【资源】视神经疾病

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Optic Nerve Disorders
ANATOMY
Intraocular Course
Intraorbital Course
Intrac**icular Course
Intracranial Course
CLINICAL EXPRESSION OF DISEASE
Pallor and Cupping
Optic Disc Swelling (edema)
Accompanying Signs
ISCHEMIC OPTIC NEUROPATHIES
Nonarteritic Anterior Ischemic Optic Neuropathy
Arteritic Anterior Ischemic Optic Neuropathy
(Giant Cell Arteritis)
Diabetic Papillopathy
Papillophlebitis
OPTIC NEURITIS
PAPILLEDEMA
Mechanism of Papilledema
Idiopathic Intracranial Hypertension (Pseudotumor cerebri)
Other Causes of Papilledema
COMPRESSIVE OPTIC NEUROPATHIES
Optic Nerve Sheath Meningiomas
Orbital Disorders
I***INSIC NEOPLASMS
Optic Nerve Glioma
Lymphoproliferative Disorders
INFLAMMATORY OPTIC NEUROPATHIES
INFECTIOUS OPTIC NEUROPATHIES
Optic Disc Edema with a Macular Star (ODEMS)
Cat-Scratch Neuroretinitis
Other Infectious Neuropathies
TOXIC AND NUTRITIONAL OPTIC NEUROPATHIES
HEREDITARY OPTIC NEUROPATHIES
Kjer's Dominant Optic Atrophy
Leber's Hereditary Optic Neuropathy
TRAUMATIC OPTIC NEUROPATHY
GLAUCOMA
ANOMALOUS OPTIC DISCS
Optic Disc Drusen
Other Optic Disc Anomalies
In the previous chapter, the organization of axons in the sensory visual system provided the basis for
understanding the patterns of visual field defects. In this chapter, the neuroanatomy of the anterior sensory visual
system forms the foundation for understanding optic nerve disorders and their clinical expression.
ANATOMY
The optic nerve originates from the confluence of ganglion cell axons as they traverse the scleral c** to exit the
eye, and ends anatomically as these axons merge with the axons of the fellow optic nerve at the chiasm. Anatomic
divisions of the optic nerve include intraocular, intraorbital, intrac**icular, and intracranial portions.
I***AOCULAR COURSE
The short intraocular course of the optic nerve is often referred to as the optic nerve head, and the portion that can
be seen with the ophthalmoscope is called the optic disc. The optic disc is a pink oval measuring about 1.5 by 1.75 mm,
with its long axis oriented vertically. In most subjects, the optic cup, devoid of axons, is seen centrally, surrounded by
the pink, doughnut-shaped neuroretinal rim. The rim consists of axons end-on, as they pass from the nerve fiber layer
and make a right-angled turn into the scleral c**. Although the number of axons in normal subjects is relatively
constant, the diameter of the scleral c** may vary among individuals. When the scleral opening is small, the axons
seem crowded into a small space. These small cupless discs are often referred to as "discs at risk," because they are
frequently associated with optic disc infarction (anterior ischemic optic neuropathy [AION]). Individuals with large
scleral openings may have large discs with large central cups, which can simulate the pathologic cupping characteristic
of glaucoma.
Optic nerve axons congregate into bundles as they pass through thelamina cribrosa. This fibrous diaphragm is
contiguous with the sclera and has 200 to 300 openings. The lamina cribrosa further divides the intraocular optic nerve
head into prelaminar, laminar, and postlaminar portions. Optic disc edema occurs when the prelaminar axons swell
from blockage of orthograde axoplasmic flow at the level of the lamina cribrosa. Axoplasmic stasis and disc swelling
can be caused by many of the optic nerve disorders discussed in this chapter and is not disease-specific.
Just behind the globe, two to six short posterior ciliary arteries (branches of the ophthalmic artery) penetrate the
sclera in a circumferential fashion around the optic nerve. These vessels form an incomplete anastomotic ring at the
level of the choroid (Zinn-Haller), supplying both the high-flow vasculature of the choroidal circulation and the optic
nerve head. Although the central retinal vessels pass through the optic nerve head, their contribution to its vascular
supply is negligible (Fig. 4-1). Insufficient blood flow through the posterior ciliary arteries from thrombosis,
hypotension, or vascular occlusion resulting from arteritis can cause optic nerve head infarction (i.e., AION).
I***AORBITAL COURSE
After passing through the lamina cribrosa, the retinal ganglion cell axons acquire myelin sheathing, doubling the
diameter of the optic nerve to greater than 3 mm. The myelin sheath is produced byogliodendrocytes, the same cell type
in the white matter tracts in the central nervous system. Pe**heral nerves are myelinated by Schwann cells. Thus the
optic "nerve" is histologically a white matter tract rather than a pe**heral nerve. This fact accounts for the frequent
occurrence of optic neuritis in demyelinating disorders of the central nervous system, such as multiple sclerosis.
The orbital portion of the optic nerve is approximately 25 mm in length from the posterior aspect of the globe to
the orbital apex. Because the globe is only 15 mm anterior to the orbital apex, the optic nerve describes a gently curved
path; the extra length allows full movement of the globe without tethering by the optic nerve. In the orbit, the optic
nerve is surrounded by the optic nerve sheath, which is continuous with the intracranial dura through the optic c**
posteriorly and bounded by the sclera anteriorly. The sheath encloses an extension of the intracranial meninges: with
pia, arachnoid, and cerebrospinal fluid continuous with the intracranial cavity. Elevated intracranial pressure can be
transmitted directly to the optic nerve head, causing bilateral optic disc edema (papilledema). Meningiomas can arise
within the orbit from the optic nerve sheath, just as they occur from the intracranial meninges.
At the orbital apex, the nerve sheath fuses with a fibrous ring (annulus of Zinn) that forms the insertion of the
superior, inferior, and medial rectus muscles. This connection explains why eye movement can cause pain when the
optic nerve is inflamed in retrobulbar optic neuritis.
The vascular supply of the intraorbital optic nerve is more robust than that of the optic nerve head. Branches of
the ophthalmic artery serve numerous longitudinal pial vessels on the surface of the optic nerve, which in turn yield
penetrating vessels that extend toward the center of the nerve. The central retinal artery enters the nerve about 10 mm
behind the globe, also contributing to the vascular supply of the proximal intraorbital optic nerve. Given such a hardy
blood supply, ischemic insults to the retrobulbar optic nerve are rare, in contrast to the frequent occurrence of optic disc
infarction (i.e., AION).
I***ACANALICULAR COURSE
The intrac**icular portion of the optic nerve is about 10 mm long; beginning where the optic nerve enters the
optic foramen in the lesser wing of the sphenoid, and ending at the point where the optic nerve exits the optic c** and
enters the intracranial cavity. From the orbit, the optic c** moves medially and superiorly to enter the intracranial
cavity. The optic c** is separated from the sphenoid sinus by very thin bone, and the course of the optic nerve can be
seen as a convexity in the lateral wall of the sinus. In addition to the optic nerve, the optic c** also contains the
ophthalmic artery.
Space-occupying lesions within the bony confines of the optic c** do not have to be large to compress the
intrac**icular optic nerve and cause visual loss (intrac**icular meningioma), and may not be easily seen on
neuroimaging. Blunt trauma to the orbital rim can transmit forces to the optic c**, causing optic nerve contusion
and/or c** fractures. Subsequent edema within this confined space may produce additional ischemic injury.
I***ACRANIAL COURSE
The intracranial portion of the optic nerve is approximately 15 mm long, extending from the nerve's entrance into
the intracranial cavity to the chiasm, but this measurement may vary greatly depending on the relative location of the
chiasm. The optic nerves angle superiorly at 45 degrees from the skull base and converge toward the midsagittal plane
to form the chiasm. The anterior clinoid is superior and lateral to the optic nerve as the nerve emerges from the optic
foramen. The frontal lobes and olfactory tracts are above the nerve. The vascular supply of the optic nerve in this
location includes the carotid arteries, located laterally, as well as the anterior cerebral arteries and the anterior
communicating arteries, located superiorly. As the carotid artery emerges from the cavernous sinus, the ophthalmic
artery originates, traveling on the inferior surface of the optic nerve to enter the optic foramen. Carotid-ophthalmic
artery aneurysms or dolichoectatic atherosclerotic enlargement and displacement of the carotid artery can cause
compression of the intracranial optic nerve.
CLINICAL EXPRESSION OF DISEASE
Optic nerve disorders commonly produce pallor, pathologic cupping, or swelling of the optic disc.
PALLOR AND CUPPING
The axons that make up the optic nerve may be affected by disease anywhere along their course, from their origin
in the inner retina to their synaptic endpoint in the lateral geniculate body. Fatal injury to an axon results in retrograde
and orthograde degeneration of the axon and eventual death of the retinal ganglion cell of origin. Axonal injury remote
from the optic disc may cause optic nerve dysfunction without any acutely observable optic disc abnormality, but over
time, optic disc atrophy and nerve fiber layer dropout in the inner retina become visible, revealing the extent of the
damage. In most neuro-ophthalmic disorders, axonal loss manifests as pallor of the normally pink neuroretinal rim,
without apparent loss of neuroretinal rim mass. Diffuse disc pallor is a final common pathway for many optic
neuropathies and is nondiagnostic. However, the location of segmental pallor is often instructive, such as the sectorial
or altitudinal pallor in AION, "bowtie" atrophy in optic tract (or chiasmal) lesions, or temporal pallor characteristic of
the toxic/nutritional or hereditary optic neuropathies. Loss of axons may also manifest as optic nerve cupping as the
central cup enlarges from axonal dropout. Optic disc cupping is characteristic of glaucoma, but can occur in other optic
neuropathies. Cupping with pallor of the remaining neuroretinal rim suggests a cause other than glaucoma.
OPTIC DISC SWELLING (EDEMA)
Swelling of the prelaminar axons causes elevation and expansion of the optic nerve head. The normally distinct
border of the optic disc becomes blurred as swollen pe**apillary axons become elevated and less transparent. Axons
swell when the normal process of axoplasmic flow is "dammed up" by mechanical or ischemic processes. Transudation
of fluids from injured axons and disc vessels is also a contributor to the disc's swollen appearance (Fig. 4-2). Many
different insults to the optic nerve can result in optic disc swelling (Box 4-1). Elevated intracranial pressure, transmitted
to the nerve head within the confines of the optic nerve sheath, can cause stasis of axoplasmic flow at the level of the
lamina because of regional pressure differentials. Ischemic optic neuropathy produces optic disc swelling as a result of
ischemia. Inflammation from infection or demyelination can also produce disc swelling. The history, examination, and
clinical course help to determine the diagnosis. Important features in developing a differential diagnosis are listed in
Fig. 4-3, with individual disorders covered in detail in the sections that follow.
Infiltration of the optic nerve head by cancer cells, inflammatory cells, and/or infectious organisms is another
mechanism of optic nerve head elevation. Generally, these processes also incite concomitant optic disc swelling.
Some anomalous, but otherwise normal, optic discs may be elevated, giving the false appearance of optic disc
edema (Box 4-2).
ACCOMPANYING SIGNS
Rapid expansion of the optic disc from edema can cause damage to the optic disc and pe**apillary vasculature,
resulting in hemorrhages at many levels: deep, dark pe**apillary subretinal hemorrhages; dot/blot intraretinal
hemorrhages; nerve fiber layer hemorrhages (usually flame-shaped); and (rarely) vitreous hemorrhages. Vascular
changes can include telangiectasia on the disc surface (increased "capillarity") or venous stasis (increased venous
caliber). Telangiectasis on the disc and of the pe**apillary vessels can accompany Leber's hereditary optic neuropathy
(LHON). Collateral ("shunt") vessels on the disc can be seen in optic nerve sheath meningioma or compensated retinal
vein occlusion. An increase in the diameter of the intraocular portion of the optic nerve from axonal swelling produces
concentric pe**apillary chorioretinal folds, called "Paton's lines" (see Fig. 4-2). Macular choroidal folds, oriented
radial to the disc, frequently occur as a result of indentation of the posterior globe by the optic nerve sheath expanded
by high cerebrospinal fluid pressure, but can also occur in Graves' disease or from an orbital mass. Macular edema can
occur from massive disc edema of any cause but is most frequently seen accompanying optic disc edema in infectious
processes ("neuroretinitis").
ISCHEMIC OPTIC NEUROPATHIES
As its name implies, anterior ischemic optic neuropathy (AION) is the result of ischemia. The designation
ofanterior implies that the ischemic insult causes damage to the optic nerve head that is visible with the
ophthalmoscope. AION is thought to be caused by occlusion of one or more of the short posterior ciliary arteries that
supply the optic nerve head.Nonarteritic AION is common and is most likely the result of vascular insufficiency from
thrombosis and/or hypotension in patients with atherosclerotic disease. A more devastating form of AION is caused by
vasculitic occlusion of the supply arteries from giant cell arteritis. Arteritic AION can cause bilateral blindness, as well
as significant systemic morbidity related to vasculitic arterial closure.
The term posterior ischemic optic neuropathy (PION) suggests an infarct of the optic nerve beyond the optic disc,
with a normal-appearing nerve initially. PION is rare and is not a well-defined clinical entity. It occurs almost
exclusively in the setting of vasculitis.
NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY
Nonarteritic AION is a common cause of sudden, painless, monocular visual loss in patients after the fourth or
fifth decade of life (Fig. 4-4). Systemic hypertension (40%) and/or diabetes mellitus (20%) is commonly present.
Frequently, patients have other systemic manifestations of atherosclerotic disease such as angina pectoris, previous
myocardial infarction, or history of stroke.
Symptoms
Visual loss in this condition ranges from profound to mild and is frequently first noted by patients when they
awaken from sleep. The visual loss is generally painless but can be associated with a mild ocular ache. Patients may
have a stepwise decline in vision over several days, but the visual deficit is usually stable after onset. A subset of
patients (5-10%) have a relentlessly progressive stepwise decline in vision for weeks following the initial event.
Signs
The visual field loss is commonly a mix of central and altitudinal visual field defects, but any disc-related visual
field defect can occur (Fig. 4-4, A). Not uncommonly, patients are specific in their histories, stating that they "have lost
the lower (or upper) half of vision." Occasionally, central acuity is spared, but the vast majority of the time, the visual
field defect includes fixation.
