6 Neuro-Ophthalmology


Three major categories of complaint in neuro-ophthalmology:

Afferent (e.g., visual loss, field or acuity, visual processing).

Efferent (e.g., diplopia, pupil abnormalities, eye lid abnormalities, jumping eyes).

Pain (e.g., headache, eye pain).

Questioning About Afferent System

Specifically define the following:

Onset (e.g., upon waking, following a headache).

Course (e.g., sudden, gradually progressive).

Duration (e.g., seconds, minutes, hours, days).

Severity of visual loss.

Q: “Could you see faces?”

Q: “Could you read?”

Q: “Could you see motion?”

Timing and onset of visual loss.

Laterality (and did the patient cover one eye to check?).




Visual field defect versus acuity loss.

Associated pain (with eye movements?), headaches, nausea, or aura.

Associated motor or sensory dysfunction.

Associated scintillations or other visual phenomena.

Efferent Localization

Q: “Where is the lesion?”

Monocular or binocular (diplopia).

Vertical or horizontal diplopia.

Worse in fields of gaze (comitance) ?

Worse throughout day or fatigable?


Q: “When, where, how much?”

Palliative and precipitating factors.

Associated symptoms.

Motility Examination

images  Head posture, head tilt, face position.

images  Fixation preference (near and distance).

images  Fixing with paretic eye or nonparetic eye.

images  Dominance or better vision in fixing eye.

images  Ductions (graded-4 [no movement] to 0 [normal]).

images  Monocular movements.

images  Cover fellow eye during testing.

images  Movements (Table 6.1 and Figure 6.1):

Supraduction or elevation: Eye moves up.

Infraduction or depression: down.

Abduction: away from midline.

Adduction: toward midline

Intorsion: inward rotation of the upper pole of the vertical meridian of each eye toward the midline of the face

Extorsion: outward rotation of the upper pole of the vertical meridian of each eye away from the midline of the face

images  Most elevation is due to superior rectus muscle (SRM) and most depression is due to inferior rectus muscle (IRM).

images  Versions.

images  Binocular movements.

images  Ductions may be better than versions.

Table 6.1 Muscle actions


Accommodative Amplitude (Right Eye and Left Eye) Deviations

Distance with or without correction.

Near with or without correction.

Primary position and diagnostic positions.

Primary and secondary deviation.

Primary: fixing with nonparetic eye.

Secondary: fixing with paretic eye.

Secondary deviation greater than primary.

More innervational effort to keep paretic eye fixating on target.

Innervation drives fellow eye to greater deviation:

Esodeviation: turns in.

Exodeviation: turns out.

Hyperdeviation: eye turned up.

Hypodeviation: eye turned down.

Torsion (incyclotorsion or excyclotorsion).

Stereoacuity Testing

40 arc seconds: 20/20 acuity.

60 arc seconds: 20/40 acuity.

100 arc seconds: 20/200 acuity.

Titmus testing (i.e., fly, animals, circles).

Double Maddox rod testing for torsion.

Distance and Near Testing

Check primary and downgaze positions.

Especially useful for superior oblique palsy.

Can be compared to funduscopic torsion.

Saccades and pursuit (horizontal and vertical).




Speed (velocity).

Motility: Special Tests

Cover-Uncover Test for Tropia or Manifest Deviation


Have the patient fixate on target.

Cover one eye and look for shift in noncovered eye.

Uncover eyes.

Repeat test covering other eye.

Absence of shift: straight (orthotropia).

Shift of noncovered eye indicates tropia.

Requires vision good enough to fixate on target.

Alternate Cover Test for Phoria or Latent Deviation


images  Check cover-uncover test first; result must be negative (no tropia).

images  Have the patient fixate on target.

images  Cover one eye.

images  Rapidly move cover to other eye and look for shift in eye as it is uncovered.

images  Latent deviation kept in check by fusion.

images  Cover-uncover test breaks down fusional control.

images  Latent deviation revealed by eye movement when cover moved to other eye.

Hirschberg Test

For patients unable to fixate. See Figure 6.2.


Hold fixation light at 33 cm.

Measure deviation of light reflex from pupil center, indicative of tropia.

Decentration of 1 mm = 7 degrees = 15 prism diopters.

Pupil edge margin = 15 degrees = 30 prism diopters.

Iris = 30 degrees = 60 prism diopters.

Limbus = 45 degrees = 90 prism diopters

Krimsky Method

For patients unable to fixate.

Hold fixation light at 33 cm.

Add prism in front of one eye until corneal light reflex is centered in both eyes.

Semiquantitative assessment of deviation.


FIGURE 6.2. Left esotropia. Note lateral displacement of Hirschberg light reflex in the LE. Pupils are pharmacologically dilated. Photograph demonstrates right ptosis and asymmetry of the red reflex, which is caused by misalignment of the eyes.

Three-Step Test for Hypertropia (Bielschowsky/Parks Test)

Step 1: Which eye is higher? Right eye (RE) or left eye (LE)?

Step 2: Is the deviation worse in right or left gaze?

Step 3: Is the deviation worse in right head tilt (RHT) or left head tilt (LHT)?


images  RE higher = right hypertropia (RHT).

images  Four possible paretic muscles.

