14 Optic Nerve Tumors

Nick Mamalis, Garrett Smith

INTRODUCTION

Tumors of the optic nerve are relatively rare lesions. However, these lesions have significant risk for visual morbidity as well as other problems related to the central nervous system (CNS). Optic nerve glioma (astrocytoma) is the most common intrinsic tumor of the optic nerve. Juvenile pilocytic astrocytomas are by far the most common optic nerve tumor of children. Malignant gliomas of the optic nerve occur much less frequently and are seen in adults. Meningiomas of the optic nerve sheath are the second largest group of tumors which may affect the optic nerve and occur more commonly in adults. Lastly, secondary tumors of the optic nerve may arise from direct invasion from intraocular malignancies, meninges, adjacent structures, as well as distant metastases.

OPTIC NERVE GLIOMAS

Gliomas (juvenile pilocytic astrocytoma) are the most important optic nerve tumor of children, accounting for 65 percent of all intrinsic optic nerve tumors.1 Gliomas are benign neoplasms arising from the neuroglia (astrocytes and oligodendrocytes). The majority of optic nerve gliomas are of astrocytic origin. However, a few rare optic nerve gliomas arise from oligodendrocytes. The descriptive term juvenile pilocytic astrocytoma is often used to describe this low-grade glioma. Gliomas grow slowly, but can spread under the dura to invade local structures. Patients typically present before the age of 20 with progressive visual loss, proptosis, and disk pallor with or without papilledema. Management includes observation, radiation, and surgery.

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Clinical Features

Age

In 1816 Antonio Scarpa first described optic nerve tumors and noted that the majority of his patients with gliomas were children. This fact has been substantiated in subsequent reports.1 In Dutton’s review of gliomas of the anterior visual pathway, the mean age of presentation was 8.8 years, with 70 percent of optic nerve gliomas occurring in the first decade of life, 20 percent in the second decade, and 10 percent between the ages of 20 and 80.1 Optic nerve gliomas are rare lesions estimated at 5 percent of intracranial tumors and 3 percent of all orbital tumors.2,3

Sex

Optic nerve gliomas show equal to a slight female preponderance. One study of 594 patients had 295 (50 percent) females and 299 (50 percent) males.1 For gliomas confined to the optic nerve, earlier studies suggest a slight female preponderance of about 2:1.4,5

Location

The size, growth pattern, and symptoms of the tumor depend upon the location of the tumor. In a study of 1278 cases, 75 percent involved the chiasm and optic nerve, while 25 percent were confined to the optic nerve alone.1 Of the lesions involving the chiasm, 7 percent were confined solely to the chiasm. Extension from the optic nerve into intraocular structures, meninges, and brain occurs in a few rare cases.6,7 It is thus helpful to divide optic nerve gliomas into two categories: orbital gliomas and intracranial or chiasmal gliomas.

Orbital gliomas vary in size and growth pattern, but are generally slow growing benign tumors. Many orbital tumors slowly enlarge to reach a plateau, then remain unchanged for many years. This stabilization phenomenon is the reason that many considered these as hamartomas. Hamartomas are a focal malformation resembling a neoplasm, but is the result of faulty organ development composed of an abnormal mixture of tissue elements.

Chiasmal gliomas seem to be more aggressive than orbital gliomas, and a few cases have reported malignant change.8,9 Of the tumors in the chiasm, 46 percent involved the hypothalamus or third ventricle, interfering with hypothalamic and pituitary function.1 Thus, patients with chiasmal tumors often present with endocrine abnormalities.

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Chiasmal tumors are also a concern because they can obstruct the third ventricle causing intracranial pressure elevation.

Presenting Signs and Symptoms

Orbital gliomas present with more orbital manifestations, while chiasmal gliomas demonstrate more neurological symptoms. However, both tumors share many of the same symptoms and many patients present with tumors involving both the orbital optic nerve and the chiasm.

Regardless of tumor location, patients may experience some degree of unilateral visual dysfunction, visual field loss, afferent pupillary defect, decreased ocular motility, optic atrophy, pain, headache, and nystagmus. In Dutton’s review, 88 percent of patients presented with vision loss, 26 percent presented with acuities between 20/20 and 20/ 40, 19 percent between 20/50 and 20/200, and 55 percent were 20/ 300 or worse.1 Visual field loss occurred in 63 percent of patients and an afferent pupillary defect was seen in 75 percent of individuals.

Visual loss occurs due to astrocyte proliferation within the confines of the dura and bone in cases of intracranial lesions. Initially, this causes longitudinal axon bundle separation and nerve fiber compression. The compression inhibits axoplasmic transport, with little loss of axonal conduction. Further compression leads to demyelination and mechanical disruption of axons. Intracranial gliomas are more confined and compress the axon faster, producing quicker vision loss. Orbital gliomas have more room to grow causing the characteristic slow progressive visual loss, because only individual axons degenerate. Spontaneous improvements in vision have been reported.10,11 This is theorized from variations in mucoid substance and hydration, and their effects on the optic nerve. In some cases rapid vision loss occurs due to occlusion of the vascular supply. Gliomas affecting the optic disk and retrolaminar portions of the nerve may compress the central retinal vein producing optic disk swelling. The visual loss is rapid and the clinical picture may simulate optic neuritis.

Proptosis is often the chief complaint of an orbital glioma in young children, occurring 94 percent of the time in orbital lesions (Fig. 14.1).1 Because the tumor arises from the nerve within the muscle cone, the proptosis is usually axial. Minimal proptosis is 2.0 to 4.0 mm ranging up to severe proptosis at 10.0 mm or more.

Nystagmus is another initial sign of both orbital and chiasmal gliomas occurring in 23 percent of patients.1 It may be vertical, horizontal, seesaw, or rotary. Pain or headaches, and limited ocular motility are other common symptoms of both types of gliomas.

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Fig. 14.1: Child with an optic nerve glioma of the left eye demonstrating proptosis with moderate inferior displacement of the left globe

On fundoscopic examination, 59 percent of patients demonstrated some degree of optic atrophy and disk pallor (Fig. 14.2). Disk swelling presents more frequently in orbital gliomas with a 48 percent occurrence rate.1 In chiasmal tumors, disk swelling occurred 22 percent of the time, and was often bilateral, due to increased intracranial pressure. Optociliary shunt vessels are occasionally seen with optic nerve gliomas, however they are far more common in optic sheath meningiomas.

Other late and infrequent orbital glioma signs are venous stasis retinopathy with iris neovascular glaucoma, anterior segment ischemia, and hemorrhagic glaucoma from retinal vascular occlusion.

In chiasmal gliomas, 27 percent of patients had third ventricle involvement causing increased intracranial pressure and 26 percent reported hypothalamic or endocrine abnormalities.1,12 The endocrine abnormalities included obesity, diabetes insipidus, panhypopituitarism, dwarfism and precocious puberty.

Association with Neurofibromatosis

Several studies have published a 15 to 21 percent occurrence rate of optic gliomas in neurofibromatosis patients. A study of 2186 published cases of patients with optic gliomas demonstrated 29 percent of them to have neurofibromatosis.1 Patients presenting to doctors with café-

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Fig. 14.2: Fundus examination of the same child showing diffuse atrophy of the optic nerve

au-lait spots and diagnosed with neurofibromatosis, should have regular ophthalmic examinations. Neurofibromatosis type 1 (NF-1) patients commonly develop multiple CNS astrocytomas and these lesions show a predilection for the orbital optic nerve and chiasm.13 NF-1 lesions tend to be multifocal and more extensive along the optic pathways than in patients without NF-1. Patients with bilateral optic gliomas usually have NF-1.14 However, the incidence of visual symptoms and progressive neurologic deficits was lower among those patients with NF-1.

