Chapter 193 – Prechiasmal Pathways—Compression by Optic Nerve and Sheath Tumors
THOMAS C. SPOOR
• Optic nerve dysfunction as a result of compression by tumor or aneurysm anywhere along the nerve’s course from globe to chiasm.
• Progressive visual field loss.
• Relative afferent pupillary defect.
• Swollen or atrophic optic disc.
• Retinal and choroidal striae.
• Opticociliary collateral vessels.
• Venous stasis retinopathy or central retinal vein occlusion.
The optic nerve extends from the back of the eye, traverses the orbit, passes through the optic canal, and has a variable intracranial course before it joins with the contralateral optic nerve to form the chiasm ( Fig. 193-1 ). Compression by a tumor or an aneurysm may cause optic nerve dysfunction anywhere along its course, from globe to chiasm.
EXTRINSIC ORBITAL OPTIC NERVE COMPRESSION
Extrinsic optic nerve compression by orbital tumors or apical orbital compression by enlarged dysthyroid extraocular muscles represents an uncommon but potentially treatable cause of optic neuropathy. These tumors may compress the optic nerve at the orbital apex ( Fig. 193-2 ).
EPIDEMIOLOGY AND PATHOGENESIS
Compression of the apical orbital optic nerve by enlarged extraocular muscles is an uncommon manifestation of dysthyroid orbitopathy ( Fig. 193-3 ). The vast majority of patients who have hyperthyroidism have mild, noninfiltrative orbitopathy. Clinically, significant infiltrative orbitopathy occurs in only 3–5% of the hyperthyroid population. The most severe infiltrative orbitopathy, dysthyroid optic neuropathy, occurred in 8.6% of 675 patients with dysthyroid orbitopathy in one large series.
Figure 193-1 Axial cadaver section that demonstrates the course of the optic nerve from the globe to the optic chiasm. Note the intraorbital, intracanalicular, and intracranial segments of the optic nerve.
Encapsulated orbital tumors are quite uncommon. Of these, cavernous hemangiomas are the most common, neurilemomas are less common, and hemangiopericytomas are rarer still.
Initially, extrinsic optic nerve compression within the orbit manifests with slowly progressive loss of visual acuity and brightness sensation, and dyschromatopsia. Visual field deterioration and relative afferent pupillary defect are seen with progression. Examination may be entirely normal, and patients who have large tumors with more anterior optic nerve compression also may have a swollen optic disc and choroidal striae. However, anterior orbital tumors more commonly occur with proptosis but without compressive optic neuropathy.
In patients with thyroid eye disease, other manifestations such as eyelid retraction and extraocular motility restriction may be seen. It may be more difficult to diagnose disease in patients who do not have other signs of thyroid eye disease, and they may be followed for months to years with progressive visual field loss and negative neuroimaging study results.
DIAGNOSIS AND ANCILLARY TESTING
The key to the diagnosis is first to consider it and then to obtain appropriate imaging studies to visualize the orbital apex. Computed tomography (CT) scanning differentiates optic nerve compression by orbital tumors from apical orbital optic nerve compression by enlarged, dysthyroid extraocular muscles (see Fig. 193-2 ). Magnetic resonance imaging (MRI) scans can help differentiate orbital tumor from the compressed optic nerve and facilitate surgical decision making.
Figure 193-2 Images of a large orbit mass adjacent or contiguous with the optic nerve. A, Computed tomography scan (axial). B, Magnetic resonance imaging shows obvious demarcation between the tumor and the adjacent optic nerve.
Figure 193-3 Computed tomography scans (axial and coronal). The optic nerves are compressed at the orbital apex by enlarged extraocular muscles.
Treatment of dysthyroid optic neuropathy is to decompress the orbital apex. Extraocular muscles may be shrunk with systemic corticosteroids or low-dose irradiation, and the orbital apex may be expanded by surgical removal of the medial orbital wall— advocates exist for each technique.  The author favors the initial use of systemic corticosteroids (prednisone 80?mg daily), followed by decompression of the medial orbital wall and orbital apex via an external ethmoidectomy. Orbital irradiation is reserved for cases refractory to corticosteroids and surgical decompression or for patients who are unwilling or unable to undergo general anesthesia and surgery. However, contrary to clinical experience, a recent study has found that external beam irradiation is not an effective treatment for Grave’s ophthalmopathy.
