(From Lawton AW: Retrochiasmal pathways, higher cortical function, and nonorganic visual loss. In: Yanoff M, Duker JS (eds) Ophthalmology, 2nd edn. St Louis, Mosby, 2004.)

Other areas

Horizontal gaze center: controls gaze to ipsilateral side; located in paramedian pontine reticular formation (PPRF) at level of CN 6 nucleus; projects to ipsilateral CN 6 nucleus and (via medial longitudinal fasciculus [MLF]) to contralateral CN 3 nucleus (Figure 4-6)

Medial longitudinal fasciculus: extends from anterior horn cells of the spinal cord to the thalamus; connects CN 3 nuclei and gaze centers (ipsilateral CN 3 and contralateral CN 6)

Vertical gaze center: originates in frontal eye fields or in superior colliculus; requires bilateral cortical input; projections travel to rostral interstitial nucleus of the MLF (riMLF) located behind red nucleus in midbrain; fibers travel to nuclei of CN 3 and 4 (Figure 4-7)

UPGAZE (lateral portion of riMLF): stimulates CN 3 nucleus (superior rectus (SR) and inferior oblique (IO))

DOWNGAZE (medial portion of riMLF): stimulates CN 3 nucleus (inferior rectus (IR)) and CN 4 nucleus

TORSIONAL MOVEMENTS: via interstitial nucleus of Cajal

Glial cells:

OLIGODENDROCYTES: myelination (begins at LGB and reaches lamina cribrosa after birth)

ASTROCYTES: support and nutrition

MICROGLIAL CELLS: phagocytosis

Figure 4-6 Horizontal eye movement pathways.

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Figure 4-7 Pathways for vertical gaze. Upgaze pathways originate in the rostral interstitial nucleus of the medial longitudinal fasciculus and project dorsally to innervate the oculomotor and trochlear nerves, traveling through the posterior commissure. Lesions to both axon bundles are necessary to produce upgaze paralysis (lesions B or C). Upgaze paralysis is a feature of the dorsal midbrain syndrome as a result of the lesion’s effect on the posterior commissure (lesion A). Downgaze pathways also originate in the rostral interstitial nucleus of the medial longitudinal fasciculus but probably travel more ventrally. Bilateral lesions also are needed to affect downgaze and usually are located dorsomedial to the red nucleus.

(From Donahue SP, Lavin PJM: Disorders of supranuclear control of ocular motility. In: Yanoff M, Duker JS (eds) Ophthalmology. London, Mosby, 1999.)

Physiology

Testing

(Reprinted with permission from Slamovits TL: Basic and clinical science course. Section 12: Retina and Vitreous. San Francisco, American Academy of Ophthalmology, 1993.)

Amsler grid

tests central 10° of the visual field (held at 35 cm); 10 cm × 10 cm grid composed of 5-mm squares; primarily used to evaluate foveal pathology

Optokinetic nystagmus (OKN)

presence suggests visual input is present; slow phase is noted in direction of moving stimulus

Parieto-occipital area controls slow pursuit, frontal lobe controls saccades

Pathway in visual association area terminates in ipsilateral pontine gaze center, resulting in pursuit movements to the same side (i.e. right visual association area controls pursuit to the right)

Can use to diagnose functional visual loss

Normal (symmetric) OKN response: occipital lobe, temporal lobe, LGB, or optic tract lesions do not interfere with pursuit

Deficient pursuit movements to side of lesion (asymmetric OKN): parietal lobe lesion

Cogan’s dictum (for homonomous hemianopia): asymmetric OKN indicates parietal lobe lesion; symmetric OKN indicates occipital lobe lesion

Reversal of OKN response: 60% of patients with congenital motor nystagmus

Dorsal midbrain syndrome: downward moving OKN drum causes convergence–retraction nystagmus

Congenital ocular motor apraxia: loss of voluntary horizontal gaze (vertical gaze intact); abnormal OKN (fast phase absent); maintained tonic deviation; requires neuroimaging

Potential acuity meter (PAM)

projects image of letter chart onto retina to test macular potential in patients with media opacities

Purkinje vascular phenomena and blue field entopic test

visualization of retinal vasculature; indicates gross retinal function

Visual Field (VF) Defects (Figure 4-9)

