Orbital Diseases

Jennifer P. Wang, MD · Murray D. Christianson, MD · Mark R. Levine, MD

Introduction

The orbit is an important site for primary and secondary disease processes. Because the volume of the orbit is small, many of the presenting signs of orbital disease are ophthalmic. An understanding of the anatomy of the orbit, including the connective tissue system, will clarify the anatomical basis for many presenting clinical findings. A careful and complete history and examination are essential in any patient with suspected orbital disease. Most often, a thorough initial exam will direct you to the ancillary test that will provide the most diagnostic information. For example, in a patient with suspected orbital bone disease, a computed tomography (CT) scan would yield more diagnostic information than magnetic resonance imaging (MRI), which would be more useful for soft-tissue abnormalities. Some distinguishing features of orbital diseases are:

Orbital Diseases in Children

Following are orbital disorders found predominantly in children

Orbital Cellulitis
Acute orbital cellulitis is a serious condition that threatens vision and life. It is usually an extension of a bacterial sinusitis, but can begin around an orbital foreign body, spread from an infection of the face or teeth, meninges, lacrimal sac, or lacrimal gland. It can also be metastatic from the bacteremia, especially in an immunocompromised patient.

Cellulitis can be classified as preseptal or postseptal (orbital). Preseptal cellulitis, most commonly Staphylococcus aureus or Streptococcus pyogenes, causes pain, lid swelling, and chemosis, along with systemic signs of fever leukocytosis. In addition to these symptoms, postseptal orbital cellulitis involves proptosis, reduced extraocular motility, and decreased vision. Younger children can present with viral coryza, spread of infection from the ethmoids and maxillary sinus, and an infection with aerobes such as haemophilus influenzae. Adults often present with recurrent sinusitis, nasal polyps, recent history of trauma or dental extraction, and have a mixed microbial infection often with anaerobic organisms. Orbital cellulitis can form a subperiosteal or orbital abscess that can lead to cavernous sinus thrombosis, meningitis, and intracranial abscess. Subperiosteal abscess is less common in children, and when treated, usually resolves without drainage or sequelae. An adult's treatment often requires sinus drainage procedures or more severe treatments. On CT scanning, there will be signs of inflammation in the medial and superior medial orbit next to an opacified sinus and a subperiosteal abscess. A recent study by Garcia and Harris showed that in children younger than 9 years of age, subperiosteal infection tended to be simple with usually only one type of bacteria. However, in patients older than 9 years of age, the infection tends to be more complex with multiple bacteria types including anaerobes. Garcia and Harris recommend the following criteria to determine surgical versus nonsurgical therapy for subperiosteal abscesses (SPA). 1

Criteria for Surgical Therapy

Slide 1

Slide 1

Nonsurgical treatment consists of observation with visual acuity and pupillary exams every 6 hours for 48 hours while on intravenously administered (IV) ampicillin/sulbactam. If any of the following signs develop, then move to drainage:

Rhabdomyosarcoma
Rhabdomyosarcoma is the most common primary orbital malignancy of childhood. It represents about 4% of all childhood mass lesions, and 1% of all orbital tumors. Onset occurs between 7 and 9 years of age. The malignancy arises from pluripotential mesenchymal precursors that normally differentiate into striated muscle.
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Slide 2
Clinical presentation is an acute to subacute onset with rapidly progressive proptosis over a few weeks to a month. Ptosis, lid edema, and discoloration with motility disturbance are present. The globe is usually inferiorly displaced because the tumor is located in the superior orbit. There may be coincidental history of trauma to the affected side, which may delay the diagnosis. CT imaging demonstrates an irregular, somewhat defined soft-tissue mass, usually in the superonasal quadrant. MRI demonstrates long relaxation times of heterogeneous to homogenous irregular mass that is isointense to muscle and hypointense to fat on T1-weighted images. The signal is hyperintense on T2-weighted images to muscle and fat. Histopathologically, tumors are classified as embryonal, alveolar, pleomorphic, or botryoid. Embryonal tumors, which are most common, are found in the superonasal quadrant and consist of a mixture of round undifferentiated cells and differentiated cells with fibrillar cytoplasm. Alveolar form is typically found in the inferior orbit and is the most malignant form of rhabdomyosarcoma. Pleomorphic tumors are the most differentiated and most rare and have the best prognosis. Treatment consists of immediate biopsy followed by definitive therapy. Chemotherapy (vincristine, actinomycin D, and cyclophosphamide) combined with radiotherapy (5,000 cGy to 6,000 cGy) has been reported to eliminate metastases. With treatment, the 5-year survival rate for embryonal rhabdomyosarcoma is approximately 90%2 (Slide 1 and Slide 2).

