NEURO-OPHTHALMOLOGY

BASICS
Sidney Y. Cheng, MD
Neuro-Visual Disorder Section
Department of Ophthalmology
University of the East Ramon Magsaysay Memorial Medical
Center
Manila, Philippines

Objectives
To emphasize:
the importance of an accurate and detailed history
the importance of a complete and detailed neuroophthalmic evaluation
value of other diagnostic modalities
anatomy of the visual pathway, pupillary light reflex
pathway, and other cranial nerves
systemic implications of various N-O conditions

Neuro-Ophthalmic Examination
History

Patient profile
Chief complaint
HPI
Medical/Surgical
Family History
Social History

Neuro-Ophthalmic Examination
Examination
Visual Acuity
Uncorrected/corrected/pinhole
Color vision
Ishihara plates/Farnsworth-Munsell/Hardy-Rand Ritter
Color saturation tests

Photostress recovery test

Differentiates between optic nerve disease and visual loss secondary to a macular
process
With optic nerve disease recovery time is normal (less than 60 secs)
Recovery time is prolonged in maculopathies (>90 to 180 secs)
Limitation: cannot be performed if VA is less than 20/80

Contrast Sensitivity

Neuro-Ophthalmic Examination
Examination
Visual Fields
Confrontation
Amsler Grid
Automated
Humphrey/Octopus

Static
Goldmann
Tangent Screen

Pupillary Testing
Size, reaction to light, shape, (+) or (-) of APD

Neuro-Ophthalmic Examination
Examination
Alignment and Motility

Ductions and versions

Saccades and pursuit
Convergence
Prism measurements
Binocularity

Orbits
Exophthalmometry
Hertels Exophthalmometer

Cranial Nerves

Neuro-Ophthalmic Examination
Examination
Slit Lamp Examination

Eyelids
Conjunctiva
Cornea
Sclerae
Anterior Chamber
Posterior Chamber

Tonometry
Applanation
Schiotz

Neuro-Ophthalmic Examination
Examination
Fundus
Dilate
Optic Nerve Head

Cup-disk ratio, disc border

Optic Disc Drusen
Edema, pseudoedema, atrophy
SVP
Hemorrhage

Macula
Vessels:

caliber
Emboli, plaque
Sheathing
Hemorrhages, drusen, exudates, IRMA

Funduscopy
c/d: 0.3-0.4, clear disc
borders, (-) edema, (-)
drusen, (-) hges
macula: clear foveal reflex
vessels:

2:3 A:V ratio

(-) sheathing
(-) exudates
(-) hges
(-) emboli, plaques

Diagnostic Modalities

Visual Fields/Perimetry
Flourescein Angiography
VER/ERG
Neuro-Imaging
CT-Scan
MRI/MRA
PET Scan

Blood Works
CBC, ESR, ANA, RF, FTA-ABS, FBS, CRP, ACE

VISUAL PATHWAY

Visual Pathway

Retina
Optic Nerve
Chiasm
Optic Tract
LGB
Optic Radiations
Occipital Cortex

Visual Pathway

Retina

Retina
Thin, semitransparent, multilayer sheet of neural tissue
Ends at the Ora Serrata
Located 6.5 mm behind Schwalbes line temporally and 5.7mm nasally
0.1 mm thick at the Ora and 0.23 mm thick at the posterior pole

Closely attached to the RPE, and thus related to Bruchs Membrane,

the choroid nd the Sclera
This attachement may be easily separated (as in retinal detachment) to form the
Subretinal Space
However, at the optic disc and at the ora serrata, the retina and the RPE are firmly
attached

Macula

Characteristics:

Located in the area of the temporal vascular arcade

Region where more than one layer of ganglion cell nuclei can be found

Fovea:

Thinner outer nuclear layer

1.5 mm in diameter
Xanthophyll pigment

Foveola:

Central depression within the fovea

Photoreceptor cells (made up mainly of Cones), glial cells, Mueller cells
Responsible for the most acute vision

Foveal Avascular Zone:

Capillary-free zone
Important landmark for treatment of subretinal neovascular membrane

Retina
Layers of the Retina:

Internal limiting membrane

Abuts the vitreous

Nerve fiber layer

axons of the ganglion cells

Ganglion cell layer

Inner plexiform layer

Axons of the bipolar and amacrine cells and dendrites of the ganglion cells and their
synapses

Inner nuclear layer

Nuclei of bipolar, horizontal, Mueller and amacrine cells

Outer plexiform layer

Made up of the connections b/w photoreceptor synaptic bodies and the horizontal and
bipolar cells
Thicker at the macula (layer of Henle)