Types

Blind spot: physiologic due to ON; 15° temporal to fixation and slightly below horizontal midline

Baring of blind spot: glaucoma, normal patients

Cecocentral scotoma: involves blind spot and macula (within 25° of fixation); can occur in any condition that produces a central scotoma, dominant optic atrophy, Leber’s optic atrophy, toxic / nutritional optic neuropathy, optic pit with serous retinal detachment, optic neuritis

Central scotoma: unilateral (optic neuritis, compressive lesion of ON, retinal lesion [macular edema, disciform scar]); bilateral (toxic optic neuropathy, nutritional deficiency, macular lesions)

Arcuate scotoma: glaucoma, optic neuritis, anterior ischemic optic neuropathy (AION), branch retinal artery occlusion (BRAO), branch vein occlusion (BVO), ON drusen

Altitudinal defect: damage to upper or lower pole of optic disc; optic neuritis, AION, hemiretinal artery or vein occlusion

Spiraling of VF: suggests malingering / functional visual loss

Pseudobitemporal hemianopia (slope and cross-vertical meridian): uncorrected refractive error, tilted optic disc, enlarged blind spot (papilledema), large central or cecocentral scotoma, sector retinitis pigmentosa (nasal quadrant), overhanging lid, coloboma

Binasal defect: most nasal defects due to arcuate scotomas (glaucoma); also, pressure on temporal aspect of ON and anterior angle of chiasm, aneurysm, pituitary adenoma, infarct

Constricted field (ring scotoma): retinitis pigmentosa, advanced glaucoma, thyroid-related ophthalmopathy, ON drusen, vitamin A deficiency, occipital stroke, panretinal photocoagulation, functional visual loss

Neurologic defect: bilateral and respects vertical midline

Figure 4-9 VF defects.

Neurologic VF defects

Congruity of VF defect (retrochiasmal lesions): the more congruous the defect, the more posterior is the lesion

Superior field: anterior retinal ganglion cells → lateral portion of optic tract → temporal lobe (Meyer’s loop) → inferior bank of calcarine fissure

Vision not reduced by unilateral lesion posterior to the chiasm (20/20 acuity with macula-splitting hemianopia)

Chiasm: pituitary tumor, pituitary apoplexy, craniopharyngioma, meningioma, ON glioma, aneurysm, trauma, infection, metastatic tumor, MS, sarcoid

ANTERIOR CHIASMAL SYNDROME: lesion at junction of ON and chiasm; involves fibers in Willebrand’s knee (contralateral nasal retinal loop); causes junctional scotoma (central scotoma in 1 eye and superotemporal defect in the other)

BODY OF CHIASM: bitemporal hemianopia; vision may be preserved

POSTERIOR CHIASM: bitemporal hemianopia; primarily involves crossing macular fibers

LATERAL COMPRESSION (very rare): binasal hemianopia (more commonly caused by bilateral ON or retinal lesions)

Optic tract: posterior sellar or suprasellar lesions; homonymous hemianopia, contralateral RAPD

Retro-LGB lesions: 90% of isolated homonymous hemianopias due to stroke

Optic radiations:

TEMPORAL LOBE (Meyer’s loop): ‘pie-in-the-sky’ (superior homonymous hemianopia), formed visual hallucinations, seizures

PARIETAL LOBE: inferior homonymous hemianopia, hemiparesis, visual perception difficulty, agnosia, apraxia, OKN asymmetry

GERSTMANN’S SYNDROME: lesion of dominant parietal lobe; acalculia, agraphia, finger agnosia, left–right confusion, associated with inferior homonymous hemianopia if optic radiation involved

Cortical blindness: bilateral occipital lobe destruction; pupillary response intact, blindsight (rudimentary visual capacity), unformed visual hallucinations, Riddoch phenomenon (perceive moving targets but not stationary ones); may deny blindness (Anton’s syndrome)

Eye Movements under Supranuclear Control

Horizontal gaze center (Figures 4-10,4-11)

Saccades: contralateral frontal eye fields (frontal lobe) → superior colliculus → pontine paramedian reticular formation (PPRF) → horizontal gaze center (CN 6 nucleus) → ipsilateral lateral rectus l (LR) and contralateral medial rectus (MR) (via MLF)

Smooth pursuit: ipsilateral parieto-occipital lobe → superior colliculus (SC) → PPRF → horizontal gaze center → ipsilateral LR and contralateral MR (via MLF)

Figure 4-10 FEM (voluntary), SEM (pursuit), and SEM (vestibular). Pathways all converge on PPRF for horizontal eye movements. VN, vestibular nuclei.