Dermoid and Epidermoid Cysts
A dermoid cyst is the most common orbital cystic lesion. Choristomas are growths arising from tissue anomalies characterized by elements not normally found in the involved site. Dermoid cysts represent a developmental choristoma derived from pouches of ectoderm trapped in the bony sutures or failure to separate from the neural tube. They are lined with keratinizing epidermis and filled with dermal appendages. Epidermoid cysts are lined by only epidermis and are usually filled with keratin. Clinical presentation, at any age, is a smooth, painless, oval mass that slowly enlarges. In 75% of cases, the lesion is located in the lateral brow adjacent to the zygomatic frontal suture. Rupture of the cyst wall will result in intense inflammatory reaction. CT imaging is indicated if the mass is fixed to the underlying bone, suggesting possible extension of a "dumbbell" shaped lesion into the orbit. CT demonstrates a round, well-circumscribed extraconal mass. An air-fluid level may be present, as well as varying signal intensities. Treatment involves complete surgical excision with an intact capsule. If the capsule is broken, copious irrigation of the site should prevent the intense inflammatory reaction.

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Slide 3

Capillary Hemangioma and Lymphangioma
The most common vascular tumor of childhood, capillary hemangiomas manifest primarily in the first year of life. There is a period of rapid growth during the first 6 to 12 months of life, followed by an involutional phase in 75% over the next 4 to 7 years. Clinical presentation is usually at birth with a mass in the upper eyelid or superior orbit, which is strawberry in color (superficial) or bluish (deeper). In half of the cases, the tumor enlarges when crying or during Valsalva maneuver. They may cause ptosis, strabismus, anisometropia, and occlusion amblyopia. CT imaging demonstrates a well-defined to infiltrating mass that may be extra- or intraconal. On MRI T1-weighted imaging, the hemangioma produces a signal that is hyperintense to muscle and hypointense to fat. Treatment consists of observation. Anisometropia, strabismus, and amblyopia are all indicators for treatment. Initial therapy consists of intralesional steroid injection. Side effects include local necrosis, fat atrophy, systemic growth retardation, and embolic visual loss. Surgical excision may be effective if the lesion is small. Interferon alpha-2 and laser photocoagulation have also been reported to be effective (Slide 3).

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Slide 4

Lymphangiomas represent hamartomas of the venous-lymphatic channels. These lesions may be found in the conjunctiva, eyelid, orbit or oropharynx, and sinuses. Often, the tumor will enlarge during an upper respiratory infection. Clinical presentation is progressive, painless proptosis, which may follow a sudden hemorrhage. Such events may result in motility impairment or compressive optic neuropathy. CT imaging reveals an irregular and heterogeneous density that infiltrates orbital structures. MRI T1-weighted imaging produces a heterogeneous signal that is mildly hyperintense to muscle and hypointense to fat. T2-weighted images are more variable with the different stages of blood. Histopathologically, lymphangiomas consist of large serum filled proteinaceous spaces lined by flattened endothelial cells. The tumors are not encapsulated and contain scattered follicles of lymphoid tissue in the interstitium. Treatment in most cases is observation because spontaneous regression often occurs. Also, because of the highly infiltrative nature of the tumor, it is difficult to resect. Dark blood or "chocolate cysts" may be visualized and evacuated surgically along with any acute hemorrhagic cysts. Intraoperative laser therapy has been a useful adjunct to surgical debridement (Slide 4).

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Slide 5

Optic Nerve Glioma
Optic nerve gliomas are uncommon neoplasms of the astrocytic glia of the optic nerve pathways. They occur in the first decade of life. The associated incidence of neurofibromatosis varies from 25% to 50%. Males and females are affected equally. Clinical presentation is a slowly progressive visual impairment associated with insidious painless axial proptosis and an afferent pupillary defect. Ocular findings include optic atrophy, papilledema, and strabismus. CT imaging reveals well-circumscribed, rounded or fusiform enlargement of the optic nerve. MRI T1-weighted images of the glioma are isointense or hypointense to gray matter. On T2-weighted images the signal is more variable and there is marked enhancement with gadolinium but less than seen with meningioma. Histopathologically, the pilocytic astrocytoma consists of elongated spindle-shaped astrocytes. Some astrocytes show cell processes that stain brightly eosinophilic (Rosenthal fibers). Treatment is controversial. Observation with serial MRIs is reserved for lesions that are confined to the orbit. When the tumor grows rapidly, the involved section of optic nerve between the eye and chiasm should be excised. Surgical debulking is recommended for large chiasmal tumors or rapidly growing tumors. Radiation therapy is considered if the tumor cannot be debulked. Chemotherapy with actinomycin D and vincristine may effectively delay the need for radiotherapy3 (Slide 5 and Slide 6).

