Optic Nerve Disorders - part 5 pps

These malignant tumors often cause enlargement of the chiasm and at least one contiguous optic nerve that enhances after administration of contrast.233–236 The optic chiasm is affected i

Up to 40% of patients who have chiasmal

gliomas with large exophytic masses develop or

present with hydrocephalus.162,187

Intraventricu-lar shunt placement is recommended Although

metastatic seeding of the peritoneum

follow-ing shunt placement rarely occurs, it is not a

contraindication.220,221

Ascites is a rare complication following

placement of a ventriculoperitoneal shunt In

the study by West et al.,222 each of three

chil-dren had a shunt for chiasmal glioma

compli-cated by hydrocephalus and developed ascites

without malignant cells The ascites resolved

after their shunt was revised to a

ventricu-loatrial system

Radiation Therapy For

chiasmatic-hypotha-lamic gliomas, 80% of patients treated with

radiation therapy at 4500 cGy to 5500 cGy

experienced stabilization or tumor shrinkage as

seen on radiologic studies.223 The effi cacy of

radiation therapy on visual outcome and tumor

progression is uncertain In studies by Hoyt

and Baghdassarian181 and Glaser et al.217 visual

outcome was not correlated with radiation

therapy in 20 patients No difference was noted

in the disease-free survival rate between the

patients who had radiation therapy and those

who did not Even tumor shrinkage on CT scan

was not correlated with clinical progression in

16 patients after radiation therapy.196

The cognitive and endocrinological side

effects of radiation therapy occur most often

in children less than 5 years of age when

chias-mal gliomas are usually diagnosed.224 Other

complications of radiation include

malignan-cies in patients with NF-1, moyamoya disease,

and aneurysms.225,226 In the study by Tao et al.,227

long-term follow-up of 29 children with

irradi-ated chiasmal gliomas reported a 10-year

sur-vival of 89% Tumor shrinkage was noted years

after radiation Vision improved in 24%,

wors-ened in 17%, remained stable in 48%, and was

not evaluated in 10% As a complication of

radiation therapy, cognitive impairment was

found in 71% and hypopituitarism in 72%

Chemotherapy No evidence supports the use

of chemotherapy in gliomas confi ned to the

optic nerve.228 Less than 10% of all diencephalic

gliomas in patients with NF-1 will require ment on the basis of progressive visual loss or radiographic enlargement.228

treat-Because radiation therapy is not an effective long-term treatment modality for all patients, especially in young children who experience cognitive and endocrinological complications, chemotherapy is a useful alternative for those who have progressive tumors The combination

of carboplatin and vincristine has been shown

to be less toxic than radiation and more effi cious than other chemotherapeutic combina-tions In a prospective study by Packer228 in which patients with recurrent or progressive low-grade gliomas received carboplatin and vincristine, 56% of patients with progressive, newly diagnosed lesions had an initial radio-graphic response, including complete tumor shrinkage Progression-free survival, as mea-sured radiographically, was about 74% for chil-dren less than 5 years of age, and about 39% for children greater than 5 years of age.228Therefore, the combination of carboplatin and vincristine is considered, at this time, the pre-ferred treatment for progressive chiasmal or hypothalamic gliomas

ca-Malignant Anterior Visual Pathway Gliomas

EpidemiologyMalignant anterior visual pathway gliomas often occur in adults with onset at approxi-mately 50 years of age.164 Men are more com-monly affected than women in an approximate ratio of 2 : 1.229–231 In contrast to the benign ante-rior visual pathway gliomas, these malignant tumors are not associated with NF-1

Symptoms and SignsBilateral and asymmetric visual loss is rapidly progressive over an average of 8.7 weeks.164 It

is commonly associated with retro-orbital pain These visual symptoms can mimic acute optic neuritis.164 Based upon a meta-analysis of previ-ous case series of patients with malignant optic gliomas,164 the levels of initial visual acuity of

the more affected eye included the following:

5% had normal visual acuity; 24% had 20/30 to

20/100; 14% had 20/200 to 20/400; 38% had

counting fi ngers to light perception; and 19%

had no light perception The fi nal visual acuity

of the more affected eye revealed that 14% had

hand motion to light perception and 86% had

no light perception As the tumor extended into

the optic chiasm in the early stages, visual loss

started in the fellow eye within 5 to 6 weeks and

then progressed to blindness.164

In the same meta-analysis of previous case

series, 94% of the patients had visual fi eld

defects These fi eld defects included any

com-bination of the following: (1) central, arcuate,

or altitudinal scotomas if the optic nerve

is affected; or (2) bitemporal hemianopias and

junctional scotomas, if the optic chiasm is

involved.164

The optic disc may appear normal in the

early stages As the tumor infi ltrates the optic

nerve, the disc may become hyperemic and

edematous, often with central retinal artery or

vein occlusion.229,231 If the tumor remains in the

more posterior aspects of the anterior visual

pathway, the disc usually becomes pale without

edema If the tumor extends intracranially, then

papilledema from increased intracranial

pres-sure may be seen In the same meta-analysis of

previous case series of patients with malignant

optic gliomas, normal optic discs were observed

in 25%, disc edema in 43%, optic atrophy in

31%, proptosis in 23%, and ophthalmoplegia

in 19%.164 The expansive effects of the tumor

is thought to cause compression on

individ-ual cranial nerve palsies or cause mechanical

limitation on the movement of the orbit itself

Convergence and other gaze abnormalities

are rare.232

Malignant gliomas commonly involve the

temporal lobes, hypothalamus, and third

ven-tricle to cause seizures, encephalopathy,

hemi-paresis, and hypothalamic dysfunction These

neurological signs occurred in 35% of patients

in the meta-analysis of previous case series.164

Neuroimaging

The CT and MRI fi ndings are nonspecifi c These

malignant tumors often cause enlargement of

the chiasm and at least one contiguous optic nerve that enhances after administration of contrast.233–236 The optic chiasm is affected in nearly all cases, either initially or later as the tumor grows.164 In the later stages of tumor growth, contiguous infi ltration of the anterior visual pathways and exophytic extension from the optic chiasm into the adjacent temporal lobes and hypothalamus/third ventricle may be seen (Table 4.4)

Based on the radiologic presentation of infi ltration of the optic chiasm and other ante-rior visual pathways, the differential diagnosis

of an adult malignant optic glioma would include malignancies, such as lymphoma; infections, such as fungi; and infl ammatory disorders, such as sarcoidosis If the tumor extends into the sellar areas, craniopharyngio-mas or malignant pituitary adenomas could be considered.164

PathologyMalignant anterior visual pathway gliomas are characterized as having cellular pleomorphism, numerous mitotic fi gures, necrosis, and hemor-rhage, as seen in anaplastic astrocytomas and glioblastoma multiforme.229,231,237 Neoplastic cells envelop the optic nerve beneath the pia mater, causing impairment of capillary perfu-sion, progressive vascular occlusion, and demy-elination Tumor usually spreads below the pia mater along the visual pathways or directly within the substance of the brain to other locations.229

Table 4.4 Frequency of locations of malignant optic gliomas based on a meta-analysis of 31 previously reported patients in the literature