Outer nuclear layer of photoreceptor nuclei

Rods and cones

Extenal limiting membrane

Layer of rods and cones
Retinal pigment epithelium
Functions:

Vitamin A metabolism, maintenance of the outer blood-retinal barrier, phagocytosis of the

photoreceptor outer segments, absorption of light, heat exchange, formation of the basal
lamina,production of mucopolysaccharides, active transport

Adjacent RPE cells are attached to each other by junctional complexes which provide
both structural and metabolic stability (outer blood-retinal barrier)

Zonula occludentes and Zonula adherentes

Thickest at the Papillomacular Bundle and thinnest at the Fovea

Optic Nerve
not really a peripheral nerve, it is actually a direct
extension of the CNS
1.88mm V, 1.77mm H
Corresponds to the blind spot in perimetry
1.2 M axons
50 mm long
Blood supply:
Circle of zinn-haller
Short PCA
Choroidal circulation
Pial vasculature

Optic Nerve
4 parts:
intra-ocular (optic nerve head)
1 mm long; 1.5 mm H; 1.8 mm V
optic disc (visible by fundoscopy)
non-myelinated axons)

intra-orbital
25 mm in length; 3 to 4.5 mm in diam
lined by dura, arachnoid and pia mater
fuses at the apex of the orbit with periosteum and annulus of zinn

intra-osseous/intra-canalicular
9 mm in length
bordered by the paranasal sinuses
Firmly anchored to the bone
Significance: a small mass lesion in the canal can cause compressive optic neuropathy
even before it becomes readiologically visible

intra-cranial
10 mm long, may vary from 3 to 16 mm
region where the carotid artery bifurcates into ACA and MCA

Optic Chiasm
Optic Chiasm
(hemidecussation): represented by 47% uncrossed temporal
(ipsilateral) fibers and 53% crossed nasal (contralateral) fibers
knee of von willebrand: artifact of fixation
lies in the tuberculum sellae (sphenoid)
borders:

below: pituitary gland

inferolateral: cavernous sinuses
lateral: supraclinoid portions of the ICA
posterior: 3rd ventricle
forms part of the anterior wall of the 3rd ventricle

anterior: ACA
superior: floor of the 3rd ventricle

Optic Tracts
Contains axons whose ganglion cells are located in the temporal
retina on the ipsilateral eye and ganglion cells representing the
nasal retina of the contralateral eye
most of the axons end at the Lateral Geniculate Nucleus
some axons terminate in the paraventricular nucleus of the
Hypothalamus
mediates visual input to control diurnal rhythm

other fibers proceed toward the Medial Geniculate Nucleus and

terminate in the Pretectal nucleus of the rostral midbrain
mediates the Pupillomotor reflex

Lateral Geniculate Nucleus

Located in the thalamus
serves as a link between the retina and the visual cortex

Optic Radiations
aka: geniculocalcarine tract
composed of the 3 major bundles:
upper: serving the inferior field
Central: macular fibers
Lower: serving the superior field
Located about 5 cm from the tip of the temporal lone
Therefore: large temporal lobectomy will produce pie in the sky
visual field defect
Meyers Loop

Occipital Cortex
aka: Primary Visual Cortex; Striate Cortex; Area 17 of Brodmann
situated in the calcarine fissure
Macular projections are located in the posterior half of the occipital
lobe; peirpheral fibers are located more anteriorly along the
calcarine sulcus

VISUAL FIELDS

Visual Fields
Traquiars definition:
island of vision in a sea of blindness

Field Testing Methods

kinetic
static

2 Areas of visual field:

central: 30 degrees
peripheral: beyond 30 degrees

Visual Field Defects

scotoma:
relative: incomplete
absolute: complete

location of lesion:

optic nerve
optic chiasm
optic tract
temporal lobe
parietal lobe
occipital lobe

monocular loss of vision

bitemporal hemianopsia
(incongrous) homonymous hemianopsia
pie in sky
pie in the floor
(congrous) homonymous hemianopsia

Visual Field Defects

location of lesion:

optic nerve

monocular loss of
vision
optic chiasm
bitemporal
hemianopsia
optic tract
(incongrous)
homonymous
hemianopsia
temporal lobe
pie in sky
parietal lobe
pie in the floor
occipital lobe
(congrous)
homonymous
hemianopsia