The optic disc edema may be diffuse or segmental. For example, a dense inferior altitudinal visual field defect
may be associated with segmental swelling of the superior pole of the optic disc, with relative preservation of the
inferior pole (Fig. 4-4, B). The discs are commonly small and cupless "discs at risk," a finding that may only be
appreciated by vi***g the contralateral (unaffected) optic disc (Fig. 4-4, B). This finding is so universal that patients
who have moderate or large cup-to-disc ratios should be considered to have some other process (such as arteritic
AION) until proven otherwise. Pe**apillary nerve fiber hemorrhages frequently accompany the disc edema. The
remainder of the fundus is generally unremarkable, although retinal arterioles may reflect systemic hypertension,
diabetes, or atherosclerotic disease. The disc swelling generally resolves within 3 to 6 weeks, leaving optic disc pallor
(Fig. 4-4, C-D).
Causes
Nonarteritic AION is thought to be a stroke of the optic nerve head, resulting from insufficient blood flow
through the posterior ciliary arteries. Atherosclerosis that accompanies aging, or that is accelerated by systemic
vascular diseases such as hypertension and diabetes, narrows the lumen to a critical level where thrombosis or even
mild hypotension results in ischemia. The crowded optic discs commonly identified in these patients may initiate and
perpetuate a cascade: ischemia causing edema, edema in the narrow confines of the crowded disc causing further
ischemia from increased tissue pressure, with a downward spiral of increasing edema and ischemia.
The timing of this ischemic event characteristically occurring at night and in the early morning may be explained
by nocturnal hypotension (Hayreh, 1994). Systemic blood pressure is normally lower at night when patients are
sleeping. Hypertension (and other vascular disorders) can damage arterial compliance and local autoregulation, such
that nocturnal hypotensive swings can reach a critical level that precipitates AION. Long-acting antihypertensive
medications may further accentuate nocturnal hypotension. Not infrequently, patients who present with AION report
having been changed to stronger or longer-acting antihypertensive medication in the weeks or months before the event.
Obviously, withdrawal of the patient's antihypertensive medications is not the answer, but it is reasonable to suggest to
the patient's medical physician that long-acting antihypertensives be taken in the morning or that shorter-acting drugs
be considered.
Differential diagnosis
The most important consideration in the differential diagnosis is distinguishing nonarteritic AION from
arteriticAION caused by giant cell arteritis (see Fig. 4-3). In every case of AION, the clinician should ask specific
questions regarding the systemic symptoms of vasculitis (see following section). AION may be difficult to distinguish
from optic neuritis in patients 35 to 45 years old, and these patients may need to have both possibilities investigated.
Evaluation
A sedimentation rate, C-reactive protein, and complete blood count should be drawn in most cases to address the
possibility of an arteritic cause. Syphilis is a rare but treatable cause, and serologic tests for this disease should also be
routine. Patients without known diabetes or hypertension should be assessed for these two diseases. Patients who are
younger than 50 years old without known risk factors require serologic evaluation for vasculitis (rheumatologic
studies), infection, or hypercoagulable states (Box 4-3).
Neuroimaging is generally not indicated as long as the history is convincing for AION (sudden onset, stable
course), and the examination is consistent (optic disc edema). If optic neuritis is a consideration, an MRI may be
needed to assess the possibility of multiple sclerosis. Patients who present with recent visual loss and optic nerve pallor
may require neuroimaging to evaluate for possible compressive neuropathy (such as a meningioma, parasellar or sellar
tumor, or Graves' orbitopathy).
Treatment
No proven, effective treatment is available for nonarteritic AION. Obviously, underlying precipitating factors
should be addressed, such as blood loss, anemia, or factors inducing hypotension. As previously discussed, a patient's
medications for systemic hypertension should be reviewed with the medical physician. Oral steroids and high-dose
intravenous steroids might theoretically be beneficial but have not been convincingly proven to help in this disorder.
The use of optic nerve sheath fenestration in this condition was explored by the Ischemic Optic Neuropathy
Decompression Trial (IONDT). The study suggested that this surgery was not beneficial and may even be harmful. The
use of a daily aspirin may decrease the risk of an event in the contralateral eye (see following section).
Clinical course
Patients should have repeat visual field tests taken after several weeks and after several months to ensure that the
visual field loss is not progressive. Once nonarteritic AION has finished its course and optic pallor ensues, this process
is unlikely to occur again in the same eye. One proposed rationale for this lack of recurrence is that the death of axons
from an ischemic event "frees up" space for the remaining axons, effectively reversing the crowding of the optic disc.
About one half of patients with nonarteritic AION may experienceminimal improvement in visual function with time,
usually manifest as slight improvement in visual acuity (Fig. 4-4,E). The incidence of occurrence in the fellow eye may
be as high as 50 to 60%, although it generally occurs years later. Simultaneous or sequential events in both eyes should
raise strong suspicions of a vasculitic cause (i.e., giant cell arteritis). Unlike retinal vascular events, the life expectancy
of patients with nonarteritic AION is not significantly shortened.
ARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY (GIANT CELL ARTERITIS)
Arteritic AION is caused by vasculitic closure of the posterior ciliary arteries from giant cell arteritis. The visual
loss is usually more profound than nonarteritic AION and may occur in both eyes at the same time or in rapid
succession. Patients with giant cell arteritis are usually more than 60 years old, and the disease becomes more common
with each decade of life (Fig. 4-5). Arteritic AION is unusual before age 60, and only a few cases of patients with this
diagnosis in their forties have been documented. Among patients with giant cell arteritis, females outnumber males 3 to
1.
Causes
Giant cell arteritis is an idiopathic systemic vasculitis consisting of inflammation in the wall of small and
medium-sized arteries, usually involving the extracranial arteries of the head. The inflammatory products may greatly
expand the wall thickness, obliterating the lumen of the vessel and obstructing blood flow with resultant ischemic
consequences.
Symptoms
Patients with giant cell arteritis may present with rapid and profound blindness from ischemic optic neuropathy in
one or both eyes. Permanent visual loss is frequently preceded by transient visual loss lasting minutes, similar to
amauroses fugax (see Table 1-3). Although the visual loss itself is painless, patients commonly complain of headache,
scalp tenderness, and jaw claudication. Scalp tenderness may be caused by tenderness over inflamed arteries or may be
secondary to scalp ischemia. Scalp tenderness may be so intense that patients complain of pain when lying on a pillow,
combing their hair, or wearing a hat. Ischemia to the muscles of mastication result in jaw pain (claudication) with
ch***g or in tongue pain. Additional manifestations of this systemic vasculitis include weight loss, poor appetite,
general malaise, myalgia, arthralgia, and low-grade fever.
Polymyalgia rheumatica (PMR) is a chronic rheumatologic disorder characterized by proximal shoulder and
buttocks pain without tenderness. PMR may be a precursor or concomitant accompaniment of giant cell arteritis.
Signs
Visual field defects from arteritic AION may be similar to those found in nonarteritic AION, although the visual
acuity and field are frequently much more severely affected. Not uncommonly, patients present with NLP vision. The
optic disc appearance may be indistinguishable from nonarteritic AION, but more commonly, it is diffusely edematous
and pale (Fig. 4-5, A). On occasion, arteritis can cause a "posterior" ischemic optic neuropathy (PION), in which the
optic disc appears normal or is only minimally affected acutely. Acute, profound visual loss in an elderly patient with
an unimpressive disc and retina or visual loss that exceeds the observed optic disc edema strongly suggest giant cell
arteritis (Box 4-4). Bilateral or rapidly sequential AION also requires immediate consideration of vasculitis. In contrast
to nonarteritic AION, glaucomatous-like optic disc cupping may develop following arteritic AION.
The occasional occurrence of a retinal infarct in the distribution of a cilioretinal artery in the setting of AION is
highly suggestive of arteritis. This association is not surprising because the optic disc and pe**apillary choroid share a
common blood supply--the short posterior ciliary arteries.
Inflamed temporal arteries (or other scalp arteries) can frequently be palpated as a firm "cord" with a poor or
absent pulse, explaining this disorder's alternate name: temporal arteritis. Fortunately, these frequently involved arteries
are also easily surgically accessible for biopsy.
Forty percent of patients with giant cell arteritis have visual loss. If the disorder is unrecognized and untreated,
visual loss in the second eye can occur in 65% of patients with arteritic AION, usually within several weeks. Early
recognition of this process is vital to prevent bilateral blindness. Other vascular consequences of giant cell arteritis are
listed in Box 4-5.
Differential diagnosis
The evaluation of cases presenting as AION is directed at determining whether the process is arteritic or
nonarteritic as discussed in the following section (see Fig. 4-3). Fluorescein angiography has been advocated by some
experts as a potential way of distinguishing these two entities. Patients who have profound narrowing of the posterior
ciliary arteries resulting from giant cell arteritis demonstrate areas of choroidal hypoperfusion on the early sequences of
IVFA, with a marked delay in choroidal filling (Fig. 4-6).
Patients with bilateral arteritic AION can be distinguished from acute papilledema by the degree of visual loss,
which is severe in AION and is usually minimal or absent in acute papilledema.
Elderly patients with acute, profound visual loss but with minimal disc or retinal changes may have PION from
giant cell arteritis; other entities in the differential diagnosis are listed in Box 4-4.
Evaluation
Although no pathognomonic laboratory test is available for identifying giant cell arteritis, an elevated Westergren
erythrocyte sedimentation rate (usually above 50) and elevated C-reactive protein add weight to the clinical suspicion
of this disorder. Liver enzymes may be elevated as well. The erythrocyte sedimentation rate (ESR) is a nonspecific
indicator of inflammation and is also elevated in patients with infectious, collagen-vascular, renal, or neoplastic
disorders. The normal sedimentation rate increases with age. The upper limit of normal for a given age can be
estimated by dividing the age by two in males and by adding ten before dividing by two in females. Anemia is
common, and a low hematocrit tends to elevate the ESR further. However, the ESR may be normal in up to 10% of
patients who have giant cell arteritis.
A definitive diagnosis can only be made by identifying characteristic pathologic features in a biopsy of an
affected artery (see Fig. 4-5, C and D). A temporal artery biopsy should be performed on all patients suspected of
having giant cell arteritis, even those patients in whom the clinical diagnosis seems certain. A positive biopsy may not
change the short-term treatment plan, but it is invaluable in managing patients in the months and years following the
diagnosis, particularly if they develop significant systemic morbidity related to steroid therapy.
The vasculitis in giant cell arteritis is not continuous and may be found in patches along an artery with normal or
healing intervening areas. Therefore, temporal artery biopsies should be at least 2 to 3 cm in length because a short
biopsy specimen, or one that is not completely serially sectioned, may miss the pathologic area. A single arterial
specimen is diagnostic in 80 to 90% of patients who have giant cell arteritis. Most clinicians advocate a biopsy of the
contralateral temporal artery or other symptomatic scalp artery if the initial temporal artery biopsy is negative. Biopsy
of two sites increases the sensitivity to more than 90%. Some clinicians biopsy the temporal artery on both sides during
the same surgery.
Thus a patient suspected of having giant cell arteritis should have an ESR and C-reactive protein drawn, and
steroids should be immediately administered (see following section). A temporal artery biopsy should be performed
within 1 to 2 weeks of beginning steroids because the rate of a positive biopsy falls over several weeks as the steroids
reverse the inflammatory changes. After months of treatment, discontinuities of internal elastic lamina may be the only
pathologic finding, suggesting "healed" arteritis.
The clinical presentation, ESR, C-reactive protein, and temporal artery biopsy are usually sufficient to establish a
definitive diagnosis. In atypical cases, neuroimaging may be required, and the differential diagnoses outlined in Fig. 4-
3 and Box 4-4 will need to be addressed. Giant cell arteritis is by far the most common vasculitis causing ischemic
optic neuropathy in patients more than 50 years old, but occasionally, laboratory studies may be needed to address
other vasculitides such as systemic lupus erythematosus, polyarteritis nodosa, rheumatoid arthritis, or herpes zoster.
Treatment
The prompt administration of steroids may prevent bilateral blindness--an outcome that is not uncommon when
diagnosis or treatment is delayed. In patients with acute visual loss, high-dose intravenous steroids may actually
recover some vision. A common regimen is 250 mg of intravenous methylprednisolone (Solu-Medrol) every 6 hours
over several days. This treatment may require hospitalization based on the age and potential for medical complications
in these patients, but it can be given in an outpatient or home healthcare setting. Patients without acute visual loss but
with clinical suspicions of arteritis should be started immediately on 60 to 80 mg of oral prednisone daily until a biopsy
can be performed.
Patients with giant cell arteritis may require oral steroids for 1 year or more. Most patients can be tapered to
lower doses over a period of months by careful monitoring of their sedimentation rate, C-reactive protein, and
symptoms. Collaboration with the patient's medical doctor is of paramount importance, given the potential systemic
complications of steroid therapy. Occasionally, alternative immunosuppressive therapies such as methotrexate may be
effective as a steroid-sparing agent (particularly in diabetic patients).
DIABETIC PAPILLOPATHY
Diabetic patients with optic disc edema may have diabetic papillopathy (diabetic papillitis) (Fig. 4-7). This
condition has features that suggest it is clinically different from typical nonarteritic AION: (1) the patients are younger
(15-40), (2) visual field defects are less severe, (3) the condition is often bilateral, and (4) the visual deficits are more
likely to improve with time. The optic disc edema is usually diffuse rather than focal, and the discs display a fine
diffuse telangiectasia that may be difficult to distinguish from neovascularization. When it is bilateral, diabetic
papillitis may mimic papilledema (often referred to as "diabetic pseudopapilledema"). Diabetic papillitis and AION
may be indistinguishable in some cases. The precise cause of diabetic papillitis is uncertain, but it likely represents a
form of optic nerve head ischemia. No known effective treatment is available. Steroids have been advocated, but this
therapy in diabetic patients frequently produces medical complications and is of unproven efficacy.
PAPILLOPHLEBITIS
Papillophlebitis is a poorly defined cause of unilateral optic disc edema that occurs most commonly in healthy
patients who are 20 to 30 years old (Fig. 4-8). Patients present with painless, mild visual loss. The optic disc shows
diffuse hyperemic disc swelling, with dilated veins and flame-shaped pe**apillary hemorrhages. The optic disc
appearance suggests a central retinal vein occlusion (CRVO), but the hemorrhages do not extend far from the disc and
are not found in the retinal pe**hery. This entity is most likely a variant of CRVO, and the clinical evaluation may
need to be the same as CRVO in a young person: assessment for hypercoagulable states (see Box 4-3).