Radiographic Findings

On plain orbital radiographs 65 percent of optic gliomas can be visualized mainly through enlargement of the optic canal.1 The classic radiographic findings are enlargement of the optic foramen and J- shaped excavation of the sella turcica. The optic canals are usually symmetrical, and a 1.0 mm difference in the diameters or a vertical height of 6.5 mm or more is considered pathologic.

Computerized tomography scans are more accurate, especially for orbital lesions. The tumor usually appears as a well-defined spindle or rounded shaped enlargement of the optic nerve.15 Kinking of the nerve is a characteristic finding in orbital gliomas, due to elongation of the nerve from secondary axial growth and downward deflection.15,16

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Fig. 14.7: Moderate power photomicrograph demonstrating a low-grade astrocytoma of the optic nerve (hematoxylin-eosin × 200)

Fig. 14.8: Moderate power photomicrograph demonstrating multiple eosinophilic staining cytoplasmic inclusions consistent with Rosenthal fibers (hematoxylineosin × 250)

filaments. Foci of calcification from axonal debris commonly appear in the fiber.

Vascular proliferation and atypia are frequently seen. These vessels are located either in the pial septa or between bundles of astrocytes. Periodically, enlarged congested sinusoidal vessels are encountered, but hemorrhagic necrosis rarely occurs.

Pale staining areas that appear microcystic on hematoxylin-eosin staining are frequently interspersed among the astrocytes. With special stains, the microcystic spaces can show mucosubstance (myxomatous

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expansion of fibrovascular trabeculae with slight cystic degeneration. The increasing nerve diameter crushes the subarachnoid space and fuses the pia mater to the arachnoid and dura.1

In both types of growth patterns the optic tumor enlarges by proliferation of neoplastic glial cells, accumulation of extracellular PASpositive mucosubstance secreted by the astrocytes, reactive gliosis, meningeal hyperplasia, and congestion within dilated blood vessels. Growth is usually slow, but accelerated expansion can result from cystic degeneration or intralesional hemorrhage. The majority of gliomas are benign and enlarge by bulk local growth causing demyelination and compression of optic nerve fibers. However, gliomas are true neoplasms and can tunnel under the dura extending along optic tracts and infiltrate the leptomeninges or intraocular structures.9,27 A few rare gliomas can undergo malignant evolution and spread throughout the cerebrospinal fluid.28,29

Gliomas and meningiomas of the optic nerve usually produce similar symptoms. Therefore, identifying which type of lesion the patient has is important. Current imaging and ultrasound techniques have become excellent at distinguishing the type of lesion the patient has, but when there is doubt many clinicians still advocate biopsy. However, even on biopsy confusion may arise. Possible reactive proliferation of meninges overlying the glioma making possible the misdiagnosis of meningioma if a very superficial biopsy of the optic nerve is done.

Management

Defining clear-cut guidelines for correct management of optic gliomas is difficult, because the natural course of gliomas is variable. Reported statistics and treatments results vary considerably causing much controversy to exist over the proper management of optic gliomas.

A study by Wright and McDonald30 showed that in half of their patients, the tumor appeared to stop growing without treatment. It is thought that in this group the tumor was stable upon presentation or slowly enlarged to reach a plateau remaining unchanged for many years. In the other half of the patients, the glioma continued growing, resulting in clinical signs and symptoms that required surgical removal. This study shows the dilemma of whether to surgically intervene causing blindness in that eye or to just follow the tumor radiographically and maintain partial vision. If the tumor appears stable it is worth watching, but if the tumor progresses intracranially, it can be deadly.

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If a patient presents with an optic glioma that appears to be fairly asymptomatic and confined to the orbit, current thought is to follow the patient without treatment.1 Because many studies have shown approximately half the gliomas plateau and remain dormant, with some cases of vision actually improving later on.30,31 Serial CT or MRI scans, pupillary reactions, visual acuity, and visual field examinations should be done to monitor tumor growth. If the tumor enlarges to cause blindness, severe proptosis, or pain, then complete removal by lateral orbitotomy is warranted.32 The risk of just monitoring gliomas is that some can spread throughout the CSF invading distant areas. A few rare gliomas undergo malignant evolution.8 Kocks reported a child who developed lumbar spinal metastases from a chiasmal glioma.33 However, the majority of gliomas grow slowly over months to years and spread by local enlargement. If on radiographic scans, the tumor shows extension along the intracranial portion of the nerve and threatens the chiasm, then surgery is also recommended. Once the tumor extends to the optic chiasm the risk of death rises to about 28 percent.1 Surgical intervention at this point does not improve survival, and has significant visual morbidity and potential mortality.

Some research suggests a short-term benefit from radiotherapy in doses exceeding 4500 cGy for chiasmal and midbrain tumors,11,34 but overall survival and ultimate recurrence show no benefit to radiotherapy.1,35 This raises the question as to whether radiotherapy is worth the side effects, because radiation in children has many permanent adverse effects on the CNS and endocrine function.36 Among 511 patients treated with radiotherapy and followed for 10 years, 69 percent demonstrated stable vision, 42 percent showed tumor progression, and 28 percent died from the disease. In contrast to the treated group, 203 similar patients were followed without treatment and showed comparable results; 77 percent demonstrated stable vision, 42 percent showed tumor progression, and 29 percent died.1 In a study by Packer et al they advocated that chemotherapy could significantly delay the need for radiation in children.14 Yet, there is little published data on the role of chemotherapy.

Although optic gliomas are benign neoplasms they can result in significant morbidity and mortality. Therefore, the clinical approach to these tumors must be vigilant, with attentive observation and aggressive intervention when necessary.

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MALIGNANT GLIOMAS OF THE OPTIC NERVE

Malignant astrocytomas of the optic nerve are a rare, but aggressive and deadly disease. The tumor arises from malignant astrocytes located in intracranial optic pathways and rapidly spreads to invade numerous structures. Patients typically are middle-aged adults that present with decreased vision, visual field loss, retro-orbital pain, and disk swelling. Most patients progress to blindness and death within a year.37

Clinical Features

In contrast to benign gliomas that occur in children, malignant gliomas are a disease of middle-age. In Dutton’s review the average of presentation was 47, with patients ranging from six to eighty.1 Malignant optic gliomas show a male preponderance, with 65 percent occurring in males, and 35 percent occurring in females.

Malignant gliomas of the optic nerve arise from malignant astrocytes that originate in intracranial optic pathways.37 Rarely, it arises in the orbital optic nerve. Malignant gliomas rapidly spread anterior and posterior to involve the optic nerve, chiasm, optic tracts, hypothalamus, third ventricle, thalamus, temporal and occipital lobes.

The clinical course is unilateral visual loss that progresses to blindness and death in an average of 11 weeks, but can range up to 60 weeks.1 The malignant astrocytes typically attack one side, then rapidly spread through the chiasm to involve both optic nerves. At presentation 64 percent of patients have bilateral visual loss. The final visual acuity reported in a study of 22 patients showed that in the less affected eye only 23 percent had vision of 20/400 or better, while 63 percent were NLP. In the more affected eye 86 percent were NLP. Visual field defects occurred in 94 percent of patients.1

On initial presentation normal optic disks are often seen, but within weeks the disk progressively swells. If the patient lives long enough optic atrophy ensues.