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Figure 4-11 Composite reminder of the course and lateralization of the 3 conjugate horizontal eye movement pathways.

(From Bajandas FJ, Kline LB: Neuro-ophthalmology Review Manual. Thorofare, NJ, Slack, 1988, p 55.)

Smooth pursuit system

slow eye movements (SEM); following movements; ipsilateral parieto-occipital junction (horizontal); interstitial nucleus of Cajal (vertical)

Tests: Doll’s head, rotation, OKN (pursuit movement)

Abnormalities: demyelination (young patients), microvascular disease (older patients)

Vergence system

maintains foveal fixation on approaching object; controlled by frontal and occipital lobes, and possibly midbrain

Types: voluntary, accommodative, fusional

Test: look from distance to near

Nonoptic reflex systems

integrate eye movements with body movements

Normal caloric and Doll’s head responses when nuclear and internuclear connections are intact

Calorics: irrigate water into ears and observe induced eye movements; mnemonic COWS (cold opposite, warm same) refers to direction of fast phase of nystagmus in awake patient (jerk nystagmus); in comatose patient, get tonic deviation in opposite direction of mnemonic (sustained slow phase movement only (Figure 4-12))

Bilateral cold water irrigation produces nystagmus with fast phase upward in awake patient and downward tonic deviation in comatose patient; opposite effects with warm water

PATHWAY: vestibular nuclei → contralateral CN 6 nuclei → ipsilateral LR and contralateral MR (via MLF); no connection to the PPRF

Doll’s head (oculocephalic reflex): turn head and observe direction of eye movements; vestibular system moves eyes; use when patient cannot voluntarily move eyes

Eyes should have tonic movement in direction opposite head rotation

INTACT DOLL’S HEAD: supranuclear lesion (cranial nerve pathways to muscles are intact) (i.e. progressive supranuclear palsy)

ABNORMAL DOLL’S HEAD: lesion is infranuclear paresis or restrictive disease (perform forced ductions)

Bell’s phenomenon: upward turning of eyes with forced closure of eyelids

INTACT BELL’S PHENOMENON: supranuclear lesion

Figure 4-12 Vestibulo-ocular reflex demonstrating right beating nystagmus. Right COWS = cold opposite, warm same. (Calorics should be performed with head back 60°.)

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Diplopia

Types

Comitant: amount of deviation same in all fields of gaze

Incomitant: amount of deviation varies in different fields of gaze

Etiology

Monocular: high astigmatism, chalazion or lid mass, corneal abnormality, iris atrophy, polycoria, cataract, subluxed crystalline lens, decentered IOL, posterior capsular opacity, retinal pathology, functional

Binocular: neuropathic (cranial nerve palsies, MS), myopathic (thyroid-related ophthalmopathy, orbital pseudotumor), neuromuscular junction (MG)

Restrictive syndromes

IOP elevation >4 mmHg when eyes directed into restricted field (thyroid, trauma, inflammatory orbital disease, neoplastic process)

Eye Movement Disorders

Central Disorders (Supranuclear) (Figure 4-13)

Often no symptoms or complaints

Figure 4-13 Supranuclear control of eye movements. The pontine horizontal gaze center (blue) and the vertical gaze center in the midbrain (yellow) receive input from the frontal eye fields to initiate saccades, and from the parietal occipital temporal junction to control pursuit. These gaze centers control ocular motility by synapsing upon the ocular motor nerve nuclei (III, IV, and VI).

(From Lavin PJM, Donahue SP: Disorders of supranuclear control of ocular motility. In: Yanoff M, Duker JS (eds) Ophthalmology, 2nd edn. St Louis, Mosby, 2004.)

