 6 Orbital apicitis may result from IOID involving the orbital apex. CT and MRI can show infiltrative tissue at the orbital apex extending anteriorly along the optic nerve or extraocular muscles. Typically, the anatomic boundaries of the extraocular muscles and optic nerve are obscured at the orbital apex (Figs 3 and 6). Symptoms may include painful ophthalmoplegia, extraocular muscle dysfunction and/or restriction, optic neuropathy, diplopia, and mild proptosis.5 A variant of pseudotumor is TolosaHunt syndrome, which can also involve the orbital apex, including the superior orbital fissure, as well
Fig 6. Orbital apicitis in IOID. Axial CT of the orbits shows the diffuse form of IOID with obliteration of the anatomic boundaries of the extraocular muscles and the optic nerve at the orbital apex (arrowheads),
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as the cavernous sinus. In Tolosa-Hunt syndrome, the ophthalmoplegia consists of palsies of the third, fourth, and sixth cranial nerves as well as the ophthalmic division of the trigeminal nerve. Most cases of Tolosa-Hunt syndrome are generally unilateral. 11 (See the article by Mark in this same issue.) Perineuritis, an unusual type of nonspecific orbital inflammation, can present with orbital pain, decreased visual acuity, and disc edema. There is often pain with eye movement and ballottement of the globe. This is in distinction to optic neuritis, which rarely presents with pain with ballottement of the globe and eye movements. MRI and CT show enlargement and enhancement of the optic nerve sheath, often with a ragged border6 (Figs 7A, B). The anterior segment is usually normal. Nonspecific inflammation involving the lacrimal gland is present in idiopathic dacryoadenitis. Tenderness is usually present in the upper outer quadrant of the orbit at the level of the lacrimal gland. Mild erythema, conjunctival chemosis, and an "S"-shaped appearance to the upper lid are common clinical features. CT and MRI characteristically show an enhancing mass in the lacrimal region, often with edema extending into Tenon's capsule. Viral dacryoadenitis can pose a similar appearance, but can often be distinguished by the presence of peripheral adenopathy and lymphocytosis (especially in mononucleosis). Chronic idiopathic dacryoadenitis can be a more difficult clinical distinction. Pain is often a feature of malignant tumors arising in the lacrimal gland. Bone destruction may be present in these cases, which is rare in idiopathic chronic dacryoadenitis. Biopsy or fine needle aspiration may be necessary.22 Nonspecific or idiopathic orbital inflammatory disease has been observed in individuals who have systemic diseases such as sarcoidosis, Wegener's granulomatosis, thyroid disease, and Langerhan's histiocytosis among others. Interestingly, orbital pseudotumor has also been observed in patients with retroperitoneal fibrosis (multifocal fibrosclerosis). Multifocal fibrosclerosis 13 defnes a constellation of pathologically similar syndromes. The most common of these include mediastinal fibrosis, retroperitoneal fibrosis, orbital pseudotumor, Reidel's thyroiditis, and sclerosing thyroiditis. Other manifestations can include Peyronie's disease, Dupuytren's contractures, vasculitis, subcutaneous fibrosis, idiopathic hypertrophic pachymeningitis, and testicular fibrosis. The disorder can be familial
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Fig 7. Perineuritis in IOID (pseudotumor). (A) Sagittal fat-suppressed contrast-enhanced T1 MR section which reveals enhancement of the anterior one half of the optic nerve sheath and enhancement of both the optic nerve and nerve sheath posteriorly. (B) Axial fat-suppressed contrast-enhanced T1 MR image demonstrates perineural infiltration of the orbital fat as well as enhancement of the optic nerve sheath,
or sporadic and has no known etiology. The clinical course of the disorder is highly variable, with the illness following a prolonged course in many individuals. Rapid deterioration has also been reported. This syndrome should be considered in patients who show intracranial extension of orbital pseudotumor, and indicates the potential for future complications of systemic disease in patients who initially present with IOID. The diversity of diseases associated with IOID and the number of disorders that can mimic IOID of the orbit is extensive. It is no surprise that IOID remains a diagnosis of exclusion, based on the results of laboratory tests, clinical history, response to therapy, and often biopsy.