OPTIC NEURITIS
Optic neuritis typically causes acute monocular visual loss in young **s aged 15 to 45, associated with pain
induced or worsened by eye movement (Fig. 4-9). Incidence in females outnumbers males 5 to 1. The term optic
neuritis literally suggests any condition that causes inflammation of the optic nerve. However, most clinicians reserve
this term for primary demyelinating events such as the optic neuropathy associated with multiple sclerosis or idiopathic
conditions that have a similar clinical course.
Symptoms
Optic neuritis usually causes monocular visual loss, described by patients as a haze, cloud, or dimness with poor
color vision. The visual loss may progress over 2 to 7 days, at which point the vision begins to slowly improve, with
normal or near-normal visual function often achieved over several weeks or months (Fig. 4-9, F). Retro-ocular pain,
made worse with eye movement, usually precedes visual symptoms and continues during the phase of visual decline.
As previously discussed, the pain likely originates from extraocular muscle traction on an inflamed optic nerve at the
annulus of Zinn. Occasionally, patients report seeing brief spots of light (phosphenes, photopsias) induced with eye
movements or by loud sounds. A neurologic history and review of symptoms may reveal previous or concomitant
neurologic events that suggest a diagnosis of multiple sclerosis, such as transient episodes of numbness, weakness, loss
of bowel or bladder control, or persistent imbalance.
About one half of patients with active or recovered optic neuritis may note dimming of vision in the affected eye
when their body temperature is elevated, such as after exercise, after a shower or sauna, or with a fever. This transient
visual loss is called Uhthoff's phenomenon and results from temporary impairment of optic nerve function, which may
be caused by elevated body temperature or changes in the pH or ion content of the blood.
Signs
Visual acuity is usually affected. Color vision deficiencies may be more severe than would be predicted from
visual acuity alone. Potential visual field defects include any optic-disc-related visual field abnormality. Although a
central scotoma is the classic finding, altitudinal visual field defects are also at least as common, making the distinction
between this disorder and AION difficult in certain cases. Finding slight visual field abnormalities in the asymptomatic
eye is not unusual. The RAPD frequently seems to be measurably larger than expected from the visual field defect.
However, patients who have had optic neuritis in the fellow eye may have a minimal or absent RAPD. Even after a
patient's visual acuity, visual field, and color vision have recovered, the RAPD tends to persist, as does the brightness
sense disparity between an affected and unaffected eye.
The prolonged conduction velocity of an affected optic nerve can be demonstrated as a delay (increased latency)
in the signal generated with VEP testing. This test is not useful in the diagnosis of optic neuritis in a symptomatic eye
because common clinical tests of visual function present more compelling evidence of a previous or current optic
neuritis. However, VEP testing is frequently employed by neurologists seeking evidence of demyelination at multiple
sites in nonocular, monosymptomatic patients with suspected multiple sclerosis. The Pulfrich phenomenon (see
Chapter 2) may be observed by patients with unilateral optic neuritis, as a direct consequence of delayed signal velocity
in an affected optic nerve.
The optic disc initially appears normal in two thirds of patients, suggesting that the demyelinating event is
posterior to the optic nerve head. The remaining one third of patients demonstrates optic disc swelling that is usually
diffuse and mild, occasionally with a few associated disc and nerve fiber layer hemorrhages (Fig. 4-9,B). The macula is
unaffected, unlike the macular edema or edema residues seen in neuroretinitis. With time, optic disc pallor becomes
evident in all patients but may be subtle. Optic disc pallor can sometimes be seen in an asymptomatic eye, suggesting a
previous subclinical optic neuritis. Uveitis and pe**heral retinal venous sheathing have been described in some patients
with multiple sclerosis.
Causes
The presumed cause of optic neuritis is an autoimmune attack on the myelin coating of the optic nerve, rather
than the axons themselves. The myelin internodes allow rapid signal conduction (saltatory conduction). Loss of the
myelin component in the optic nerve dramatically affects vision because the transfer of visual ***rmation is slowed
when saltatory conduction breaks down. With time, incomplete repair occurs and function returns to near-normal. This
is the same process of myelin damage that occurs in the myelinated white matter tracts in the brain with multiple
sclerosis. A high percentage of patients with optic neuritis will eventually have other areas of white matter affected,
yielding a diagnosis of multiple sclerosis.
Differential diagnosis
The differential diagnosis in young patients with recent profound visual loss, a large RAPD, and a normal optic
disc is a relatively short list consisting of optic neuritis and a series of other less likely disorders (see Box 4-4).
Compressive optic neuropathy is possible in such patients, but the necessity of neuroimaging in patients with optic
neuritis (see following section) addresses this potential diagnosis. A longer list of potential causes must be considered
in those patients with disc swelling, including AION, LHON, and infiltrative and infectious neuropathies (see Fig. 4-3).
Evaluation
The Optic Neuritis Treatment Trial (ONTT) was a national, prospective, randomized study directed at the effects
of treatment on optic neuritis. In considering a multitude of clinical tests in young patients presenting with classic optic
neuritis, the ONTT established that neuroimaging was the only helpful test in determining treatment. As will be
discussed in the following section, the presence of other white matter plaques suggests treatment with high-dose
intravenous steroids (Fig. 4-9, D). An MRI of the brain and orbits with gadolinium should be obtained to address
treatment considerations, evaluate for systemic multiple sclerosis, and look for any unexpected findings (such as an
optic nerve sheath meningioma). MRI of the orbits with fat suppression often demonstrates variable enhancement of
the involved optic nerve (Fig. 4-9, C) but may be normal.
Treatment
The ONTT randomized 455 patients with optic neuritis into three treatment groups: (1) no treatment (placebo
tablets), (2) moderate-dose oral prednisone, and (3) high-dose IV methylprednisolone for 3 days (followed by oral
prednisone for 11 days). The outcomes of the study and resultant treatment recommendations are outlined in Table 4-1.
Patients in the intravenous steroid group in the ONTT were admitted to hospital and were treated with 250 mg of
intravenous methylprednisolone every 6 hours for 3 days, followed by an 11-day oral prednisone taper. Many clinicians
have modified this regimen to make it practical for home intravenous therapy, administering 500 mg of
methylprednisolone twice a day, or even 1000 mg daily, for 3 to 5 days.
Another consideration in determining who to treat includes any underlying medical conditions that would present
a significant risk to the patient with steroid use. Complications from intravenous steroid therapy in the young,
otherwise healthy subjects in the ONTT were rare but included transient psychosis, elevated blood sugar, and acute
pancreatitis.
Clinical course
The ONTT demonstrated that 90% of patients improved within one year to 20/40 or better, regardless of
treatment. Subjective and objective improvement in the visual field should be evident in 3 to 5 weeks after onset (Fig.
4-9, E-F). Failure to improve is still compatible with a diagnosis of optic neuritis, but at that point, other items in the
differential diagnosis should be considered. A continued, relentless decline in vision over months is not typical for
optic neuritis and requires reinvestigation, often with repeat views of the orbit and optic nerve with MRI or CT.
Steroid-dependent optic neuropathies improve while a patient is on steroids but worsen when the steroids are
stopped. This pattern is far more typical of inflammatory processes or neoplasia than of optic neuritis, and additional
investigation should be directed accordingly (Box 4-6).
Patients with white matter plaques on MRI or other neurologic symptoms in addition to visual loss should be
evaluated by a neurologist for multiple sclerosis. Sixty to eighty percent of females with optic neuritis, and a lower
percentage of males, eventually develop clinically diagnosable multiple sclerosis in their lifetimes (Box 4-7). The
diagnosis of multiple sclerosis requires symptoms or signs of at least two lesions separated in space (anatomic location)
or time. Among patients with a definitive diagnosis of multiple sclerosis, virtually all can be shown to have optic nerve
dysfunction (for example with VEP), but only one half of these patients have had a symptomatic event.
Variations
Optic neuritis can occur in response to a viral illness or immunization, or may be "idiopathic," with a presentation
and course identical to the optic neuritis associated with multiple sclerosis but without ever manifesting systemic
symptoms.
Children may present with bilateral optic disc edema and visual loss, presumably from a postinfectious optic
neuritis or meningoencephalitis. These cases are not generally associated with a risk of development of multiple
sclerosis. Symptomatic bilateral optic neuritis in **s is unusual, although the optic neuritis treatment trial
demonstrated minimal visual field defects in the asymptomatic eye of many patients with optic neuritis. Devic's disease
is a variant of multiple sclerosis consisting of bilateral optic neuritis with lower extremity weakness and paresthesia
from upper spinal cord demyelination usually occurring in children and young **s (see Fig. 1-1).
PAPILLEDEMA
The term papilledema means swelling of the papilla (optic disc). However, the term is generally reserved to
describe bilateral optic disc edema that results from elevated intracranial pressure.
MECHANISM OF PAPILLEDEMA
Cerebrospinal fluid (CSF) is produced by the choroid plexus in the lateral ventricles, flowing through the midline
third ventricle and cerebral aqueduct to the fourth ventricle. From the fourth ventricle, CSF flows through the foramina
of Magendie and Luschka into the subarachnoid space surrounding the brain and spinal column, as well as into the
orbital extension of the subarachnoid space bounded by the optic nerve sheath. CSF is absorbed by the arachnoid
granulations into the adjacent superior sagittal sinus.
High CSF pressure in the brain is conveyed through the optic c** into the space bounded by the optic nerve
sheath in the orbit, increasing tissue pressure within the optic head, inducing stasis of axoplasmic flow. Axoplasmic
stasis causes swelling of prelaminar axons, resulting in optic disc swelling. Secondarily, compression of the venous
structures within the nerve head leads venous engorgement and capillary dilation with hemorrhage. Trabeculations
exist between the optic nerve sheath and pia of the optic nerve, and vary between individuals in their impedance to
transmission of CSF between the brain and the orbit. Variation in sheath anatomy may account for the marked
asymmetry or unilaterality of optic disc edema, or (rarely) the absence of disc edema in patients with intracranial
hypertension.
Elevation of the superior sagittal sinus venous pressure (venous sinus thrombus, dural AVMs, right heart failure,
radical neck dissection) reduces CSF absorption and may cause intracranial hypertension. Damage or malfunction of
the arachnoid granulations (meningitis, subarachnoid hemorrhage, toxins or drugs) or obstruction of ventricular outflow
(aqueductal stenosis, tumor) can also raise CSF pressure (Table 4-2). Expanding brain tumors are obviously one of the
more worrisome causes of papilledema.
Although many of the causes of intracranial hypertension are evident on neuroimaging, a significant group of
patients have normal neuroimaging (Box 4-8). Idiopathic intracranial hypertension (pseudotumor cerebri) refers to a
group of predominantly obese females with elevated intracranial pressure and papilledema without an obvious cause.
IDIOPATHIC I***ACRANIAL HYPERTENSION (PSEUDOTUMOR CEREBRI)
Idiopathic intracranial hypertension (IIH) is a condition of unknown cause that produces elevated intracranial
pressure and papilledema, primarily in obese females between puberty and menopause. Neuroimaging is essentially
normal, without tumor or identifiable obstruction of the ventricular system (Box 4-9). The female-to-male ratio of
patients with IIH is about 8 to 1. Obesity is present in more than 90% of females with this disorder (Fig. 4-10).
The terminology surrounding this condition is somewhat confusing and imprecise. This clinical disorder is often
called pseudotumor cerebri, but this term technically includes any condition other than tumor that causes intracranial
hypertension. Use of the termbenign intracranial hypertension (BIH) raised objections because the condition can
occasionally have severe visual consequences. The designation idiopathic intracranial hypertension seems to clearly
define the clinical group discussed here, but in some cases a potential cause can be implicated with reasonable certainly
and the disease may not qualify as truly idiopathic (see Box 4-8). The best suggestion is to use the term IIH for the
idiopathic condition discussed in this section, unless an identifiable cause can be named to complete the designation,
such as "intracranial hypertension secondary to vitamin A toxicity."
Symptoms
The most common symptom associated with IIH is headache, although in some cases it can be conspicuously
absent. Often, patients note that the headache is more painful with bending over or with coughing. Another frequent
finding is pulsatile tinnitus, often described as "hearing a swishing heartbeat" in one or both ears. Patients describe brief
episodes of unilateral or bilateral visual loss with postural changes, typically lasting seconds, calledtransient visual
obscurations. The phenomenon is most likely related to deficient maintenance of perfusion of the swollen optic nerve
head with even slight changes in blood pressure. Permanent visual loss may occur if the optic disc swelling becomes
chronic. Marked engorgement of the optic nerve sheath can also flatten the posterior aspect of the globe. This condition
can produce blurred vision as the result of macular choroidal folds or can create a hyperopic shift in the patient's
refraction by shortening the axial length of the eye. Transient or lasting horizontal diplopia may occur from associated
sixth cranial nerve dysfunction.
Important concerns in the patient's history include medications taken over the previous year, weight gain or loss,
head trauma, symptoms of sleep apnea, and any previous intracranial or head/neck surgery. Vitamin A consumption by
tablet or diet (liver, fad diets) should be assessed. Menstrual irregularities are common in females in this age group, so
their reported association with IIH is tenuous at best.
Signs
The appearance of optic disc swelling may be variable. The classic appearance is a diffuse, uniform elevation of
the optic disc that gives it a "champagne cork" appearance. Nerve fiber layer hemorrhages and deep pe**apillary
retinal hemorrhages are common (Fig. 4-10,A). The optic disc edema is often asymmetric between the two eyes, and
occasionally is unilateral. Not infrequently, distinguishing anomalous optic discs from true edema may be difficult (see
Box 4-2). Patients with optic disc edema reportedly lack the normal pulsations of the central retinal vein at the optic
disc. However, at least one third of normal discs lack pulsations, so their absence is a "soft" sign at best.
Visual function is relatively normal with early disc swelling. Expansion of the optic disc and the resulting lateral
and upward displacement of the pe**apillary retina produce both relative and absolute enlargement of the blind spot on
formal perimetry. Over time, chronic disc swelling and ischemic damage causes axonal death and optic atrophy,
producing visual field defects. Nasal steps are the most common defect seen initially (Fig. 4-10, B), with concentric
depression of the entire visual field in advanced stages. Central vision is rarely affected until late in the course (or with
acute fulminant disc swelling); thus visual acuity alone is of little help in assessing the disease's progress. Rarely,
central vision can be affected by an associated pe**apillary choroidal neovascular membrane and subretinal
hemorrhage, choroidal folds, or macular edema.