Site of malignant optic gliomas Frequency (%) Chiasm and orbital optic nerve 22.6 Chiasm and optic tracts 48.4 Chiasm and hypothalamus 54.8 Chiasm and third ventricle 25.8 Chiasm and basal ganglia 12.9 Chiasm and temporal lobe 19.4

In some patients, multiple sites were involved Adapted from Dutton 164

Prognosis and Treatment

Malignant optic gliomas cause rapidly

deterio-rating vision and death within a year in

middle-aged men.229 In a review of 39 reported cases of

adult malignant optic glioma by Dario et al.,237

no statistically signifi cant difference between

the survival of patients with only optic

involve-ment and patients with extraoptic involveinvolve-ment

was observed Patients treated with radiation

therapy had more favorable survival curves,

with a median of 5.5 months, compared to those

who were not treated, with a median survival of

3 months No statistically signifi cant difference

was seen in those who received radiation

therapy and chemotherapy (median survival, 6

months) and those who did not (median

sur-vival, 3 months) Although complete resection

of the tumor is not feasible, biopsy of the optic

nerve with poorest vision or partial resection of

the tumor is usually possible No statistically

signifi cant difference was seen in patients who

underwent biopsy of the tumor versus partial

resection of the tumor

Ganglioglioma of the Optic Nerve

Gangliogliomas are composed of mature

gan-glion cells and mature glial cells that usually

grow in the fl oor of the third ventricle, but may

rarely arise within the optic chiasm or

intracra-nial portions of the optic nerves

Ganglioglio-mas have been reported to infi ltrate one or

both optic nerves.238 Vision worsened gradually

or suddenly Lu et al.239 described a 38-year-old

man who developed acute right visual loss with

right orbital pain and headaches MRI of the

orbits with contrast revealed an enhancing

fusi-form dilation of the optic nerve

On histopathology, gangliogliomas have

neo-plastic astrocytic proliferation The glial and

neuronal components are well differentiated to

the degree that they may mimic pleomorphic

fi brillary astrocytomas.240

Most gangliogliomas have a natural course

similar to that of low-grade astrocytomas and

have a good prognosis If chiasmatic infi ltration

is present, the survival rate may be slightly

lower Some tumors may have malignant

fea-tures often occurring in the glial component of

the tumor, and metastases may occur.240

Secondary Tumors Infi ltrating the Optic Nerve

Leptomeningeal Metastases to the Optic Nerve

Meningeal metastasis can infi ltrate the optic nerve to cause visual loss.241 Malignant cells invade the subarachnoid space of the optic nerve with minimal invasion of the optic nerve parenchyma In some instances, the infi ltrative process becomes compressive as the malignant cells grow and expand into the subarachnoid space around the optic nerve Approximately 30% to 40% of patients with carcinomatous meningitis develop visual loss,242,243 whereas other studies have found 15% of cases affecting the optic nerves.244

Symptoms and SignsVisual loss in patients with meningeal carcino-matosis commonly occurs after the diagnosis of the primary lesion (lung or breast) has been established The visual loss may be an isolated

fi nding245 or may occur with other signs of chronic meningitis.246 Patients with carcinoma-tous infi ltrative optic neuropathy often present with painless acute or subacute visual loss in one or both eyes Blindness may even occur within several days

An afferent pupillary defect, decreased color vision, and visual fi eld defects, such as a central scotoma or nerve fi ber bundle defect, may be the initial signs of an infi ltrative optic neuropa-thy The optic disc usually appears normal at the onset of visual loss Only after about 6 to 8 weeks does the optic disc show atrophy.245,246

Diagnostic Testing

On MRI of the brain with gadolinium, ment and enhancement of the orbital and cana-licular segments of the optic nerve may be seen Dural metastases appear as curvilinear con-trast-enhancement patterns beneath the inner table of the skull In contrast, leptomeningeal tumor appears as contrast-enhanced areas that follow gyral convolutions and may also be seen

enlarge-as nodular deposits on the leptomeninges The diagnosis of meningeal carcinomatosis also

requires CSF cytology; approximately 20 mL or

more CSF is often needed to detect malignant

cells.247

Management

Aggressive therapy with intrathecal

chemo-therapeutic agents, such as methotrexate, can

improve symptomatology in some patients with

leptomeningeal metastases, and may even

occa-sionally prolong their median survival period

for 8 months.247 If bulky meningeal metastases

are associated with leptomeningeal ones, then

local radiation therapy can be added.247

Other Metastases to the Optic Disc

In addition to metastases by CSF circulation

within the subarachnoid space, tumor may

spread to the optic nerve by the adjacent

choroid or retina, by the vascular supply to the

optic nerve, or by orbital metastases invading

intraocularly.249 Isolated metastases to the optic

nerve are extremely rare and occur in 1.3%

with histologically proven carcinoma metastatic

to the eye and orbit250 and in 4% with

intraocu-lar metastases referred to a tertiary cancer

center.251 Bilateral optic nerve metastases

occurs in approximately 18% of patients.252

Breast and lung carcinomas are the most

common metastatic tumors to the optic nerve

and uvea In a study of 29 cases of isolated optic

nerve metastasis by Arnold et al.,253 the primary

cancers consisted of 27% breast cancer (4

cases), 27% lung cancer (4 cases), 27% stomach

cancer (4 cases), 20% sarcoma (3 cases), and

6% pancreas (1 case) Other types of cancers

that have been reported to spread to the optic

nerve include prostatic, esophageal, uterine,

ovarian, vaginal, hepatic, renal, adrenal, thyroid,

and lip carcinomas Melanomas from the skin

have also been reported to metastasize to the

optic nerve and optic nerve sheath

Symptoms and Signs

Visual loss usually progresses over several

months The optic disc is swollen and may have

a yellow-white mass of tumor cells.254 Vitreous

tumor cells and hyperemia of uninvolved nerve

can also be seen Compression of venous outfl ow by the mass of tumor cells may cause retinal venous engorgement and central retinal vein obstruction If the mass becomes necrotic, then hemorrhage into the optic nerve can occur Associated choroidal metastases appear as yellow subretinal lesions with a serous detach-ment of the sensory retina in about 75% of cases.249

The differential diagnosis of optic disc tasis includes primary optic nerve tumors, such

metas-as metas-astrocytoma, melanocytoma, and capillary hemangioma; optic nerve granulomas, includ-ing sarcoid and juvenile xanthogranuloma; and optic nerve macroaneurysm Metastasis involv-ing the optic nerve posterior to the lamina cribrosa may mimic retrobulbar neuritis When metastases extend into the optic nerve posteri-orly into the lamina cribosa, the disc may appear normal, mildly hyperemic, or pale, mimicking retrobulbar optic neuritis The optic disc may also be swollen from increased intracranial pressure from central nervous system (CNS) metastases.249