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Slide 6

Histiocytosis X
Histiocytosis X is a group of disorders of Langerhans cell proliferation. The basic disease in all subtypes is an accumulation of proliferating histiocytes in various tissues. The diseases vary from benign lesions with spontaneous resolution to fatal dissemination. Previously, these diseases were referred to as eosinophilic granuloma, Hand-Schuller-Christian, and Letter-Siwe, and are now termed unifocal and multifocal eosinophilic granuloma of bone. Clinical presentation is a rapidly expanding painful mass, upper eyelid swelling, ptosis, and displacement of the globe. CT scan demonstrates a soft-tissue mass of moderate density near the superotemporal bony orbital rim. The mass is found adjacent to an osteolytic defect with "punched-out" borders. Enhancement with gadolinium on MRI imaging is marked and heterogeneous. Intracranial extension may be demonstrated on MRI, but not visualized on CT. Histopathologically, Langerhans cells are large histiocytes with grooved or folded nuclei. The Langerhans cells can be confirmed by a positive immunohistochemical reaction for CD1a. Also, characteristic Birbeck granules are visualized in the Langerhans cell on electron microscopy. Treatment consists of either surgical curettage of the lesion, low-dose radiotherapy, or intralesional steroids. Prognosis for vision and survival is good.2

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Slide 7

Leukemia
Acute myelogenous leukemia has (AML) been associated with an extramedullary solid tumor, referred to as chloroma or granulocytic sarcoma. It is the most common form of leukemic infiltrate involving the orbit seen in 30% of patients with AML. Clinical presentation is in 8- to 9-year-old children with proptosis and diplopia. The lesion is typically a unilateral mass in the lateral orbital wall that causes a medial displacement of the globe. A CT scan demonstrates an irregular mass with bony erosion. Histopathologically, they may be composed entirely of myeloblasts, which are large cells with ovoid nuclei. Histochemical staining for chloroacetate esterase (Leder stain) or immunostaining for myeloperoxidase, or both, confirms the diagnosis. Radiotherapy is the treatment of choice for localized lesions. Chemotherapy is prescribed for lesions with systemic involvement. Prognosis is poor with only 20% tumor-free survival of 5 years.

Orbital Pseudotumor (Idiopathic Orbital Inflammation)
Idiopathic orbital inflammation may range from acute to chronic, and it is not associated with systemic disease.
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Slide 8
This disease affects any age group. As the name implies, it is a benign, nongranulomatous, inflammatory process of unknown origin. The inflammatory process is typically diffuse but may involve specific orbital structures, in which case it is subclassified on the basis of the anatomic target area. Rootman subdivides pseudotumor into anterior, diffuse, apical, myositic, and lacrimal.4 Clinical presentation is typically an acute onset of unilateral lid edema, pain, proptosis, injection, and chemosis. Half of the patients may experience diplopia secondary to restriction of extraocular muscles. Posterior orbital involvement may lead to glaucoma, uveitis, or retinal detachment. CT imaging demonstrates an irregular, heterogeneous area that molds along the globe. The extraocular muscles along with their tendons of insertion are thickened, as opposed to thyroid orbitopathy, which spares the tendons. Bone erosion is uncommon. On MRI T1-weighted imaging, there is a heterogeneous, poorly defined signal that is isointense to muscle and hypointense to fat. The T2-weighted image may be hyper- or isointense depending on whether the lesion is acute or chronic. Histopathologically, the lesion appears as a mixture of lymphocytes, plasma cells, macrophages, and eosinophils. Treatment consists of systemic steroids, which resolve about 60% of cases. For patients who are unresponsive, radiotherapy at 1,500 cGy to 2,000 cGy is helpful. Prognosis is good but in patients with unresponsive lesions, the diagnosis should be confirmed by biopsy4 (Slides 7 and Slide 8).

