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Approach To Optic Neuropathies: Clinical Update
Approach To Optic Neuropathies: Clinical Update
FIGURE 3. Visual field defects in patients with optic neuropathies (grayscale output of Humphrey automated perimetry 关A, C, D,
and F兴 and kinetic Goldmann perimetry 关B and E兴). A, Central scotoma in a patient with right optic neuritis. B, Centrocecal scotoma
(connecting to physiologic blind spot) in a patient with optic neuropathy due to B12 deficiency. C, Superior altitudinal central sco-
toma in a patient with inferior optic nerve compression due to a meningioma. D, Inferior arcuate altitudinal scotoma in a patient
with nonarteritic ischemic optic neuropathy. E, Superior altitudinal scotoma in a patient with arteritic ischemic optic neuropathy. F,
Inferonasal step in a patient with glaucomatous optic neuropathy. (Color figure available online at www.theneurologist.org.)
FIGURE 13. Fundus photographs of the right eye in a pa- FIGURE 15. Fundus photograph of the right eye in a patient
tient with right nonarteritic anterior ischemic optic neuropa- with chronic disc swelling. Note blurred disc margins (black
thy. Note blurring of the disc margin and swelling of the arrows) and an optociliary shunt vessel (white arrow). (Color
optic nerve head (black arrows), splinter hemorrhages (white figure available online at www.theneurologist.org.)
arrows), as well as dilated capillaries and luxury perfusion of
the nerve head (asterisk). (Color figure available online at
www.theneurologist.org.) Infectious conditions are other frequent cause of optic neu-
ropathy.29 Neuroretinitis, in which optic neuropathy coexists with
characteristic peripapillary or macular exudates, may be due to cat
scratch disease (Bartonella henselae), syphilis (Treponema palli-
dum), or Lyme disease (Borrelia burgdorferi). In most cases, Bar-
tonella infection is self-limited and does not require treatment, but
doxycycline may be effective in severe cases. Other infectious
causes of optic neuropathy include HIV and opportunistic infections
including toxoplasmosis, cytomegalovirus, and cryptococcus. Para-
nasal sinusitis or mucocele may lead to either compressive or
inflammatory optic neuropathy.
A variety of compressive mass lesions can cause a progres-
sive optic neuropathy. The optic disc will be swollen in cases of
intraorbital compression, but in cases of retro-orbital compression
disc swelling will only occur if intracranial pressure is elevated.
Chronic disc edema due to compressive lesions may be accompa-
nied by optociliary shunt vessels and glistening white bodies on the
disc surface (pseudodrusen from extruded axoplasm) (Fig. 15).
FIGURE 14. Coronal T1-weighted postgadolinium MRI in a Important causes of compressive optic neuropathy include neoplasm
patient with left optic neuropathy from neurosarcoidosis. Note (including optic nerve sheath or skull base meningioma, pituitary
swelling and enhancement of right optic nerve (white arrow). adenoma, and craniopharyngioma), sinus lesions, bony processes
(such as fibrous dysplasia), enlarged extraocular muscles (as in
Graves ophthalmopathy), or aneurysms (Fig. 16).
it is mandatory to perform a thorough work-up for entities such as GCA Primary optic nerve neoplasms include benign juvenile pilocytic
and other inflammatory, infiltrative processes. In the correct clinical glioma in children, and rarely malignant glioblastoma in adults30 (Fig.
context, PION may be the result of severe blood loss, anemia, hyper- 17). Juvenile pilocytic astrocytoma is often associated with neurofibro-
viscosity syndromes, and prolonged surgical procedures (notably spinal matosis type 1 and may be managed conservatively with frequent
surgery). PION often causes a central scotoma, because interruption of ophthalmologic examination through adolescence. When clinical or
the normal blood supply to the posterior optic nerve (via the anastomotic radiographic progression is detected, chemotherapy should be first-line
circumferential pial plexus) causes watershed ischemia within the center of therapy, followed by radiation and rarely surgery.30 Malignant optic
the nerve, where the macular fibers lie.27 In postsurgical PION, tissue nerve glioblastoma is much rarer, affects adults, and has a considerably
perfusion may be compromised as a result of increased orbital venous worse prognosis.31 Other neoplastic conditions include lymphoma,
pressure due to orbital edema and simultaneous arterial hypotension.22 leukemia, carcinomatous meningitis, and optic nerve metastasis. Al-
most any form of carcinoma can metastasize to the optic nerve; breast
Other Conditions and lung carcinomas are the most common.
Inflammatory conditions are an important cause of subacute Optic neuropathy may occur as a delayed effect of radiation
optic neuropathy. Optic nerve involvement is common in neurosar- therapy, and can sometimes be difficult to distinguish from tumor
coidosis, which can be accompanied by anterior uveitis or posterior recurrence.32 Radiation optic neuropathy is suggested by exposure
segment vitritis28 (Fig. 14). Visual loss due to this condition is often (typically 50 Gy dosage), characteristic 6 to 24 month time-lag to
steroid-responsive. Optic neuropathy may also occur with other symptoms, and accompanying radiation changes in proximal tissues. Pro-
inflammatory disorders, such as systemic lupus erythematosus and gression occurs over weeks to months, and spontaneous recovery is rare.
Sjögren’s syndrome. Corticosteroids may help by reducing edema in the affected optic nerve.