Diagnostic Testing

On fl uorescein angiography, the optic disc tumor may be hypofl uorescent in the early phases of the study Leakage of dye occurs in the hyperemic areas of the optic disc If retinal venous fl ow is compressed by the tumor, then

a delay in venous fi lling may be seen.249

If the diagnosis is uncertain and the patient has no prior history of cancer, then a systemic workup is needed to search for the primary lesion and to exclude other possible etiologies Neuroimaging with CT, MRI, and ultrasonog-raphy may be needed to delineate the intraocu-lar lesion Lumbar puncture may be necessary

to evaluate for any intracranial involvement Cytology of vitreous or CSF may be required

to obtain a histological diagnosis.249

ManagementTreatment options include observation, radia-tion therapy, chemotherapy, and enucleation Observation may be indicated in patients with good visual acuity, especially those who are improving on chemotherapy External-beam

radiation may be appropriate if vision is

impaired In adults, about 30 Gy to 35 Gy can be

given in divided doses over 3 to 4 weeks For

patients with metastatic optic disc tumors with

good visual acuity, chemotherapy to control the

tumor growth is recommended If visual acuity

is decreased, external-beam radiation may be

needed Secondary optic atrophy may be a

complication of radiation therapy Enucleation

would be reserved for those patients with a

blind and painful eye.250

Prognosis

The prognosis of patients with metastases to

the optic nerve is poor The mean survival

of patients with metastatic carcinoma was 9

months after onset of ocular symptoms.250 The

prognosis for survival is likely infl uenced by the

course of the primary malignancy In a series of

300 patients with ocular metastases, the mean

survival of patients with breast carcinoma was

18 months compared with 8 months for patients

with lung carcinoma and 5 months for patients

with cutaneous melanoma.250

Lymphomatous Infi ltration of

the Optic Nerve

Epidemiology

Infi ltration of the optic nerve occurs in 0.5%

of patients with non-Hodgkin’s lymphoma

(NHL).255 Infi ltration of the optic nerve in

Hodgkin’s disease is even less common In both

NHL and Hodgkin’s lymphoma, the infi ltration

of optic nerves arises from extension of CNS

tumor In primary CNS lymphoma (PCNSL),

the incidence of ocular involvement is as high

as 20% to 25% at the time of diagnosis The true

incidence of isolated ocular lymphoma is diffi

-cult to ascertain because a signifi cant

propor-tion of patients are not accurately diagnosed

until they present with subsequent CNS disease

Nevertheless, ocular lymphoma with or without

CNS disease affects up to 500 patients per year

and is a very rare condition.256 The average age

of onset for isolated ocular lymphoma is in the

late fi fties to sixties Women are affected twice

as frequently as men

Symptoms and SignsVisual symptoms usually present after the diag-nosis of lymphoma, but visual loss may occa-sionally be the initial presenting sign.257, 258 The location and extent of the lymphoma deter-mines whether the visual loss is slowly pro-gressive259 or acute.260 In patients with ocular lymphoma as part of the spectrum of PCNSL

or in isolation, the visual symptoms are cal to those of idiopathic vitreitis or uveitis A lymphomatous infi ltrative optic neuropathy can even present in patients thought to be in clinical remission The most common presenta-tion are fl oaters, which may enlarge in size to gradually obscure vision Blurry vision and scotomas are also occasionally present Bilat-eral involvement occurs in more than 80% of patients Those who appear to have unilateral symptoms at onset often have bilateral disease

identi-on examinatiidenti-on or develop it during the course

of their illness About 50% of patients with ocular lymphoma have no visual symptoms when cells and fl are are seen on slit lamp exam-ination Further funduscopic exam often reveals subretinal deposits of lymphoma and even retinal detachment.261

Diagnostic Testing

On cytological evaluation of a vitrectomy men, the presence of malignant lymphocytes establishes the diagnosis.262 Most of these cells are B-cell tumors that stain with B-cell immu-nohistochemistry markers Although some reactive T cells are seen, fl ow cytometry or molecular analysis of the vitreous specimen can confi rm the diagnosis and rule out an infl ammatory reaction, as seen in idiopathic vitritis.262 Further testing for elevated levels

speci-of inter leukin-10 (IL-10), interleukin-6 (IL-6), and interleukin-12 (IL-12) may provide sup-portive evidence, in addition to cytological results, of ocular lymphoma Vitreous IL-10 is elevated in ocular lymphoma, but not in idiopathic vitritis, which is associated with ele-vated levels of IL-6 and IL-12 Monitoring of the levels of IL-10 may also be helpful in measuring therapeutic response in patients with ocular lymphoma.263

Infi ltration of the optic nerve by lymphoma is

seen as an enlarged high-density enhancing

lesion on CT scan On MRI, the infi ltrated optic

nerve can be seen as an enhancing lesion that

is iso-, hyper-, or hypointense on T1-weighted

imaging and hyperintense on T2-weighted

imaging.260

Management

Prior use of corticosteroids can be cytotoxic to

malignant lymphocytes and may cause transient

remission of the ocular lymphoma, which often

recurs when corticosteroids are discontinued

for weeks to sometimes months Most patients

become refractory to repeated courses of

corticosteroids.256

When the CNS is involved, survival without

treatment is very limited such that most patients

survive for only a few weeks Radiotherapy,

cor-ticosteroids, and vitrectomy can induce

remis-sion but do not substantially improve long-term

survival.256

Leukemic Infi ltration of the Optic Nerve

Epidemiology

Based on a study by Allen and Straatsma,264

half the patients who died of leukemia had

ocular involvement The acute form of

leuke-mias affected the eye four times more often

than the chronic form About 90% of cases with

optic nerve involvement occur in patients with

the acute forms of leukemia.264,265 By the time

the optic nerve head is infi ltrated by leukemic

cells, the disease is often active in the bone

marrow.265

Symptoms and Signs

In contrast to the good visual function observed

with other types of optic disc edema, this infi

l-trative-related disc edema is associated with

decreased visual acuity, variable visual fi eld

defects, and a relative afferent pupillary defect

unless the infi ltration is bilateral and

symmet-ric It is often associated with peripapillary and

peripheral retinal hemorrhages.265 Leukemic

cells may also infi ltrate the optic disc to form a

circumscribed, white elevated lesion associated with yellow deposits and peripapillary hemor-rhage.266 Subretinal fl uid may also develop sec-ondary to retinal pigment epithelial damage.267–269The visual acuity in such patients is relatively preserved, unless the infi ltration or associated edema and hemorrhage extends into the macula.270 In addition, optic disc swelling and neovascularization may occur as a local phe-nomenon in the setting of diffuse retinopathy

of acute leukemia.271The differential diagnosis of optic disc edema

in patients with leukemia includes leukemic infi ltration of the CNS with secondary increased intracranial pressure, pseudotumor cerebri related to prolonged corticosteroid use, tumor infi ltration of the optic nerve resulting in isch-emic papillitis, and perivascular tumor infi ltra-tion leading to venous engorgement.266