Malignant gliomas typically arise intracranially or in the chiasm and generally affect intracranial optic pathways. Thus, neurological symptoms are more common than proptosis. Neurological signs include convergence and gaze abnormalities, paresthesias, partial ophthalmoplegia, seizures, confusion, and hallucinations. Hypothalamic involvement usually occurs in the final stages and causes many of the deaths.37

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Retro-orbital pain is a common symptom. The visual loss and retroorbital pain often lead to an initial diagnosis of optic neuritis. Rapid and progressive visual loss should include radiological imaging.

Radiology

Plain orbital radiographs rarely reveal malignant gliomas. Computerized tomography provides a 79 percent chance of disclosing the tumor on initial examination.1 Images portray an enlarged chiasm and optic nerves. Few reported cases have used MRI, but MRI has revealed the tumor in all cases.38,39

Pathology

Histological examination is consistent with malignant astrocytoma showing atypical pleomorphic astrocytes with numerous mitotic figures. Secondary vascular and endothelial proliferation can also be found.40 The malignant cells encircle and compress the optic nerve inhibiting axoplasmic transport and capillary perfusion, causing demyelination and axonal degeneration. The neoplastic cells usually extend under the pia along the optic pathways or directly within the brain substance. The tumor can spread to invade the orbit, hypothalamus, third ventricle, basal ganglia, or intraparenchymal brain.

Prognosis

Malignant gliomas are a sad and devastating disease with the overall mortality rate of 97 to 100 percent with a mean survival of 8.7 months following diagnosis.1 Some patients treated with 5000 to 6000 cGY radiotherapy showed temporary visual acuity improvements and slightly prolonged life, but ultimately died from the disease. Advances in cancer research will hopefully led to better treatments.

OPTIC NERVE MENINGIOMAS

Meningiomas are the second most common optic nerve tumor, after gliomas.41 Meningiomas are benign neoplasms arising from meningothelial cells typically in the arachnoid. Patients generally are middle-aged adults and present with decreased vision, visual field loss, proptosis, disk atrophy, disk swelling, and later on optociliary shunt vessels. Meningiomas grow slowly, but are invasive and infiltrate surrounding structures. Management includes conservative monitoring, radiotherapy, and surgery.

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Clinical Features

In contrast to gliomas, meningiomas occur later in life. In Dutton’s review of optic nerve meningiomas, a study of 256 patients demonstrated the average age of presentation to be 40.8 years.41 The average age for males was 36, and the average age for females was 42. Even though the average age for females was older, meningiomas show a slight female preponderance at 61 percent female and 39 percent male. Approximately 4 to 10 percent of meningiomas occur in children and tends to be more aggressive.22,41 Therefore, meningiomas should still be included in the differential diagnosis of a lesion causing proptosis and progressive visual loss in a child. Similar to gliomas, there is a proven higher incidence of meningiomas in patients with neurofibromatosis.42

Researchers classify optic nerve meningiomas into three types based on tumor origin. Primary tumors if they originate from the meninges in the optic nerve and secondary tumors if they originate from cranial meninges and then extend into the orbit. Approximately 90 percent of meningiomas affecting the optic nerve are secondary, extending from the olfactory groove and sphenoid ridge.43,44 A third rare type, ectopic (extradural) arise from congenitally displaced meningothelial cells along the floor or roof of the orbit.

Signs and Symptoms

The signs and symptoms of meningiomas depend upon the origin and location of tumor growth. For ease of understanding, meningiomas affecting the eye can be divided into four groups depending upon location: (i) dura restricted, (ii) orbital, (iii) intracanalicular, and (iv) secondary. The natural course of meningiomas is unpredictable, because they can invade any surrounding structure. Therefore, different tumors share many of the same clinical and pathologic signs. Ninety-five percent of primary meningiomas have unilateral involvement, but 5 percent are bilateral.41 The bilateral meningiomas typically arise within the optic canal or chiasm (intracanalicular).41,43

The most common symptom of all meningiomas is gradual vision loss occurring over one to five years. A study of 380 patients demonstrated 96 percent to have decreased vision; with 45 percent presenting with acuities between 20/20 and 20/40, 31 percent between 20/60 and 20/400, and 24 percent with counting fingers or worse.41,45

The second most common symptom was visual field loss occurring in 83 percent of patients.41,46 Peripheral constriction was the most characteristic visual field loss. Central, centrocecal, paracentral

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scotomas, and increasing blind spot visual field losses also occurred. Decreased color vision was reported in 73 percent of the patients. Early or rapid vision loss occurs in dura-restricted meningiomas. These meningiomas grow similar to a glioma, and remain confined within the dura. As the meningothelial cells proliferate within the subdural spaces, the tumor begins compressing the optic nerve and inhibits axoplasmic transport. Further compression leads to demyelination and mechanical disruption of axons. Similarities to gliomas also occur when the meningioma infiltrates the nerve and widens the septa.

More characteristic slow visual loss occurs when the meningioma penetrates the dura and grows outside of the dura (orbital meningiomas). In this situation, meningothelial cells proliferate for many months to years within the orbit and the tumor becomes very large before compressing the optic nerve. The tumor begins to slowly push on the posterior pole of the globe causing axial proptosis, hyperopia, and striae. Axial proptosis is often the presenting symptom of meningiomas and occurred in 59 percent of the study patients.41 In this situation, when the tumor enlarges outside the dura, it can impinge upon the extraocular muscles limiting ocular motility. Forty-seven percent of study patients complained of limitation of ocular motility. The tumor infrequently encroaches on one of the cranial nerves, causing cranial nerve palsy.44 In dura-restricted meningiomas, as the tumor enlarges it impinges and stiffens the optic nerve causing a mechanical restriction of extraocular muscle function.

Disk swelling is an early finding in 48 percent of patients of all types.41 Disk swelling occurs due to compression of the central retinal vein and meningeal vasculature or spread of tumor cells to the anterior end of the perineural space, with interference of disk circulation. As compression of the optic nerve progresses the incidence and degree of optic atrophy increases. Forty-nine percent of patients progress to develop optic atrophy.

The classic pathognomonic triad for meningiomas of gradual unilateral vision loss, optic atrophy, and optociliary shunts (Fig. 14.10) occurs in 30 percent of patients.41 Imes et al47 followed the development of optociliary shunts over eight and a half years in a woman with an optic nerve meningioma. The first two years the woman had chronic disk swelling and congestion of the central retinal vein. After two years, Imes observed the dilation of regressed, but vestigeal, retinociliary anastomoses that were present in earlier embryonic development. The prolonged inhibition of retinal vein circulation re-established the flow of blood from retinal veins through optociliary shunts into the choroidal circulation. Then as the optic atrophy worsened in the woman, the shunts regressed over the years.

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Fig. 14.10: Fundus photograph of the optic nerve from an elderly female patient demonstrating optociliary shunt vessels with atrophy of the nerve

Meningiomas affecting the optic canal or chiasm (intracanalicular) may simulate atypical retrobulbar neuritis with decreased visual acuity and optic atrophy. Proptosis and disk edema are rarely seen. Tumors in the sphenoid ridge may also affect the nerves to the extraocular muscles resulting in strabismus as a presenting sign.