Pupils

Pathway of the Pupillary Light Reflex

Afferent Limb

retina (rods and cones)

optic nerves
chiasm (decussation)
optic tracts
exits before the LGN and enters
the brainstem via brachium of
the superior colliculus

pretectal nuclei
Edinger-Westphal Nucleus
ipsi- and contra- lateral

Pathway of the Pupillary Light Reflex

Efferent Pathway
Parasympathetic Pathway

efferent fibers exit the midbrain and run together with CN III
initially located superiorly and then moves inferiorly at the level of the cavernous sinus
synapse at the ciliary ganglion
short ciliary nerves
iris sphincter and ciliary body

Sympathetic Pathway
First Order Neuron: originates in the post. Hypothalamus extends to intermediolateral
cell column of the spinal cord at C8 to T2 (Ciliospinal center of Budge)
Second Order Neuron/Preganglionic fibers: exit spinal cord and enter the cervical
sympathetic chain and terminates at the superior cervical ganglion
Third Order Neuron/Post-ganglionic fibers: ascend with the ICA, joins the ophthalmic
nerve and then enters the orbit through the superior ophthalmic fissure; sudomotor and
vasomotor fibers to the face travel with the ECA

Pupillary Light Reflex

Direct Pupillary Light Reflex
Consensual Light Reflex
Swinging Flashlight Test
key points in proper testing
dark room
non-accomodative target
light should cross fairly rapidly and remain for a few seconds

Pupillary Abnormalities
Afferent Pupillary Defect (Marcus-Gunn Pupil)

elicited by the swinging flashlight test

weak direct light reflex, normal consensual reflex
commonly seen with optic nerve lesions
gradation:
3 to 4 + APD: immediate dilatation of the pupil
1 to 2 + APD: no change then dilatation
trace APD:
initial constriction but with greater escape

indicative of an optic nerve pathology

Pupillary Abnormalities
Adies Tonic Pupil:

idiopathic
usually unilateral (80%)
more common in females (70%)
young: 20 to 40
dilated pupil with poor to absent light reflex
sectoral vermiform constriction

slow constriction to near-effort with subsequent slow redilation

may be associated with accomodative paresis
demonstrates cholinergic supersensitivity
0.125 % pilocarpine

Adies Syndrome: tonic pupil with diminished DTRs

Pupillary Abnormalities
Argyll-Robertson Pupils

miotic, irregular pupils

iris atrophy
absence of constriction to light, normal constriction to near-effort
bilateral but may be assymetric
poor dilatation in dark and to mydriatics
etiology:
neurosyphyllis, diabetes mellitus, alcoholism, multiple sclerosis,
sarcoidosis

Pupillary Abnormalities
Horners Syndrome:
Signs and Symptoms

miosis more apparent in dark

ptosis
apparent enophthalmos.
anhydrosis
heterochromia of the iris
congenital Horners

Diagnosis
Cocaine Test ( 4 % or 10 % cocaine eye drops)
confirms the presence of a Horners

Paredrine Test
differentiates between a 1st and 2nd order lesion and a third order lesion

Ocular Motor System

CN III (Oculomotor Nerve)

Originates within the brainstem, follows a subarachnoid
course, exits the skull base in the posterior, superolateral
aspect of the cavernous sinus
Nuclei are located along the midline of the dorsal brainstem
Blood supply:
Medial aspect: direct branches from the Basilar Artery
Fascicular portion: posterior cerebelar art., superior cerebellar art.

CN III (Oculomotor Nerve)

Nuclei:
Eyelids not affected
Bilateral superior rectus palsy

Fasciculus
Vascular or metastic
Often accompanied by other symptoms
Nothangel Syndrome:
Cerebellar ataxia

Benedickt Syndrome:
Involvement of the red nucleus and medial lemniscus
Contralateral loss of sensation and tremor

Weber Syndrome:
Contralateral spastic paralysis

CN III (Oculomotor Nerve)

Subarachnoid
Aneurysm of the PCA, inflammation, mass lesion
PCA aneurysm is the most common spontaneous cause of complete 3rd nerve palsy with
pupil involvement

Intracavernous
CCSF, aneurysm, tumors, infectious and granulomatous processes
May be accompanied by other cranial nerve disorders
CN V, CN VI, CN VII

Orbital
Divides into superior and inferior branches before the superior orbital fissure
Superior:
SR, levator palpebrae superioris

Inferior:
MR, IO, IR, parasympathetic fibers to ciliary ganglion

Trauma, infections, neoplasm

CN IV (Trochlear)
Function:
innervates the Superior Oblique (depression, abduction, intorsion)

longest of the cranial nerves

only one to originate dorsally and innervate contralaterally
most susceptible to trauma
only one to exit the dorsal surface of the brain stem
diagnosed by using the 3-step test