Elevated intracranial pressure does not seem to damage intracranial structures, and neurologic deficits apart from
visual loss should raise suspicion of some other disorder. The single exception to this rule is sixth cranial nerve paresis.
Presumably, changes in intracranial pressure (and the brain's position in the cranium) may stretch and injure the sixth
cranial nerves, given their firm attachment to the brainstem and to the skull base.
Causes
In IIH, there is no overt structural obstruction to the circulation of CSF. Convincing studies have shown that the
problem lies in defective reabsorption of CSF at the level of the arachnoid granulations. The association of this
condition with certain medications is consistent with this idea because toxins could potentially interfere with the active
transport mechanisms required for CSF absorption by the arachnoid granulations (see Box 4-8).
The role of obesity in this disorder is unclear, but it seems to be a causative factor because IIH often resolves with
weight loss alone. Many investigators have suspected a hormonal mechanism related to lipid metabolism. IIH may be
associated with sleep apnea, a disorder that is also more common in obese patients.
Differential diagnosis and evaluation
The differential diagnosis of bilateral disc elevation is found in Fig. 4-3. The most important entities to address in
the differential diagnosis of papilledema include brain tumors, obstruction of the ventricular system, or dural-sinus
thrombosis. For this reason, neuroimaging should be performed immediately. Although a CT scan is capable of ruling
out an intracranial mass, an MRI with contrast is superior to CT in imaging venous-sinus thrombosis, arteriovenous
malformations, and infiltrating tumors (Fig. 4-11). Blood pressure should be measured (with appropriate-sized cuffs)
on all patients because malignant hypertension may present with bilateral disc edema (Fig. 4-12). In addition, patients
with intracranial hypertension and systemic hypertension may have a poorer visual prognosis. Abrupt lowering of
blood pressure in either circumstance (IIH or malignant hypertension) may precipitate acute, severe, permanent visual
loss.
Truly idiopathic intracranial hypertension is uncommon in males. Some males with this initial diagnosis have
been discovered to harbor occult dural arteriovenous malformations, have sleep apnea, or have other identifiable causes
of papilledema.
Baseline automated perimetry (such as Humphrey 30-2 or 24-2) and optic disc photographs should be performed
because these parameters are the most reliable indicators of disease progression and treatment effectiveness.
A lumbar puncture must be performed to make the diagnosis of IIH, even when the clinical presentation is
classic. In addition to documenting the opening pressure, CSF can be examined for evidence of hemorrhage, infection,
or neoplasm. The opening pressure is measured in the lateral decubitus position with legs and head in a relaxed
position. Opening pressures greater than 250 mm confirm the presence of intracranial hypertension; pressures between
200 to 250 mm are suggestive but less certain. Only rarely are additional lumbar punctures of any utility. This
procedure is not an effective form of treatment because the CSF volume is quickly regenerated. Lumbar puncture is
also not a reliable way of monitoring the effectiveness of medical treatment because CSF pressure has marked hour to
hour fluctuations.
Diagnosis and treatment of this disorder are best performed when an ophthalmologist and neurologist work
together. The ophthalmologist follows the important indicators of disease and the potential for lasting morbidity--the
visual fields and disc appearance. The neurologist's role is to confirm the diagnosis with a neurologic examination and
lumbar puncture, and to help in the medical management of headache.
Treatment
Treatment alternatives include observation, diet, medication, and surgery. Patients without significant visual field
defects may not require medical or surgical treatment, especially if a suspected precipitating cause has been eliminated,
such as vitamin A or antibiotics, patients recovering from meningitis or head trauma, or obese patients in a successful
weight loss program.
Acetazolamide (Diamox) reduces intracranial pressure by decreasing CSF production. This drug is generally
effective when given in doses of 500 mg twice a day, often with convincing improvement in 3 to 4 weeks (see Fig. 4-
10). Side effects include paresthesias of extremities and face, dysgeusia (especially with carbonated beverages), and
dyspepsia. Fortunately, serious side effects, including anaphylaxis, aplastic anemia, and Stevens-Johnson syndrome, are
extremely rare. Furosemide (Lasix) is less effective in the treatment of this disorder. Steroids may be helpful, but the
inevitable weight gain associated with steroid use is counterproductive. Short-term, high-dose intravenous steroids may
be useful in fulminant cases.
An optic nerve sheath fenestration or neurosurgical shunting procedure (ventriculoperitoneal or lumboperitoneal
shunt) may be required for patients with progressive visual field loss despite medical therapy. Optic nerve sheath
fenestration effectively reduces the transmitted CSF pressure at the optic disc by opening the sheath, thereby allowing
CSF to be diverted into the intraconal tissues for absorption. Optic disc edema is reliably reversed by this procedure,
but its long-term effectiveness is uncertain. The CSF pressure (as measured by lumbar puncture or intracranial monitor)
is not affected by optic nerve sheath fenestration, but clinicians have reported improvement in patients' headaches and
in the appearance of the contralateral disc in some patients. However, patients with severe headaches that are
unresponsive to vigorous medical treatment may benefit most from a neurosurgical shunt.
Clinical course
Frequent, formal visual field tests are required to follow the course of a patient with chronic papilledema because
visual acuity may remain 20/20 despite severe pe**heral visual field loss. Serial observations of the optic discs and
perimetry are required regardless of the treatment because treatment failures may occur at any time. Shunt failure may
occur without causing headache and may produce insidious pe**heral visual loss that may go unnoticed until visual
loss is severe and damage to the optic disc is irreversible.
The majority of patients respond well to Diamox, with resolution of optic disc edema over 3 to 6 months. When
the optic disc edema is gone, a trial period off Diamox with careful observation is reasonable, especially if the patient
has been successful with weight loss. Some patients never have a recurrence, while in others the condition is a chronic,
lifelong problem.
OTHER CAUSES OF PAPILLEDEMA
Because many of the signs and symptoms of elevated intracranial pressure involve the eyes, the ophthalmologist
is often the first physician to encounter patients with intracranial tumors, dural-sinus thrombosis, and other neurologic
or neurosurgical conditions. Many of these conditions are diagnosed when the ophthalmologist investigates
papilledema with neuroimaging. Obviously, prompt referral to the appropriate specialist is the most important course of
action. However, the ophthalmologist still has an important role in the multidisciplinary management of such patients
because his or her serial observations of optic disc appearance and visual fields often determine the therapeutic course.
COMPRESSIVE OPTIC NEUROPATHIES
Mechanical compression of the optic nerve can cause axonal death or demyelination without permanent axonal
injury. Ischemia also plays a major role in the pathogenesis of compressive neuropathies because tumors can disrupt
local perfusion by mechanical pressure or "steal" the blood supply. Unlike other cranial nerves, optic nerve axons do
not regenerate after a lethal injury. However, successful reversal of optic nerve (or chiasmal) compression can result in
significant improvement in visual field defects, presumably from recovery of demyelinated and partially injured axons.
Prompt diagnosis is therefore important, as early intervention may offer the best chance for visual recovery.
OPTIC NERVE SHEATH MENINGIOMA
Optic nerve sheath meningiomas are a cause of unilateral progressive visual loss, most common in females
(female-to-male ratio of 3 to 1) in their fourth decade of life (Fig. 4-13). Meningiomas of the optic nerve sheath
represent 5% of all orbital tumors and 1% of all meningiomas (most are intracranial).
Symptoms and signs
Patients describe an insidious, painless loss of vision in one eye. Any type of optic-nerve-related visual field
defect can occur. A classic pattern seen with Goldmann perimetry is a central scotoma that gradually connects (or
"breaks out") to the pe**hery. Proptosis may develop, depending on the bulk and location of the meningioma. Diplopia
can occur if the tumor restricts free movement of the globe. Rarely, gaze-dependent amaurosis can occur as
compression of the optic nerve or its vascular supply is induced with eccentric gaze.
The classic triad of findings with optic nerve sheath meningiomas includes (1) disc pallor, (2) optic disc collateral
vessels, and (3) progressive visual loss; however, not all of these elements are invariably present. The optic nerve may
be pale or edematous, depending on the location and duration of the lesion. Retinociliary venous vascular collaterals
("optociliary shunts") on the optic disc occur in response to obstruction of central retinal venous outflow.
Neuroimaging may show thickening of the nerve/nerve sheath complex. CT imaging of the orbits often shows
enhancement of the sheath, which spares the nerve itself, appearing as a "railroad track" on axial images and as a "bull's
eye" on coronal views.
Causes
Optic nerve sheath meningiomas arise from the meningeal components of the optic nerve sheath in the orbits.
Similar to intracranial meningiomas, the tumor rarely metastasizes but causes local injury by compression of adjacent
structures. In the orbit, the tumor tends to encircle the optic nerve, causing injury by myelin displacement, axonal
disruption, or compromise of the optic nerve's blood supply. Some meningiomas have hormone receptors, with
potentially massive growth when exposed to exogenous hormones or the high levels of progesterone and estrogen
produced during pregnancy.
Variations
Optic nerve sheath meningiomas may extend into the optic c** or may originate from the dura within the optic
c**. The confines of the c** may allow a small meningioma to cause marked compression of the optic nerve that
may be difficult to visualize on neuroimaging. Meningiomas arising from the orbital sheath often extend through the
optic c** and into the intracranial cavity. Meningiomas can also arise from the intracranial dura, compressing the
intracranial optic nerve or the chiasm. Sphenoid wing meningiomas commonly have intraorbital and intracranial
components. These tumors can also extend laterally, producing a characteristic "filling in" of the temporal fossa that
can be palpated on examination.
Unlike **s, meningiomas in children tend to be aggressive and often result in death.
Differential diagnosis and evaluation
The triad of pallor, optic disc shunt vessels, and progressive visual loss can also be present with sarcoidosis or
optic nerve glioma. Optic nerve sheath meningiomas can also produce a disc appearance similar to retinal vein
occlusions; vein occlusions can produce shunt vessels similar to those seen with optic nerve sheath meningiomas,
meningiomas can secondarily produce an element of venous stasis, and both conditions may cause disc edema. The
optic disc edema and visual field loss from optic nerve sheath meningioma may initially look similar to ischemic optic
neuropathy or optic neuritis, but a slow, relentless decline in vision is highly suggestive of a compressive optic
neuropathy (Fig. 4-13, F).
Neuroimaging is required when a compressive optic neuropathy is suspected, either with an MRI of the brain and
orbits (with contrast and orbital fat suppression) or CT imaging of the brain and orbits with contrast (including true
coronal orbital cuts). Sometimes, the enlarged appearance of the nerve may be difficult to distinguish from optic nerve
glioma or inflammatory conditions such as sarcoidosis or optic neuritis. Performing both MRI and CT may narrow the
diagnosis and aid in assessing the intracranial extent of growth. In some cases, biopsy of the mass is required to make a
diagnosis and plan treatment. Meningioma biopsies should be **yzed for estrogen and progesterone receptors.
Treatment
Excision of an optic nerve sheath meningioma invariably st**s the vascular supply of the optic nerve, resulting in
blindness. Thus patients with useful vision are generally not candidates for surgical excision. Surgical excision of an
optic nerve sheath meningioma is usually only considered when the tumor is confined to the orbit and the eye is blind.
The decision to excise a tumor when intracranial extension is present is complex and depends on (1) whether the
contralateral optic nerve or chiasm is threatened; (2) the size, location, and growth of the tumor; and (3) remaining
sight in the affected eye. Radiation therapy for optic nerve sheath meningiomas is currently emerging as a viable
treatment option.
The effectiveness of medical treatment generally depends on the hormonal responsiveness of the tumor.
Tamoxifen, an estrogenic competitive inhibitor, and mifepristone (RU486), an antiprogesterone agent, may slow the
growth of selected receptor-positive meningiomas. Steroids have only a short-term effect.
Observation may be the only reasonable initial "treatment." Although biopsy may confirm the diagnosis,
histologic appearance does not correlate well with biologic behavior. The natural history of optic nerve sheath
meningiomas is highly variable; they may remain static for many years or they can progress relatively rapidly. Careful
monitoring of optic nerve function in patients with optic nerve sheath meningioma is vital because it provides a guide
for management. Tumor progression is evaluated by monitoring visual fields, visual acuity, contrast sensitivity, color
vision, and RAPD, as well as repeat neuroimaging.
ORBITAL DISORDERS
Orbital Graves' disease can cause compression of the optic nerve by marked enlargement of the extraocular
muscles. The manifestations of Graves' disease are discussed in detail in Chapter 8. However, a compressive optic
neuropathy can occur even in the absence of the external signs of Graves' disease (see Fig. 8-4).
Space-occupying lesions in the orbits, such as capillary hemangiomas, orbital varices, mucoceles, metastatic
tumors, fibrous dysplasia, or infectious cysts, can also present as compressive optic neuropathies.
I***INSIC NEOPLASMS
OPTIC NERVE GLIOMA
Optic nerve gliomas occur primarily in children; 75% of patients present before age 20 (Fig. 4-14). Decreased
vision may be the presenting complaint, but strabismus and nystagmus resulting from poor vision may often be noted
first by the child's family. Proptosis can occur, depending on the extent and bulk of orbital involvement.
About one half of optic nerve gliomas arise in the orbital portion of the optic nerve, with the remainder arising
intracranially. Fifty percent of patients with optic nerve gliomas have neurofibromatosis type I. Fifteen percent of
patients with neurofibromatosis type I harbor an optic nerve glioma.
Pathologically, the tumor is a pilocytic astrocytoma (juvenile type), with a benign cytologic appearance. In
children, the tumor enlarges slowly or may appear inactive. Gliomas of the anterior visual pathway that arise in
**hood behave differently, exhibiting malignant behavior and rapidly leading to blindness and death (Fig. 4-15).
Neuroimaging of childhood gliomas typically reveals a fusiform swelling of the optic nerve and/or chiasm.
Involvement of the chiasm may be associated with endocrine dysfunction and hypothalamic involvement, necessitating
an endocrine evaluation in all children with optic nerve or chiasmal glioma. As previously discussed, a pediatric
evaluation for systemic signs of neurofibromatosis is also required.
Treatment is controversial, but most clinicians favor a conservative "watch and wait" approach given the usual
static course in children. Surgical resection may be considered in patients with a blind eye and disfiguring proptosis or
isolated orbital involvement. Indications and effectiveness of radiation treatment or chemotherapy are uncertain.