Although most infi ltrative optic neuropathies are attributed to acute leukemias, chronic leu-kemias may cause more slowly progressive and less severe visual loss The optic disc edema is similar to that seen in patients with acute leu-kemias but without the retinal changes.272Similar to lymphomatous infi ltrative optic neuropathies, MRI demonstrates abnormal enhancement in optic nerves infi ltrated by leu-kemia This lesion is iso-, hyper-, or hypointense

on T1-weighted imaging and hyperintense on

T2-weighted imaging.263

PathologyLeukemic infi ltration of the optic nerve via the pial septae causes optic disc swelling This edematous appearance may mimic papilledema caused by increased intracranial pressure The leukemic cell infi ltration proximal to the optic nerve just posterior to the lamina cribrosa con-tributes to the disruption of axoplasmic fl ow and compression of nerve fi bers to cause disc edema.266–268 Hemorrhagic necrosis and tumor cells can be seen in the edematous disc and in the retrolaminar interneuronal spaces.272

ManagementEarly, aggressive radiation therapy is the most effective treatment of incipient optic nerve head infi ltration by leukemia In a study by

Rosenthal et al.,265 four eyes with leukemic

infi ltration were treated with 2000 rads

exter-nal-beam radiation over a 1- to 2-week period

Visual function rapidly returned to normal or

near normal, and the disc edema resolved On

histopathological examination of these eyes,

tumor cells were absent in the prelamnar and

retrolaminar regions of the optic nerve

Myelomatous and Other Lymphoreticular

Tumor Infi ltration into the Optic Nerve

Multiple myeloma, lymphomatoid

granuloma-tosis, and Langerhans’ cell histiocytosis may

cause an infi ltrative and/or compressive optic

neuropathy.273 Bourdette and Rosenberg274

described a patient with polyneuropathy,

organomegaly, endocrinopathy, monoclonal

gammopathy, and skin changes (POEMS) who

developed an infi ltrative orbitopathy and had

blind spot enlargement that improved after

corticosteroid treatment Another report275

described a patient who developed an optic

neuropathy and a chiasmal syndrome resulting

from infi ltration from reactive

lymphohis-tiocytosis secondary to phenytoin use Vision

improved after treatment with corticosteroids

and radiation therapy.275,276

Infl ammatory Infi ltrative

Optic Neuropathies

Sarcoidosis

Epidemiology

Sarcoidosis is a relatively common disorder,

occurring as often as 82 cases per 10,000 persons

in the United States It affects blacks more

severely, and they have twice the frequency

of ocular involvement as Caucasians Most

symptomatic patients are between 20 and 40

years of age

Sarcoidosis is the most common infl

amma-tory etiology of infi ltrative optic neuropathies

About 1% to 5% of patients with systemic

sar-coidosis have optic nerve involvement.277 Optic

nerve dysfunction occurs in patients with

neu-rosarcoidosis Coexisting uveitis may obscure

optic nerve involvement In a study of 68 patients with neurosarcoidosis reported by Zajicek et al.,278 the optic nerve or chiasm was affected in 38% Of these patients, 69% had unilateral optic nerve involvement and 31% had bilateral involvement

Symptoms and SignsSarcoidosis may cause an ischemic optic neu-ropathy, papilledema from a compressive process, or an anterior or retrobulbar optic neu-ritis from a granulomatous infi ltrative process.279Visual acuity loss is associated with decreased color vision, visual fi eld defect, and a relative afferent pupillary defect, unless the involve-ment is bilateral and symmetric An isolated infi ltrative optic neuropathy can manifest initially, or it may occur with other signs of hypothalamic dysfunction, hypothalamic hypo-pituitarism, or both.279 Sarcoidosis also causes perioptic neuritis

On funduscopic examination, the optic disc

is usually elevated diffusely or sectorially with nodules This yellow-white caulifl ower-like formation over the disc can also be clearly seen

on ultrasonography Surface disc blood vessels appear dilated, and peripapillary hemorrhages may be seen Pressure from the lesion can cause

a branch retinal vein obstruction Noncaseating granulomas usually infi ltrate the optic disc uni-laterally Although it is not often associated with anterior uveitis, posterior uveitis and retinal phlebitis occur in 80% of cases.280 Sar-coidosis may affect the posterior retrobulbar or intracanalicular portion of the optic nerve to cause gradual visual loss and a normal optic disc that gradually becomes pale Visual acuity ranges from 20/20 to hand motions.281

Although sarcoid-related disc edema in the setting of progressive visual loss commonly occurs in association with ocular infl amma-tion,282 it may be diffi cult to distinguish it from compressive optic neuropathies, such as optic nerve sheath meningiomas A retrobulbar pre-sentation of sarcoidosis can also mimic optic neuritis Atypical features of peripapillary hem-orrhages or the persistent dependence of visual function on steroids may help differentiate sarcoid optic neuropathy.282

Diagnostic Testing

The diagnosis is usually confi rmed by other

sys-temic clinical, radiographic, and laboratory

evi-dence of sarcoidosis Laboratory tests supporting

the diagnosis of sarcoidosis include an elevated

angiotensin-converting enzyme (ACE) level

and histological evidence of sarcoidosis by

biopsy Sensitivity of serum ACE is 84% and

the specifi city is 95% The combined use of

ACE levels and gallium scans can also increase

specifi city.283 Furthermore, abnormal uptake on

gallium scanning may represent areas suitable

for biopsy Affected conjunctival or lacrimal

glands may also be biopsied Epithelioid and

giant cell infi ltration forming noncaseating

granulomas can be seen on biopsy of the optic

nerve.284 On CSF analysis, the CSF protein is

elevated in 73% of patients with

neurosarcoid-osis; the lymphocytic count is elevated; CSF

glucose levels are usually normal; CSF

oligoclo-nal bands are present in 55%; and CSF ACE

levels are elevated in up to 50% of patients.278

The optic neuropathy may be subclinical in

some cases In patients with neurosarcoidosis,

48% (23 of 50) patients had visual evoked

potential (VEP) abnormalities, but none had

visual symptoms Fluorescein angiography

shows early hypofl uorescence, then hyperfl

uo-rescence from leakage of disc blood vessels

within the lesion.277 On MRI, the enlargement

and contrast enhancement of the orbital portion

of the optic nerve are nonspecifi c for

sarcoid-osis The posterior orbital portion of the optic

nerve often reveals enlargement and contrast

enhancement on MRI and CT, and the optic

foramen is often enlarged Sarcoidosis may

extend even more posteriorly to infi ltrate the

basal meninges, the intracranial portion of the

optic nerve, and the optic chiasm.278

Pathology

Histologically, the optic nerve can be infi ltrated

by noncaseating granulomas consisting of

epi-thelioid and infl ammatory foreign-body giant

cells Asteroids, star-shaped acidophilic bodies,

and Schaumann bodies, ovoid, basophilic,

birefringent calcium oxalate crystals, may be

found within or surrounded by the epithelioid

or giant cells.284

ManagementCorticosteroids are the main treatment of sar-coidosis Oral prednisone at 40 mg to 80 mg daily is recommended for neurosarcoidosis Higher pulse treatments are required when patients are unresponsive Steroid-sparing agents, such as cyclosporine, azathioprine, methotrexate, and cyclophosphamide, may be required for long-term immunosuppression.285

Idiopathic Perioptic Neuritis

EpidemiologyPerioptic neuritis affects older patients with a range from 24 to 60 years of age, in which 36% are older than 50 years of age, compared to optic neuritis, in which 15% are older than 50 years of age The exact prevalence of this rare disorder is not known at this time.286,287