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Slide 9

Neurofibroma
Neurofibroma is a tumor composed mainly of proliferating Schwann cells within nerve sheaths. They are infiltrative tumors associated with neurofibromatosis type 1 (von Recklinghausen disease). Neurofibromatosis type 1 is a phakomatosis, inherited in an autosomal-dominant fashion with irregular penetrance. The disorder has a constellation of symptoms such as café-au-lait spots, axillary freckling, fibroma molluscum, plexiform neurofibromas, dysplasia of orbital walls, congenital glaucoma, and optic nerve gliomas. Treatment is surgical excision, although complete excision is rare (Slide 9 and Slide 10).

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Slide 10

Metastatic Neuroblastoma
Metastatic neuroblastoma is the most common tumor that is metastatic to the orbit in children. It consists of a malignant neoplasm of primitive neuroblasts, which normally differentiate into sympathetic nerves and ganglia. The primary tumor is usually located in the adrenal medulla, and the sympathetic or parasympathetic tissues of the abdomen or chest. Clinical presentation is an abrupt ecchymotic proptosis that may be bilateral. Optic disc edema and dilated retinal vessels may be visualized on funduscopic exam. A CT scan demonstrates a large, irregular, poorly defined mass with or without bony destruction. MRI reveals mild to marked enhancement with gadolinium. Histopathologically, the tumor consists of small regular cells with round deeply staining nuclei and scant cytoplasm. Special neuron-specific stains help differentiate neuroblastoma from other small cell tumors. Treatment consists of chemotherapy. One-third of children develop visual loss. Prognosis is poor once orbital metastases have occurred.

Orbital Diseases in Adults

The following are orbital disorders found predominantly in adults:

Thyroid Ophthalmopathy
Thyroid ophthalmopathy is the most common cause of proptosis in adults. It is a cell-mediated, autoimmune disorder of unknown etiology. Women are more commonly affected than men by 3:1. It most commonly affects patients 25 to 50 years old. Clinical presentation is chronic progression of a constellation of symptoms such as proptosis (bilateral or unilateral), lid retraction, restrictive myopathy, diplopia, compressive optic neuropathy, conjunctival injection, chemosis, and exposure keratopathy. Clinical signs are the result of an increase in orbital volume caused by local accumulation of glycosaminoglycans with subsequent water binding. The resultant orbital congestion may result in pain and glaucoma. Symptoms progress over years and then stabilize and improve. CT imaging demonstrates proptosis of the globe and enlarged extraocular muscles with relative sparing of their tendinous insertions. The most commonly involved muscles are the inferior rectus and the medial rectus. The enlarged muscles are best appreciated on the coronal images and this is the hallmark of the disease. Histopathologically, the inflammatory infiltrate is restricted to the extraocular muscles and there is little spill over into the adjacent orbital fat that distinguishes it from orbital pseudotumor. Treatment consists of supportive therapy during the active phase of the disease. In cases of significant orbital congestion, systemic steroids may be helpful. Low-dose radiotherapy was also believed to be beneficial, but newer studies question its efficacy. Once the patient has been stable for 6 to 12 months, surgical options such as orbital decompression, strabismus correction, and eyelid correction may be considered. Most patients stabilize after 3 to 5 years with relatively good vision.5

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Slide 11

Orbital Pseudotumor
Orbital pseudotumor was discussed above in the Orbital Diseases in Children sections. The disease affects all age groups with the same presentation.

Cavernous Hemangioma
Cavernous hemangioma is the most common benign neoplasm of the orbit in adults. It is a benign, noninfiltrative, slow-growing tumor of large endothelial channels, typically located intraconally. It most commonly affects middle-aged women. Clinical presentation is a slowly progressive, painless proptosis. Decreased vision may occur in cases of optic nerve compression or induced hyperopia. CT imaging reveals a well-defined oval or round mass typically within the muscle cone, the density of which is homogenous and greater than that of the surrounding muscle. T1-weighted MRI reveals a mass that is isointense to muscle and hypointense to fat. On T2-weighted imaging, the mass is hyperintense to fat and brain and enhances with gadolinium. Histopathologically, the tumor is well circumscribed with large cavernous spaces lined by flattened endothelial cells and scant stroma. Treatment consists of surgical excision for symptomatic lesions with excellent results and resolution of symptoms (Slide 11 and Slide 12).