Parks-Bielschowsky 3-Step Test

Parks-Bielschowsky 3-Step Test

HYPER

Primary

Lateral

Head
Tilt

IPSI:
INFERIOR

IPSI:
OBLIQUE

CONTRA:
RECTUS

CONTRA:
SUPERIOR

IPSI:
OBLIQUE

CONTRA:
RECTUS

CN IV (Trochlear)
Nucleus
Arises in the periaqueductal gray matter beneath the aqueduct of
sylvius, continous with CN III
Isolated CN IV nuclear palsy - rare occurrence
Vascular disease, trauma, demyelination

Fasciculus
Susceptible to compression by the pineal gland

Subarachnoid
Runs just below the tentorium
Susceptible to damage at this area (compression, surgery)

Intracavernous
susceptible to damage secondary to surgical procedures around the
optic apex and canal

CN VI (Abducens)
Nucleus
Arises in the floor of the 4rd ventricle, looped over by the 7th n., and
the MLF passes medial to it
Mediates conjugate gaze
Sends projections to contralateral MLF and contralateral MR

Damage causes a conjugate gaze palsy

Ischemia, neoplasm, inflammation

Fasciculus
Exits the brainstem at the pontomedullary juntion
Pathology in the fascicular area is commonly associated with other
signs and symptoms
Millard-Gubler: ipsilateral abduction weakness and contralateral
hemiplegia

Vascular disease

CN VI (Abducens)
Subarachnoid
Passes along the clivus where it is vulnerable to compression or
infiltration
Lesions around the cerebellopontine angle may involve the 6th n. at
this location
Meningiomas, acoustic neuromas
Associated with unsteadiness and hearing loss

Also vulnerable to trauma

Basal skull fractures
Otorrhea, facial and auditory dysfunction

Increased ICP (ex.pseudotumor cerebri)

Secondary to stretching
Headache, nausea, vomitting, papilledema, 6th nerve paresis

CN VI (Abducens)
Petrous Pyramid
Dorellos canal
May be vulnerable to compression from the inf. Petrosal sinus (ex.
Carotico-Cavernous Fistula)
Infection and inflammation from the middle ear or mastoid (Gradenigo
Syndrome)

Intracavernous
Only nerve to run freely within the cavernous sinus
Joined by the sympathetic plexus and the 1st division of the 5th CN
Post-ganglionic horners with 6th N palsy

Gaze Centers

Supranuclear Control
Horizontal Gaze Center
Dorsal pons --> PPRF --> 6th nerve nucleus --> ipsilateral conjugate
gaze

Vertical Gaze Center

Primary vertical gaze centers are located in the RiMLF (located
dorsomedial to the anterior end of the red nucleus)
Pathways for up and down movement are separated in the midbrain

Internuclear Connections
MLF:
primary link between the horizontal and vertical gaze centers
Carries information from the infranuclear centers
Conveys information from the contralateral 6th n. nucleus to the ipsilateral
3rd n. subnucleus innervating the ipsilateral MR
INO: damage to the MLF; produces an adduction deficit; most commonly
secondary to demyelination (MS)

Supranuclear Control
Infranuclear Input
Vestibular Subnuclei
located in the pontomedullary junction
provides the tonic input to the horizontal and vertical gaze centers
determines the resting position of the eye

Supranuclear Input
Visually directed
Occipital lobes and calcarine cortex and superior colliculus

Non-visually directed
Pre-motor areas of the frontal lobes

Saccadic System
Saccades:
Rapid conjugate eye movements which are
initiated in the PPRF
3 characteristics:
Latency: time it takes to initiate a saccadic movement
Velocity: determined by the size of the saccades ( the
larger the saccade, the faster the velocity)
Accuracy:
Dysmetria: abnormality in saccadic accuracy
Hypometria: undershoot
Hypermetria: overshoot

Neural Integrator
Keeps the eye in the primary position
Elasticity of tissues surrounding the eye tend to move it
towards the center of the orbit --> the neyral integrator
sends impulses to the nerves innervating the EOMs to
keep the eyes in the primary position of gaze
Located in the nucleus prepositus hypoglossi in the area of
the medial vestibular nuclei at the level of the rostral
medulla
May be affected by alcohol and medications