Symptoms and SignsPerioptic neuritis may manifest as orbital or ocular pain, decreased vision, and a normal or swollen optic disc that may mimic acute optic neuritis It is usually an isolated, idiopathic dis-order that involves infl ammation of the optic nerve sheath.286 In contrast to optic neuritis that affects central vision, paracentral or arcuate defects are more commonly seen in perioptic neuritis Although vision often spontaneously recovers in optic neuritis, visual loss often pro-gresses over weeks in perioptic neuritis.287

Diagnostic Testing

If vitreous cells or retinal infi ltrates are seen, then screening for sarcoidosis, syphilis, Lyme disease, and tuberculosis is necessary on serum and CSF CSF results for these disorders would reveal a normal opening pressure and a mild pleocytosis

In perioptic neuritis, MRI enhancement of the optic nerve with occasional streaks of enhancement of the orbital fat with or without extraocular muscle enhancement can be seen.287Enhancement of the lesion on T1-fat-suppressedimaging is nonspecifi c but is also highly sugges-tive of this disorder.288 In optic neuritis, MRI

enhancement of the optic nerve with or without

white matter lesions is usually observed

Pathology

On histopathology, lymphocytic infi ltration and

fi brotic thickening of the optic nerve sheath

with foci of degenerating collagen can be seen.289

Granulomatous infl ammation in the nerve

sheath, vasculitis in the nerve sheath, and optic

nerve demyelination or infarction have also

been reported.289,290

Management

In contrast to patients with optic neuritis, those

with perioptic neuritis often experience

recur-rence of visual loss and are not predisposed

to developing a demyelinating disease In

con-trast to the corticosteroid treatment protocol

of the ONTT for patients with optic neuritis,

oral prednisone is given at 80 mg daily.287

Other steroid-sparing agents may need to be

admini stered on a long-term basis to prevent

irreversible visual loss and to induce remission

Mycobacterium tuberculosis is an obligate

aerobe and facultative intracellular parasite

that can survive in mononuclear phagocytes

and is able to invade local lymph nodes to

spread by hematogenous routes Since 1985, the

incidence of tuberculosis has increased in

asso-ciation with the acquired immunodefi ciency

syndrome (AIDS), affecting adults 25 to 40

years of age and during a later peak about 70

years of age

Symptoms and Signs

As a granulomatous infl ammatory disease,

tuberculosis causes a papillitis more often than

it infi ltrates the optic nerve.291 Lana-Peixoto

et al.292 reported an intrinsic tuberculoma of the left intracranial optic nerve on autopsy of a 1.5-year-old child with tuberculous meningitis and disseminated military tuberculosis In a report

by Iraci et al.,293 a 25-year old man with severe visual loss, diabetes insipidus, and sexual impo-tence from tuberculous meningitis had a tuber-culoma encasing and growing into the anterior optic pathways Biopsy confi rmed the diagnosis, and antituberculous treatment led to recovery

of vision in one eye

NeuroimagingMRI of the brain often reveals basilar menin-geal enhancement and communicating or non-communicating hydrocephalus Tuberculomas

in the brain parenchyma and optic pathways appear as multiple ring-enhancing nodular lesions that represent caseating granulomas Old tuberculomas often calcify.294

The primary diagnostic and screening test for tuberculosis is the tuberculin skin test with purifi ed protein derivative (PPD) and is posi-tive in 50% to 80% of cases CSF analysis reveals a lymphocytic predominance with ele-vated protein and decreased glucose CSF acid-fast bacillus smear is positive in about one-fourth

of cases CSF culture is positive in about third of cases CSF polymerase chain reaction (PCR) testing is not sensitive but is specifi c.295

one-PathologySmall white tubercles are scattered mainly over the basal meninges The tuberculomas can both encase and invade the optic nerve to cause an infi ltrative and compressive optic neuropathy They consist of a central core of caseation sur-rounded by epithelioid cells, giant cells, lym-phocytes, plasma cells, and connective tissue

An exudate, consisting of fi brin, lymphocytes, plasma cells, and other monocytes, also obliter-ates the pontine and interpenduncular cisterns and can spread to the optic chiasm and cranial nerves via the subarachnoid space.296

ManagementThe treatment of tuberculosis requires early treatment If resistance to isoniazid and rifampin

is suspected, then pyrazinamide and

etham-butol should be added Pyridoxine is added

to prevent peripheral neuropathy from

isonia-zid neurotoxicity Prednisone or

dexametha-sone for edema from tuberculous meningitis

improves morbidity and mortality An

infec-tious disease specialist should also be consulted

for management.296

Cryptococcosis

Epidemiology

Cryptococcus neoformans is an opportunistic

fungus that often infects those with underlying

illness or immunodefi ciency, such as AIDS

Since the development of antiretroviral therapy

and fl uconazole prophylaxis, the incidence of

cryptococcal meningitis has decreased Without

these medications, cryptococcal meningitis is

one of the most common CNS complications of

immunocompromised patients in the

develop-ing world.297 It affects adults more commonly

than children

Symptoms and Signs

Visual loss may be either acute and severe,

occurring in less than 24 h, or gradually

progres-sive Patients may begin with mild visual loss

and then progress to severe visual impairment

over weeks to months In a study by Rex et al.,298

the predictive factors for either acute or gradual

visual loss were the presence of papilledema, an

elevated CSF opening pressure, and a positive

CSF India ink preparation Medications that

reduced intracranial pressure most consistently

improved vision in patients who had gradually

progressive visual loss Corticosteroids did not

signifi cantly improve visual outcome

In a study of 80 human immunodefi ciency

virus (HIV) seropositive patients with

crypto-coccal infection,299 32.5% (26 of 80) patients

developed papilledema Visual loss and sixth

nerve palsy occurred in 9%, and optic atrophy

was observed in 2.5% of patients Among the

62 patients treated with oral conazoles, optic

nerve-related visual loss was less frequent

com-pared to the 18 patients treated with

ampho-tericin B or a combination of amphoampho-tericin B

and conazoles Although direct invasion of

intraocular structures by Cryptococcal

neofor-mans was a rare complication in this study,

direct invasion of the optic nerve by the ism has been demonstrated so far in at least

organ-40 patients.298

PathologyCryptoccocal organisms can infi ltrate the optic nerve to cause visual loss over several days

In a pathological study of a patient with AIDS who developed cryptococcal meningitis,300 focal necrosis of the right intracanalicular optic nerve and the left intraorbital optic nerve adjacent to the optic canal was thought to have caused sudden bilateral visual loss The meninges sur-rounding the optic nerve, chiasm, and tracts were

fi lled with cryptococcal organisms Blood vessels supplying the optic chiasm were normal Gener-alized cerebral edema and vacuolization of peri-ventricular white matter were also observed The visual loss from cryptococcosis can also occur more gradually over a period of months.301–304Cryptococcal organisms in the optic nerve sheath have been shown to be present at the time of sheath fenestration Despite the visual loss that can occur from papilledema in cryptococcal meningitis, it was concluded that the poor visual outcome after this procedure could have been related to the direct invasion of cryptoccocal organisms into the optic nerve.301–304