Horizontal Gaze Palsies

Congenital

Must distinguish between supranuclear and infranuclear causes; often abnormality of CN 6 or interneurons; vertical movements usually unaffected

Möbius’ Syndrome

Horizontal gaze palsy with CN 6, 7, 8, and 9 palsies (facial diplegia, deafness, abnormal digits)

Ocular Motor Apraxia

Saccadic palsy; impairment of voluntary horizontal eye movements with preservation of reflex movements; male > female; congenital or acquired (Balint’s syndrome); extensive bilateral cerebral disease involving supranuclear pathways (usually bilateral frontoparietal); usually benign and resolves in congenital disease

Associations

Gaucher’s disease, spinocerebellar degeneration, MR, ataxia-telangiectasia, Wilson’s disease, hypoplasia of corpus callosum, hydrocephalus; rarely cerebellar mass lesion (perform magnetic resonance imaging [MRI])

Acquired

Frontoparietal lesion (stroke, trauma, or infection)

tonic deviation of eyes to side of lesion (contralateral area 8 unopposed); seizure will move eyes away from lesion

Doll’s head testing and calorics

can turn eyes contralateral to lesion (intact vestibular pathway)

Parieto-occipital lesion

ipsilateral pursuit palsy (cogwheel pursuit)

Parkinson’s disease

reduced blinking, reduced saccades, reduced glabellar reflex suppression, blepharospasm, oculogyric crisis

Huntington’s chorea

Metabolic disorders: hyperglycemia, Wernicke’s encephalopathy, Wilson’s disease

Drug-induced

tricyclic antidepressants, phenytoin, phenothiazines

Pseudogaze palsies

myasthenia gravis, chronic progressive external ophthalmoplegia (CPEO), Duane’s syndrome

Internuclear ophthalmoplegia (INO) (Figure 4-14)

lesion of MLF; inability to adduct ipsilateral eye with nystagmus of fellow eye; may have skew deviation, vertical diplopia, and gaze-evoked, upbeat nystagmus; rule out myasthenia gravis

Unilateral: ischemia (older), demyelination (young patients), tumor, infection (meningitis, encephalitis), trauma, compression

Bilateral (involves both MLF near junction with the 3rd nerve nucleus in midbrain): demyelination / MS (most common), trauma, ischemia, infection, Chiari malformation, toxicity (amitriptyline, ethanol, benzodiazepine)

Types:

ANTERIOR (midbrain): preserved convergence

POSTERIOR (pons): impaired convergence (WEBINO = wall-eyed bilateral INO)

Figure 4-14 1. Right internuclear ophthalmoplegia (INO) 2. Bilateral INO.

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

One-and-a-half syndrome (Fisher syndrome) (Figure 4-15)

lesion of CN 6 nucleus and ipsilateral MLF; causes ipsilateral gaze palsy and INO; only movement is abduction of contralateral eye (with nystagmus); supranuclear lesion therefore convergence intact; called paralytic pontine exotropia when patient appears exotropic; patients with recovery from syndrome may develop oculopalatal myoclonus

Etiology: stroke (most common), MS, basilar artery occlusion, pontine metastases

Figure 4-15 Right acute syndrome (paralytic pontine exotropia).

(From Bajandas FJ, Kline LB: Neuro-Ophthalmology Review Manual. Thorofare, NJ, Slack, 1988.)

Vertical Gaze Abnormalities

Progressive Supranuclear Palsy (Steele-Richardson-Olszewski Syndrome)

Progressive vertical (early) and horizontal (late) gaze palsy (downward gaze usually affected first); no Bell’s phenomenon; doll’s head maneuver gives full range of movement (ROM), indicating supranuclear nature of disorder; eventually frozen globe to all stimuli, spasm of fixation, decreased blink rate, blepharitis, blepharospasm; occasionally, apraxia of eye opening; also, axial rigidity, dysarthria, and dementia

Whipple’s Disease

Oculomasticatory myorhythmia (vertical eye movements and facial activity similar to myoclonus)

Olivopontocerebellar Atrophy

Hereditary or sporadic; onset early adulthood; unsteady gait, slurred speech, dementia, optic atrophy, retinal degeneration