Right depressors (R-IR, right superior oblique muscle [R-SO]).

Left elevators (L-SR, left inferior oblique muscle [L-IO]).

images  If deviation is worse in left gaze:

Only R-SO and L-SR act in gaze to the left (deviation worse in gaze toward paretic muscle).

images  If deviation is worse in RHT:

In tilt right, RE intorts and LE extorts to maintain position.

Of the R-SO and L-SR, only the R-SO is an intorter of RE (L-SR is intorter of LE).

Intorsion deficit is made up by the following: RE intorter = R-SR; therefore, secondary elevation by R-SR makes the RHT worse.

images  Diagnosis: R-SO palsy.

Step 4: Measure ocular torsion (if torsion mismatch consider alternative diagnosis of hyperdeviation such as skew/ocular tilt reaction).

Mnemonic: SINRAD = Superiors INtort Recti ADduct.



Nonorganic visual loss may manifest as loss of visual acuity or visual field. No organic lesion can be identified by examination, and nonphysiologic responses confirm the diagnosis.

Signs and Symptoms

May be unilateral or bilateral.

May be any form and severity of visual loss.

Evaluation of Nonorganic Visual Loss

Optokinetic Nystagmus Drum for Severe Loss (Not as Useful for Mild or Moderate Loss)

Horizontal jerk nystagmus.

One-inch-wide stripes indicate vision of at least 20/400.

If “loss” occurs in only one eye:

Rotate drum before both eyes.

Once good nystagmus elicited, cover unaffected eye.

Nonorganic loss continues jerk.

Optokinetic nystagmus (OKN) may be suppressed by inattention.

Mirror Test for No Light Perception

Move mirror back and forth.

Rotate and twist mirror.

If acuity greater than LP, then nystagmoid movement.

Difficult to suppress response.

Proprioception Testing for Severe Visual Loss

Ask the patient to touch the left and right fingertips together.

A patient with organic disease performs the task easily; one with nonorganic disease cannot.

This is a test of proprioception, not vision.

Forced Acuity Testing

Start with smallest line (20/10).

Tell the patient that you are showing a line of “doubled” size.

Show next larger line (20/15).

Works best with computerized projections of multiple Snellen lines of same size.

Repeat until the patient is able to read line.

Express incredulously, “You can’t see these ‘big’ letters?”

Near Vision Testing

A discrepancy of near versus distance vision, if not refractive error or media, is usually evidence of nonorganic loss.

Potential Acuity Meter

Measure best corrected acuity.

Dilate pupil.

Tell the patient that the test “bypasses” visual problem.

Improved PAM vision is evidence for ocular media opacity or nonorganic loss.

Red-Green Glasses


Project red/green duochrome slide.

Red lens over abnormal eye.

If the patient is able to read the entire line, then nonorganic visual loss.

Red sees letters on both sides of the screen.

Green lens, only green side.

Mnemonic: “green over good eye.”

May use Ishihara color plates.

Polarized lenses.

American Optical polarizing test.

Polarized glasses.

Project-O-Chart slide.

Color testing.

Optic neuropathy often causes color defect.


Test binocularly first.

RE 20/20 and LE 20/200 = stereo of 180 seconds of arc.

OU 20/20 has 40 seconds of arc.

Normal stereopsis = nonorganic acuity loss.

Pupil Responses

Eye with no light perception (NLP) should not react to light if from anterior visual pathway disease (patients will have normal pupil responses if cortical visual loss).

Evaluation of Nonorganic Visual Field Defects

Constricted Field

images  Test with tangent screen.

Test at two different distances (e.g., 1 and 2 m). Increasing the distance from the screen should increase the mapped field proportionately.

Size of object varied (i.e., if double test distance, double test object).

A field that fails to expand at any distance (“tunnel”) is nonorganic.

images  Monocular hemianopias or binasal or bitemporal hemianopia.

Test monocular and binocular field.

images  Overlapping field from other hemifield.

If field loss persists under binocular conditions, then nonorganic.

Saccadic Testing

Saccades in supposedly blind peripheral field are a nonorganic finding.

Tell the patient that it is a test of eye movements.

Visual Field Defects Suggestive of Nonorganic Disease

Bilateral constriction without expansion at increasing distance (tunnel field).

Overlapping or inversion of isopters.

Spiraling of isopters.

Nasal hemianopias when tested monocularly that persist on binocular testing.


Types of Visual Field Defects

Etiology and evaluation based on pattern of visual field loss.

Unilateral Nerve Fiber Bundle Defect

Arcuate or altitudinal in shape.

Scotoma extends to blind spot.


Ipsilateral optic nerve or retinal lesion.

Field defect size, density, and shape correspond to retinal or optic nerve lesion.

Central or paracentral scotomas suggest macular or optic nerve disease.

Bilateral nerve fiber layer or retinal defects may occur (e.g., glaucoma, retinal detachment).

Compressive lesions may cause nerve fiber defects (optic neuropathy).


Careful ophthalmoscopy.

Optic nerve head examination.

Exclude artifact of testing.

Exclude retinal disease.

Exclude glaucoma.

Exclude optic neuropathy.