Lymphoproliferative Disorders
Lymphoid tumors of the orbit may be either polyclonal (reactive lymphoid hyperplasia) or monoclonal (lymphoma). Lymphomas are typically monoclonal B cell tumors. Genetic markers and special stains are used to study the surface immunoglobulins on the lymphocytes and determine whether the tumor is polyclonal or monoclonal.
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Slide 12
Yet some patients who are initially diagnosed with reactive lymphoid hyperplasia later develop systemic lymphoma. Clinical presentation of l ymphoid tumors is a painless, progressive proptosis or ptosis. Most often, it occurs in people between 45 and 65 years of age. Vision and motility are preserved. The lesions tend to occur in the anterior orbit where they may present as a salmon-colored lesion underneath the lid in the subconjunctiva. The lacrimal gland is frequently involved. CT imaging demonstrates an irregular mass with density similar to muscle that molds along the globe. On T1-weighted MRI, the tumors are isointense to muscle and hyperintense to fat. On T2-weighted images, the tumor is isointense or hyperintense to muscle and fat and there is increased intensity with gadolinium. Histopathologically, reactive lymphoid hyperplasia consists of a mixture of small and large lymphocytes as well as plasma cells and macrophages. This designation is given when a single clonal population cannot be demonstrated. Lymphomas are diffuse proliferations of neoplastic lymphocytes. Most lymphomas consist of a cell population of small round lymphocytes. Unfortunately, well-differentiated lymphomas are difficult to distinguish from reactive hyperplasia without immunophenotyping. Treatment of reactive lymphoid hyperplasia consists of systemic steroids for nonclonal lesions. If the patient does not respond to steroids, then radiotherapy may be initiated at 2,000 cGy to 3,000 cGy. The incidence of progression to lymphoma has been reported to be between 15% and 36%. Treatment of lymphoma begins with a systemic work-up for staging. Low-grade tumors may be observed or radiated at 2,500 cGy to 3000 cGy. Less well-differentiated tumors and patients with systemic involvement require chemotherapy. Prognosis depends on staging. Overall, the 5-year survival rate is 93%.6

Meningioma
Optic nerve sheath meningiomas arise from the menigiothelial cells of the arachnoid tissue surrounding the optic nerve. Meningiomas most commonly occur in women between 30 and 50 years old. The woman:man ration is 3:2. Clinical presentation is gradual visual field and vision loss. Gaze-evoked amaurosis is a common feature. Later, patients develop painless progressive axial proptosis. Eventually, the patient will develop disc edema and optic atrophy. Optociliary shunt vessels and a relative afferent papillary defect are present. CT imaging demonstrates optic nerve tubular enlargement. T1-weighted MRI of meningiomas produces an isointense signal to gray matter that becomes slightly hyperintense to hypointense on T2-weighted images. With administration of gadolinium, there is marked enhancement of the tumor with regard to the optic nerve, which is best demonstrated on fat suppressed images. Histopathologically, the tumor consists of small nodules of tumor cells in a whorled pattern. Psammoma bodies may be present. Treatment consists of observation if the vision is good. If the tumor is confined to the orbit and there is progressive visual field loss, radiation therapy should be considered. If, on MRI, there is intracranial extension or severe visual loss with severe proptosis, the optic nerve is excised with the tumor from the back of the globe to the chiasm. Prognosis for survival is good, but the prognosis for vision is poor.2,3

References

  1. Garcia G, Harris G. Criteria for nonsurgical treatment of subperiosteal abscesses of the orbit. Ophthalmology. 2000;107:1454-1456.
  2. Christianson MD. Orbital tumors and inflammations. In: Stephenson CM, ed. Ophthalmic Plastic, Reconstructive, and Orbital Surgery. Boston, MA: Butterworth-Heinemann; 1997:357.
  3. Dutton JJ, Byrne SF, Proia AD. Diagnostic Atlas of Orbital Diseases. Philadelphia, PA: WB Saunders; 2000.
  4. Rootman J, Nugent R. The classification and management of acute orbital pseudotumors. Ophthalmology. 1982;89:1040.
  5. Bahn RS, Heufelder AE. Pathogenesis of Graves' ophthalmopathy. N Engl J Med. 1993;329:1468-1475.
  6. Jakobeic FA, Neri A, Knowles DM. Genotypic monoclonality in immunophenotypically polyclonal orbital lymphoid tumors: A model of tumor progression in the lymphoid system. Ophthalmology. 1987;94:980.