Diagnostic TestingMRI of the brain reveals basilar meningeal enhancement and gelatinous-appearing pseu-docysts extending along enlarged perivascular spaces, especially in the basal ganglia.305CSF analysis reveals a lymphocytic predomi-nance, but polymorphonuclear cells may be present; protein is usually 50 to 1000 mg/dL, and glucose is often less than 40 mg/dL A defi -nite diagnosis of cryptococcal meningitis is

established by a positive CSF culture for C.

neoformans, a positive CSF India ink stain, or

a reactive CSF cryptococcal antigen test.306

ManagementFor acute therapy of cryptoccal meningitis, intravenous amphotericin B with oral fl ucyto-

sine for at least 2 weeks is followed by oral fl

u-conazole to complete a 10-week course until

the CSF is sterile After this 10-week course, if

CSF is still not sterile, maintenance therapy

with a lower dose of fl uconazole should be

started If the patient has AIDS, then

antiretro-viral therapy needs to be started An infectious

disease specialist should also be consulted for

management.307

Other Infectious Etiologies

Although toxoplasmosis and cytomegalovirus

commonly cause a posterior uveitis, rare

evi-dence shows that these organisms can primarily

affect the optic nerve In a retrospective study

of 13 patients with toxoplasmosis affecting the

optic nerve head,308 patients with primary

toxo-plasmic involvement of the optic nerve head

who were treated had a fi nal visual acuity of

20/25 or better Visual fi eld defects were arcuate

or altitudinal This anterior toxoplasmic optic

neuropathy is diffi cult to diagnose because

there is typically no associated vitritis or

cho-rioretinitis Cytomegalovirus infi ltration of the

optic nerve is an unusual manifestation Only

one case report documents the presence of

cytomegalovirus invasion of the optic nerve

head in a 51-year-old immunocompromised

patient suffering from lymphoma No

lym-phoma cells were seen in the optic nerve.309

References

1 Cushing H, Eisenhardt L Meningiomas: their

classifi cation, rational behavior, life history, and

surgical end results Springfi eld: Thomas; 1938.

2 Wilson WB Meningiomas of the anterior visual

system Surv Ophthalmol 1981;26(3):109–27.

3 Dutton JJ Optic nerve sheath meningiomas

Surv Ophthalmol 1992;37(3):167–83.

4 Cunliffe IA, Moffat DA, Hardy DG, Moore AT

Bilateral optic nerve sheath meningiomas in a

patient with neurofi bromatosis type 2 Br J

Ophthalmol 1992;76(5):310–2.

5 Sarkies NJ Optic nerve sheath meningioma:

diagnostic features and therapeutic

alterna-tives Eye 1987;1(pt 5):597–602.

6 Wright JE, McNab AA, McDonald WI Primary

optic nerve sheath meningioma Br J

Ophthal-mol 1989;73(12):960–6.

7 Sibony PA, Krauss HR, Kennerdell JS, Maroon

JC, Slamovits TL Optic nerve sheath mas Clinical manifestations Ophthalmology 1984;91(11):1313–26.

8 Trobe JD, Glaser JS, Post JD, Page LK Bilateral optic canal meningiomas: a case report Neuro- surgery 1978;3(1):68–74.

9 Alper MG Management of primary optic nerve meningiomas Current status: therapy in con- troversy J Clin Neuro-Ophthalmol 1981;1(2): 101–17.

10 Hart WM Jr, Burde RM, Klingele TG, ter JC Bilateral optic nerve sheath meningio- mas Arch Ophthalmol 1980;98(1):149–51.

11 Liano H, Garcia-Alix C, Lousa M, Marquez M, Nombela L, de Miguel J Bilateral optic nerve meningioma Eur Neurol 1982;21(2):102–6.

12 Mark LE, Kennerdell JS, Maroon JC, baum AE, Heinz R, Johnson BL Microsurgical removal of a primary intraorbital meningioma

Rosen-Am J Ophthalmol 1978;86(5):704–9.

13 Jakobiec FA, Depot MJ, Kennerdell JS, et al Combined clinical and computed tomographic diagnosis of orbital glioma and meningioma Ophthalmology 1984;91(2):137–55.

14 Tien RD, Chu PK, Hesselink JR, Szumowski J Intra- and paraorbital lesions: value of fat- suppression MR imaging with paramagnetic contrast enhancement AJNR Am J Neurora- diol 1991;12(2):245–53.

15 Dutton JJ, Anderson RL Idiopathic infl tory perioptic neuritis simulating optic nerve sheath meningioma Am J Ophthalmol 1985; 100(3):424–30.

16 Ing EB, Garrity JA, Cross SA, Ebersold MJ Sarcoid masquerading as optic nerve sheath meningioma Mayo Clin Proc 1997;72(1):38–43.

17 Liauw L, Vielvoye GJ, de Keizer RJ, van Duinen

SG Optic nerve glioma mimicking an optic nerve meningioma Clin Neurol Neurosurg 1996;98(3):258–61.

18 Nerad JA, Kersten RC, Anderson RL gioblastoma of the optic nerve Report of a case and review of literature Ophthalmology 1988; 95(3):398–402.

19 Rubio A, Meyers SP, Powers JM, Nelson CN, de Papp EW Hemangioblastoma of the optic nerve Hum Pathol 1994;25(11):1249–51.

20 Kleihues P, Burger PC, Scheithauer BW The new WHO classifi cation of brain tumours Brain Pathol 1993;3(3):255–68.

21 Samples JR, Robertson DM, Taylor JZ, Waller

RR Optic nerve meningioma Ophthalmology 1983;90(12):1591–4.

22 Wright JE Primary optic nerve meningiomas:

clinical presentation and management Trans

Sect Ophthalmol Am Acad Ophthalmol

Oto-laryngol 1977;83(4 pt 1):617–25.

23 Als E Intraorbital meningiomas encasing the

optic nerve A report of two cases Acta

Oph-thalmol (Copenh) 1969;47(4):900–3.

24 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.

25 Kayan A, Earl CJ Compressive lesions of the

optic nerves and chiasm Pattern of recovery of

vision following surgical treatment Brain

1975;98(1):13–28.

26 Egan RA, Lessell S A contribution to the

natural history of optic nerve sheath

meningio-mas Arch Ophthalmol 2002;120(11):1505–8.

27 Saeed P, Rootman J, Nugent RA, White VA,

Mackenzie IR, Koornneef L Optic nerve sheath

meningiomas Ophthalmology 2003;110(10):

2019–30.

28 Andrews DW, Faroozan R, Yang BP, et al

Frac-tionated stereotactic radiotherapy for the

treat-ment of optic nerve sheath meningiomas:

preliminary observations of 33 optic nerves in

30 patients with historical comparison to

obser-vation with or without prior surgery

Neurosur-gery 2002;51(4):890–902.

29 Pitz S, Becker G, Schiefer U, et al Stereotactic

fractionated irradiation of optic nerve sheath

meningioma: a new treatment alternative Br J

Ophthalmol 2002;86(11):1265–8.