BILATERAL OPTIC NEUROPATHY: DIFFERENTIAL FIGURE 24. Fundus photograph of the left eye in a patient
DIAGNOSIS AND CLINICAL CLUES with central retinal vein occlusion. Note mild disc swelling
and hyperemia (asterisks), engorgement of retinal veins
Papilledema (black arrows), and intraretinal dot-and-blot hemorrhages
The term papilledema refers specifically to optic disc swelling (for example, white arrows). (Color figure available online at
that occurs secondary to increased intracranial pressure (Fig. 5). www.theneurologist.org.)
Disc swelling in papilledema results from blockage of axoplasmic
flow in nerve fibers, with a consequent increase in the volume of
axoplasm in the optic disc. Although papilledema is typically bilat-
eral, it can be asymmetric based on anatomic differences in the
meningeal covering of the intracranial optic nerves, leading to
differences in transmitted pressure. In the acute phase of papill-
edema, there is a mismatch between a markedly swollen disc and
relatively spared optic nerve function, particularly central visual
acuity. When acute papilledema is accompanied by decreased acuity
(and possible metamorphopsia), the cause is typically extension of
fluid within the nerve fiber layer, reaching the macula itself. As
increased intracranial pressure and papilledema persist, optic nerve
axons are damaged and visual field loss develops. At this stage, optic
disc swelling lessens and disc pallor occurs (atrophic papilledema)
(Fig. 25).
Other Causes
Hypertensive emergency may produce bilateral optic disc
swelling that is indistinguishable from papilledema. Encephalo-
pathic signs are common, but not always present. Peripapillary
cotton-wool spots are also a prominent funduscopic feature in
patients with malignant hypertension.
Diabetic papillopathy is a rare cause of bilateral (or some-
times unilateral) disc swelling in patients with type I diabetes. This
entity is distinct from typical NAION in that there is often bilateral,
simultaneous optic nerve involvement; often optic nerve dysfunction
is minimal, with blind spot enlargement and a mild deficit in acuity.
Disc edema is accompanied by capillary telangiectasias overlying
the disc surface. The pathogenesis may relate to impaired blood flow
causing disc swelling, but not severe enough to significantly impair
optic nerve function, as in the case of incipient NAION.26 In many
cases, the optic disc edema resolves without residual visual deficit.
A toxic/nutritional optic neuropathy is suggested by painless,
symmetrical visual loss. Occasionally, involvement of one eye may
manifest before the fellow eye. The optic nerves may appear normal
or atrophic. Classically, toxic/nutritional optic neuropathies are FIGURE 26. Visual evoked potentials from a patient with
associated with centrocecal scotomas (central scotomas that connect right optic neuritis. The P100 response from the left eye is
to the normal blind spot). Tobacco-alcohol amblyopia refers to an normal (96 milliseconds). From the right eye the P100 re-
optic neuropathy putatively related to combined malnourishment sponse is abnormally prolonged (127 milliseconds), indicat-
and chronic, toxic exposure to alcohol and tobacco. Vitamin B12 ing a prechiasmatic conduction delay.
deficiency is a common cause of nutritional optic neuropathy.
Finally, ethambutol causes optic neuropathy, with a dose-toxicity
relationship. Although most toxic optic neuropathies present with
systemic features, serum testing may be considered for syphilis,
normal-appearing optic discs, disc edema is characteristic of meth-
Lyme disease, toxoplasmosis, cat scratch fever, West Nile Virus,
anol poisoning.
HIV infection, and Herpes virus infection, as well as serum ACE
level, antinuclear antibodies, and Sjogren antibodies. In cases of
CONDUCTING AN APPROPRIATE WORK-UP suspected inflammatory or infectious optic neuropathy, lumbar
Once the differential diagnosis has been narrowed on the puncture is necessary.
basis of the clinical history and physical examination, an appropriate Finally, genetic testing for Leber optic neuropathy is useful in
diagnostic work-up is imperative to confirm the correct diagnosis. patients with painless visual loss that is severe or bilateral, particu-
All patients with typical optic neuritis should undergo brain larly if they are young men. In the appropriate setting, genetic
MRI to assess the risk of MS. MRI of the orbits may confirm optic testing for other hereditary conditions, such as mitochondrial dis-
nerve enhancement in the majority of patients with optic neuritis and eases, may be considered.
may be helpful to exclude alternative causes of optic neuropathy.
Testing for NMO-IgG (neuromyelitis optica antiaquaporin-4 anti- CONCLUSIONS
body) is useful in patients with recurrent, bilateral, or severe optic A patient with an optic neuropathy may demonstrate a num-
neuritis, especially in patients with longitudinally extensive trans- ber of abnormalities on careful examination, including decreased
verse myelitis. acuity, color vision, a RAPD, visual field loss, and an abnormal disc
OCT is usually normal in acute optic neuritis, but may reveal appearance. Recognizing patterns of these deficits permits the cli-
thickening of the nerve fiber layer consistent with mild edema. OCT nician to distinguish an optic neuropathy from other causes of
evaluates tissue thickness to a resolution of less than 10 m, monocular vision loss. Furthermore, knowledge of the characteris-
evaluating the echo time delay of back-scattered near infrared light. tics of various causes of optic neuropathy helps to narrow a broad
It may be helpful in distinguishing some retinal conditions from differential diagnosis and execute an efficient, targeted work-up.
optic neuropathy. An electroretinogram may be helpful in patients
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