Radiology

Plain orbital radiographs rarely see meningiomas. Cases of hyperostosis of neighboring bone will show up, but these are rare.48 Computerized tomography has revolutionized diagnosing optic nerve tumors, with visualization of 97 percent of meningiomas.41 CT scans should be obtained before and after iodinated contrast medium infusion. Thin sections (1.5 to 3 mm) should be taken to demarcate tumor edges. Dura-restricted meningiomas often appear as a welldefined smooth tubular enlargement of the optic nerve.48 The majority (64%) of meningiomas shows this diffuse tubular thickening of the optic nerve.49 Orbital tumors growing outside the dura show globular perioptic or irregular and serrated enlargement, unlike dura-restricted tumors that demonstrate a fusiform shape.48,49 The dura-restricted tumors are commonly confused with gliomas, because they both are ensheathed by the dura. Helpful findings are calcifications, which are usually present in meningiomas and not typically found in gliomas.50 Another important radiographic sign helpful in diagnosing meningiomas is tram tracking.41 In tram tracking the optic nerve can be seen as a central black line through the whitish mass (Fig. 14.11). Tram tracking, however, may also be visualized in inflammatory

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Fig. 14.11: CT scan of the eye and orbit showing a diffuse meningioma of the nerve anteriorly with the “tram-track” sign

perioptic pseudotumor and other diffuse sheath thickenings.51 In coronal views the denser and thickened optic nerve sheath appears as a dense circle around the more radiolucent optic nerve.

Magnetic resonance imaging offers more precise and sensitive detection of intracanalicular or intracranial extension of meningiomas than CT.48,52 T1-weighted images should include fat-suppressed finecut axial and coronal images with and without gadolinium enhancement. The T1-weighted images disclose the characteristic tram-track appearance of the optic nerve in meningiomas. Axial and coronal T2weighted images provide the most sensitive method of determining the extent of tumor involvement.

An additional imaging technique called OctreoScan is used to support and follow the diagnosis of meningiomas. OctreoScan (Indium-111 pentetreotide) is a radio-labeled ligand that binds to the somatostatin receptors in meningiomas. The binding is highly sensitive, but not very specific because other classes of tumors also bind somatostatin. OctreoScan is therefore helpful in following tumor progression in cases of observation or tumor treatment response.52

Histopathology

Meningiomas can arise from any of the different cells that comprise the meninges (Fig. 14.12). However, current researchers believe the majority of meningiomas arise from the meningothelial cap cells found in arachnoid villi.41,42 Arachnoid villi are smaller and similar to arachnoid granulations (grape-like tufts of arachnoid that penetrate dural venous sinuses and affect transfer of CSF to the venous system). Arachnoid villi are collected along the intraorbital and canalicular

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Fig. 14.12: Gross photograph of an optic nerve sheath meningioma

portions of the optic nerve and also along the sphenoid ridge, tuberculum sellae, olfactory groove, and other areas of the meninges.

Neoplastic meningothelial cap cells are spindle or oval shaped and form densely packed concentric whorls with psammoma bodies (Figs 14.13A and B). Psammoma bodies are calcifications that develop in the whorl centers from hyalinization and deposition of calcium salts (Figs 14.14A and B). This pattern is the meningothelial pattern and is the most idiosyncratic degenerative change found in meningiomas. Meningiomas rarely show mitotic figures or malignant degeneration.22

Cells from the arachnoidal trabeculae of the meninges are of mesodermal origin and can proliferate to cause fibroblastic meningiomas. This type may metastasize.41 A combination of meningothelial and fibroblastic is called the transitional pattern. Meningiomas are benign neoplasms that grow slowly over months to years. Similar to gliomas, meningiomas can tunnel in the subdural spaces traveling along the optic pathways and infiltrate intraocular structures. However, unlike gliomas, meningiomas are invasive and can penetrate the dura to invade adjacent orbital structures, such as the extraocular muscles, sclera, or bone.22 Optic nerve meningiomas arising in the orbit can spread posteriorly through the optic canal to the chiasm or into the middle cranial fossa. At present, it is thought that meningiomas do not invade the brain or pituitary, and it appears meningiomas have little effect on the pituitary-hypothalamic axis or increasing ICP.42,44,53 Meningiomas can infiltrate the bone by entering the haversian canals and initiate hyperostosis and bony proliferation.54

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Management

The management of optic nerve meningiomas is controversial because their course is unpredictable. Traditional management includes observation, radiotherapy, and surgery. Traditionally, if a patient presents with the tumor confined to the orbit and visual acuity better than 20/40, observation was recommended.46 Observation includes ophthalmic examinations and CT or preferably MRI scans every six months. If visual acuity is progressively lost below 20/40, the visual field is constricting, or imaging scans show dangerous growth the patient is encouraged to undergo radiotherapy for preservation of vision.46,52 If the eye is totally blind and the meningioma confined to the orbit then the patient can choose to monitor the tumor or surgically excise it. If the meningioma is spreading posterior or enlarging and causing proptosis then total removal should be performed.

Because of the characteristic slow growth and benign pattern of primary optic nerve meningiomas, the overall tumor-related mortality rate is 0 percent according to Dutton’s major review.41 This fact coupled with the risks of radiation or surgery are the reasons many researchers advocate observation in patients over 40. The disadvantages to sole observation is the possible risk of tumor spread. Of 228 orbital lesions only 20 percent showed posterior extension.41 However, tumors originating in the canal or chiasm have a 38 percent chance of contralateral involvement.52

The most obvious disadvantage of simple observation is gradual vision loss. Kennerdell et al showed that of 39 patients that did not receive treatment of any kind, not one maintained good visual acuity for more than four years.46 This is in striking contrast to patients treated with radiotherapy where 73 percent of them had improved vision.41

Radiotherapy is the most promising treatment modality because of its ability to inhibit tumor growth and restore vision.46,55 Older radiation treatments were less precise and exposed the chiasm, contralateral optic nerve, and surrounding tissues to ionizing radiation, causing optic neuropathy and secondary malignancies. Leber et al56 studied the dose to damage relationship of older modalities. They found that the patients receiving less than 10 Gy per day had no incidences of optic neuropathy. 26.7 percent of patients receiving 10 to 15 Gy developed sequelae and 77.8 percent of patients receiving greater than 15 Gy developed sequelae. The newer conformal radiotherapy is much more precise and attains an improved therapeutic ratio. The accuracy of computer-guided stereotactic radiotherapy only

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exposes the patient to 1.8 Gy.52 This explains why many current researchers advocate radiotherapy as primary management in all optic nerve meningiomas as well as adjuvant treatment for incompletely resected tumors.46,55,57,58

A few successful therapeutic surgical interventions have been reported in tumors confined to the anterior or middle third of the optic nerve.46,52,59-61 However, most surgical intervention results in blindness, typically attributed to ischemia of the optic nerve.46,52 In blind eyes surgical excision of the tumor is warranted if the tumor threatens, the optic canal, chiasm, or intraocular structures. Surgical removal is also indicated in blind eyes if the enlarging tumor causes pain or proptosis.

Although optic nerve meningiomas are benign neoplasms, they can result in blindness. Many technological advances have helped patients maintain their vision, but the clinical approach must be attentive and when necessary aggressive treatment implemented.

SECONDARY OPTIC NERVE TUMORS

The majority of tumors involving the optic nerve are from secondary malignancies. Only 18 percent of tumors arise within the optic nerve itself, while 82 percent invade the nerve secondarily.62 There are four main routes of invasion into the optic nerve: direct extension from the eye, meninges, adjacent structures, and blood-borne metastatic invasion via the ophthalmic artery. Ginsberg et al63 presented a review of 117 cases of secondary optic nerve tumors. They found 39 percent to arise from intraocular tumors, 33 percent from blood-borne tumor seeding, 20 percent from meningeal tumors, and 8 percent invaded from adjacent structures.