Bilateral Cecocentral or Central Scotomas

May be bilateral optic neuropathy of any cause (e.g., compressive), but more common causes are listed below.


Toxic or nutritional amblyopia.

Bilateral demyelinating (optic neuritis).


Bilateral macula-involving occipital lesions.

Bilateral macular disease.

Leber hereditary optic neuropathy.


Exclude toxic optic neuropathies (e.g., heavy metals, ethambutol).

Consider nutritional amblyopia (vitamin B12, folate, complete blood cell count [CBC]).


Testing for Leber hereditary optic neuropathy.

Junctional Visual Field Defects


images  Usually, a mass lesion–compressing junction of optic nerve at chiasm (e.g., pituitary adenoma, craniopharyngioma, aneurysm).

Ophthalmic Findings

images  Ipsilateral central or cecocentral visual field defect and superotemporal field defect in contralateral eye (junctional scotoma) (Figure 6.3).

images  Monocular ipsilateral hemianopic (nasal or temporal) visual field defect (junctional scotoma of Traquair).

Although purported to be from contralateral crossing fibers extending into ipsilateral optic nerve (Willbrand knee), it is unlikely to exist anatomically, but the clinical localizing finding of the junctional scotoma to the junction of the optic nerve and chiasm remains valid.


Neuroimaging (preferably magnetic resonance imaging [MRI]) of junction of the optic nerve and chiasm.

Bitemporal Step or “Flavor” Visual Field Defect

See Figure 6.3.


FIGURE 6.3. Schematic illustration of the visual pathway and visual field defects produced by lesions in various areas of the pathway. (ON, optic nerve; CH, chiasm; OT, optic tract; LGB, lateral geniculate body; ML, Meyer loop; OR, optic radiations) (Reproduced from Tasman W, Jaeger E. The wills eye hospital atlas of clinical ophthalmology, 2nd ed. Lippincott Williams & Wilkins, 2001, with permission.)


Chiasmal lesion until proven otherwise.

Pseudochiasmal fields (not respecting midline).

Tilted disk.


Bilateral nasal retinal disease (e.g., schisis).


Bilateral optic neuropathy.

Lesions affecting the chiasm:

Pituitary adenoma.



Internal carotid artery aneurysm.

Other tumors.

Demyelinating disease.



Neuroimaging with attention to the chiasm.

Homonymous Hemianopsia

See Figure 6.3.


images  Retrochiasmal disease.

images  Complete homonymous hemianopsia is not further localizing (i.e., localizes only to contralateral retrochiasmal pathway).

images  More congruous (equal in appearance, size, shape of field) lesions are more posterior.

images  Congruity does not apply to complete hemianopsia.

Signs and Symptoms

Signs and symptoms to help localize homonymous hemianopsia:

Optic tract:

Contralateral APD.

Band or bow-tie optic disk atrophy (contralateral).

Generally incongruous homonymous hemianopsia.

Lateral geniculate body:

Incongruous wedge defects “spears to fixation” (anterior choroidal branch of internal carotid artery).

May spare or selectively involve horizontal strip of field (lateral choroidal branch).

Temporal lobe:

Defect denser superiorly (Meyer loop); “pie in the sky” scotoma (Figure 6.3).

Parietal lobe:

Incongruous defect, denser inferiorly (Figure 6.3).

More likely complete with macular splitting.

Other clinical signs:

 Right-sided lesions.

 Constructional apraxias.

 More severe neglect.

 Left-sided lesions.

 Gerstmann syndrome:

 Finger agnosia.

 Right-left confusion.






 Often isolated neurologically.

 Usually very congruous.

 May be paracentral.

 Macular sparing (central 5 degrees) due to dual circulation from middle and posterior cerebral arteries.

May spare or selectively involve a temporal monocular crescent at anterior tip of calcarine cortex (Figure 6.3) supplied by anterior cerebral artery.

Optic Nerve Head Disorders



A coloboma is an excavated defect in the optic nerve that is due to incomplete closure of the embryonic fissure associated with a PAX6 mutation.


Congenital: incomplete or abnormal closure of proximal end of embryonic fissure.

Signs and Symptoms

May be asymptomatic.

May have visual loss.

Ophthalmic Findings

images  Abnormal appearance of optic nerve.

images  Glistening white bowl-shaped excavation occupies an enlarged optic disk (Figure 6.4).

images  Bare sclera visible because of absence of retina, retinal pigment epithelium (RPE), and choroid adjacent to and continuous with optic nerve.

images  Usually inferonasal.

images  Unilateral or bilateral.

images  Absolute scotoma corresponding to coloboma.

images  Associated findings:

May be isolated.

May be associated with iris, ciliary, or choroidal colobomas.

May be associated with other ocular abnormalities (microphthalmia, choroidal colobomas).

May be associated with other systemic abnormalities (e.g., Aicardi syndrome, Goldenhar syndrome, and CHARGE syndrome).




Usually static.


Brodsky MC. Congenital optic disc anomalies. Surv Ophthalmol 1994;39:89–112.

Optic Pit


An optic pit is a congenital excavated defect or depression in the optic nerve due to a defect in the lamina cribrosa.



Signs and Symptoms

May be asymptomatic.

May have visual loss.

May have metamorphopsia.