LYMPHOPROLIFERATIVE DISORDERS
Neoplastic involvement of the optic nerve may present with grotesque infiltration and elevation of the optic nerve
head, or as an initially normal-appearing disc that gradually turns pale from a retrobulbar process. Acute leukemic
infiltrative optic neuropathy is a true oncologic emergency because prompt radiation treatment may be sight-saving
(Fig. 4-16). Infiltrative optic neuropathies should be considered in patients with visual loss and a known
lymphoproliferative disorder, patients who are systemically ill, or those whose history and examination do not fit the
patterns of common optic neuropathies. Infectious (such as tuberculosis) and inflammatory (sarcoidosis) entities may
be infiltrative in nature and should be considered in the differential diagnosis (Box 4-10). In addition, patients whose
optic neuropathy improves with steroids only to worsen when steroids are stopped ("steroid-dependent" neuropathy)
may have an infiltrative optic neuropathy (see Box 4-6). MRI of brain and orbits with contrast may show optic nerve
enhancement or other intracranial foci.
INFLAMMATORY OPTIC NEUROPATHIES
Inflammation of the optic nerve can be caused by many processes. Primary idiopathic inflammatory optic
neuropathies include sarcoidosis (Box 4-11) and orbital inflammatory pseudotumor (discussed in Chapter 8).
Inflammation accompanies infectious, neoplastic, autoimmune, and other optic neuropathies, making it difficult to
categorize the primary disease process (Box 4-10).
INFECTIOUS OPTIC NEUROPATHIES
OPTIC DISC EDEMA WITH A MACULAR STAR
Optic disc edema with a macular star (ODEMS) is a desc**tive term that includes several different disease
processes, characterized by the presence of optic disc edema and macular edema. The termneuroretinitis is often used
interchangeably with ODEMS, but neuroretinitis has come to specifically imply an infectious cause.
Noninfectious entities that often produce coexistent disc and macular edema include hypertensive retinopathy,
and postoperative cystoid macular edema (Irvine-Gass syndrome). Hypertensive retinopathy is invariably bilateral with
other retinal signs (see Fig. 4-12), and cystoid macular edema does not usually develop a "star." Exudative lesions in
the retinal pe**hery (Coats' disease, capillary hemangiomas) can cause macular stars, but the disc is usually unaffected.
Diabetic maculopathy, occasionally accompanied by diabetic papillopathy or optic disc neovascularization, tends to
produce circinate edema residues and is not likely to be confused with this entity. Macroaneurysms of retinal vessels
near the disc can cause macular exudates and optic disc edema. Optic disc edema from any cause, when extreme, may
be associated with macular edema and a "star." This observation suggests that all causes of disc edema may need to be
considered in the differential diagnosis of ODEMS when the degree of optic disc swelling is extreme.
The precise pathophysiology of infectious neuroretinitis is not known, but it likely involves an exudative process
in the vessels of the disc and macula triggered by the infectious agent or the subsequent immune response to the agent.
The availability of sensitive serologic tests for the etiologic agent in cat-scratch disease (Bartonella henselae)
demonstrates that this organism is a common cause of neuroretinitis. Other organisms that can cause neuroretinitis
includeToxoplasma gondii, syphilis, Lyme disease, and viral entities. A bilateral, recurrent, idiopathic neuroretinitis
with a poor visual outcome has been described (Purvin, 1994).
CAT-SCRATCH NEURORETINITIS
Patients with neuroretinitis from cat-scratch disease (CSD) are typically young people or children who develop a
febrile illness several weeks after exposure to a kitten (Fig. 4-17). The disease is transmitted by a scratch from an
infected cat, or may be transmitted by fleas from the cat to the human.
Symptoms
The systemic symptoms include fever, malaise, and general adenopathy that usually resolve after 1 or 2 weeks.
Only a small percentage of patients with CSD develop neuroretinitis and visual loss. Visual symptoms usually begin 2
to 3 weeks after the systemic symptoms have subsided. Many patients do not recall an antecedent systemic illness. The
examiner should question the patient specifically about fever, malaise, cough, adenopathy, exposure to cats and kittens,
as well as known or potential sexually transmitted diseases when appropriate.
The time course of visual loss is similar to optic neuritis, as it may progress over several days and tends to
improve over several months. Pain with eye movement can occur but not nearly as frequently as with optic neuritis.
Signs
Central and cecocentral scotomas are the most common visual field defect. The visual deficit generally cannot be
accounted for by the maculopathy alone, suggesting optic nerve dysfunction as well. As with optic neuritis, color vision
defects and the presence of an RAPD are present.
The optic disc shows mild to moderate diffuse edema, frequently with a focal elevation of the optic disc that has
the appearance of an optic disc granuloma. The optic disc edema is accompanied by white edema residues in the inner
macula that line up radially in Henle's layer, forming a star. Acutely, the macular edema may be subtle and the patient
may be thought to have optic neuritis. Usually, within a week or so of the onset of visual symptoms, the characteristic
edema residues in the macula appear. The radial star pattern may completely encircle the fovea or may be limited to
only one sector. A few vitreous cells may be present. Deep, white, choroidal patches are occasionally seen in the retinal
pe**hery, even in the fellow asymptomatic eye (Fig. 4-17, C).
Evaluation
Patients with a classic history and examination may not require an extensive evaluation. All patients should have
blood pressure measured because macular stars can occur in hypertensive retinopathy. Laboratory studies that may be
helpful include a complete blood count with differential, toxoplasmosis titer, and syphilis and Lyme disease serologies.
A positive serologic titer (IFA) for Bartonella henselae is specific and thus may be helpful in confirming the suspected
cause. However, a negative titer does not exclude CSD.
Treatment
The visual prognosis for CSD neuroretinitis is good, with most patients experiencing a significant recovery
regardless of treatment. This natural history of recovery makes it difficult to assess the efficacy of treatment. Many
clinicians treat CSD neuroretinitis with a course of ciprofloxacin, doxycycline, or other antibiotics.
OTHER INFECTIOUS NEUROPATHIES
Infectious agents can affect the optic nerve (1) by direct infiltration of the optic nerve by the organism, (2) by
inciting a local inflammatory response or autoimmune attack on the optic nerve, (3) by local mass effect from an
infectious focus, or (4) by compromise of the vascular supply by vasospasm or vascular occlusion from the products of
an inflammatory response. Many agents have been implicated (see Box 4-10), but syphilis can affect the visual
pathway in so many varied ways that it should be included in the differential in most forms of optic neuropathy.
TOXIC AND NUTRITIONAL OPTIC NEUROPATHIES
Slow, bilateral, and symmetric loss of central vision is characteristic of toxic and nutritional optic neuropathies.
Toxins and nutritional deficiencies are usually grouped together for two reasons: (1) in many cases, they are both
present as co-conspirators causing an optic neuropathy, and (2) toxins and nutritional deficiencies produce clinical
findings that are essentially identical.
Visual fields reveal bilateral cecocentral scotomas (Fig. 4-18). The optic discs may appear normal but frequently
show temporal pallor. Careful observation may reveal nerve fiber layer dropout in the papillomacular bundle. Common
causes discussed in the following paragraphs include alcoholism, ethambutol toxicity, and vitamin B12 deficiency.
Additional causes are listed in Box 4-12.
Alcoholism is a common cause of toxic/nutritional optic neuropathy. The nutritional deficiencies that inevitably
accompany alcoholism may be the most damaging factor, but a toxic effect of alcohol and its byproducts may also play
a role. Most patients demonstrate remarkable improvement with vitamin supplementation, particularly with folate and
thiamine. Referral to a substance abuse specialist is needed to prevent the cycle of alcohol abuse and nutritional
deprivation from repeating. The combination of alcoholism and cigarette smoking may have synergetic optic nerve
toxicity ("tobacco-alcohol amblyopia").
Ethambutol is commonly used to treat tuberculosis and atypical mycobacterial infections. Toxicity to the optic
nerve may occur at a previously tolerated dose when other toxic agents are added to a patient's regimen or when weight
loss from the chronic infection increases the dose per kilogram of body weight. Stopping the medication usually allows
slow improvement of the patient's vision, often taking several months.
Pernicious anemia from malabsorption of vitamin B12 may be difficult to diagnose because the optic neuropathy
may occur before a significant anemia and macrocytosis develop. Testing for urinary methylmalonic acid or performing
the Schilling's test aids in the diagnosis.
HEREDITARY OPTIC NEUROPATHIES
The designation of hereditary optic neuropathy describes many different genetic abnormalities that are
transmitted in a variety of inheritance patterns. Autosomal recessive inheritance is associated with severe visual loss
from infancy. Dominant inheritance patterns characteristically have milder disease with delayed onset, which may be
difficult to distinguish from toxic/nutritional neuropathies. Optic atrophy may also occur with heritable
neurodegenerative disorders associated with spinocerebellar disorders, deafness, ataxia, and motor and sensory
neuropathies.
KJER'S DOMINANT OPTIC NEUROPATHY
This dominantly inherited disorder causes a bilateral, symmetric, slowly progressive central or cecocentral visual
field loss (Fig. 4-19). Visual abnormalities usually begin in childhood, between the ages of 4 to 10, and may progress
into the early teens. By the midteens, the vision stabilizes, typically with a visual acuity around 20/100. Classically, the
Farnsworth-Munsell 100 hue test demonstrates a tritanopic axis. The inheritance pattern may not be obvious in the
family history, as incomplete penetrance is common. Although many patients are aware that their vision has been
subnormal their entire life, some patients are not symptomatic until **hood. The family history should be explored in
detail by constructing a family tree if possible, identifying known or potentially affected individuals. The optic discs
typically display temporal pallor but may appear relatively normal. Nerve fiber layer defects in the papillomacular
bundle may be evident.
LEBER'S HEREDITARY OPTIC NEUROPATHY
Leber's hereditary optic neuropathy (LHON) is a heritable disorder that tends to affect males in their second and
third decades of life (Fig. 4-20). This genetic defect is peculiar because it manifests as acute visual loss in one eye,
typically followed by a similar event in the fellow eye within weeks. The precipitating factors are unknown, but in
some cases, alcohol or tobacco abuse or a nutritional deficiency is suspected. The visual field defect is usually a central
or cecocentral scotoma that may continue to worsen over several months. The effect on the visual acuity ranges from
mild to profound. Some patients have an inexplicable spontaneous recovery years later.
The optic disc may be mildly hyperemic with swelling of the pe**apillary nerve fiber layer or may appear
normal. Pe**apillary telangiectatic dilation of small retinal capillaries is the classic finding, but it is difficult to identify
unless specifically sought. These vessels do not leak on intravenous fluorescein angiography and may be best seen in
an unaffected eye. Disc pallor develops shortly after visual loss, with loss of the pe**apillary vascular changes.
The genetic abnormality responsible for LHON is in themitochondrial DNA. Although most genetic ***rmation
is contained in the nuclear DNA (chromosomes), small strands of circular DNA in the mitochondria code for certain
crucial components involved in energy metabolism. The list of disorders thought to be related to abnormalities in
mitochondrial DNA is growing. At least three genetic defects in mitochondrial DNA have been conclusively linked to
LHON. These disorders are designated by the position of the point mutations in well-conserved regions of the
mitochondrial DNA sequence: 11778 (also called the "Wallace mutation"), 14484, and 3460.
The inheritance pattern of mitochondrial genetic disorders is unique. At conception, the mitochondrial DNA in
the sperm is excluded from the fertilized egg. The offspring receives mitochondrial DNA exclusively from the mother.
Thus the genetic defect in LHON is passed from a female carrier to both male and female offspring. All daughters are
carriers and can occasionally manifest the disease. All sons have the genetic defect and frequently manifest the disease
but do not pass the defect to their children. The disorder is therefore exclusively maternally inherited but manifests
mostly in male offspring.
Many patients with LHON are initially thought to have optic neuritis because the clinical presentation may be
similar. However, pain with eye movement (a common finding in optic neuritis) is absent in LHON. The diagnosis can
be made by identifying the specific genetic mutations from a blood specimen, but this molecular genetic evaluation
generally takes weeks to perform. Unless the case is absolutely classic with an established family history, most patients
have neuroimaging and laboratory studies to evaluate for other potential causes of visual loss. Once the mutation has
been identified, genetic counseling for the patient and family is indicated. Because of a potential association with
cardiac conduction abnormalities, an electrocardiogram should be obtained in patients with LHON. Also, patients at
risk for LHON should be advised not to use tobacco and to limit alcohol intake, as environmental factors may play a
role in triggering visual loss. No proven effective treatment is available, but many clinicians recommend dietary
supplementation with vitamins and co-enzymes.
TRAUMATIC OPTIC NEUROPATHY
Trauma to the optic nerve can be produced directly or indirectly. Examples of direct trauma include the impact of
a BB shot on the intraorbital nerve, injury from a needle during retrobulbar injection, or impalement of the nerve by a
bone fragment from a fracture of the optic c** (Fig. 4-21).Indirect trauma frequently occurs with blunt trauma
involving the orbital rim or forehead, with the conical shape of the bony orbit transmitting forces to the apex and optic
c**, causing a contusion of the optic nerve even in the absence of a fracture involving the optic c** (Fig. 4-22).
Symptoms
Visual loss is often immediate at the time of trauma and does not change over time. An important subgroup of
patients may have a "lucid interval," followed hours or days later by a precipitous drop in vision caused by expanding
optic nerve edema or hemorrhage.
Signs
Traumatic optic neuropathy may initially present with a normal-appearing optic disc. Optic disc pallor, and
occasionally cupping (in young patients), becomes evident over several weeks or months.
Optic nerve trauma only occasionally appears as an isolated finding. The potential for coincident trauma
involving the adnexa, orbit, and globe, as well as head and body trauma, must be actively addressed.
Causes
The mechanism of direct trauma is no mystery. Axons and their support tissue are damaged by shearing,
compression, contusion, or accompanying interruption of their vascular supply. Indirect trauma can be just as severe,
with contusion of the optic nerve from shock waves transmitted by the orbital bones to the orbital apex and optic c**.
Additional damage to the optic nerve may be caused by optic nerve edema within the confines of the bony optic c**.
A compartment syndrome may develop with ischemia to the optic nerve, causing even further edema and compression.
This cycle of edema and ischemia is most likely the mechanism in patients whose visual loss is delayed for hours or
days following trauma.
Differential diagnosis
In most cases, the presentation of traumatic optic neuropathy is self-evident, with history, examination, and other
manifestations of trauma leaving little doubt. Occasionally, patients may present with a pale optic nerve and an
uncertain history; these patients require neuroimaging. Progressive visual loss with optic nerve pallor is not consistent
with traumatic optic neuropathy and suggests a compressive optic neuropathy.