Granulomatous Disease Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various etiologies with a common histopathological substrate. Infection by various bacterial pathogens (mycobacterium tuberculosis, histoplasma capsulatum, mycobacterium leprae, treponema pallidum) and variety of suspected immune-mediated diseases (Wegener's granulomatosis, sarcoidosis, Langerhan's cell histiocytosis, Sj6gren's syndrome, Erdheim-Chester disease, xanthogranulomatous disease) cause a granulomatous inflammatory response within the orbit. Granulomatous disease that primarily affects the gastrointestinal system such as Crohn's disease, ulcerative
colitis, and Whipple's disease rarely may also affect the orbit. Wegener's granulomatosis. Wegener's disease is characterized by necrotizing granulomatous vasculitis and can involve multiple organ systems including the respiratory tract, kidneys, and the eyes. The disease is twice as common in men as in women, with the peak incidence in the fifth decade of life. Although the etiology is unknown, the disease may result from hypersensitivity to an unidentified antigen. Immune-related complexes have been found in biopsy specimens of involved tissues. 14 Before the introduction of immunosuppressive therapy, Wegener's disease was typically fatal, usually from the sequela of renal failure. 15 The orbit can be involved as a part of disseminated Wegener's disease or as a localized abnormality. 16 Isolated orbital involvement may be the initial sign of the disease. The most common ocular features are progressive marginal ulcerative keratitis, scleritis, episcleritis, and conjunctival inflammation. Posterior segment involvement includes retinitis with venous congestion, uveitis, and optic neuropathy. MRI or CT findings are nonspecific and most commonly demonstrate the orbital adnexal involvement or sinus inflammation (Fig 8). Patients may develop a "saddle nose" deformity from destruction of the nasal cartilages. Unilateral or bilateral orbital masses may be present 17 (Fig 9). The nasolacrimal ducts may be obstructed and the lacrimal glands enlarged. Occasionally, lid nodules
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Fig 8. Wegner's granulomatosis. (A) Thickened, enhancing scleral characteristic of posterior scleritis is apparent along with enhancement of the optic nerve sheath. (B) Enhancement of the superior rectus muscle is apparent.
(granulomas), dacryoadenitis, and lid swelling are present. 18Bilateral orbital involvement is common. A chronically progressive orbital apex syndrome has also been associated with Wegener's granulomatosis. 15,19The orbital manifestations of Wegener's disease should be differentiated from metastatic disease, idiopathic orbital inflammatory disease (pseudotumor), and lymphoproliferafive disease of the orbit, 2° usually by biopsy. Sarcoidosis. Sarcoidosis, an idiopathic systemic granulomatous disorder, primarily occurs in the third and fourth decades of life. The disease seems to represent an immune response to an unknown antigen. Because of the high frequency of pulmonary and hilar manifestations at the time of presentation, many researchers believe the antigen is airborne. Antigen-stimulated T-helper cells that
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secrete lymphokines, which activate monocytes to differentiate into epithelioid and multinucleated giant cells, mediate the granulomatous response. Although the disease can involve multiple systems, the lungs, skin, and eyes are most often affected. Sarcoidosis is 10 to 20 times more common in the African-American population than in Caucasians. The visual system is affected in approximately one fourth of cases and may be the initial presentation of the disease (19% in o n e s e r i e s ) . 22 Anterior granulomatous uveitis is the most common ocular manifestation of sarcoidosis. 21 Nodules develop on the iris at the pupillary margin (Koeppe's nodules) or in the superficial stroma (Busacca's nodules) as a result of granuloma formation. Uveitis can be associated with facial nerve palsy and fever (Heerfordt's syndrome). Circulating immune complexes are the etiology of Lofgren's syndrome (acute iritis, erythema nodosum, malaise, bilateral hilar lymphadenopathy, arthralgias) which generally has a good prognosis. The posterior segment is involved in about one quarter of patients with ocular sarcoid, and such involvement correlates with a high incidence of central nervous system involvement? 1,22 The optic nerve is occasionally affected, often with the central nervous systemY Several mechanisms have been proposed by which the optic nerve may be affected, including optic disk papillitis due to intraocular inflammation, papilledema secondary to increased intracranial pressure, optic atrophy, and primary infiltration of the optic nerves and nerve sheaths. On gadoliniumenhanced MRI, the optic nerves may demonstrate perineural enhancement, enlargement, or atrophy (Fig 10). Chiasmatic involvement can be present. Optic nerve enlargement in sarcoidosis may resemble a primary neoplasm of the optic nerve or nerve sheath. 24 A trial of corticosteroids can help differentiate optic nerve involvement by sarcoid from optic nerve sheath meningioma, preventing unnecessary optic nerve biopsy. Granulomatous lesions of the optic nerve usually show a decrease in size and contrast enhancement on MRI after steroid treatment. Meningiomas do not typically respond to steroids? 3 Differentiation from optic neuritis associated with demyelinating disease, particularly multiple sclerosis, may be difficult. Evaluation of the brain parenchyma is often helpful, revealing a pattern of demyelination consistent with multiple sclerosis. Leptomeningeal enhancement is strong supporting evidence of neurosarcoid-
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Fig 9. Wegener's granulomatosis. (A) Axial CT section the orbits reveals diffuse infiltration of the orbital contents leading to a "frozen" orbit, The globe maintains its normal contour (B) Coronal and axial {C) CT section demonstrates the diffuse pronounced bony thickening and sclerosis of the walls of the maxillary sinuses. The septal erosion and perforation may lead to the "saddle nose" deformity in Wegener's granulomatosis.