Ophthalmic Findings

Small excavated defect (pit) in optic nerve rim (Figure 6.5).

Usually temporal (may be nasal or central).

Bilateral in 15% of cases.

May be associated with serous retinal detachment.

Adjacent to optic pit.

May extend into macula.


FIGURE 6.5. Optic pit temporally on the optic nerve. May have an associated serous retinal detachment. (Reproduced from Tasman W, Jaeger E. The Wills eye hospital atlas of clinical ophthalmology, 2nd ed. Lippincott Williams & Wilkins, 2001, with permission.)

Special Tests

Fluorescein angiography for serous detachment.


No treatment unless serous detachment.

Laser treatment if serous detachment though often unsuccessful.

Vitrectomy in unresponsive cases.


Often, self-limited serous detachment.

May recur.


Brodsky MC. Congenital optic disc anomalies. Surv Ophthalmol 1994;39:89–112.

Optic Nerve Hypoplasia and Dysplasia


Optic nerve hypoplasia is a congenitally small optic nerve.



Aplasia (rare).



Signs and Symptoms

Sometimes asymptomatic.

May have decreased acuity.

Range: 20/20 to NLP.

Usually nonprogressive.

Cannot judge level of acuity from appearance of disk.

Visual field defects.

Ophthalmic Findings

Unilateral or bilateral.


Nystagmus (including see-saw).

May have superimposed amblyopia.

Strong association with astigmatism.

Fundus signs.

Small optic disk.

One third to half the normal size.

With or without pallor.

Normal optic nerve dimension: horizontal, 1.38 mm; vertical, 1.46 mm.

“Double ring sign” (Figure 6.6).

May be confused with peripapillary atrophy.

Outer ring: junction of sclera and lamina cribrosa.

Inner ring: abnormal extension of retina and RPE.

Decreased nerve fiber layer thickness.

Normal-sized retinal vessels that may be tortuous.

Associated Signs

Developmental delay, most common.

Hypothalamic or pituitary dysfunction.

Endocrine dysfunction.

Facial abnormalities.

Skeletal abnormalities.

Ocular abnormalities (e.g., coloboma).

Risk Factors (Usually Idiopathic)

Young maternal age.

Use of medicines in pregnancy (e.g., alcohol, phenytoin).

Maternal diabetes (superior segmental hypoplasia).

Trisomies 13, 18, and 21.

Intrauterine cytomegalovirus and hepatitis.


Pediatric endocrinology consultation.

Hypothalamic hypopituitarism.

Neonatal hypoglycemia.

Diabetes insipidus.

Growth hormone deficiency.

Thyroid hormones.


Special Tests

Stereo disk photos.

Formal visual field tests when the patient is old enough.


Underlying endocrine disease.

Trial of patching for amblyopia.

Correct refractive errors (astigmatism).

Safety spectacles.

Developmental Abnormalities of Midline Brain Structures (De Morsier Syndrome—Septooptic Dysplasia)

Agenesis of anterior commissure.

Absent septum pellucidum and corpus callosum.

Central nervous system (CNS) basal encephalocele.

Testing for pituitary endocrine dysfunction is warranted.


Brodsky MC. Congenital optic disc anomalies. Surv Ophthalmol 1994;39:89–112.

Tilted Optic Disk

Other names:

Fuchs coloboma.

Inferior conus.

Inversion or dysversion of disk.


The optic disk may be congenitally tilted in one or both eyes, and this may result in a visual field defect.

Signs and Symptoms

Eighty percent of cases bilateral.

Ophthalmic Findings

See Figure 6.7.

Oval disk (with reduction in disk diameter).

Depression usually inferiorly.

Elevation usually superiorly.

Crescent, usually inferior (in direction of tilt).

Oblique direction of retinal vessels (emerging from superotemporal disk, sweep nasally before turning temporally).

Hypopigmentation (wedge-shaped area, opposite defective portion of the disc).

Visual field defects (usually superotemporal, may have bitemporal field defects simulating a chiasmal lesion, but defects do not respect vertical midline).


Optic disk photos.

Attention of field testing to vertical meridian.

Ectasia should match field defect location.

If vertical step in field, MRI scan.


Usually static.


FIGURE 6.7. The congenital tilted optic disk is apparent as the oval of nerve tissue superiorly. There is no apparent optic cup.




Giuffe G. The spectrum of the visual field defects in the tilted disk syndrome: clinical study and review. Neuroophthalmology 1986;6:239–246.



Papilledema is a term that should be reserved for optic disk edema attributable to increased intracranial pressure. All other forms of optic disk swelling should be referred to as optic disk edema.


Any cause of increased intracranial pressure:

Neoplastic (e.g., glioblastoma multiforme).

Infectious (e.g., abscess, meningitis).

Inflammatory (e.g., sarcoid).



Vascular (e.g., arteriovenous malformation [AVM]).

Subarachnoid hemorrhage.

Venous sinus thrombosis.


Pseudotumor cerebri.

Signs and Symptoms

Usually bilateral but may be unilateral or asymmetric.

Usually preserved visual acuity and color discrimination early.

May have transient visual loss (TVL) lasting for a few seconds resulting in obscurations of vision.