Extension from the Eye

The most common secondary optic nerve malignancy is from intraocular structures.62 Retinoblastoma and uveal melanoma constitute the majority of secondary intraocular tumors.

Retinoblastoma has been known for many years to invade the optic nerve, with 26.7 percent of patients with retinoblastoma in a mass eye and ear study showing extension into the optic nerve.62 The tumor is usually limited by the lamina cribrosa, but may extend past it to invade the chiasm or brain.64 Predisposing factors to nerve invasion include elevated intraocular pressure, glaucoma, tumor seeding into the vitreous, and necrotic retinoblastoma.65 The prognosis significantly worsens once the tumor progresses beyond the lamina. Kopelman

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et al66 reported that the most dangerous risk factor of retinoblastoma was penetration of the coats of the eye, and the second most significant risk factor was the degree of optic nerve invasion.

Uveal melanomas invade the nerve less than retinoblastoma, with 6.5 percent of uveal melanomas invading the optic nerve.62 The diffuse melanomas have a more malignant cell type than typical nodular melanomas. Thus, diffuse melanomas are more aggressive at invading the optic nerve and carry a worse prognosis. Juxtapapillary melanomas can invade the nerve by direct extension causing hyperemia and disk edema. The lamina cribrosa generally limits the tumor growth, but posterior extension into the orbit, chiasm,65 and brain67 have been reported. Weinhaus et al68 on univariate analysis found a direct correlation between tumor death and the degree of optic nerve invasion. Predisposing factors for invasion include elevated intraocular pressure, juxtapapillary location, glaucoma, and necrotic tumors.

Blood-Borne Metastasis

Hematopoietic malignancies involving the optic nerve include leukemia, lymphomas, and myeloma. In most forms of leukemia the optic nerve and nerve head become infiltrated with abnormal white blood cells. Children with acute lymphoblastic leukemia are the most affected with 13 percent of patients having optic nerve invasion.69 In 384 autopsy specimens, Kincaid et al70 found 82 percent of patients to have ocular involvement. Unilateral or bilateral visual loss is the most common clinical symptom. Disk swelling, as well as pallor, splinter hemorrhages from infiltration, and increased intracranial pressure often occur. Histologically, perivascular and discrete tumor infiltration can be seen. Combined intrathecal chemotherapy and localized radiotherapy have improved visual function in some cases.71

A few cases of Hodgkin’s and Non-Hodgkin’s lymphomas involving the optic nerve have been reported.62 Invasion into the optic nerve occurs from both chronic systemic lymphoma and CNS lymphoma that invades via the meninges. Multiple myeloma occasionally invades the eye, but only one case of optic nerve invasion has been reported.72

Solid tumors that metastasize to the eye and optic nerve are rare and typically occur in parallel with widespread systemic metastasis. In Ginsberg’s review of primary metastatic sites to the optic nerve, breast cancer was the most recurrent distant tumor at 33 percent. Lung cancer followed second at 11 percent and stomach third at 6 percent. Others included pancreas 3 percent, mediastinum 3 percent, skin 3 percent, melanoma 2 percent, uterine 2 percent, and ovarian at 2 percent.63

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Extension from the Meninges and Brain

Neoplastic cells gain access to the optic nerve by anterior progression through the optic canal via the subarachnoid space. Neoplasms entering the nerve by this route include primary intracranial tumors (meningial carcinomas, reticuloendothelial sarcomas) plus secondary metastatic tumors to the CNS, which include lymphomas, melanoma, and myeloma.65 The course of these neoplasms is variable depending on the aggressiveness of the tumor. Slow growing tumors can spread anteriorly producing papilledema and visual dysfunction after the disease is advanced. Aggressive, rapidly proliferating neoplasms invade the axonal bundles, causing early visual loss and disk edema. The prognosis is poor once visual loss occurs from metastasis, with survival less than two years.73 Palliative treatment consisting of chemotherapy and radiation has resulted in transient improvement in visual function in some cases.74

Primary tumors from the CNS (ependymoblastoma, pituitary adenoma) rarely invade the optic nerve, but will commonly compress the optic nerve causing a neuropathy.62

Extension from Adjacent Structures

Tumors arising in the orbit, nasal sinuses, and nasopharynx generally compress the optic nerve instead of invading it. Visual field loss, proptosis, and pain are common presenting symptoms. Treatment for orbital tumors involves radiation, which often causes optic neuropathies.

REFERENCES

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3.Reese AB. Tumors of the Eye. Harper and Row: Hagerstown 1976;163-64.

4.Borit A, Richardson EP Jr. The biological and clinical behavior of pilocytic astrocytomas of the optic pathways. Brain 1982;105:161-87.

5.Desoretz DE, Blitzer PH, Wang CC. Management of glioma of the optic nerve and/or chiasm. Cancer 1980;45:1467-71.

6.Grimson BS, Perry DD. Enlargement of the optic disk in childhood optic nerve tumors. Am J Ophthalmol 1984;97:627-31.

7.Lloyd LA. Gliomas of the optic nerve and chiasm in childhood. Trans Am Ophthalmol Soc 1973;71:488-535.

8.Wilson WB, Feinsod M, Hoyt WF, et al. Malignant evolution of childhood chiasmal pilocytic astrocytoma. Neurology 1974;26:322-25.

182 Manual of Neuro-ophthalmology

9.De keizer RJW, de Wolff-Rouendaal D, Bots GTA. Optic glioma with intraocular tumor seeding in a child with neurofibromatosis. Am J Ophthalmol 1989;108:717-25.

10.Frohman LP, Epstein F, Kupersmith MJ. Atypical visual prognosis with an optic nerve glioma. J Clin Neuro-ophthalmol 1985;5:90-94.

11.Hoyt WF, Baghdassarian SA. Optic gliomas of childhood—natural history and rational for conservative management. Br J Ophthalmol 1969;53:793-98.

12.Albert D, Puliafito C. Foundation of Ophthalmic Pathology. Appleton-Century- Crofts: New York 1979.

13.Riccardi VM, Eichner JE. Neurofibromatosis: Phenotype, Natural History and Pathogenesis. Johns Hopkins University Press: Baltimore 97, 1986.

14.Packer RJ, Sutton LN, Bilaniuk LT. Treatment of chiasmal/hypothalamic gliomas of childhood with chemotherapy—an update. Ann Neurol 1988;23:79-85.

15.Jakobiec FA, Depot MJ, Kennerdell JS. Combined clinical and computed tomographic diagnosis of orbital glioma and meningioma. Ophthalmol 1984;91:137-55.

16.Imes RK, Hoyt WF. Magnetic resonance imaging signs of optic nerve gliomas in neurofibromatosis-1. Am J Ophthalmol 1991;111:729-34.

17.Brown EW, Riccardi VM, Mawad M, et al. MR imaging of optic pathways in patients with neurofibromatosis. Am J Neuroradiol 1987;8:1031-36.

18.Haik BG, Saint-Louis L, Bierly J, et al. Magnetic resonance imaging in the evaluation of optic nerve gliomas. Ophthalmol 1987;94:709-17.

19.Holman RE, Grimson BS, Drayer BP, et al. Magnetic resonance imaging of optic gliomas. Am J Ophthalmol 1985;100:596-601.

20.Patronas NJ, Dwyer AJ, Papathanasiou M, et al. Contributions of magnetic resonance imaging in the evaluation of optic gliomas. Surg Neurol 1987;28: 367-71.