osis provided that other causes, such as tuberculosis, fungal disease, and neoplasm, have also been excluded. In the absence of CNS involvement, laboratory studies may be helpful. Peripheral seventh nerve palsy is a common finding with neurosarcoidosis, but not in multiple sclerosis. The lacrimal gland is often involved in orbital sarcoidosis, presenting as a chronic dacryoadenitis (Fig 11). Extensive involvement of the lacrimal glands and salivary glands may result in xerostomia and tear hyposecretion (Mikulicz syndrome). Metastatic disease and lymphoma involving the lacrimal gland usually shows high signal intensity on T2weighted MR images in contrast to sarcoidosis and orbital pseudotumor. Infiltrating retrobulbar orbital
masses resulting in proptosis or myositis may occur in sarcoidosis 19 and are indistinguishable from pseudotumor o n M R [ . 23,25 Erdheim-Chester. Erdheim-Chester disease is a rare form of systemic xanthogranulomatous disease that occurs in adults. The disease uncommonly involves the orbit. However, orbital involvement, when present, mimics orbital pseudotumor and is most often bilateral. Patients typically demonstrate bilateral exophthalmos that can lead to ophthalmoplegia and visual loss as a result of compression from infiltration of the orbital fatty reticulum. 26 At biopsy, fibrosing xanthogranulomas, xanthogranulomatous histiocytes, and occasional Touton giant cells are present. Radiological findings include soft
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Fig 10. Sarcoidosis. (A) An inversion recovery MR image reveals abnormal high signal intensity present along the right optic nerve and optic nerve sheath extending intracranially (arrow). (B) Coronal MR image shows abnormal high signal involving the right optic nerve and nerve sheath. A similar appearance may be observed with optic neuritis associated with multiple sclerosis, or neoplasms such as meningioma, or optic glioma.
tissue infiltration of the orbital fat and enlarged extraocular muscles and lacrimal gland. 27 Systemic manifestations include infiltration of the lungs, kidneys, heart, bones, and retroperitoneum. Neerobiotic xanthogranuloma. Necrobiotic xanthogranuloma is a disease characterized by multiple waxy, yellow, indurated or inflamed subcutaneous nodules or plaques. The disease has a predilection for the periorbital regions, especially the eyelids and
occasionally the anterior orbit. The disease is associated with paraproteinemia and hematologic proliferative disorders, especially multiple myeloma. It has also been reported in leukemia patients. Typically, the subcutaneous lesions exhibit prominent tracts of necrobiosis surrounded by palisading histiocytes and Touton giant cells. Chemotherapy has been found to be the most efficacious treatment although response to steroids has been observed. 19
Inflammatory Bowel Disease
Fig 11. Sarcoidosis. Axial T1 MR image shows mild, bilateral enlargement lacrimal glands, The lacrimal glands remain low in signal intensity.