Ophthalmic Findings

images  Optic disk edema (Figure 6.8)

Disk hyperemia: congestion of fine optic nerve capillaries.

Opacification of nerve fiber layer.

Peripapillary hemorrhages.

Cotton-wool spots.

Loss of the physiologic cup is a late sign.

Venous dilation: elevation of optic nerve head.

Retinal exudates.

Circumferential retinal folds (Paton lines) in peripapillary region.

images  Visual field defects (enlarged blind spot, generalized constriction).

Glaucomalike defects.

images  No afferent pupillary defect unless severe and asymmetric.

images  Absent spontaneous venous pulsations.


Neuroimaging (to exclude mass lesion). Cranial MRI with contrast MR venogram (MRV) to exclude cerebral venous sinus thrombosis is recommended.

Lumbar puncture.

Opening pressure.

Cell count.

Glucose, protein, cytologic testing, cultures.

Differential Diagnosis


Optic disk drusen.

Hyperopic disks.

Other causes of bilateral optic disk edema.

Anterior ischemic optic neuropathy (ION).

Diabetic papillitis.

Optic neuritis.

Inflammatory or infiltrative optic disk edema.


Treat underlying cause.


Corticosteroids (but may worsen weight gain or pseudotumor cerebri).

Surgical, if the patient fails medical therapy.

Optic nerve sheath fenestration.

Ventriculoperitoneal or lumboperitoneal shunt.

Bariatric surgery for weight loss in pseudotumor cerebri.

Pseudotumor Cerebri


Pseudotumor cerebri is defined as increased intracranial pressure with normal neuroimaging and normal cerebrospinal fluid (CSF) content.


Usually idiopathic. Multiple associations:

images  Venous outflow obstruction.

Sagittal sinus thrombosis.

Radical neck surgery.

images  Endocrine, metabolic, or systemic diseases.


Addison disease.

Renal disease.

Systemic lupus erythematosus.

Behçet disease.

images  Exogenous agents.

Vitamin A.


Steroid withdrawal.

Nalidixic acid.

Anabolic steroids.



Usually young, obese women.

Beware of the diagnosis of pseudotumor cerebri in men, thin patients, or elderly individuals.

Signs and Symptoms

Papilledema (does not have to be present for diagnosis) (Figure 6.9).

Nonlocalizing sixth-nerve palsy, but no other cranial nerves involved or focal neurologic signs.


Transient visual obscurations (seconds).

Pulsatile tinnitus.


Neuroimaging. Preferably MRI with contrast MRV.

Lumbar puncture, check opening pressure.


FIGURE 6.9. Papilledema secondary to pseudotumor cerebri. Both optic nerves had a similar appearance.



Severe intractable headache unresponsive to headache medications.

Progressive visual loss.

Treat underlying associated conditions.

Eliminate exogenous factors.

Weight loss.



Less commonly, other medicines (e.g., digoxin, furosemide, topiramate).

Corticosteroids (see warning above).

Surgical therapy:

Optic nerve sheath fenestration.

Ventriculoperitoneal or lumboperitoneal shunt.

Special Testing

Visual field testing.

Optic disk photography.


Corbett JJ, Thompson HS. The rational management of idiopathic intracranial hypertension. Arch Neurol 1989;46: 1049–1051.

Wall M, George D. Idiopathic intracranial hypertension (pseudotumor cerebri): a prospective study of 50 patients. Brain 1991; 114:155–180.

Optic Nerve Head Drusen


Optic nerve head drusen are calcified hyaline bodies within the optic disk substance that may cause visual field loss.



Autosomal dominant in some cases.


Hyaline bodies; may be calcified.

Acellular laminated concretions in optic nerve substance.


Usually white patients.

Uncommon in black patients.

Signs and Symptoms

Usually asymptomatic.

May have visual field defects (slow progression).

(often arcuate, an enlarged blind spot, or visual field constriction).

Decreased visual acuity is rare, usually not due to drusen alone.

May have transient visual obscurations.

Differential Diagnosis

Arteritic ischemic optic neuropathy (AION).

Retinal artery or vein occlusion.

Subretinal neovascular membrane.

Subretinal exudation or heme.

Systemic Diseases

Associated conditions:

Retinitis pigmentosa.

Pseudoxanthoma elasticum.

Angioid streaks.

Retinal hemorrhages.

Chorioretinal folds.


Ophthalmic Findings

Usually bilateral (66%).

Discrete, amorphous deposits in optic nerve (Figure 6.10).

More often nasal than temporal.

Absent cup, small disk.

Anomalous disk vasculature.

No exudates or disk telangiectasias.

Tend to become more apparent with age.

Buried disk drusen in children.

Drusen transilluminate within disk head.

Subfoveal neovascularization.


A clinical diagnosis.

Examine family members.


FIGURE 6.10. Optic nerve drusen cause the surface of the optic nerve to appear bumpy. These drusen can become calcified and are visible on ultrasonography.

Special Tests

Ultrasound of nerve head (for buried drusen).

Computed tomography (CT) scan (rarely needed) may show calcific drusen.

Preinjection fluorescein angiography.


Probably not helpful in buried drusen.

May show delay in filling of peripapillary choroid.

Stereo disk photos.