Treatment of optic nerve compression by an encapsulated orbital tumor entails surgical removal of the tumor. MRI may help to differentiate the tumor from the optic nerve and ascertain the tumor’s position in reference to the optic nerve. The latter is important in planning an appropriate surgical approach for tumor excision.
Figure 193-4 Magnetic resonance imaging of a large optic nerve glioma and optic canal confined to the orbit.
OPTIC NERVE COMPRESSION BY OPTIC NERVE AND SHEATH TUMORS
The optic nerve may be invaded by intrinsic tumors (such as gliomas) arising from the neuroglia or neurons, or compressed by extrinsic tumors arising from the meninges (such as meningiomas). Optic nerve gliomas and optic nerve sheath meningiomas are the most common tumors to involve the optic nerve. Less commonly, the optic nerve also may be involved by lymphomas, leukemias, malignant gliomas, and metastatic cancers.
GLIOMAS AND MALIGNANT GLIOMAS
Epidemiology and Pathogenesis
Gliomas of the anterior visual pathways are the most common tumors of the central nervous system. They account for 2% of all gliomas and 5% of childhood gliomas and occur most commonly during the first two decades of life—65% occur within the first decade, and 90% occur before 20 years of age. Rarely, a glioma may occur in a previously asymptomatic adult as an expanding orbital mass. Gliomas of the anterior visual pathways account for 65% of all intrinsic optic nerve tumors. Malignant gliomas of the optic nerve are rare. Gliomas that involve the intraorbital optic nerve are most common (47%), those that involve the orbital and intracranial optic nerve are second most common (26%), followed by intracranial and chiasmal involvement (12%) and gliomas confined to the optic chiasm (5%).
Patients who have optic nerve gliomas usually experience exophthalmos, decreased visual function, and dyschromatopsia accompanied by a relative afferent pupillary defect. The optic disc may be normal, swollen, or atrophic. Central retinal vein occlusion may occur.
Patients who have malignant gliomas of the optic nerve have rapidly progressive, painful visual loss accompanied by signs of an optic neuropathy.  Initial visual loss may be unilateral or bilateral (chiasmal involvement), but rapid progression to bilateral blindness and death are constant features. Depending on the initial location of the tumor, visual loss may be accompanied by exophthalmos, extraocular motility dysfunction, venous stasis retinopathy, and an optic disc that is swollen, atrophic, or of normal appearance.
Intrinsic enlargement of the optic nerve on MRI is evident in patients who have optic nerve gliomas. The presence and extent of optic nerve gliomas is best demonstrated by MRI ( Fig. 193-4 ). Although rarely missed with high-resolution CT scans, optic nerve enlargement by an intrinsic glioma may be confused with compression by a resectable orbital tumor; MRI may help to differentiate these (see Fig. 193-3 ).
For patients who have orbital nerve gliomas and neurofibromatosis type 1, MRI demonstrates a typical double-intensity tubular thickening caused by perineural arachnoid gliomatosis, and elongation and downward kinking of the midorbital optic nerves.
Imaging studies of an optic nerve glioma may show enlargement of the optic forearm that arises from secondary meningeal hyperplasia. Consequently, enlargement of the optic forearm is not firm evidence of intracranial extension of an optic nerve glioma.
Imaging studies of malignant gliomas of the optic nerve demonstrate enlargement of the involved regions of the optic nerve and chiasm, although initially normal imaging study results have been reported. The diagnosis of this devastating disease should be confirmed by biopsy of the involved portion of the optic nerve.
The differential diagnosis of visual loss from optic nerve glioma is the differential diagnosis of any slowly progressive optic neuropathy. Differentiation between gliomas and other causes of optic nerve compression in a child is best accomplished using appropriate imaging studies (see above).