Whipple's disease. Whipple's disease is a rare multisystem chronic noncaseating granulomatous bacterial infectious disease. Propionibacterium acnes has been cultured from involved lymph nodes. The gastrointestinal system is predominately affected, often resulting in steatorrhea in advanced disease. The cardiovascular, respiratory, central nervous, and musculoskeletal systems are also frequently involved. Orbital manifestations are often found early in the disease and consist of ophthalmoplegia, nystagmus, gaze palsy, ptosis, and papilledema. Ocular findings may include kerafitis uveitis, inflammatory vitreous opacities, vitreous hemorrhage, retinal hemorrhage, and vasculitis involving the retinal and choroidal vessels. 28,29 The ocular disease is often secondary to
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central nervous system involvement. CT and MRI findings are nonspecific. Crohn's disease and ulcerative colitis. Ocular complications are observed in approximately 10% of patients with Crohn's disease and less frequently in ulcerative colitis. The orbital disease can be divided into primary, secondary, and coincidental complications. 3° Primary complications occur during periods of active disease in the gut and respond to treatment of the gut. Episcleritis, uveitis, and keratopathy are seen most commonly as primary manifestations of Crohn's disease. However, orbital pseudotumor and optic neuropathy can also occur.31,32 Episcleritis is not a manifestation of ulcerative colitis. A specific sign of Crohn's disease on ophthalmic examination is multiple gray densities that occur in the anterior cornea. 33 Secondary complications occur usually as a result of malnutrition, particularly vitamin A deficiency as a result of malabsorption. Kimura's disease. Kimura's disease or angiolymphoid hyperplasia with eosinophilia is an idiopathic inflammation of the skin that involves the head and neck region, usually in the fourth or fifth decade of life. A slight male preponderance has been observed. Orbital findings simulate orbital pseudotumor and can involve the orbit and the orbital adnexa, most commonly unilaterally, although bilateral involvement has been reported. 34 Grossly, the lesions are well-circumscribed, firm, reddish brown masses with increased vascularity. These lesions pathologically consist of a central area of proliferation of blood vessels surrounded by an infiltrate containing scattered numerous eosinophils and lymphocytes.3s Systemic findings include peripheral blood eosinophilia, multiple nodular, macular skin lesions, and lymphadenopathy. The disease is thought to represent a benign inflammatory process rather than a true neoplasm.
ENDOCRINE DISEASE
Several common endocrine systemic diseases often present with striking orbital manifestations. The two endocrine diseases that most commonly present with orbital complications include Graves' disease and diabetes mellitus. However, acromegaly may also present with orbital findings.
Grave's Disease
Graves' disease, or thyroid ophthalmopathy, is an autoimmune inflammatory condition of orbital tissues, particularly the extraocular muscles and orbital fat. The inflammatory reaction has both humeral and cell-mediated components. The lacrimal gland may also show inflammatory change, although it is usually not as severe. The histology of the inflammatory infiltrate is primarily lymphocytes, plasma cells, and occasional mast cells. A fibroblast reaction is present with production of mucopolysaccharides, especially hyaluronic acid. In the adult population, hyperthyroidism is more prevalent in women than men (4:1 ratio). It is relatively uncommon in children. Orbital symptoms include lid retraction, lagophthalmos, conjuncrival and periorbital edema, restrictive extraocular myopathy, and proptosis. Enlarged episcleral vessels over the rectus muscle insertions, diplopia, and glaucoma can occur owing to enlargement, restriction, and vascular engorgement of the rectus muscles. Long-standing inflammation leads to fibrosis of the muscles. 36 Most clinicians consider thyroid ophthalmopathy to be a component of Graves' disease. A recent Japanese study of 21 patients with untreated Graves' disease and no clinical manifestations of thyroid eye disease showed that 7 1% of these patients did have extraocular muscle enlargement when imaged with MRI. 37 However, thyroid eye disease may present before, coincident with, or after the onset of the systemic disease, causing some investigators to believe that they are separate diseases. 38,39 Nevertheless, the diagnosis is usually established by clinical means, most commonly, laboratory tests. CT and MRI characteristically show enlargement of the extraocular muscles. The sparing of the tendons of the affected rectus muscles is typical and can be helpful in distinguishing thyroid ophthalmopathy from IOID of the orbit. The inferior rectus muscle is the most frequently affected followed by the medial rectus and the superior rectus-levator complex4°,41 (Fig 12). With gadolinium-enhanced MRI, the muscle bellies show marked enhancement (Fig 13). This is in contradistinction to other skeletal muscles, which usually reveal little contrast enhancement. The margins of the muscles are generally well-defined. The lateral rectus muscle
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Thyroid ophthalmopathy should be distinguished from other causes of extraocular muscle enlargement including IOID, metastatic disease, lymphoid diseases, acromegaly, amyloidosis, and vascular malformations with subsequent rectus muscle enlargement. HEMATOLOGIC AND HEMATOPOIETIC DISEASES
Some hematologic and hematopoietic diseases may exhibit relatively specific orbital manifestations, whereas in other cases the orbital changes may be only incidental to the disease. This topic is
Fig 12. Thyroid ophthalmopathy. Coronal T1 MR image demonstrates the extraocular muscle enlargement in thyroid eye disease. Note the normal size of the lateral rectus muscle, whereas the inferior, medial, and superior rectus muscles are enlarged.