Rosenberg MA, Savino PJ, Glaser JS. A clinical analysis of pseudopapilledema, I: population, laterality, acuity, refractive error, ophthalmoscopic characteristics, and co-incident disease. Arch Ophthalmol 1979;97:65–70.



A melanocytoma is a congenital pigmented abnormality of the optic disk head.



Signs and Symptoms

Usually asymptomatic.

Ophthalmic Signs

Black optic nerve head lesion (Figure 6.11).

May be slightly elevated.


FIGURE 6.11. Melanocytomas are black lesions frequently found off the optic nerve. They represent benign melanocytic proliferation.

Special Tests

Usually, none needed.


May grow slowly.



Differential Diagnosis


Combined hamartoma of the retina and RPE.


Joffe L, Shields JA, Osher RH, et al. Clinical and follow-up studies of melanocytomas of the optic disc. Trans Am Acad Ophthalmol Otolaryngol 1979;86:S1067–S1078.

Myelinated Nerve Fiber Layer


Myelination normally terminates at the lamina cribrosa but may occur in the nerve fiber layer of the retina.



Signs and Symptoms

Usually asymptomatic.

Ophthalmic Findings

White myelin in distribution of nerve fiber layer, often radiating from the optic nerve, but may occur only in the peripheral retina (Figure 6.12).


Clinical diagnosis.





Differential Diagnosis

Cotton-wool patch.

Retinal infiltrate.

Arteriole occlusion.

Optic Nerve and Chiasm Disorders

Ischemic Optic Neuropathy


ION is a clinical syndrome characterized by acute loss of vision, evidence for an optic neuropathy, and usually a swollen optic nerve in an elderly patient.


Arteritic ION: giant cell arteritis (GCA).

Nonarteritic ION: other vasculopathic risk factors (e.g., diabetes, atherosclerosis).

Signs and Symptoms

images  Nonarteritic:

Acute loss of visual acuity and/or visual field (usually altitudinal defect) (Figure 6.13).


Usually unilateral.

Usually painless.

images  Arteritic:

Usually more severe visual loss.

May be bilateral.

Constitutional symptoms and signs (headache, jaw claudication, scalp tenderness, malaise, fever, weight loss, anorexia, etc.).


Usually occurs in older patients (>40 years).

Elderly patients evaluate for GCA (>50 years).

Patients often have vasculopathic risk factors.

Ophthalmic Findings

Usually swollen optic nerve (anterior ION).

Relative afferent pupillary defect in unilateral or bilateral asymmetric cases.

Absent anterior or posterior segment inflammation.


FIGURE 6.13. Inferior altitudinal defect in a patient with anterior ION. Notice that the defect respects the horizontal midline. (From Miller N, Newman N. Walsh and Hoyt’s clinical neuro-ophthalmology, 4th ed., vol. 1. Baltimore, MD: Williams & Wilkins, 1995:213, with permission.)

Systemic Findings

images  Nonarteritic anterior ION:


Hypertension (left ventricular hypertrophy).



Hypotension (e.g., postsurgical, nocturnal, other) or anemia.

Collagen-vascular disease.

images  Arteritic:


Special Tests

Erythrocyte sedimentation rate (ESR) and/or C-reactive protein test for GCA.

Complete blood count with platelet count.

Temporal artery biopsy for GCA.


Temporal artery inflammation with or without giant cells for GCA.

Disruption of internal elastic lamina.

Intimal hyperplasia.

Disease Course

images  Nonarteritic:

Often, static visual loss.

May spontaneously improve.

May have progressive visual loss.

Small cup-to-disk ratio predisposing factor (“disk at risk”).

images  Arteritic:

Often, severe visual loss.

Untreated disease leads to bilateral severe visual loss.


images  Nonarteritic:

Treat underlying vasculopathic risk factors.

Aspirin (one per day) therapy may reduce risk in fellow eye (conflicting data).

No role for optic nerve sheath decompression (see Ischemic Optic Neuropathy Decompression Trial study).

images  Arteritic:

Oral prednisone (1.0 to 1.5 mg/kg/day).

Consider intravenous (i.v.) steroids for monocular patients, bilateral, or severe visual loss.


Nonarteritic: as needed.

Arteritic: 65% of patients develop arteric ION in fellow eye if untreated.

Follow ESR and clinical symptoms.

Taper steroids slowly.

Differential Diagnosis

Infectious optic neuropathy.

Inflammatory optic neuropathy.

Infiltrative optic neuropathy.

Compressive optic neuropathy.

Toxic optic neuropathy.

Hereditary optic neuropathy (Leber hereditary optic neuropathy).


Hayreh SS, Podhajsky PA, Raman R, et al. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol 1997;123:285–296.

The Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA 1995;273:625–632.

The Ischemic Optic Neuropathy Decompression Trial Research Group. Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol 1996;114:1355–1374.

Optic Neuritis


Optic neuritis is a general term that is used to describe idiopathic or demyelinating optic neuropathy.


Idiopathic: most frequent.

Demyelinating diseases: multiple sclerosis (MS).

Infectious diseases: viral disease, syphilis, cat scratch disease, Lyme disease, etc.

Inflammatory diseases: collagen-vascular disease, sarcoid, etc.