Eye movements progressively slow in all directions, finally complete external ophthalmoplegia

Kernicterus

Progressive loss of eye movements

Also, metabolic diseases (maple syrup disease, Wernicke’s encephalopathy), drug-induced

Nystagmus

Rhythmic involuntary oscillations of the eyes due to disorder of SEM system. Direction named after fast phase (brain’s attempt to correct problem), even though abnormality is noted with slow phase

Childhood Nystagmus

Most commonly, congenital, latent, sensory, and spasmus nutans (see Ch. 5, Pediatrics / Strabismus)

Physiologic Nystagmus

Several forms of nystagmus, including end-gaze, optokinetic, caloric, and rotational

Acquired Nystagmus

Pattern helps localize pathology, may have oscillopsia

Bruns’

Combination of gaze-paretic nystagmus when looking toward lesion (fast phase toward the lesion), and vestibular imbalance nystagmus when looking away from lesion (fast phase away from lesion) (i.e., with right-sided lesion: high-amplitude, low-frequency, right-beating nystagmus on right gaze; low-amplitude, high-frequency, left-beating nystagmus on left gaze)

Gaze-paretic component is of high amplitude and low frequency (because of impairment of horizontal gaze mechanism on side of lesion)

Vestibular component is of low amplitude and high frequency, with fast phase away from damaged vestibular nuclei on side of lesion

Due to cerebellopontine angle mass (usually acoustic neuroma or meningioma)

Convergence-Retraction

Cocontraction of lateral recti produces convergence movement (abnormal saccades) on attempted upgaze

Due to periaqueductal gray matter or dorsal midbrain lesion (Parinaud’s syndrome, pinealoma, trauma, brain stem arteriovenous malformation [AVM], MS)

Dissociated

Asymmetric between the 2 eyes (different direction, amplitude, frequency, etc); always pathologic

Due to posterior fossa disease, MS

Downbeat

Eyes drift upward with corrective saccade downward; worsens in downgaze, improves in upgaze; oscillopsia

Due to lesion that affects pathways responsible for downgaze; cervicomedullary junction lesion (Arnold-Chiari malformation, tumor, syrinx: 33%), spinocerebellar degeneration, intoxication, lithium, paraneoplastic cerebellar degeneration, 50% with no identifiable cause

Periodic Alternating Nystagmus (PAN)

Changes horizontal direction; jerks right 90 seconds, 5- to 10-second pause, jerks left 90 seconds, repeats; remains horizontal in vertical gaze; usually acquired

Due to disease of vestibulocerebellar system (albinism, cranio-cervico junction lesion [Arnold-Chiari malformation], MS, syphilis, tumor, vascular, dilantin, spinocerebellar degeneration)

Treatment

baclofen; surgery (large recession of all 4 recti muscles)

Upbeat

Eyes drift downward with corrective saccade upward

Due to medullary lesions, midline cerebellar (vermis) lesions, medulloblastoma, cerebellar degeneration, MS

Voluntary

Unsustainable for longer than 30 seconds; associated with hysteria and malingering

Other Eye Movement Disorders

Ocular Bobbing

Intermittent conjugate rapid downward eye movements followed by slow return to primary position

Often secondary to hemorrhage; patient usually comatose

Ocular Dipping

Opposite of ocular bobbing; intermittent rapid upward eye movements followed by slow return to primary position

Ocular Myoclonus

Vertical pendular nystagmus associated with synchronous palatal (uvula) beating

Due to bilateral pseudohypertrophy of inferior olives in medulla, lesion in myoclonic triangle (red nucleus, ipsilateral inferior olive, contralateral dentate nucleus)

Oscillopsia

Illusion of movement in the seen world

Usually occurs in SO myokymia and acquired nystagmus; rarely in congenital nystagmus

Due to vestibulo-ocular reflex abnormality

Cranial Nerve Palsies (FIGURE 4-16)

Oculomotor Nerve (CN 3) Palsy

Anatomy

nucleus in rostral midbrain; fascicle travels ventrally through midbrain, traversing red nucleus and corticospinal tract in cerebral peduncle; nerve enters subarachnoid space, passes between posterior cerebral and superior cerebellar arteries, then courses lateral to posterior communicating artery and enters lateral wall of cavernous sinus; receives sympathetics from internal carotid plexus; passes through superior orbital fissure and divides into superior (supplies SR and levator) and inferior (supplies IR, MR, IO, iris sphincter, and ciliary muscle) divisions.