30 Narayan S, Cornblath WT, Sandler HM, Elner

V, Hayman JA Preliminary visual outcomes

after three-dimensional conformal radiation

therapy for optic nerve sheath meningioma Int

J Radiat Oncol Biol Phys 2003;56(2):537–43.

31 Subramanian PS, Bressler NM, Miller NR

Radiation retinopathy after fractionated

ste-reotactic radiotherapy for optic nerve sheath

meningioma Ophthalmology 2004;111(3):

565–7.

32 Girkin CA, Comey CH, Lunsford LD, Goodman

ML, Kline LB Radiation optic neuropathy

after stereotactic radiosurgery Ophthalmology

1997;104(10):1634–43.

33 Stafford SL, Pollock BE, Leavitt JA, et al A

study on the radiation tolerance of the optic

nerves and chiasm after stereotactic

radiosur-gery Int J Radiat Oncol Biol Phys 2003;55(5):

1177–81.

34 Guyer DR, Miller NR, Long DM, Allen GS

Visual function following optic canal

decom-pression via craniotomy J Neurosurg 1985; 62(5):631–8.

35 Schrell UM, Rittig MG, Anders M, et al Hydroxyurea for treatment of unresectable and recurrent meningiomas II Decrease in the size

of meningiomas in patients treated with hydroxyurea J Neurosurg 1997;86(5):840–4.

36 Paus S, Klockgether T, Urbach H, Schlegel U Meningioma of the optic nerve sheath: treat- ment with hydroxyurea J Neurol Neurosurg Psychiatry 2003;74(9):1348–50.

37 Grunberg SM, Weiss MH, Spitz IM, Ahmadi J, Sadun A, Russell CA, Lucci L, Stevenson LL Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone J Neurosurg 1991;74(6):861–6.

38 Shields JA Optic nerve and meningeal tumors In: Shields JA, editor Diagnosis and manage- ment of orbital tumors Philadelphia: Saunders; 1989:170–91.

39 Bartley GB, Fatourechi V, Kadrmas EF, et al The incidence of Graves’ ophthalmopathy in Olmsted County, Minnesota Am J Ophthalmol 1995;120:511–7.

40 Friedman JM, Fialkow PJ The genetics of Graves’ disease Clin Endocrinol Metab 1978;7(1):47–65.

41 Feldon SE, Muramatsu S, Weiner JM Clinical classifi cation of Graves’ ophthalmopathy Iden- tifi cation of risk factors for optic neuropathy Arch Ophthalmol 1984;102(10):1469–72.

42 Kennerdell JS, Rosenbaum AE, El-Hoshy MH Apical optic nerve compression of dysthyroid optic neuropathy on computed tomography Arch Ophthalmol 1981;99(5):807–9.

43 Barrett L, Glatt HJ, Burde RM, Gado MH Optic nerve dysfunction in thyroid eye disease:

CT Radiology 1988;167(2):503–7.

44 Trobe JD, Glaser JS, Lafl amme P Dysthyroid optic neuropathy Clinical profi le and rationale for management Arch Ophthalmol 1978;96(7): 1199–209.

45 Glaser JS The orbit and neuro-ophthalmology Semin Neurol 1986;6(2):124–34.

46 Newell FW Choroidal folds The seventh Harry Searls Gradle Memorial lecture Am J Ophthal- mol 1973;75(6):930–42.

47 Cangemi FE, Trempe CL, Walsh JB Choroidal folds Am J Ophthalmol 1978;86(3):380–7.

48 De La Paz MA, Boniuk M Fundus tions of orbital disease and treatment of orbital disease Surv Ophthalmol 1995;40(1):3–21.

49 McKenzie JM, McCullagh EP Observations against a causal relationship between the long-

acting thyroid stimulator and ophthalmopathy

in Graves’ disease J Clin Endocrinol Metab

1968;28(8):1177–82.

50 Atta HR, McCreath G, McKillop JH, et al

Oph-thalmopathy in early thyrotoxicosis:

relation-ship to thyroid receptor antibodies and effects

of treatment Scott Med J 1990;35(2):41–4.

51 Wiersinga WM, Smit T, van der Gaag R,

Koornneef L Temporal relationship between

onset of Graves’ ophthalmopathy and onset of

thyroidal Graves’ disease J Endocrinol Invest

1988;11(8):615–9.

52 Sergott RC, Glaser JS Graves’

ophthalmopa-thy A clinical and immunologic review Surv

Ophthalmol 1981;26(1):1–21.

53 Sridama V, DeGroot LJ Treatment of Graves’

disease and the course of ophthalmopathy Am

J Med 1989;87(1):70–3.

54 Hallin ES, Feldon SE Graves’ ophthalmopathy:

I Simple CT estimates of extraocular muscle

volume Br J Ophthalmol 1988;72(9):674–7.

55 Jacobson DH, Gorman CA Endocrine

ophthal-mopathy: current ideas concerning etiology,

pathogenesis, and treatment Endocr Rev

1984;5(2):200–20.

56 Hufnagel TJ, Hickey WF, Cobbs WH, Jakobiec

FA, Iwamoto T, Eagle RC

Immunohisto-chemical and ultrastructural studies on the

exenterated orbital tissues of a patient with

Graves’ disease Ophthalmology 1984;91(11):

1411–9.

57 Jakobiec FA, Font RL Orbit In: Spencer WH,

editor Ophthalmic pathology, vol 3, 3rd ed

Philadelphia: Saunders; 1986.

58 Wakelkamp IM, Baldeschi L, Saeed P, Mourits

MP, Prummel MF, Wiersinga WM Surgical or

medical decompression as a fi rst-line treatment

of optic neuropathy in Graves’

ophthalmopa-thy? A randomized controlled trial Clin

Endo-crinol (Oxf) 2005;63(3):323–8.

59 Marcocci C, Bartalena L, Tanda ML, et al

Com-parison of the effectiveness and tolerability of

intravenous or oral glucocorticoids associated

with orbital radiotherapy in the management of

severe Graves’ ophthalmopathy: results of a

prospective, single-blind, randomized study

J Clin Endocrinol Metab 2001;86(8):3562–7.

60 Marcocci C, Bartalena L, Bogazzi F,

Bruno-Bossio G, Lepri A, Pinchera A Orbital

radio-therapy combined with high dose systemic

glucocorticoids for Graves’ ophthalmopathy is

more effective than radiotherapy alone: results

of a prospective randomized study J

Endocri-nol Invest 1991;14(10):853–60.

61 Carter KD, Frueh BR, Hessburg TP, Musch DC Long-term effi cacy of orbital decompression for compressive optic neuropathy of Graves’ eye disease Ophthalmology 1991;98(9):1435– 42.

62 Hallin ES, Feldon SE, Luttrell J Graves’ thalmopathy: III Effect of transantral orbital decompression on optic neuropathy Br J Oph- thalmol 1988;72(9):683–7.

63 Shorr N, Neuhaus RW, Baylis HI Ocular ity problems after orbital decompression for dysthyroid ophthalmopathy Ophthalmology 1982;89(4):323–8.