Signs and Symptoms

images  Typical optic neuritis is characterized by the following clinical features:

Unilateral, acute visual loss.

Pain worse with eye movement.

images  Atypical features:

Bilateral simultaneous onset in adults.

Anterior or posterior segment inflammation.

Macular star figure.

Lack of pain.


NLP vision.

Significant retinal hemorrhages or cotton wool patches.

Lack of significant improvement.

History or examination findings suggestive of underlying inflammatory or infectious process.


Usually young adults, but may occur in any age group.

Often female patients, but may be either gender.

Ophthalmic Findings

Decreased visual acuity and/or visual field.

Relative afferent pupillary defect in unilateral or bilateral but asymmetric cases.

Absence of anterior or posterior uveitis.

Normal (65%) or swollen (35%) optic nerve (most cases are retrobulbar).

Systemic Findings

Associated with MS.

Special Tests

MRI of the brain and orbits to look for demyelinating white matter disease (Figure 6.14).


Optic nerve demyelination.

Disease Course

Ninety percent of cases improve to normal or near-normal vision with or without treatment.


Typical optic neuritis:

MRI to evaluate for demyelinating disease.

No further laboratory evaluation necessary.

Atypical optic neuritis

MRI head and orbit with fat suppression and contrast.

Laboratory evaluation directed by history and physical examination (e.g., syphilis serologic testing, antinuclear antibody testing, chest radiography, and lumbar puncture).


images  If normal MRI imaging and typical optic neuritis:

Can observe for improvement.

Consider i.v. steroids (methylprednisolone 1,000 mg/day for 3 days followed by oral steroid taper [See Optic Neuritis Treatment Trial study]). I.V. steroids hasten visual recovery but do not change ultimate visual outcome.

images  If abnormal MRI consistent with MS:

Consider i.v. steroids.

Consider further evaluation for MS.

Neurologic consultation for consideration of immunomodulatory treatments (interferon beta).


Visual recovery over 4 to 6 weeks.

Risk of MS.

Differential Diagnosis

Infectious optic neuropathy.

Inflammatory optic neuropathy.


Infiltrative optic neuropathy.

Compressive optic neuropathy.

Toxic optic neuropathy.

Hereditary optic neuropathy (Leber hereditary optic neuropathy).


Beck RW, Cleary PA, Trobe JD, et al. The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. N Engl J Med 1992;326:581–588.

Beck RW, Trobe JD, the Optic Neuritis Treatment Group. What we have learned from the Optic Neuritis Treatment Trial. Ophthalmology 1995:102;1504–1508.

Toxic or Nutritional Optic Neuropathy


Patients with toxic or nutritional optic neuropathies usually present with bilaterally symmetric, slowly progressive visual loss.

Signs and Symptoms

Visual field defect: typically central or cecocentral scotomas.

Visual acuity loss.

Bilateral and symmetric visual loss.

Slowly progressive.

Optic nerve may appear normal until late in course.

Optic atrophy usually develops eventually.


images  Nutritional deficiencies:

Pernicious anemia.

Dietary deficiency (e.g., veganism, alcoholism).

Vitamin B12 deficiency.


images  Toxins:




Aniline dyes.




Carbon disulfide.

Carbon tetrachloride.








Disulfiram (Antabuse).






Ethchlorvynol (Placidyl).

Ethylene glycol.


Glue sniffing.

Halogenated hydroxyquinolone.

Heavy metals (e.g., arsenic, lead, mercury).



Iodopyracet (Diodrast).




Methyl acetate.

Methyl bromide.


Organophosphate pesticides.


Phenazone (antipyren).

Pheniprazine (Catron).



Sodium fluoride.


Styrene (vinyl benzyl).




Tolbutamide (Orinase).




MRI of the head.

Vitamin B12 level.

Folate level (serum and erythrocyte).


Urine heavy metal screen (mercury, lead, arsenic) if history is suggestive.

Leber Hereditary Optic Neuropathy


Leber hereditary optic neuropathy is a rare inherited mitochondrial optic neuropathy that affects young male patients.


Hereditary defect in mitochondrial DNA.


Affects men, usually in their twenties.

Rarely affects women (10% to 20% of cases).

Mitochondrial inheritance.

Signs and Symptoms

images  Visual acuity loss:

Usually acute, rapid, unremitting, and painless.

Usually 20/200 to hand motions but 20/20 to NLP range.

images  Visual field loss (central or cecocentral scotomas).

images  Bilateral involvement (second eye affected days to weeks to months later but 40% to 50% have simultaneous onset).

images  Fundus findings at the time of visual loss.

images  Triad of the “suspect fundus”:

1. Telangiectatic microangiopathy of optic neuropathy (Figure 6.15).

2. Apparent swelling of nerve fiber layer around disk.

3. Fluorescein angiogram often shows pseudoedema, but usually no leakage of dye at edge of disk.

images  Fundus appearance after visual loss:

Attenuated arterioles.

Nerve fiber layer loss, especially, papillomacular bundle.

Optic nerve pallor (temporally).

May develop nonglaucomatous cupping.


Usually systemically normal but may have some associated findings.

Occasional cardiac conduction defects.

Dystonia and other minor neurologic deficits.