may also show enlargement, but it is generally in conjunction with enlargement of other muscles. If the rectus muscle enlargement is severe, extrinsic pressure on the optic nerve, especially at the orbital apex, can result in vision loss and visual field deficits42 (Fig 14). Coronal imaging is superior to axial imaging in the evaluation of the rectus muscles. The orbital fat volume is also frequently expanded and should be suspected in patients with severe exophthalmos. The optic nerve often becomes stretched. The orbital septum bulges anteriorly (Fig 15). The orbital fat has a somewhat "dirty" appearance on CT as a result of increased densities within the fat which have been proven to represent lymphocytic infiltrations. Rarely, the optic nerve can appear slightly enlarged. Bone changes can also occur in conjunction with thyroid ophthalmopathy. This is usually observed when there is extreme enlargement of the medial recti, which causes medial bowing of the lamina papyracea. This appearance has been called the "soda bottle" contour.43 Short tan inversion recovery (STIR) MR imaging has recently shown increased signal within the muscles during active periods of the orbital disease. 44 Cine MR can show the extraocular muscle restriction and reduced elasticity with eye movement from the disease in its "burnt out" phase. Reduced elasticity is manifest by failure of the extraocular muscle to stretch with eye movement44 (Fig 16). These MR findings can be an adjunct to therapeutic planning. 44
Fig 13. Thyroid ophthalmopathy. Axial pre {A) and post (B) contrast images show enlargement and enhancement of the medial and lateral rectus muscles in thyroid ophthalmopathy.
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regarding this entity, which comprises a diverse group of lesions ranging from benign lymphoid hyperplasia to malignant lymphoma. Clinical evaluation, imaging, and pathological tissue analysis are problematic in these related disorders.45 Lymphoid proliferations may occur anywhere in the orbit and mimic many different orbital diseases. There are no absolute clinical, imaging, or laboratory criteria that can facilitate a distinction among the benign and malignant lesions. It has been suggested that the periocular lymphoproliferative diseases be classified into three groups based on their histological and cytological features. These include pseudolymphoma (including reactive lymphoid hyperplasia), atypical lymphoid hyperplasia, and malignant lymphoma.46,47 Other investigators believe that the various lymphoid proliferations are more properly classified as a continuum from benign to malignant disease. Accurate classification of lymphoid proliferative disease requires histopathological analysis as well as imrnunophenotypic and molecular genetic analysis. In general, a pleomorphic cellular infiltrate is correlated with more benign biological activity than an infiltrate with a more uniform cellular appearance.48 These lesions have overlapping histology, and malignant transformation of a benign process is not uncommon. Therefore, all patients presenting
Fig 14. Thyroid ophthalmopathy. (A) Oblique sagittal T1 MR image through the left orbit demonstrates optic nerve compression as a result of enlargement of the superior rectus-levator muscle complex. The mid portion of the optic nerve is displaced inferiorly. (B) Coronal T1 MR image demonstrates bilateral EOM involvement.
so extensive that the discussion here will be limited to only lymphoproliferative disease of the orbit and amyloidosis with anecdotal mention of sickle cell anemia.
Lymphoproliferative Disease of the Orbit Lymphoproliferative disease of the orbit is one of the most common disease entities found in orbital pathology. Much controversy still exists
Fig 15. Thyroid ophthalmopathy. Axial T1 MR image demonstrates expansion of the intraorbital fat with associated proptosis. Very subtle high signal can be seen in the rectus muscles suggesting early fatty infiltration, commonly observed in association with atrophy of the muscle in chronic thyroid eye disease.