Figure 4-16 Cranial nerve pathways.

(Copyright Peter K. Kaiser, MD.)

Only 1 subnucleus (midline location) supplies both levator palpebrae superioris; fibers from superior rectus (SR) subnucleus supply contralateral SR; Edinger-Westphal nucleus supplies both pupils (Figure 4-18)

Figure 4-18 Anatomy of the 3rd nerve nucleus. The 3rd nerve nucleus consists of a single, central, caudally located nucleus for the levator palpebrae, paired bilateral subnuclei with crossed projections that innervate the superior recti, and paired bilateral subnuclei with uncrossed projections that innervate the medial recti, inferior recti, and inferior oblique muscles. Parasympathetic input to the ciliary body and iris sphincter arises from the Edinger-Westphal nucleus.

(Redrawn from Warwick R: Representation of the extraocular muscles in the oculomotor nuclei of the monkey. J Comp Neurol 98:449–503,1953.)

Findings

ptosis, hypotropia, exotropia; may involve pupil (fixed and dilated); may cause pain

7 syndromes (Figure 4-17)

Nuclear CN 3 palsy (Figure 4-17,

): extremely rare; contralateral SR paresis and bilateral ptosis; pupil involvement is both or neither

Fascicle syndromes (see Figure 4-17,

): ischemic, infiltrative (tumor), or inflammatory (rare)

NOTHNAGEL’S SYNDROME: lesion of fascicle and superior cerebellar peduncle that causes ipsilateral CN 3 paresis and cerebellar ataxia

BENEDIKT’S SYNDROME: lesion of fascicle and red nucleus that causes ipsilateral CN 3 paresis, contralateral hemitremor (resting and intentional), and contralateral decreased sensation

WEBER’S SYNDROME: lesion of fascicle and pyramidal tract that causes ipsilateral CN 3 paresis and contralateral hemiparesis

CLAUDE’S SYNDROME: combination of Nothnagel’s and Benedikt’s syndromes

Uncal herniation (see Figure 4-17,

): supratentorial mass may cause uncal herniation compressing CN 3

Posterior communicating artery (PCom or PCA) aneurysm (see Figure 4-17,

): most common nontraumatic, isolated, pupil involving CN 3 palsy; aneurysm at junction of PCom and carotid artery compresses nerve, particularly external parasympathetic pupillomotor fibers; usually painful

Cavernous sinus syndrome (see Figure 4-17,

): associated with multiple CN palsies (3, 4, V₁, 6) and Horner’s; CN 3 palsy often partial and pupil sparing; may lead to aberrant regeneration

Orbital syndrome (see Figure 4-17,

): tumor, trauma, pseudotumor, or cellulitis; associated with multiple CN palsies (3, 4, V₁, 6), proptosis, chemosis, injection; ON can appear normal, swollen, or atrophic

After passing through the superior orbital fissure, CN 3 splits into superior and inferior divisions; therefore, CN 3 palsies distal to this point may be complete or partial

Pupil-sparing isolated CN 3 palsy (see Figure 4-17,

): small-caliber parasympathetic pupillomotor fibers travel in outer layers of nerve closer to blood supply (but more susceptible to damage by compression); fibers at core of nerve are compromised by ischemia; may explain pupil sparing in 80% of ischemic CN 3 palsies and pupil involved in 95% of compressive CN 3 palsies (trauma, tumor, aneurysm)

ETIOLOGY:

ADULTS: vasculopathic / ischemic (diabetes mellitus [DM], hypertension [HTN]), trauma, giant cell arteritis (CGA), occasionally tumor, aneurysm (very rare)

CHILDREN: congenital, trauma, tumor, aneurysm, migraine

14% of PCom aneurysms initially spare pupil

20% of diabetic CN 3 palsies involve pupil

Microvascular CN 3 palsies usually resolve in 3 to 4 months

Myasthenia gravis may mimic CN 3 palsy