21.Seiff SR, Brodsky MC, MacDonald G, et al. Orbital optic glioma in neurofibromatosis—magnetic resonance diagnosis of perineural arachnoidal gliomatosis. Arch Ophthalmol 1987;105:1689-92.

22.Spencer WH, Rao NA. Ophthalmic Pathology: An Atlas and Textbook (4th ed) WB Saunders: Philadelphia 1996;580-608.

23.Jenkin D, Angyalfi S, Becker L, et al. Optic glioma in children—surveillance, or irradiation? Int J Radiat Oncol Biol Phys 1993;25:215-25.

24.Yanoff M, Davis RL, Zimmerman LE. Juvenile pilocytic astrocytoma (glioma) of the optic nerve—clinicopathologic study of sixty-three cases. In Jakobiec FA (Ed): Ocular and Adnexal Tumors. Ala: Aesculapius:Birmingham, 1978;685-707.

25.Cutarelli PE, Rossmann UR. Immunohistochemical properties of human optic nerve glioma. Investigative Ophthalmol and Visual Sci 1991;32:2521-24.

26.Stern J, Jakobiec FA. The architecture of optic nerve gliomas with and without neurofibromatosis. Arch Ophthalmol 1980;98:505-11.

27.Dossetor FM, Landau K, Hoyt WF. Optic disk glioma in neurofibromatosis type 2. Am J Ophthalmol 1989;108:602-03.

28.Civitello LA, Packer RJ, Rorke L, et al. Leptomeningeal dissemination of low grade gliomas in childhood. Neurology 1988;38:562-66.

29.Bruggers CS, Freidman HS, Phillips PC, et al. Leptomeningeal dissemination of optic pathways gliomas in three children. Am J Ophthalmol 1991;111:719-23.

30.Wright JE, McDonald WI. Management of optic nerve gliomas. Br J Ophthalmol 1980;64:545-52.

Optic Nerve Tumors 183

31.Glaser JS, Hoyt WF, Corbett J. Visual morbidity with chiasmal glioma—long- term studies of visual fields in untreated and irradiated cases. Arch Ophthalmol 1971;85:3-12.

32.Shields JA, Shields CL. Atlas of Orbital Tumors Lippincott William and Wilkins: Philadelphia 1999;91-102.

33.Kocks W, Kalff R, Reinhardt V, et al. Spinal metastasis of pilocytic astrocytoma of the chisama opticum. Child Nerv Syst 1982;5:118-20.

34.Chang CH, Woods EH. The value of radiation therapy for gliomas of the anterior visual pathway. In Brockhurst SA, Borouchoff BT, et al (Eds): Controversy in Ophthalmology WB Saunders: Philadelphia, 1977;876-86.

35.Alvord EC, Lofton S. Gliomas of the optic nerve or chiasm. J Neurosurg 1988;68:85-98.

36.Kingsley DPE, Kendall BE. CT of the adverse effects of therapeutic radiation of the central nervous system. Am J Neuroradiol 1981;2:453-60.

37.Hoyt WF, Meshel LG, Lessell S, et al. Malignant optic glioma of adulthood. Brain 1973;96:121-32.

38.Evens PA, Brihaye M, Buissert T, et al. Gliome malin du chiasma chez l’adulte. Bull Soc Belg Ophthalmol 1987;224:59-60.

39.Hufnagel TJ, Kim JH, Lesser R. Malignant glioma of the optic chiasm eight years after radiotherapy for prolactinoma. Arch Ophthalmol 1988;106:1701-05.

40.Hamilton AM, Garner A, Tripathi RC, et al. Malignant optic nerve glioma— report of a case with electron microscope study. Br J Ophthalmol 1973;57: 253-64.

41.Dutton JJ. Optic nerve sheath meningiomas. Surv Ophthalmol 1992;37:167-83.

42.Spencer WH. Primary neoplasms of the optic nerve and its sheaths—clinical features and current concepts of pathogenetic mechanisms. Trans Am Ophthalmol Soc 1972;70:490-528.

43.Craig WM, Gogela LJ. Intraorbital meningiomas—a clinicopathologic study. Am J Ophthalmol1949;32:1663-80.

44.Wilson WB. Meningiomas of the anterior visual system. Surv Ophthalmol 1981;26: 109-27.

45.Alper MG. Management of primary optic nerve meningiomas. J Clin Neuroophthalmol 1981;1:101-17.

46.Kennerdell JS, Maroon JC. The management of optic nerve sheath meningiomas. Am J Ophthalmol 1988;106:450-57.

47.Imes RK, Schatz H, Hoyt WF. Evolution of opto-ciliary veins in optic nerve sheath meningioma. Arch Ophthalmol 1985;103:59-60.

48.Mafee MF, Goodwin J, Dorodi S. Optic nerve sheath meningiomas, role of MR imaging. Radiologic Clin North Am 37: 37-58.

49.Sibony PA, Krauss HR. Optic nerve sheath meningiomas—clinical manifestations. Ophthalmol1984;91:1313-26.

50.Jakobiec FA, Depot MJ, Kennerdell JS. Combined clinical and computed tomographic diagnosis of orbital glioma and meningioma. Ophthalmol 1984;91:137-55.

51.Dutton JJ, Anderson RL. Idiopathic inflammatory perioptic neuritis simulating optic sheath meningioma. Am J Ophthalmol 1985;100:424-30.

52.Fineman MS, Augsburger JJ. A new approach to an old problem. Surv of Ophthalmol1999;43:519-24.

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53.Newell FW, Beamon TC. Ocular signs of meningiomas. Am J Ophthalmol 1958;45:30-40.

54.Als E. Intraorbital meningiomas encasing the optic nerve. Acta Ophthalmol 1969;47:900-03.

55.Kupersmith MJ, Warren FA, Newall J, et al. Irradiation of meningiomas of the intracranial anterior visual pathway. Ann Neurol 1987;21:131-37.

56.Leber KA, Borgloff J, Pendl G. Dose-response to tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereo tactic radiosurgery. J Neurosurg 88: 43-50, 1998.

57.Smith JL, Vuksanovic MM, Yates BM. Radiation therapy for primary optic nerve meningiomas. J Clin Neuroophthalmol1981;1:85.

58.Barbo NM, Gutin PH, Wilson CB, et al. Radiation therapy in the treatment of partially resected meningiomas. Neurosurgery1987;20:525.

59.Cristant L. Surgical treatment of meningiomas of the orbit and optic canal—a retrospective study with particular attention to the visual outcome. Acta Neurochir 19984;126:27-32.

60.Delfini F, Missori P, Tarantino R, et al. Primary benign tumors of the orbital cavity—comparative data in a series of patients with optic nerve glioma, sheath meningioma or neurinoma. Surg neurol 1996;45:147-54.

61.Clark WC, Theofilos CS. Primary optic sheath meningiomas. J Neurosurg 1989;70:37-40.

62.Christmas NJ, Mead MD, Richardson EP, et al. Secondary optic nerve tumors. Surv Ophthalmol 1991;36:196-206.

63.Ginsberg J, Freemond AS, Calhoun JB. Optic nerve involvement in metastatic tumors. Ann Ophthalmol 1970:2:604-17.

64.Merriam GR. Retinoblastoma—analysis of seventeen autopsies. Arch Ophthalmol 1974;44:71-108.

65.Spencer WH. Optic nerve invasion of intraocular neoplasm. Am J Ophthalmol 1975;80:465-71.