Evaluation
Because a search for skull and orbital fractures is indicated in most cases, a CT scan of the brain and orbits is
more appropriate than MRI as an initial study. True coronal slices provide the most ***rmation, but the flexion or
extension of the neck may be impractical and require clearance of the cervical vertebrae first. Evaluation of optic nerve
injury is also complicated by the fact that these patients frequently have "higher priority" traumatic injuries that may be
life-threatening.
Treatment
Debate regarding the treatment of traumatic optic neuropathy is ongoing. Theoretically, the use of high dose
steroids in the acute setting seems reasonable, but to date there is no convincing evidence that this treatment is
effective. Surgical decompression of the optic c**, either neurosurgically or with an ethmoid sinus approach, has also
been offered as a treatment of traumatic optic neuropathy. The efficacy of this procedure is unproven, and the potential
for surgical morbidity must be considered. Stable, metallic foreign bodies in the orbit may not require removal. Surgery
to relieve fracture fragments compressing or impinging on the optic nerve is controversial.
Clinical course
Sequential evaluation of visual function is crucial in the immediate posttrauma period. After this period, visual
function is expected to be unchanging, and documenting this visual stability with perimetry several months after the
event is useful.
GLAUCOMA
Primary open-angle glaucoma is the most common disorder causing an optic neuropathy (Fig. 4-23). Because an
entire volume in this series is devoted to this disorder, this discussion is limited to aspects of interest to neuroophthalmology.
Patients with primary open-angle glaucoma typically have elevated intraocular pressures, gradual enlargement of
the optic cup, and pe**heral visual field defects. However, the intraocular pressure does not always correlate with
progressive visual field loss, and visual loss may occur even in patients with normal pressures. Atrophy of axons causes
enlargement of the optic cup, predominantly with loss of neuroretinal tissue at the superior and inferior aspects of the
cup, resulting in vertical elongation of the cup that "notches" the neuroretinal rim. Glaucoma does not typically cause
pallor of the neuroretinal rim. Patients with cupping and rim pallor likely have another underlying diagnosis and require
further investigation.
Visual field loss from glaucoma usually correlates relatively well with the degree and location of optic disc
cupping. The pattern of visual field loss is remarkably similar to chronic optic disc edema, with preservation of central
vision until late in its course. New visual field changes may be heralded by characteristic flame-shaped hemorrhages at
the disc margin.
Occasionally, other optic neuropathies are misdiagnosed as glaucoma. Visual field defects that do not correlate
with optic disc cupping, the presence of pallor of the neuroretinal rim, and early loss of central vision suggest a
diagnosis other than glaucoma. Patients with "normal pressure" (or low tension) glaucoma may require consideration of
other diagnostic possibilities, such as a compressive optic neuropathy or syphilitic optic atrophy.
ANOMALOUS OPTIC DISCS
OPTIC DISC DRUSEN
Optic disc drusen are mineralized hyalinelike crystals of unknown origin embedded in the substance of the
prelaminar optic nerve head (Fig. 4-24). Optic disc drusen are present in about 1% of Caucasians and are frequently
bilateral (75%). Optic disc drusen can be inherited as an autosomal-dominant trait with incomplete penetrance.
Microscopically, drusen appear as concentric layers of hyalinoid material, with positive staining for amino acids,
acid mucopolysaccharide, calcium, and hemosiderin, but not amyloid.
Symptoms
Optic disc drusen are frequently an incidental discovery during an eye examination. Occasionally, patients
present complaining of pe**heral visual loss. Rarely, patients may experience a relentless, progressive, stepwise
decline in pe**heral vision. Transient visual obscurations, similar to those seen in papilledema, may occur with disc
drusen.
Signs
In young patients, optic disc drusen may be buried within the disc and not visible with ophthalmoscopy (Fig. 4-
25). These discs are elevated, often with a "lumpy-bumpy" contour, and may simulate optic disc edema
(pseudopapilledema) (see Box 4-2). Over time, the drusen "emerge," perhaps because of atrophy of the overlying nerve
fibers. Disc drusen in older patients are usually evident with the ophthalmoscope, appearing as glistening, yellowish,
"rock candy" crystals poking through the nerve fibers of the disc. Pe**apillary choroidal neovascular membranes can
occur in association with disc drusen. Optic disc drusen may be associated with retinitis pigmentosa and angioid
streaks.
Optic-disc-related visual field defects, with corresponding loss of the retinal nerve fiber layer, may be present.
Curiously, central visual acuity is almost never affected. Profound pe**heral visual field loss with central sparing from
optic disc drusen is a potential cause of pe**heral constriction with preservation of central vision (see Table 3-3).
Causes
The precise mechanism of visual loss in patients with optic disc drusen is unknown, but it likely relates to the
typical crowded configuration of these patients' optic discs. Axonal atrophy may occur secondary to compression of
optic nerve axons, but the position and extent of disc drusen do not correlate well with the visual field defects. Some
patients present with an acute event, demonstrating true optic disc edema in addition to the presence of disc drusen,
implicating a drusen-related AION.
Differential diagnosis and evaluation
Buried disc drusen may give the appearance of optic disc edema ("pseudopapilledema"). On the other hand, the
tiny, glistening edema residues often accompany chronic optic disc edema and should not be mistaken for drusen (see
Box 4-2). Disc drusen not evident with the ophthalmoscope are best identified with orbital ultrasound, appearing as
focal, highly echoic densities (Fig. 4-24, C-D). The calcific component of the drusen also makes them highly visible on
computerized tomography images that include the optic nerve head (Fig. 4-25, B). Drusen exhibit autofluorescence,
demonstrated with the standard barrier and exciter filters of the fluorescein angiogram camera, without the need of
fluorescein. This property is more interesting than useful, however, because the drusen that can be seen with this
method are usually evident with the ophthalmoscope (Fig. 4-24, B).
Systemic hypotension may be a risk factor for visual loss. Patients with stepwise visual field loss and optic disc
drusen should be evaluated for orthostatic hypotension.
The discovery of optic disc drusen in a patient with elevated discs may save the patient from an extensive
evaluation for optic disc edema. However, the presence of drusen does not preclude other diseases; for example,
patients with optic disc drusen can also have true papilledema. The clinician should actively seek evidence of other
potential disorders and investigate any clues not consistent with disc drusen. Progressive visual loss requires an
extensive evaluation including neuroimaging to look for possible optic nerve compression.
Treatment
As previously discussed, the mechanisms of visual loss from optic disc drusen are not entirely understood. The
presence of systemic orthostatic hypotension in some patients with progressive visual field loss suggests that vascular
hypoperfusion may play a role. Rarely, a patient may need medical treatment for hypotension. Some clinicians suggest
topical agents to lower the intraocular pressure in an effort to improve the ocular perfusion gradient.
OTHER OPTIC DISC ANOMALIES
The term anomalous optic disc implies a congenital rather than acquired abnormal optic disc appearance. Disc
anomalies may be minor and may not affect optic nerve function (crowded, elevated, or tilted discs; or myelinated
retina nerve fibers), or may represent significant maldevelopment of the visual pathway (hypoplasia, aplasia, or
coloboma) (Fig. 4-26).
Crowded optic discs
Small discs that are "cupless" may be at risk for AION (see previous discussion) (Fig. 4-26, A).
Elevated discs without drusen
Some anomalous optic discs that appear elevated may not harbor disc drusen (Fig. 4-26, B). This optic disc
appearance typically occurs in young patients and is usually bilateral, mimicking papilledema. Concern is heightened
when drusen are not clinically identified. Some of these optic discs may eventually develop drusen. Box 4-2 lists some
characteristics to help distinguish true from pseudopapilledema.
Tilted optic discs
This anomaly results from an oblique insertion of the optic nerve on the globe and is a frequent finding in axial
myopia (Fig. 4-26,C). The nasal edge of the disc is elevated, and the temporal edge and adjacent retina are depressed
relative to the normal plane of the pe**apillary retina. These discs appear vertically elongated, with a crescent-shaped
white area temporally where the retinal pigment epithelium stops short of the disc edge. The depression of retina
temporal to the disc may cause a scotoma, occasionally simulating the bitemporal visual field defects of chiasmal
disorders (see Box 3-2).
Myelinated retinal nerve fibers
Myelination of the anterior visual pathway begins at the lateral geniculate body during gestation, proceeding
anteriorly and reaching the lamina cribrosa of the optic nerve head at about term. In less than 1% of the population,
myelination abnormally proceeds into the eye and retinal nerve fiber layer for a variable extent. This creates white,
opaque patches in the nerve fiber layer of the retina, usually adjacent to the optic disc, that may be confused with optic
disc swelling. Myelinated retinal nerve fibers are not associated with disease, and generally do not cause symptomatic
visual loss.
Hypoplasia
Optic disc hypoplasia represents incomplete development of the optic disc, characterized by a small optic disc
with a larger concentric variably pigmented ring ("double-ring sign") (Fig. 4-26,E). Visual function may be poor or
relatively good. Disc hypoplasia may occur in one or both eyes and has been reported in children born to diabetic
mothers or mothers who have been exposed to alcohol, *** (lysergic acid diethylamide), quinine, or antiepileptic
drugs during pregnancy. Disc hypoplasia is one component of septo-optic dysplasia (de Morsier syndrome), which also
includes absence of the septum pellucidum and neuroendocrine axis dysfunction (often resulting in short stature). A
hypoplastic appearance of the optic disc can also be caused by arrested development resulting from
craniopharyngiomas or glioma. Neuroimaging and determination of endocrine function may be required in the
evaluation of optic disc hypoplasia in children, especially in bilateral cases.
Aplasia
A complete failure of optic nerve development is rare and is usually associated with lethal congenital neural
abnormalities.
Coloboma
Incomplete closure of the fetal fissure in ocular development can initiate a broad spectrum of optic disc and
chorioretinal development abnormalities, termed colobomas. One extreme coloboma is the "morning glory syndrome,"
consisting of marked excavation of an enlarged disc with embryonic glial remnants extending from the disc in the
shape of a flower. Optic nerve pits represent a mild abnormality in the spectrum of developmental disc anomalies, but
associated macular subretinal fluid can cause a profound effect on vision (Fig. 4-26, F). Optic disc and chorioretinal
colobomas are typically located inferior and temporal to the disc, along the site of the fetal fissure (Fig. 4-27). Visual
dysfunction generally parallels the degree of optic disc malformation. Developmental optic disc abnormalities may be
associated with forebrain abnormalities, particularly basal encephaloceles.
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4-1
The vascular supply to the anterior optic nerve. Observe that the prelaminar and laminar portions of the optic
nerve head do not receive their blood supply from the central retinal artery but depend on the short posterior ciliary
arteries.
(From Hart Jr WM: Clinical perimetry and topographic diagnosis in diseases of the afferent visual system. In
Slamovits TL, Burde R, associate editors: Neuro-ophthalmology, vol 6. In Podos SM, Yanoff M, editors: Textbook of
ophthalmology, St Louis, 1991, Mosby.)
4-2
Optic disc edema. Massive optic disc edema is present in this patient with intracranial hypertension and systemic
hypertension. The optic nerve is elevated and enlarged. Hemorrhage is present in the nerve fiber layer (flame-shaped
hemorrhages) and within the retina (dot/blot hemorrhages). The swollen nerve elevates and laterally displaces the
choroid and retina, creating concentric retinal folds called Paton's lines. (See color plate.)
4-3
Common causes of optic disc swelling. Although optic disc swelling has many causes, a thorough history and
examination helps to narrow the possibilities. The more common diagnostic possibilities can often be distinguished by
whether one or both optic discs are involved, the age of the patient, and the degree of visual loss.
4-4
Nonarteritic anterior ischemic optic neuropathy. A 62-year-old male awoke with painless visual loss in his left
eye. A, A dense inferior altitudinal visual field defect was present in the left eye; the visual field in the right eye was
normal. B, The right disc was normal, but note the absence of a central cup. The left optic disc was swollen. The optic
disc edema primarily involves the upper half of the optic disc, corresponding to the inferior visual field defect. (See
color plate.) C, After six weeks, the upper pole of the left optic disc was less swollen but pale. Paradoxically the lower
pole appeared more swollen, with telangiectatic vessels that may represent "luxury perfusion" to the remaining normal
nerve. (See color plate.) D, After six months, the upper portion of the left optic disc was now pale, and the lower half
remained pink. (See color plate.) E, Clinical course of visual loss. The visual loss in this disorder is sudden, but may
decline stepwise over several days. Some patients may have slight improvement in their central vision with time, but
the visual field defect is generally permanent.;E>
4-5
Arteritic anterior ischemic optic neuropathy (giant cell arteritis). A 74-year-old female described brief episodes of
visual loss in her right eye for several days, followed by a "skim" over the right eye two days before her evaluation, and
awoke the next day with "no vision" in the right eye. She reported general malaise and tenderness over the temples for
two weeks. The examination showed only light perception vision in the right eye, with pale optic disc swelling.
Although the ESR was relatively normal for her age (41 mm/hr), giant cell arteritis was suspected on the basis of the
history and examination. The patient was admitted for high-dose intravenous steroids, and a temporal artery biopsy
confirmed the diagnosis of giant cell arteritis. A, Pale optic disc edema was present in the right eye. (See color plate.)
B, Temporal artery exposed at biopsy. The artery appeared large and pale. (See color plate.)C, Temporal artery cross
section, H&E stain, 100. The lumen is obliterated by massive thickening of the arterial wall. Fracture of the internal
elastic lamina is seen (arrow). (See color plate.) D, A multinucleated giant cell is seen at higher magnification (circle).
(See color plate.)
(Photomicrographs (C and D) courtesy of Constance Stanton, M.D.);D>
4-6
Intravenous fluorescein angiogram in arteritic anterior ischemic optic neuropathy. The early phase of an
intravenous fluorescein angiogram shows a large nonfilling segment of the choroid in a patient with anterior ischemic
optic neuropathy from giant cell arteritis(arrows).
4-7
Diabetic papillitis. A 37-year-old insulin-dependent diabetic patient described a sudden change in the vision of
his left eye. A, The right optic disc is relatively normal, but diabetic retinopathy is evident in both eyes. The left optic
disc is diffusely edematous with disc and pe**apillary hemorrhages. B, Automated perimetry of left eye showed only a
small inferior nasal step, far less than expected from the degree of optic disc edema. The visual acuity was 20/80. The
visual field in the right eye was normal.C, Three months later, the optic disc edema in the left eye was nearly resolved,
with mild pallor remaining. The central acuity improved to 20/40, but visual field defect remained unchanged.