64 Young JD Ocular complications of transantral decompression for thyrotrophic exophthalmos Proc R Soc Med 1971;64(9):929–31.

65 Stiglmayer N, Mladina R, Tomic M, et al nasal endoscopic orbital decompression in patients with Graves’ ophthalmopathy Croat Med J 2004;45(3):318–22.

66 Shepard KG, Levin PS, Terris DJ Balanced orbital decompression for Graves’ ophthal- mopathy Laryngoscope 1998;108(11 pt 1): 1648–53.

67 Jacobiec FA, Jones IS Orbital infl ammations In: Jones IS, Jakobiec FA, editors Disease of the orbit Hagerstown: Harper and Row; 1979.

68 Curtin HD Pseudotumor Radiol Clin N Am 1987;25(3):583–99.

69 Atlas SW, Grossman RI, Savino PJ, et al Surface-coil MR of orbital pseudotumor AJR

Am J Roentgenol 1987;148(4):803–8.

70 Richardson GS Pituitary tumors In: Samuels

MA, Feske SK, editors Offi ce practice of rology Philadelphia: Churchill Livingstone; 2003.

71 Trobe JD Chromophobe adenoma presenting with a hemianopic temporal arcuate scotoma

Am J Ophthalmol 1974;77(3):388–92.

72 Hoyt WF, Rios-Montenegro EN, Behrens MM, Eckelhoff RJ Homonymous hemioptic hypo- plasia Fundoscopic features in standard and red-free illumination in three patients with con- genital hemiplegia Br J Ophthalmol 1972; 56(7):537–45.

73 Gittinger JW Jr Tumors of the pituitary gland In: Miller NR, Newman NJ, editors Walsh and Hoyt’s clinical neuro-ophthalmology, 5th

ed Baltimore: Williams & Wilkins; 1999 p 2141– 222.

74 Tokumaru AM, Sakata I, Terada H, Kosuda S, Nawashiro H, Yoshii M Optic nerve hyperin- tensity on T 2 -weighted images among patients

with pituitary macroadenoma: correlation with

visual impairment AJNR Am J Neuroradiol

2006;27(2):250–4.

75 Peter M, De Tribolet N Visual outcome after

transsphenoidal surgery for pituitary

adeno-mas Br J Neurosurg 1995;9(2):151–7.

76 Randeva HS, Schoebel J, Byrne J, Esiri M,

Adams CB, Wass JA Classical pituitary

apo-plexy: clinical features, management and

outcome Clin Endocrinol (Oxf) 1999;51(2):

181–8.

77 McFadzean RM, Doyle D, Rampling R,

Teasdale E, Teasdale G Pituitary apoplexy and

its effect on vision Neurosurgery 1991;29(5):

669–75.

78 Muller-Jensen A, Ludecke D Clinical aspects

of spontaneous necrosis of pituitary tumors

(pituitary apoplexy) J Neurol 1981;224(4):

267–71.

79 Ahmed M, Rifai A, Al-Jurf M, Akhtar M,

Woodhouse N Classical pituitary apoplexy

pre-sentation and a follow-up of 13 patients Horm

Res 1989;31(3):125–32.

80 Cardoso ER, Peterson EW Pituitary apoplexy:

a review Neurosurgery 1984;14(3):363–73.

81 Symon L, Rosenstein J Surgical management of

suprasellar meningioma Part 1: The infl uence

of tumor size, duration of symptoms, and

micro-surgery on surgical outcome in 101 consecutive

cases J Neurosurg 1984;61(4):633–41.

82 Huber A Eye signs and symptoms in brain

tumors, 3rd ed St Louis: Mosby; 1976.

83 Rosenberg LF, Miller NR Visual results after

microsurgical removal of meningiomas

involv-ing the anterior visual system Arch

Ophthal-mol 1984;102(7):1019–23.

84 Chicani CF, Miller NR Visual outcome in

surgi-cally treated suprasellar meningiomas J

Neuro-Ophthalmol 2003;23(1):3–10.

85 O’Connell JE, Du Boulay EP Binasal

hemiano-pia J Neurol Neurosurg Psychiatry 1973;36(5):

697–709.

86 Weisberg LA, Numuguchi Y Neuroimaging in

neuroendocrine diseases Neurol Clin 1986;4(4):

783–800.

87 Demailly P, Guiot G Meningioma of the sellar

diaphragm Bull Soc Ophtalmol Fr 1970;70(2):

191–6.

88 Guiot G, Montrieul B, Goutelle A, Comoy J,

Langie S Retro-chiasmatic suprasellar

menin-giomas Neurochirurgie 1970;16(4):273–85.

89 Boulos PT, Dumont AS, Mandell JW, Jane JA Sr

Meningiomas of the orbit: contemporary

con-siderations Neurosurg Focus 2001;10(5):E5.

90 Gregorius FK, Hepler RS, Stern WE Loss and recovery of vision with suprasellar meningio- mas J Neurosurg 1975;42(1):69–75.

91 Rosenstein J, Symon L Surgical management of suprasellar meningioma Part 2: Prognosis for visual function following craniotomy J Neuro- surg 1984;61(4):642–8.

92 Jaaskelainen J Seemingly complete removal of histologically benign intracranial meningioma: late recurrence rate and factors predicting recurrence in 657 patients A multivariate anal- ysis Surg Neurol 1986;26(5):461–9.

93 Kajiwara K, Fudaba H, Tsuha M, et al sis of recurrences of meningiomas following neurosurgical resection No Shinkei Geka 1989;17(12):1125–31.

94 Marks SM, Whitwell HL, Lye RH Recurrence

of meningiomas after operation Surg Neurol 1986;25(5):436–40.

95 Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza RL Meningioma: anal- ysis of recurrence and progression following neurosurgical resection J Neurosurg 1985;62(1): 18–24.

96 Carella RJ, Ransohoff J, Newall J Role of tion therapy in the management of meningi- oma Neurosurgery 1982;10(3):332–9.

97 Goldsmith BJ, Wara WM, Wilson CB, Larson

DA Postoperative irradiation for subtotally resected meningiomas A retrospective analysis

of 140 patients treated from 1967 to 1990

J Neurosurg 1994;80(2):195–201.

98 Lunsford LD Contemporary management

of meningiomas: radiation therapy as an adjuvant and radiosurgery as an alternative to surgical removal? J Neurosurg 1994;80(2): 187–90.

99 Miralbell R, Linggood RM, de la Monte S, Convery K, Munzenrider JE, Mirimanoff RO The role of radiotherapy in the treatment

of subtotally resected benign meningiomas

J Neuro-Oncol 1992;13(2):157–64.

100 Wilson CB Meningiomas: genetics, malignancy, and the role of radiation in induction and treat- ment The Richard C Schneider Lecture J Neu- rosurg 1994;81(5):666–75.

101 De Monte F Current management of mas Oncology (Williston Park) 1995;9(1): 83–91, 96.

meningio-102 De Jesus O, Toledo MM Surgical management

of meningioma en plaque of the sphenoid ridge Surg Neurol 2001;55(5):265–9.

103 Morita A, Coffey RJ, Foote RL, Schiff D, Gorman D Risk of injury to cranial nerves after