Frequently, optic nerve gliomas are found in association with neurofibromatosis type 1 (only rarely with neurofibromatosis type 2), which is present in 25% of patients who have optic nerve gliomas, while 15% of patients with neurofibromatosis have optic nerve gliomas. Increased intracranial pressure and chiasmal and optic tract involvement are more common in patients who do not have neurofibromatosis. Precocious puberty is more common in children who have gliomas and neurofibromatosis. 
Optic nerve gliomas are intrinsic tumors that arise from the neuroglia—usually astrocytes, but occasionally oligodendrocytes (see Fig. 193-3 ). Three histopathological patterns exist:
• Transitional areas in which the tumor merges with normal optic nerve and which may be difficult to differentiate from reactive gliosis
• Areas of tumor necrosis, which may appear as cystic spaces that contain reticulated, myxomatous material
• Areas where astrocytes may show spindle cell formation and contain cytoplasmic, eosinophilic structures called Rosenthal fibers ( Fig. 193-5 )
These patterns are characteristic but not diagnostic of optic nerve gliomas. Arachnoid hyperplasia, secondary to infiltration by the glioma through the pia, may mimic an optic nerve sheath meningioma.
Biopsy specimens of malignant gliomas of the optic nerve demonstrate bizarre, atypical malignant astrocytes that separate disrupted myelin sheaths.
If visual function is good, isolated intraorbital optic nerve gliomas may be observed. Visual function may be followed with serial visual field testing, and MRI should be done every 6–12 months to detect any intracranial extension. If vision is poor, or exophthalmos is excessive and unsightly, the lesion may be removed via a craniotomy and superior orbitotomy. If intracranial extension by a glioma initially confined to the orbit is documented, the tumor should be removed completely via craniotomy in an effort to avoid chiasmal, hypothalamic, or third ventricle involvement.
Figure 193-5 Optic nerve glioma. Many astrocytes contain intracytoplasmic eosinophilic structures, called Rosenthal fibers (R).
Unfortunately, no successful treatment exists for malignant gliomas of the optic nerve.
Course and Outcome
Optic nerve gliomas are true neoplasms that characteristically demonstrate early growth followed by long periods of stability in many cases. They have a poor prognosis for vision, but if confined to the optic nerve, long-term survival is excellent. If the chiasm, hypothalamus, or third ventricle are involved, the prognosis for life diminishes. Once the hypothalamus is involved, mortality rises to over 50%. No therapy exists of proven benefit. Spontaneous regression may occur. There is a tendency for vision in the worse eye to deteriorate and vision in the better eye to remain stable regardless of treatment or neurofibromatosis status. 
Patients who have malignant gliomas of the optic nerve experience painful visual loss and rapidly progress to bilateral blindness within 6–8 weeks. Death invariably follows within 6–9 months after the initial symptoms. 
OPTIC NERVE SHEATH MENINGIOMAS
Meningiomas are benign neoplasms that arise from the meningothelial cells of the meninges. The optic nerve may be compressed by meningiomas confined to the optic nerve or by orbital extension of intracranial tumors. Slowly progressive, relentless visual loss may be accompanied by proptosis and extraocular motility dysfunction.
EPIDEMIOLOGY AND PATHOGENESIS
Optic nerve sheath meningiomas represent 1–2% of all meningiomas. After gliomas, these are the second most common type of optic nerve tumor and primarily affect middle-aged adults, usually women.
Slowly progressive visual loss is the hallmark of an optic nerve sheath meningioma. A relative afferent pupillary defect and dyschromatopsia invariably are present. The optic disc may be swollen or atrophic. Opticociliary collateral vessels and retinal and choroidal folds may be evident on fundus examination. Extraocular motility dysfunction is present in some cases.
Neuroimaging confirms the diagnosis of optic nerve sheath meningioma. CT scans demonstrate fusiform, tubular, or irregular enlargement of the optic nerve. The borders of the enlarged optic nerve may enhance after administration of intravenous
Figure 193-6 Computed tomography scan of optic nerve sheath meningioma.
Figure 193-7 Gadolinium-enhanced magnetic resonance imaging demonstrates the intracranial extension of an optic nerve sheath meningioma.