4-8
Papillophlebitis. A 35-year-old male described a "smudge" in the vision of his right eye. The best corrected visual
acuity was 20/40 in the right eye and 20/20 in the left eye. A, Optic disc edema with pe**apillary hemorrhages, cotton
wool spots, and venous engorgement was present in the right eye. Unlike a central retinal vein occlusion, no
hemorrhages were present in the retinal pe**hery. The fundus abnormalities and symptoms gradually cleared over four
months.B, Automated perimetry of the right eye showed minimal diffuse depression with a mean deviation of 4.43.
The left eye had a normal visual field (mean deviation of 2.00 decibels).
4-9
Optic neuritis and multiple sclerosis. A 32-year-old female had pain with eye movement and decreased vision in
her right eye. A, The initial visual field of the right eye showed dense visual field loss in three quadrants. The visual
acuity was 20/80 and a 1.2 log unit RAPD was present. The left eye was normal. B, Mild diffuse disc edema was
present in the right eye; the left optic disc was normal. (See color plate.) C, An MRI of the orbits (T1-weighted image
with contrast, coronal view) revealed enhancement of the right optic nerve (arrow). D, The MRI of the brain (T2-
weighted image, axial view) revealed periventricular white matter plaques characteristic of multiple sclerosis(arrows).
Additional T2 signal abnormalities were seen in the right pons (not shown). As suggested by the ONTT, three days of
high-dose intravenous methylprednisolone were administered.E, Within three weeks of onset, the visual field
demonstrated dramatic improvement. A shallow central scotoma remained, with a visual acuity of 20/40. Eventually,
the visual field and acuity normalized, but a small RAPD was still present two years later.F, Time course of visual loss.
Optic neuritis typically causes a decline in vision over several days to a week, followed by a slow but steady recovery
over several months. Patients often achieve near-normal visual acuities and visual fields, but they may indefinitely note
a subjective difference in the brightness or quality of vision in the affected eye.
4-10
Idiopathic intracranial hypertension. A 40-year-old female presented with a history of headache and transient
visual obscurations in her left eye for eight months and blurred vision in her left eye for two months. A, Bilateral optic
disc edema at presentation. Paton's lines can be seen at the temporal edge of the left disc. (See color plate.) B, The
visual field in the left eye showed a dense inferior altitudinal visual field defect. In the right eye, an inferior nasal step
is identified. The presence of visual field defects suggested that the papilledema was chronic, rather than acute. An
MRI with contrast of the brain was normal, and a lumbar puncture revealed an opening pressure of 368 mm of water
with normal CSF studies. Acetazolamide 500 mg BID and an effective weight loss program was instituted, with
resolution of optic disc edema in about six months. C, These optic disc photographs from one year after presentation
show resolution of the optic disc edema, with mild pallor remaining. (See color plate.)D, The visual field defects also
improved, but a dense inferior nasal step remains in the left eye.
4-11
Intracranial hypertension from dural sinus thrombosis. A 32-year-old female complained of severe headache,
increasing in intensity over three weeks. A, Optic disc edema was present bilaterally, more prominent in the left eye. B,
The visual fields were relatively normal, with only mild enlargement of the blind spots.C, MRI of the brain (T2-
weighted image, axial view) revealed bright signal (rather than the normal flow void) in the right transverse (arrows)
and sigmoid dural sinuses, indicative of thrombus. D, Magnetic resonance angiography (MRA) demonstrated absence
of flow in the right transverse(arrows) and sigmoid sinus. The patient was admitted to the neurology service and treated
with both acetazolamide and anticoagulants. Although the optic disc edema resolved within two months, headache has
continued to be a chronic problem.
4-12
Bilateral optic disc edema from malignant hypertension. A 9-year-old male was referred for blurred vision and
"papilledema." Bilateral hyperemic optic disc edema was present, with retinal hemorrhages, cotton-wool spots, retinal
arteriolar narrowing, and macular edema residues. The blood pressure was 200/105. The patient was admitted to
pediatric ICU for management of malignant hypertension. Neuroimaging was normal. Further evaluation confirmed
renovascular hypertension.
4-13
Optic nerve sheath meningioma. A 51-year-old female had left optic disc edema for three years, with normal CT
scans. A subjective decline in vision led to further investigation, with the diagnosis of an optic nerve sheath
meningioma based on MRI studies. A, Chronic, diffuse edema of the left optic disc is present. B, Automated perimetry
of the left eye at the time of diagnosis shows an inferior nasal step. The visual acuity was 20/20. C, Four years later, the
nasal step has enlarged, and is nearly an altitudinal defect. The visual acuity at this time is 20/40. D, MRI of the orbit
(with enhancement, coronal plane). The meningioma is seen as an enhancing mass surrounding the compressed,
nonenhancing optic nerve(arrow). E, MRI (axial plane) reveals that the meningioma is present in the orbit and extends
through the optic foramen intracranially but does not include the chiasm(arrows). F, Clinical course. A steady decline
of vision is the general rule with compressive lesions.
B
4-14
Optic nerve glioma and neurofibromatosis. A 6-year-old female was seen by her ophthalmologist with a "right
eye turning in." A diagnosis of neurofibromatosis (NF-1) had recently been made on the basis of cafe-au-lait spots and
a known family history of NF-1. A right optic nerve glioma was discovered. The patient's visual acuity was 20/80 at the
time of diagnosis and has remained stable for more than three years without treatment. A, Diffuse elevation and edema
of the right optic disc is evident. The left disc is normal. B, MRI (T1 axial view) reveals massive enlargement of the
right optic nerve (arrow), causing mild proptosis.;A>;B>
4-15
Glioma of the anterior visual pathway in an **. A 36-year-old male with a diagnosis of glioblastoma
multiforme in the right parietal region had received both conventional and gamma knife radiation therapy. A complete
left homonymous hemianopic visual field defect was present. The patient presented with visual loss in the right eye,
decreasing to NLP over two weeks. Marked optic disc elevation and retinal venous stasis is present in the right eye; the
left optic disc is normal (pictured). Repeat neuroimaging demonstrated anterior extension of the malignant glioma into
the right optic nerve.
4-16
Acute leukemic optic nerve infiltration. A 10-year-old male with acute lymphocytic leukemia presented with
bilateral blurred vision. Both optic nerves were enlarged and elevated, with hemorrhages and cotton wool spots present,
suggesting acute leukemic optic nerve infiltration(pictured). Urgent radiation of the optic nerves resulted in partial
recovery of visual loss.
4-17
Neuroretinitis from cat-scratch disease. A 10-year-old female complained of blurred vision in her left eye that
began two weeks after a self-limited, four-day febrile illness. She frequently played with the family's kitten. Enzyme
immunoassay for Bartonella henselae was positive. A, The left fundus showed optic disc edema and edema residues
forming a macular star. Focal disc elevation suggesting a granuloma can be seen on the temporal disc. (See color plate.)
B, Goldmann perimetry initially showed a dense cecocentral scotoma. Visual acuity was CF 2`. The patient was treated
with oral doxycycline hyclate, 100 mg daily for 10 days. In one month, the acuity improved to 20/200, and was 20/20
within four months, with normalization of the visual field defect. C, Pe**heral fundus. Deep chorioretinal white spots
are often present in both eyes even when the neuroretinitis is confined to one eye, as demonstrated in another patient
with cat-scratch neuroretinitis.
4-18
Toxic/nutritional optic neuropathy. A 59-year-old male reported the gradual onset of poor vision in both eyes. He
admitted drinking "too much" alcohol but believed he ate a well-balanced diet. Visual acuity was 20/80 in each eye,
with a normal slit-lamp and ophthalmoscopic examination. A, The visual field on presentation showed bilateral
cecocentral scotomas, best appreciated by looking at the total deviation plots. A nutritional optic neuropathy was
suspected, and the patient was started on a multivitamin, as well as folate 1 mg daily, and referred to his general
medical doctor to address his diet and probable alcoholism. B, Four weeks later, the automated visual field had
improved significantly, with improvement of visual acuity to 20/30 in each eye. The patient's visual acuity and visual
fields were normal when tested after an additional six weeks. The patient said he was compliant with his vitamin
therapy, but admitted his alcohol was only minimally reduced.
4-19
Kjer's dominant optic atrophy. A 43-year-old female has had subnormal vision her entire life. With a known
family history of visual loss, she also brought her 18-year-old asymptomatic daughter for evaluation.A, The mother's
optic discs show diffuse pallor, with more striking pallor temporally. B, Bilateral cecocentral scotomas were present
with Goldmann perimetry. The visual acuity was 20/200 in both eyes. C, The daughter's optic discs showed bilateral
temporal pallor. (See color plate.) D, The daughter's automated perimetry showed bilateral shallow central scotomas.
The visual acuity was 20/50 in each eye.Continued
4-20
Leber's hereditary optic neuropathy (LHON). A 19-year-old male described the sudden onset of blurred vision in
his right eye, which continued to progressively worsen. Two months after the onset of visual loss in his right eye, the
vision in the left eye declined rapidly. LHON was confirmed with the identification of a mitochondrial DNA mutation
at position 3460. A, Optic discs, two months after onset of visual loss in the right eye, just before symptoms began in
the left eye. Mild temporal pallor of the right optic disc is present. The left optic disc is hyperemic, with subtle
pe**apillary telangiectatic vessels present. (See color plate.) B, Left optic disc, three months after presentation, after
both eyes are affected. The disc hyperemia and telangiectasia have resolved, with mild temporal pallor now present. C,
Goldmann visual fields demonstrate bilateral cecocentral scotomas.
4-21
Direct optic nerve trauma. A 12-year-old male was injured when a BB struck his right orbit. The entry wound
was in the temporal conjunctiva, missing the globe. The visual acuity was 20/50 and a cecocentral scotoma was
present. The CT scan (axial image) shows the BB adjacent to the right optic nerve. Acutely, the right optic disc
appeared normal, but it turned pale over the following four weeks.
4-22
Indirect traumatic optic neuropathy. Forces generated from a blow to the orbital rim can be transmitted to the
optic c**, contusing the optic nerve even in the absence of fracture.
4-23
Primary open-angle glaucoma. A 44-year-old male has primary open-angle glaucoma. A, The cup of the right
optic disc is enlarged, and the neuroretinal rim has an inferior "notch." Note that the neuroretinal rim is thin but not
pale. B, Automated perimetry shows a dense superior altitudinal visual field defect in the right eye, corresponding to
the notching of the inferior neuroretinal rim.
4-24
Optic disc drusen and visual field loss. A 62-year-old male reported that vision in his right eye has been better
than in his left eye for many years. A, The right disc appears normal; optic disc drusen are evident on the left. B, By
using the barrier filters for fluorescein angiography without fluorescein dye injection, autofluorescence can be detected.
Faint autofluorescence can be seen in the inferior portion of the right disc, suggesting buried disc drusen. Diffuse
autofluorescence of the left optic disc is evident. C, B-mode ultrasound of the right eye shows the highly echoic buried
disc drusen (arrow), even though it is not seen with the ophthalmoscope. D, B-mode ultrasound of the left eye shows
the bright echo signals from florid optic disc drusen (arrow). E, In the left eye, dense pe**heral visual field loss is
evident, with preservation of the central acuity (20/25). The right eye has a normal visual field and acuity.
4-25
Pseudopapilledema from buried optic disc drusen. A 16-year-old female was noted to have elevated optic discs
and headaches. Visual acuity and visual fields were normal. A CT scan of the brain was reportedly normal. B-mode
ultrasound of the optic discs revealed buried optic disc drusen (as in Fig. 4-24). A, The optic discs are elevated with a
"lumpy-bumpy" contour. B, A review of the patient's CT scan (axial view, bone windows) also revealed the radiodense
drusen.;A>;B>
4-26
Anomalous optic discs. A, Small cupless optic discs.B, Anomalously elevated optic discs without clear evidence
of drusen. C, Tilted optic discs with an inferior temporal conus in a patient with high myopia. D, Myelinated nerve
fiber layer simulating optic disc edema. E, Optic disc hypoplasia with a "double-ring" sign. F, Optic nerve head pit
(arrow).
4-27
Ocular coloboma. A, Bilateral inferonasal iris defects suggest that this patient had incomplete closure of the fetal
tissue during embryonic development. B, This "fundusmap" of the patient's right eye was digitally created from many
individual 30-degree photographs. A large coloboma involves the retina and optic disc (seen at the superior edge). The
left eye was nearly identical.
(B, courtesy of R. Hackell.);B>
4-1
Findings and recommendations of the ONTT
Findings Recommendations
Patients who received oral steroids alone had a significantly higher rate of recurrence of optic neuritis than the
other two treatment groups. Do not treat patients with optic neuritis with oral prednisone alone.
Patients with white matter plaques on an infused MRI were more likely to have neurologic events suggestive of
MS following optic neuritis than were those with a normal MRI. The risk of developing MS was reduced in those
patients with MRI findings who received intravenous steroids, but only for about two years; by three years no lasting
affect was evident. An MRI with contrast is helpful in predicting the probability of MS, and should be done if
the diagnosis is uncertain. Those patients with white matter plaques should be considered for intravenous
methylprednisolone treatment to reduce the short-term risk of developing other neurologic symptoms.
Since there is no proven long-term advantage, prescribing
no treatment is also a reasonable approach.
Patients treated with intravenous steroids improved more quickly than untreated patients, but all patients
improved to the same degree within six months to a year. Although intravenous steroids offer no long-term
advantage for visual recovery, a more rapid recovery may be beneficial in patients whose only or better eye is affected.