Exclude other causes for an optic neuropathy.

Primary mitochondrial DNA mutation (e.g., mtDNA 11778, 3460, 14484).


Reducing metabolic stress on the optic nerve (e.g., smoking, known optic nerve toxins, and trauma).

Medical therapy remains unproven.



Vitamin B12.


Idebenone and other coenzyme Q10 analogues.


FIGURE 6.15. Hyperemic optic disk with telangiectatic vessels in a young male patient with Leber hereditary optic neuropathy.


Some patients experience spontaneous improvement.

Most remain unchanged.


Chalmers RM, Harding AE. A case-control study of Leber’s hereditary optic neuropathy. Brain 1996;119:1481–1486.

Riordan-Eva P, Sanders MD, Govan GG, et al. The clinical features of Leber’s hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain 1995;118:319–337.

Infiltrative or Inflammatory Optic Neuropathy


Infiltration or inflammation of the optic nerve may mimic demyelinating or idiopathic optic neuritis.

Signs and Symptoms

Visual loss.

Decreased color vision.

Ophthalmic Findings

Unilateral or bilateral.

Afferent pupillary defect.

Optic disk pallor or swelling.

Optic disk may appear normal (retrobulbar).

Atypical features for optic neuritis:

Bilateral simultaneous onset.

Lack of pain.

Lack of improvement.

Anterior or posterior segment inflammation.

Progressive or recurrent episodes.

Steroid responsive or steroid dependent.


images  Neoplastic:


Carcinomatous meningitis.



images  Paraneoplastic disease.

images  Infectious:

Cryptococcal meningitis.


Tuberculosis (TB).


images  Systemic inflammatory diseases:

Contiguous sinus disease.


Systemic lupus erythematosus.

Inflammatory bowel disease.


images  MRI of the head (and orbit if orbital signs present).

images  CBC.

images  Syphilis serologic testing (e.g., fluorescent treponemal antibody, absorbed [FTA-Abs], rapid plasmin reagin [RPR]).

images  Antinuclear antibody test.

images  Chest radiograph.

images  Angiotensin-converting enzyme, lysozyme.

images  Lumbar puncture.

images  Consider gallium or PET scan if suspect sarcoidosis.

images  Purified protein derivative skin testing if TB suspected.

images  Anti–double-stranded DNA, complement levels if systemic lupus erythematosus suspected.

Optic Pathway Tumors

Two common tumors of the optic pathway include optic nerve gliomas and meningiomas.

Optic Gliomas


Optic gliomas are glial tumors that may affect the optic nerve, chiasm, or tract and are found primarily in children and young adults.



Can occur at any age.

Seventy percent of patients with gliomas are diagnosed by age 10.

Ninety percent of gliomas are detected by age 20.

Reported in adults.

No gender predilection.


Neurofibromatosis (NF) type 1.

Incidence (Uncommon)

One to three percent of all orbital tumors.

One percent of intracranial neoplasms.

Three to six percent of intracranial tumors in childhood.


One or both optic nerves.

Optic chiasm or tract.

In general, the more anterior, the better the prognosis.

Disease Course

Most gliomas are benign juvenile pilocytic astrocytomas.

Mortality: depends more on location than histologic appearance.

Optic nerve alone, 14%.

Chiasm, 47% (variable).

With hydrocephalus, 77%.

Hypothalamic involvement, 91%.

Malignant optic nerve gliomas occur rarely in adults, usually men.

Signs and Symptoms

Painless progressive visual loss (optic neuropathy).

Overall vision loss 87%.

Vision of 20/20 to 20/40, 26%.

Vision of 20/50 to 20/200, 19%.

Vision of 20/300 or worse, 55%.

Hypothalamic symptoms or endocrinologic.

Diabetes insipidus.

Diencephalic wasting.

Precocious puberty.


Growth failure.

Visual field defects (central or bitemporal).

Ophthalmic Findings

Proptosis (orbital, 94%; chiasmal, 18%).

Disk swelling (35%) or atrophy (60%).

Rare optociliary shunt vessels.

Fifty percent of intraorbital tumors have disk edema.

Only 20% of chiasmal tumors have disk edema.

Strabismus (27%).

Nystagmus (spasmus nutans–like or see-saw nystagmus).


Consider glioma in any child with the following:

Unexplained decreased visual acuity.

Monocular or asymmetric nystagmus.

Optic atrophy.

Hypothalamic symptoms.

Diencephalic syndrome.

Spasmus nutans.

See-saw nystagmus.



MRI scan head and orbit with fat suppression with gadolinium superior to CT scan (Figure 6.16).

Can appear as a fusiform enlargement of optic nerve and/or kinking of optic nerve.

Search for stigmata of NF.

Assessment of growth and monitoring for precocious puberty.

Examine family members.

No biopsy usually indicated:

If clearly intrinsic to nerve or chiasm.

Intra-axial tumor.

History of NF type 1.

Possible biopsy indications.

Atypical features.

Infiltration or compression of chiasm.


FIGURE 6.16. Magnetic resonance image with gadolinium enhancement of a fusiform, hyperintense lesion corresponding to an optic nerve glioma.

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Sep 28, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on 6 Neuro-Ophthalmology

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