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Fig 16. Thyroid ophthalmopathy. (A) Axial T1 MR image with gaze directed to the left (medial). Notice the normal medial rectus muscle tendon and the enlarged medial rectus muscle belly. The lateral rectus muscle, relatively unaffected in this patient, has stretched to allow rotation of the eye medially. The lateral rectus muscle belly is thin (closed arrow). (B) Axial T1 MR image in the same patient with gaze directed to the right (lateral). Note the restriction of lateral gaze as a result of reduced elasticity of the medial rectus muscle. The medial rectus muscle belly remains thickened. Contrast this to the lateral rectus muscle, which stretches with medial gaze and thickens with lateral gaze (open arrow).
with orbital lesions should have a noninvasive systemic evaluation including chest CT, abdominal CT, and bone scan. Other laboratory tests and a bone marrow aspirate should also be performed. Systemic disease is present in approximately 30% of cases of orbital lymphoid disease. However, of all patients with orbital lymphoma, 75% have or will have systemic disease. 48 The MRI and CT features of lymphoproliferative disease are nonspecific, and it may be impossible to differentiate lymphoma from orbital pseudotumor, lacrimal gland tumors, Graves' ophthalmopathy, and other primary orbital tumors. Clinical signs and symptoms may be helpful. The typical patient with lymphoproliferative disease of the orbit is usually older than 50 and presents with slowly progressive ocular displacement or mass formation, accompanied by minimal injection or pain. Because the majority of lymphoproliferative disease tends to occur in the superior orbit, proptosis often is associated with downward displacement of the globe (Fig 17). On MRI or CT, the mass tends to be homogeneous and circumscribed. 49 Anterior lesions may show a mass with an irregular contour that may appear to mold around the globe or to be in contiguity with the lacrimal gland (Fig 18). Posterior lesions may also mold around the globe, and linear densities may project from the edge of the lesion in a perpendicular or angular fashion as a
result of infiltration into potential spaces defined by facial planes. 5°,51 The optic nerve may be deviated. When the lesion extends along the extraconal space, the margins of the adjacent rectus muscles (often the medial or lateral rectus muscle) are often obliterated (Fig 19). Rarely, the lymphoid infiltration can be confined to an extraocular muscle. Lymphomatous infiltrates can also be scattered throughout the orbit and observed as multiple ill-defined lesions. A large diffuse homogenous mass obliterating the orbital contents can also be present. Lid lesions are not uncommonly associated with systemic lymphoma and can be observed as a mass arising anterior to the globe. Conjunctival lesions may be visible clinically as orange- or "salmon"-colored patches. Lid and conjunctival lesions may be impossible to distinguish on CT or MRI (Fig 20). Bone destruction is distinctly uncommon in lymphoproliferative disease of the orbit. The proliferation is usually confined to the orbit or orbital adnexa, although extension through the orbital fissures does occur. There is usually little enhancement following iodinated contrast administration for CT. However, with gadoliniumenhanced MRI, there is usually moderate to marked enhancement. The tumor or infiltrate is usually of low signal intensity on Tl-weighted images and variable on T2-weighted images.
Fig 17. Lymphoma. (A, B) Coronal T1 MR images demonstrates a large mass in the anterior superior orbit, which conforms to the shape of the globe and slightly displaces the globe inferiorly. (C) Coronal contrast-enhanced T1 MR image reveals marked enhancement of the tumor.
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Fig 18. Lymphoma. Axial CT sections: (A) Soft tissue w i n d o w setting and (B) bone w i n d o w setting reveal an infiltrating preseptal soft tissue mass which conforms to the shape of the globe and osseous structures without evidence of bone destruction or erosion.
Amyloidosis Amyloidosis encompasses a diverse collection of diseases characterized by the presence of extracellular deposits of insoluble fibrillar, proteinaceous material with a beta-pleated sheet ultrastructure. Clinically, amyloidosis can be categorized into two forms: systemic and localized. Systemic amyloidosis is a serious and often fatal disease that can be further divided into three subsets: (1)
idiopathic or primary amyloidosis (associated with B cell or plasma cell dyscrasias and monoclonal light chain fragments); (2) reactive or secondary amyloidosis (associated with acute phase lipoprotein serum amyloid A); and (3) familial amyloidosis. Familial amyloidosis is present in less than 2% of amyloidosis cases. Focal amyloidosis frequently involves the head and neck and carries a better prognosis than the systemic disease. Common sites
Fig 19. Lymphoma. (A) Four contiguous coronal T1 MR sections show a mass arising from the medial rectus muscle. Note the lesion causes only minimal deviation of the globe and tends to conform to the shape of the globe and optic nerve. (B) Four contiguous axial contrast enhanced T1 MR sections revealing an enhancing mass arising form the medial rectus muscle, deviating the optic nerve laterally. The medial rectus muscle is obliterated with both intraconal and extraconal extension.