4-2
Causes of intracranial hypertension related to impediments of CSF flow and absorption
Segment of CSF pathway affected Cause of increased intracranial pressure Mechanism
CSF is produced in the choroid plexus of the lateral and fourth ventricles, Choroid plexus papillomas produce
excess CSF CSF overproduction is only rarely a cause of increased intracranial pressure.
flows through the ventricular system . . . Aqueductal stenosis and other causes
of noncommunicating hydrocephalus Expanding ventricles from obstruction of outflow
into the subarachnoid space, and
is absorbed by the arachnoid
granulations . . . Meningitis (bacterial, viral, parasitic), carcinomatous meningitis. See other causes in Box 4-
8. Injury to the arachnoid villi with inadequate absorption, or toxic effects
into the adjacent superior sagittal venous sinus. Venous blood flows though the dural venous sinuses, draining
into . . . Dural sinus thrombosis, dural AVM Elevation of venous sinus pressure retards CSF egress.
the jugular system in the neck, Radical neck dissection (with sacrifice
of jugular system), superior vena cava syndromes Venous pressure in the cranial venous sinuses can be
elevated by any impediment to distal venous blood flow.
superior vena cava, and right heart. Right heart failure, congestive heart
failure, cor pulmonale
4-1
Causes of Optic Disc Elevation*
Papilledema (elevated intracranial pressure)
Optic neuritis (demyelinating)
Anterior ischemic optic neuropathy
nonarteritic
giant cell arteritis
diabetic papillitis
Compression
Graves' disease
meningioma
orbital masses
Infiltration (inflammatory and neoplastic)
sarcoidosis
lymphoproliferative disorders
glioma
Infection
syphilis
cat-scratch disease
toxoplasmosis
Leber's hereditary optic neuropathy (LHON)
Venous congestion
retinal vein occlusion
papillophlebitis
dural-cavernous fistula
Other ocular disorders
uveitis
hypotony
cystoid macular edema
Systemic
malignant hypertension
severe anemia
hypoxemia
cyanotic heart disease
uremia
Anomalous discs
optic disc drusen
gliosis
Optic disc tumors
hemangiomas
melanocytoma
metastasis
Other
trauma
*Both "true" and "pseudo" optic disc swelling.
4-2
Distinguishing True Optic Disc Edema from Anomalous Optic Discs (Pseudopapilledema)
Common features of anomalous optic discs
Often "cupless" with small diameter
Venous pulsations often present, but may be absent
Increased number of central retinal vessels arising from the apex of the disc
Abnormally increased branching of central retinal vessels on the disc
Scalloped border or lumpy contour when buried drusen are present
Visible optic disc drusen may be present
Common features of "true" optic disc edema
Central cup usually preserved unless edema is extreme
Increased "capillarity" of optic disc
Concentric pe**apillary chorioretinal folds (Paton's lines)
Radial choroidal folds
Leakage on intravenous fluorescein angiography
Glistening tiny "pseudodrusen" edema residues on disc
Associated cotton wool spots
Associated retinal hemorrhage (can occasionally occur with anomalous discs)
4-3
Hematalogic Abnormalities That Can Cause Vascular Occlusions
Hypercoaguable states
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Antiphospholipid antibodies
Lupus anticoagulant
Anticardiolipin antibodies
Factor V Leiden mutation (activated protein C
resistance)
Erythrocyte disorders
Polycythemia
Sickle-cell disease and others
4-4
Acquired Causes of Profound Visual Loss with a Relatively Unremarkable Fundus Examination
Retrobulbar optic neuritis: Young **s with monocular visual loss and RAPD.
Compressive optic neuropathy: Optic disc becomes pale eventually but may look normal at first.
Giant cell arteritis (posterior ischemic optic neuropathy):
patients more than 55 years old with acute visual loss and symptoms of systemic vasculitis.
Acute traumatic optic neuropathy: Pallor may take weeks to develop following injury.
Unilateral retrochiasmal lesions: Homonymous visual field defects do not affect visual acuity.
Bilateral occipital lobe infarction: Bilateral, symmetric visual loss with relatively equal visual acuities and
congruous field loss.
Retrobulbar inflammatory or infiltrative disorders: Neurosarcoidosis, orbital inflammatory pseudotumor
may not initially cause pallor or edema.
Retinal artery occlusion: After the acute retinal edema has resolved, retinal findings may be subtle.
Paraneoplastic retinopathy: Bilateral, symmetric, slowly progressive visual loss.
Toxic and nutritional optic neuropathies (or maculopathies): Bilateral, progressive loss of central vision.
4-5
Ischemic Consequences of Giant Cell Arteritis
Ophthalmic
Anterior ischemic optic neuropathy
Posterior ischemic optic neuropathy
Central retinal artery occlusion
Ocular ischemic syndrome
Ischemic cranial neuropathies
Ischemia of extraocular ocular muscles
Systemic
Common
Jaw and tongue claudication
Scalp ischemia
Uncommon
Myocardial infarction
Mesenteric insufficiency
Stroke
4-6
Steroid "Dependent" Disorders Affecting Vision
NEOPLASTIC
Optic nerve glioma
Optic nerve sheath meningioma
Chromophobe adenoma
Craniopharyngioma
Medulloblastoma
Lymphoproliferative optic nerve infiltration/
compression
Meningeal carcinomatosis
PARANEOPLASTIC
Retinopathy
Optic neuropathy
INFLAMMATORY
Sarcoidosis
Orbital inflammatory pseudotumor
Vasculitis (giant cell arteritis)
OTHER
Autoimmune optic neuropathy
4-7
Muliple sclerosis
Multiple sclerosis (MS) is an autoimmune disorder with focal, patchy destruction of white matter in the brain,
spinal cord, and optic nerves of unknown cause. The disease is more common in females (2 to
1 female-to-male ratio), and is most common in the young ** age group (25 to 40 years). The risk of
developing MS increases 20-fold in first-degree relatives of patients with multiple sclerosis. The incidence of MS rises
with increasing distance from the equator.
Patients who move after the age of 15 carry the risk
of their original locale with them. Patients who move before the age of 15 seem to acquire the risk of a new
location.
The disease is a chronic relapsing, remitting
disorder that commonly causes visual symptoms,
including optic neuritis and diplopia. Systemic findings include extremity weakness, cerebellar dysfunction
(causing vertigo and ataxia), paresthesias of the face and body, and urinary retention or incontinence.
Many patients have episodes of reversible neurologic dysfunction that may be separated by many months
or years. Approximately one third of patients with
MS have no physical disability or decreased life expectancy, but 10% of patients have a relentlessly progressive
form. Patients who are older at the time of
diagnosis have a poorer prognosis than do younger
patients.
A diagnosis of multiple sclerosis is made by identifying neurologic symptoms that are separated in time and
space (affecting different areas of the central nervous system). Although MRI with contrast and CSF findings are
supportive, multiple sclerosis remains a clinical diagnosis.
4-8
Differential Diagnosis of IIH*
Highly Likely
Decreased Flow through Arachnoid Granulations
Scarring from previous inflammation (e.g., meningitis, sequel to subarachnoid hemorrhage)
Obstruction to Venous Drainage
Venous sinus thrombosis
Hypercoagulable states
Contiguous infection (e.g., middle ear or mastoid, otitic hydrocephalus)
Bilateral radical neck dissections
Superior vena cava syndrome
Increased right heart pressure
Endocrine Disorders
Addison's disease
Hypoparathyroidism
Obesity
Steroid withdrawal
Nutritional Disorders
Hypervitaminosis A (vitamin, liver, or isotretinoin intake)
Hyperalimentation in deprivation dwarfism
Arteriovenous Malformations
Probable Causes
Anabolic steroids (may cause venous sinus thrombosis)
Kepone (chlordecone)
Ketoprofen or indomethacin in Bartter's syndrome
Systemic lupus erythematosus
Thyroid replacement therapy in hypothyroid children
Uremia
Possible Causes
Amiodarone
Diphenylhydantoin
Iron-deficiency anemia
Lithium carbonate
Nalidixic acid
Sarcoidosis
Sulfa antibiotics
Causes Frequently Cited But Unproven
Corticosteroid intake
Hyperthyroidism
Hypovitaminosis A
Menarche
Menstrual irregularities
Multivitamin intake
Oral contraceptive use
Pregnancy
Tetracycline use
*Cases must meet the modified dandy criteria of IIH except that a cause is found.
From Wall M: Idiopathic intercranial hypertension. In Breen L, editor: Neurologic clinics 9(1):73-95, 1991.
4-9
Clinical Definition of IIH (Modified Dandy Criteria)
Signs and symptoms of increased intracranial pressure
No localizing neurologic findings (sixth cranial nerve palsies are allowed)
Normal neuroimaging (with the exception of an empty sella)
Opening pressure on lumbar puncture of greater
than 250 mm water, with normal CSF (protein may
be low)
No other cause of increased intracranial pressure present
4-10
Infiltrative Optic Neuropathies
Lymphoproliferative disorders
Leukemia
monocytic
acute myelocytic
acute lymphocytic
chronic lymphocytic
Lymphoma
Plasmacytoma
Multiple myeloma
Metastatic carcinoma (esp. breast and lung)
Carcinomatous meningitis (esp. breast and lung)
Inflammatory Disorders
Sarcoidosis
Systemic lupus erythematosus
Wegener's granulomatosis
Infectious
Tuberculosis
Cryptococcosis
Toxoplasmosis
Toxocariasis
Cytomegalovirus
Coccidiomycosis
Aspergillus
Lyme disease
4-11
Sarcoidosis
Sarcoidosis is a multisystem idiopathic granulomatous inflammatory disorder that frequently affects the eye,
orbit, and intracranial visual system. The disease is commonly diagnosed in patients in their thirties and forties, but it
can occur at any age. In the United States, sarcoidosis is at least ten times more prevalent in African-Americans than in
Caucasians.
Pathologically, affected tissues are infiltrated with noncaseating granulomas. Although this disorder is clinically
and pathologically similar to tuberculosis, no causative agent has been identified in sarcoidosis.
Although some patients with proven sarcoidosis are asymptomatic, others may exhibit severe systemic and
neurologic consequences. Most patients present with constitutional symptoms: malaise, weakness, fever, weight loss,
and diaphoresis. Pulmonary involvement is common, and is manifest as hilar and mediastinal adenopathy often evident
with a routine chest radiograph. Lung parenchymal involvement can cause coughing, shortness of breath, and
wheezing. Cutaneous manifestations include erythema nodosum, nodular granulomas, lupus pernio, and mucous
membrane (including conjunctival) lesions.
Similar to hilar adenopathy, painless and symmetric pe-
**heral lymphadenopathy is common. Other affected organs include the liver, spleen, parotid glands, muscles,
heart, and central nervous system.
Potential ocular and orbital involvement includes granulomatous uveitis, as well as infiltration of the conjunctiva,
extraocular muscles, lacrimal gland, and optic nerve.
Involvement of the central nervous system is designated asneurosarcoidosis and commonly affects the optic
nerves, chiasm, and optic tracts. Other cranial neuropathies, especially facial nerve palsies, are also common.
Meningeal or ventricular disease can cause elevated intracranial pressure and papilledema. Meningeal neurosarcoidosis
can also have a mass effect with compression of adjacent structures; it may be difficult to distinguish from meningioma
both clinically and neuroradiologically. Parenchymal disease can cause neuroendocrine disturbances (such as diabetes
insipidus from hypothalamic involvement), encephalopathy, or white matter changes that mimic multiple sclerosis.
A diagnosis of sarcoidosis may be based on the physical examination, imaging studies (hilar adenopathy, brain
MRI), or serologic tests (elevated ACE, hypercalcemia, hypergammaglobulinemia). In some cases, a lumbar puncture
and CSF **ysis may be needed to distinguish neurosarcoidosis from infectious and neoplastic processes. Pathologic
diagnosis can be made by identifying affected tissues (examination, gallium scan, and other imaging) that may be
biopsied (bronchoscopy, skin, lymph node, lacrimal gland, or conjunctival biopsy).
Sarcoidosis almost always responds promptly to treatment with intravenous or oral steroids; therefore, failure to
respond to treatment should lead to questioning this diagnosis. Steroid sparing agents and surgical therapy
for the complications of sarcoidosis are occasionally required.
4-12
Common Toxic/Nutritional Optic Neuropathies
Drugs
Ethambutol
Rifampin
Isoniazid (INH)
Chloramphenicol
5-Flurouracil
Disulfiram
Toxins
Methanol
Ethylene glycol
Heavy metals
Tobacco and alcohol
Nutritional deficiencies
Thiamine (B1)
Vitamin B12 (pernicious anemia)
Folate
MAJOR POINTS
Anterior ischemic optic neuropathy is a common cause of unilateral optic disc edema and sudden visual loss in
patients more than 45 years old.
AION may be nonarteritic or secondary to giant cell
arteritis.
A prompt diagnosis and treatment of giant cell arteritis can prevent bilateral blindness.
When giant cell arteritis is suspected, an ESR should be performed and steroid therapy should be instituted
immediately, with a temporal artery biopsy
arranged within a few days.
Optic neuritis is a cause of visual loss in young patients characterized by pain with eye movement and an optic
disc that may be edematous or normal in appearance.
High-dose intravenous steroids should be considered when patients with optic neuritis have white matter changes
visible on MRI.
Papilledema may be caused by intracranial tumors and ventricular obstruction, or it may be an idiopathic disorder
in young obese females.
Papilledema should be initially investigated by a
blood pressure measurement, neuroimaging, and lumbar puncture (if imaging reveals no mass or
obstruction).
Chronic papilledema can cause profound visual field loss despite normal visual acuity; patients must be followed
with serial perimetry.
A gradual, insidious decline in vision with optic nerve pallor suggest a compressive optic neuropathy such as a
meningioma, orbital mass, or orbital Graves' disease.
Optic nerve gliomas in children are frequently associated with neurofibromatosis (type I) and commonly behave
in a benign fashion.
Acute leukemic infiltrative optic neuropathy is an emergency; radiation therapy may be sight-saving.
The term neuroretinitis designates optic disc edema associated with macular edema (with edema residues that
typically form a macular star), which is often the result of an infectious process.
Toxic and nutritional deficiencies cause progressive, bilateral, cecocentral scotomas.
Leber's hereditary optic neuropathy (LHON) is associated with specific point mutations in mitochondrial DNA
and typically causes acute visual loss in one eye, followed within weeks by a similar event in
the other eye, usually of young males.
Trauma to the optic nerve can occur without fractures because the forces from blunt trauma to the brow or cheek
are mechanically funneled to the orbital apex and optic c**.
Optic disc drusen can be associated with pe**heral (not central) visual field defects.
4-19, cont'd
E, Four generations of this family are known or suspected to be affected by this autosomally dominant hereditary
neuropathy (Kjer's). (1. the mother, 2. the daughter.);E>

蝎***缸

因为最近忙期末考试，过一段时间，就翻译给大家
多包涵

迪*夫

俺啥也看不懂!

大*

希望楼主翻译成中文
太过深奥!!!
谢谢

s****8

强烈建议翻译成中文！！！！！！！！！！！！！！111

老*头

建议楼主把中文翻译发上来，斑竹好给您加分。要不请大家帮忙翻译也行，俺的英文不是很好，看着太吃力啊。不过我估计是个好文章，送花先！