Figure 193-8 Meningioma of optic nerve. This biopsy shows a proliferation of meningothelial cells. As is often the case, no psammoma bodies are present. B, blood vessels; N, nests of meningothelial cells.
contrast, to leave a central, linear lucency within the optic nerve sheath (tram-track sign; Fig. 193-6 ). Extensive or segmental calcifications also may be present.
MRI fat suppression and gadolinium–diethylenetriamine-pentaacetic-acid (Gd-DTPA) enhancement can detect and demarcate precisely the degree of intracanalicular and intracranial extension of optic nerve sheath meningiomas ( Fig. 193-7 ). The majority of intraorbital and intracranial meningiomas are detected by CT scans, but only gadolinium-enhanced MRI reliably demonstrates a meningioma that involves the intracanalicular optic nerve (see Fig. 193-7 ). Studies with high-quality MRI demonstrate that, even with small tumors, intracranial extension is the rule rather than the exception.
Meningiomas arise from the meningothelial cells of the arachnoid villi. Histopathology demonstrates patterns of whorls and sheets of meningothelial cells ( Fig. 193-8 ). A variable amount of fibrous and vascular tissue occurs in fibroblastic pattern
Intracranial Causes of Compressive Optic Neuropathies
Syphilis-meningitis or gumma
• sphenoid ridge
• planum sphenoidale, suprasellar, intrasellar
Paranasal sinus tumors
meningiomas, with psammoma bodies present in psammomatous and mixed meningiomas.
Treatment of optic nerve sheath meningiomas is conservative, because these tumors usually grow very slowly. Observation, serial automated visual fields, and regular MRI scans with gadolinium enhancement are appropriate for patients who have good vision and no evidence of intracranial or intracanalicular extension of tumor. Patients for whom MRI evidence exists of such extension should be offered a neurosurgical opinion, but they should be informed that these tumors may grow very slowly. It may be appropriate to follow a small amount of intracranial extension with serial MRI, with craniotomy reserved for those patients who have documented progressive intracranial extension of tumor.
Intraorbital or intracranial surgical removal of selected tumors or intracranial optic canal decompression may improve vision in some patients, but the improvement rarely lasts. Patients who have blind eyes and severe exophthalmos may benefit from extirpation of intraorbital and intracranial tumor. Documented intracanalicular or intracranial progression of tumor growth warrants neurosurgical removal of the tumor.
A large, recent series in which visual outcome was reviewed in a group of patients who underwent radical tumor resection of cranio-orbital meningiomas reported improved visual function in 27%, stable visual function in 62%, and worsening vision in 11%. The postoperative visual outcome is related to the degree of preoperative visual impairment. These results seem better than those previously described.
Recurrent tumor and progressive visual loss may be treated with radiation. Treatment is controversial. Radiation therapy has been used in patients who have progressive visual loss and good visual function, and in patients who have recurrent tumor. Preliminary results are encouraging, but too few patients have been treated with this modality and its long-term advantage for vision remains unknown and unproved. More recently, excellent results actually reversing visual loss utilizing 3-dimensional conformal radiation have been reported.
COURSE AND OUTCOME
The clinical course of optic nerve sheath meningiomas is slowly progressive, relentless visual loss in the affected eye. The prognosis
for life is excellent, with an overall tumor-related mortality of near zero.
INTRACANALICULAR AND INTRACRANIAL COMPRESSIVE LESIONS
The optic nerves may be compressed within the optic canal or intracranially by any entity that can compress the optic chiasm, depending upon the length of the intracranial optic nerves and their position relative to intracranial structures (e.g., pre- or postfixed optic chiasm; see Chapter 195 ). Aneurysms, tumors, infection, inflammation, mucoceles, and processes that involve the sphenoid bone, such as fibrous dysplasia, may cause a compressive optic neuropathy ( Box 193-1 ). The involved optic nerves may appear normal, atrophic, swollen, or excavated. Optic disc excavation in the absence of elevated intraocular pressure may indicate a compressive optic neuropathy, especially if accompanied by pallor of the neuroretinal rim.
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