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tion from infection. MRI has also recently been shown to be of value in separating these processes. MRI can show hemorrhage and edema within the marrow, findings that are suggestive of infarction. Hemorrhage is distinctly unusual with inflammation related to infection in sickle cell disease patients. 53 DISORDERS OF CONNECTIVE TISSUE AND JOINTS
Fig 20. Lymphoma. Axial CT section revealing nodular thickening of the anterior sclera/conjunctiva. The lesion also conforms or " m o l d s " to the shape of the globe.
of focal involvement include the larynx and oropharynx. The orbital masses have been occasionally reported in a few cases of familial amyloidosis. These lesions have usually shown calcification on CT scans but little or no enhancement after contrast administration. Amyloid deposits have been shown to have a MR signal intensity that follows that of skeletal muscle on all pulse sequences. This is a helpful diagnostic feature because most neoplasms have a more fluid-like structure than amyloid and thus tend to be high in signal intensity on T2weighted images: 2 Clinical features include blepharoptosis caused by infiltration of the upper eyelid levator muscle and oculomotor palsies resulting from infiltration of multiple extraocular muscles. When deposits occur in the lacrimal gland, the disease can mimic lacrimal gland neoplasms. Sickle Cell Anemia Sickle cell disease has been noted to involve all ocular and orbital structures, including the conjunctiva, iris, vitreous, retina, and orbital apex. Bone infarction is a well-known complication of sickle cell disease. Bone infarction can also involve the orbit and adjacent sinuses, where it may mimic periorbital cellulitis, including the presence of a fluid collection beneath the periorbita. In the case of infection, the subperiosteal fluid collection is composed of inflammatory cells, whereas in cases of infarction, inflammatory cells or hemorrhage may be present. Tc-99m bone scans have been used in the past with some success to distinguish infarc-
Ocular lesions owing to connective tissue diseases and the arthritides are rarely imaged by the radiologist. However, because of the significant number of patients with these disorders, recognition of the MRI and CT appearance of manifestations within the orbit may prevent unnecessary biopsy and undue clinical concern for such lesions. SjOgren' s Syndrome Sj6gren's syndrome is commonly associated with connective tissue disease (rheumatoid arthritis, systemic lupus erythematosus, vasculitis, scleroderma) and is characterized by xerostomia and keratoconjuctivitis sicca (lacrimal deficiency). It may also occur in the absence of any systemic disease and is a multisystem autoimmune disorder primarily involving the lacrimal glands, salivary glands, and mucous-secreting gland of the GI and respiratory tracts. The lacrimal and salivary glands become infiltrated by periductal lymphocytes that eventually cause destruction of the acini with subsequent atrophy and fibrosis. The disease is commonly bilateral and can be similar in appearance to Wegener's granulomatosis and lymphoproliferative disease of the orbit. Sj6gren's syndrome is observed in about 25% of patients with rheumatoid arthritis, whereas a full 60% of patients with Sj6gren's syndrome have an associated connective tissue disease. Rheumatoid Arthritis Pseudorheumatoid nodules usually occur in association with juvenile rheumatoid arthritis and present as focal masses in the dermis of children. They are thought to represent sites of previous trauma and consist of zonular granulomas surrounding areas of necrobiosis. The lesions may appear histologically similar to necrobiotic xanthogranulomas
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o f adults, d i f f e r i n g o n l y in the p a u c i t y o f g i a n t cells. The disease may involve the periorbital region, and t h e l e s i o n s are easily m a n a g e d b y excision.19,2° A h i g h i n c i d e n c e o f p o s t e r i o r scleritis h a s b e e n r e p o r t e d i n p a t i e n t s w i t h c o n n e c t i v e t i s s u e disease,
p a r t i c u l a r l y r h e u m a t o i d arthritis. 54 T h e p o s t e r i o r scleritis in t h e s e cases m a y b e diffuse or nodular. I n r h e u m a t o i d arthritis, t h e h i s t o l o g y o f t h e l e s i o n s is s i m i l a r to t h e s u b c u t a n e o u s n o d u l e s also o b s e r v e d in t h e disease.
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