66.Kopelman JE, Mclean IW, Rosenburg SH. Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation. Ophthalmol 1987;94: 371-77.

67.Jones DR, Scobie IN. Intracerebral metastases from ocular melanoma. Br J Ophthalmol 1988;72:246-47.

68.Weinhaus RS, Seddon JM, Albert DM, et al. Prognostic factor study of survival after enucleation for juxtapapillary melanoma. Arch Ophthalmol 1985;103:1673-77.

69.Allen RA, Straatsma BR. Ocular involvement in leukemia and allied disorders. Arch Ophthalmol 1961;66:490-508.

70.Kincaid MC, Green WR. Ocular and orbital involvement in leukemia. Surv Ophthalmol 1983;27:211-32.

71.Murray KM, Paolini F, Goldman JM, et al. Ocular involvement in leukemia— report of three cases. Lancet 1977;1:829-31.

72.Gudas PP Jr. Optic nerve myeloma. Am J Ophthalmol 1971;71:1085-89.

73.Miller NR. Secondary tumors of the central nervous system. In Miller NR (Eds): Walsh and Hoyt’s Clinical Neuro-Ophthalmology. Williams and Wilkins: Baltimore 1988;1662-709.

74.Altrocchi PA, Reinhardt PH, Ecman PB. Blindness and meningeal carcinomatosis. Arch Ophthalmol 1972;88:508-12.

Reena M Choudhry, Saurabh Choudhry, Amar Agarwal

OPTIC ATROPHY

Optic atrophy is characterized by loss of conducting function of the optic nerve, with an increase in pallor of the disk as a result of gliosis and loss of capillaries of the disk.1-16 Optic atrophy results from injury to any portion of the retino-geniculate pathway (from retinal ganglion cells to lateral geniculate body).

•Primary optic atrophy is caused by lesions which cause a death of the axons of the optic nerve without causing a swelling of the optic nerve. The lesions may affect the visual pathway from retrolaminar portion of the optic nerve to the lateral geniculate body. Causes of primary optic atrophy can be retrobulbar neuritis, compression due to aneurysms or tumors, toxic and nutritional neuropathies and trauma.

•Secondary optic atrophy is caused by conditions, which produce swelling of the optic nerve head. The causes include papilledema, papillitis, and anterior ischemic optic neuropathy.

•Consecutive optic atrophy is a result of retinal or choroidal disease leading to destruction of ganglion cells. It could occur following chorioretintis, Retinitis pigmentosa, pathological myopia, central retinal artery occlusion and after pan retinal photocoagulation.

•Cavernous (Glaucomatous) optic atrophy is caused by loss of nerve fibers in advanced glaucoma. The neuroretinal rim is healthy in glaucomatous optic atrophy in contrast to primary optic atrophy with a large cup.

•Segmental optic atrophy is usually seen in toxic and nutritional neuropathies and ischemic optic neuropathies.

•Hereditary optic atrophy may be congenital or associated with Leber’s optic neuropathy, Kejr syndrome, Behr syndrome and other systemic syndromes like Friedreich’s ataxia.

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Fig. 15.1: Optic atrophy

Clinical Features

•Primary optic atrophy shows chalky white disk (Fig. 15.1) with sharply defined margins and normal appearing retinal vessels and surrounding retina (Table 15.1).

•Secondary optic atrophy shows dirty gray pallor of the optic nerve head with poorly defined margins, obliterated cup, sheathing and narrowing of arteries in the peripapillary area.

•Consecutive optic atrophy shows waxy pallor of the disk with marked attenuation of the arteries. Signs of associated retinal pathology are present.

•Cavernous optic atrophy shows a pale disk with pathological cupping, thinning of the neuroretinal rim, nerve fiber layer loss and laminar dot sign.

•Segmental optic atrophy shows pallor of the temporal side or other segments with sharply defined margins and no retinal pathology.

•Relative afferent pupillary defect is present in unilateral and asymmetric cases.

•Color vision is reduced in correlation with the visual loss.

•Visual fields show varied defects depending upon the cause of the optic atrophy.

•Kejr syndrome: This is an hereditary optic atrophy which is bilateral and is autosomal dominant. It occurs between the ages of 4-10 years.

•Behr syndrome: This is autosomal recessive and is another hereditary optic atrophy condition. Occurring during the first 10 years of life.

•Wolfram syndrome: This is another hereditary optic atrophy disease and is also referred to as DIDMOAD = Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness.

Abnormalities of Optic Nerve Head 187

Table 15.1: Differences between primary, secondary and consecutive optic atrophy

•Foster-Kennedy syndrome: There is unilateral papilledema and contralateral optic atrophy. It occurs due to frontal lobe tumors.

•Pseudo Foster-Kennedy syndrome: In this there is optic atrophy in one eye and a disk swelling in the other eye due to AION.

Differential Diagnosis

One should differentiate between primary, secondary and consecutive optic atrophy (Table 15.1).

Optic Neuritis

Optic neuritis is defined as an inflammatory or demyelinating disorder of the optic nerve characterized by sudden loss or diminision of vision, associated with ocular pain and dyschromatopsia.1-16 Most common cause of optic neuritis is demyelinating disorders like multiple sclerosis. Viral (mumps, measles, herpes zoster, cytomegalovirus, or HIV), bacterial (tuberculosis, syphilis or lymes disease) and other (histoplasmosis,cryptococcosis,toxoplasmosis or toxocariasis) infections can also cause optic neuritis. In children optic neuritis can occur post-immunization. Other possible causes are adjacent paranasal sinus inflammation, systemic collagen vascular diseases and intra ocular inflammation.

188 Manual of Neuro-ophthalmology

Clinical Features

•Decreased visual acuity ranging from 6/9 to no perception of light. There is rapid worsening in next few days reaching maximum deficit by 1-2 weeks. Recovery occurs over next 4-6 weeks.

•Decreased color vision, which is more than the visual deficit. Acquired optic nerve disease tends to cause red-green defects. An exception occurs in glaucoma and in autosomal dominant neuropathy which initially causes blue-yellow deficit. It has been recently found that visual field loss in glaucoma is detected earlier if perimetry is performed using a blue light stimulus on a yellow background. Acquired retinal disease tends to cause blue-yellow defects except in cone dystrophy and Stargardt’s disease which cause a predominantly red-green defect.

•Contrast sensitivity and stereoacuity is reduced.

•Relative afferent pupillary defect (RAPD) is present in unilateral or asymmetric cases.

•Visual fields show central, centrocaecal or arcuate field defects.

•Cells may be seen in the vitreous.

•Fundus examination:

Retrobulbar neuritis: Optic disk appears normal (most common

presentation in adults).

Papilitis: The disc appears swollen and hyperemic (Fig. 15.2A), associated with or without peripapillary flame shaped hemorrhages. Cells in the posterior vitreous may be present. Retina can show venous sheathing in the peripapillary area.

Neuroretinitis: Disk edema associated with macular star (least common).

On fluorescein angiography (Fig. 15.2B) there is pre-papillary capillary dilatation and leakage very similar to papilledema. There is hyperfluorescence of the disk with late leakage possibly involving the nerve fiber layer. With resolution of the swelling there is a pale disk with variable loss of the pre-papillary capillaries evidenced on fluorescein angiogram.

There is ocular pain, which worsens on ocular movements. Age at presentation ranges between 20-45 years and women are more commonly affected than men. In children the involvement is bilateral. Some patients may complain of defective color vision. Patients with multiple sclerosis may have transient obscurations of vision on exertion or rise in body temperature (Uhthoff’s symptom).

Abnormalities of Optic Nerve Head 189

Figs 15.2A and B: Papillitis: (A) color picture (B) FFA

Management

•In mild cases (vision 20/30 or better) only observation is indicated, as the disease is self-limiting.

•In cases where vision is 20/40 or worse intravenous (IV) methylprednisolone 1 gm daily for 3 days followed by oral steroids 1 mg/kg body weight for 11 days is administered.

Optic Neuritis Treatment Trial (ONTT)

•Patients treated with intravenous methylprednisolone followed by oral steroids recovered vision faster than patients treated with oral steroids alone.

•The final visual outcome at 1 year was same with or without IV steroids.

•Patients treated with oral steroids alone had higher rate of recurrences and increased rate of second eye involvement.

Abnormalities of Optic Nerve Head 191

Table 15.2: Differences between papillitis and papilledema

2.Established stage: In this stage patient may be asymptomatic or complain of transient visual obscuration lasting few seconds. During these episodes the vision may vary from mild blurring to complete blindness. Ophthalmoscopically there is gross elevation of optic nerve head with engorged veins. The disk margins are markedly blurred and edematous nerve fiber layer obscures the traversing blood vessels. Peripapillary splinter hemorrhages, cotton wool spots, choroidal folds and retinal striae (Paton’s lines) are present. The macula may have hard exudates forming an incomplete star.

3.Chronic stage: Constriction of peripheral fields may be associated with the enlargement of the blind spot. Ophthalmoscopically hemorrhages and disk edema slowly resolves. The cup ultimately obliterates and nerve fiber layer begins to atrophy giving gray white color to the disk.

4.Atrophic stage; Secondary optic atrophy ensues. The optic disk is pale to white with indistinct margins and attenuated and sheathed

vessels in the peripapillary area. Severe atrophy of nerve fiber layer is present.

Other signs are:

•The pupillary reactions are normal.

•The color vision is unaffected in early stages but as the chronic papilledema progresses to optic atrophy the color vision becomes abnormal.

•Visual fields—In the initial stages enlargement of the blind spot is present but as the atrophy sets in constrictions of peripheral fields are seen.

•Unilateral or bilateral sixth nerve palsy may be present due to stretching of the sixth nerve in the posterior fossa as a result of raised ICP.

Abnormalities of Optic Nerve Head 193

Management

The treatment is focused towards the cause of raised ICP. If increased ICP is related to a mass lesion, removal of the mass is the obvious treatment of choice. Medical treatment in the form of carbonic anhydrase inhibitors may help reduce the ICP. If the lesion cannot be removed, or if the CSF absorption is reduced then treatment is directed towards shunting of the CSF into the peritoneal cavity (Lumboperitoneal shunts). In cases of idiopathic intracranial hypertension optic nerve sheath decompression has been advocated by some authors to alleviate fluid retention within the surrounding meninges by creating a small fenestration site within the intraorbital portion of the nerve. While this procedure has yielded some positive results, it is extremely complex work and may fail in up to one-third of all cases.

ARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY (AAION)

Etiology

AAION is infarction of the prelaminar or laminar portion of optic nerve head due to inadequate perfusion by posterior cilliary arteries and is most commonly associated with giant cell arteritis (GCA). GCA is the most common cause of AAION. Other conditions that may cause AAION are herpes zoster, rheumatoid arthritis, relapsing polychondritis, Takayasu’s arteritis, systemic lupus erythematosus, and periarteritis nodosa.

Classic Signs

•Unilateral visual loss (gross reduction of vision).

•Relative afferent pupilliary defect (RAPD) is present in unilateral cases.

•Fundus examination shows pale and swollen disk. Splinter hemorrhages at and around the disk margins may be present. Within 1-2 months the disk swelling subsides and optic atrophy ensues.

•Visual fields commonly have altitudinal defect in eyes which can be tested.

•In few cases cranial nerve palsy may be present as an associated sign.

•Systemic signs of GCA are tender, palpable non-pulsatile temporal arteries.

194Manual of Neuro-ophthalmology

•Involvement of other arteries may lead to myocardial infarction, renal failure and brainstem stroke. In some cases central retinal artery occlusion may be an associated finding.

•Erythrocyte sedimentation rate (ESR) and C-reactive protein are invariably raised.

Symptoms

Patients classically present with sudden onset unilateral visual loss (partial or complete), which may rapidly become bilateral. Average age of presentation is usually 55 years and above. Women are affected more commonly than men. Patients may give history of amaurosis fugax before the onset of visual loss. Diplopia may be present in few cases. Systemic complaints of headaches, jaw claudication, scalp tenderness, myalgia, fever and weight loss may be present.

Differential Diagnosis

1.Non-arteritic anterior ischemic optic neuropathy

-Patients are younger than those with GCA.

-The visual loss is less severe.

-Systemic hypertension or diabetes mellitus is frequently present.

-Erythrocyte sedimentation rate (ESR) is usually normal.

-Involvement of other eye is less common.

-No benefit from systemic steroids.

2.Optic neuritis (papillitis)

-Affects younger age group (20-40 years).

-The visual loss is severe and recovery is better.

-Pain during ocular movements is frequently present.

-The disk swelling is hyperemic and associated with cells in posterior vitreous.

3.Compressive optic neuropathy

-Visual loss is gradual in onset and slowly progressive.

-Disk edema may be absent.

-Proptosis or restricted ocular movements are often present (associated with orbital disease).

-Systemic signs and symptoms of GCA are absent.

Work-up

1.Temporal artery biopsy should be performed in patients where GCA is suspected before starting steroid therapy or within 2 weeks. (The biopsy specimen should be at least 2.5 cm long and if the

Abnormalities of Optic Nerve Head 195

biopsy is negative but response to steroids is positive biopsy of opposite artery should be considered).

2. Temporal artery Doppler can also be done.

Risk Factors

In AAION associated with GCA the involvement of other eye without treatment is seen in 50 percent of cases within days to few weeks.

Management

AAION is a medical emergency and needs to be treated with intra venous methyl prednisolone 1 gm daily for 3 days followed by 80100 mg oral corticosteroids on a slow tapering dose for a period of 6 months to 1 year to prevent involvement of the other eye. Patients of GCA confirmed by temporal artery biopsy are maintained on initial dose of corticosteroids for 4 weeks until ESR normalizes and slowly tapered while monitoring the ESR levels.

Pharmacology

Rare instances of anaphylactoid (e.g., bronchospasm) reactions have occurred in patients receiving parenteral corticosteroid therapy so appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug. There are also reports of cardiac arrhythmias and/or circulatory collapse and/or cardiac arrest following the rapid administration of large IV doses of methylprednisolone sodium succinate (greater than 0.5 gram administered over a period of less than 10 minutes). Bradycardia has been reported during or after the administration of large doses of methylprednisolone sodium succinate, and may be unrelated to the speed or duration of infusion.

POSTERIOR ISCHEMIC OPTIC NEUROPATHY (PION)

In the posterior variety (PION) there is no disk edema noted in the acute phase although the symptoms and clinical findings are otherwise similar to the anterior variety. The circulation impairment affects the posterior vessels and there is no impairment of the axoplasmic flow .

The PION is seen more frequently in cases with acute severe blood loss or sustained hypotension, postsurgical complications, migraine, collagen vascular diseases and giant cell arteritis.

196 Manual of Neuro-ophthalmology

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