Smooth Pursuit System

Responsible for maintaining fixation on a
moving target

Selected Neuro-Ophthalmic
Disorders

Anterior Ischemic Optic Neuropathy

Rapid, painless loss of vision, optic disc
edema which should typically resolve within 6
to 8 weeks followed by atrophy of the disc
2 types:
Arteritic Ischemic Optic Neuropathy
Non-Arteritic Ischemic Optic Neuropathy

Arteritic Ischemic Optic Neuropathy

Commonly associated with Giant Cell Arteritis (inflammatory disorder
of the large and medium sized vessels)
More common in the 7th or 8th decades of life
Patients suspected o having GCA should be treated aggressively
because the incidence of visual loss in the other eye may be as high as
90%
Signs and symptoms
Systemic:

Weight loss, loss of appetite, body malaise, scalp tenderness, jaw claudication,
tenderness or aching of the muscles and joints, fever

Ophthalmic

Amaurosis fugax, sudden visual loss, diplopia

ESR
Temporal artery biopsy

skip lesions
Granulomatous inflammation with epithelial cells, lymphocytes, giant cells
and disruption of the lamina elastica

Treatment

IV methylprednisone
Oral prednisone
Monitor ESR

Non-arteritic Ischemic Optic Neuropathy

Generally younger than patient with AION
Risk factors
HPN, DM, small vessel disease
disc at risk: tight, full looking optic disc with virtually no cup to disc
ratio

Risk of recurrence in the same eye is rare; risk for the other
eye is about 10 to 15 %
May have spontaneous recovery in 40%
Treatment
Optic Nerve Sheath Decompression
IONDT: not effective, may even make vison worse

Aspirin
Anecdotally said to decrease the chances for small vessel obstructive
disease

No treatment!

Optic Neuritis

Acute/subacute visual loss, pain on eye movement

Women, 15 to 45 years of age
(+) RAPD, generalized depression of the visual field
2/3 retrobulbar (patient cannot see, doctor does not see
pathology); 1/3 papillitis
Recovery of vision in majority of cases
95 % recover to 20/40 vision in one year

Diagnosis:
History
Neuroimaging
MRI: enhancement of the optic nerve sheath

Optic Neuritis
Treatment:
According to the ONTT
IV methylprednisone followed by oral taper
Does not influence final visual outcome
May have a 2 year protective effect against the development of MS
Oral steroids alone:
Should not be given --> increases the recurrence of attacks

No treatment:
A viable option
VA at one year the same whether patient was treated or not

Prognosis:
Visual: very good
90% of patients recover vision

Systemic Implications:
Multiple Sclerosis:
Patients with optic neuritis have a greater risk than the normal population of
developing MS
About 60 of patients with optic neuritis will go on to develop MS

Hereditary Optic Neuropathy

Dominant Optic Atrophy

mild to moderate visual loss in school age children (1st graders) -->
range 5 to 10
Tritanopic color defect on FM-100
pizza-pie optic atrophy
Central/cecocentral visual field defect

Lebers Hereditary Optic Neuropathy

Males in their late teens to early twenties are predominantly affected

Central/cecocentral visual field loss
Mya have spontaneous visual recovery in about 10 to 20%
Secondary to mutation in mitochondrial DNA, therefore transmission is
maternal in pattern
Ophthalmoscopic features
Hyperemia of the disc, peripapillary telangiectasia (w/o any evidence of
leakage on flourescein angiography), tortuosity of vessels

No treatment

Toxic/Nutritional Optic Atrophy

Causes:
Ethambutol, rifampicin, vitamin B12 deficiency,
thiamine deficiency, methanol

Painless, symmetric, bilateral loss of vision

Central/cecocentral visual field loss

Clinical classification of optic disc swelling

papilledema
strictly refers to edema of the disc secondary to an
increase in intra-cranial pressure

optic disc edema

may be secondary to an ischemic, inflammatory, or
infiltrative process

pseudoedema
conditions that may present clinically with an
appearance of a swollen disc or blurred disc margin

Optic Disc Edema

refers to edema of the disc due to other causes
With Optic Nerve
dysfunction

AION
Optic Neuritis
LHON
Intraorbital compression
Infiltrative Optic Neuropathy
Toxic and Metabolic Optic
Neuropathy

Without Optic Nerve

Dysfunction
CRVO
Papillophlebitis
Diabetic papillopathy

Pseudoedema
Definition: conditions that may present clinically with an
appearance of a swollen disc or blurred disc margin
Optic Disc Drusen
Congenitally full discs
Hyaloid remnants
Hyperopic eyes
Gliosis
Myelination

Optic Atrophy

The end result of diseases or

injuries to the optic nerve.

Funduscopy will show a very pale

optic disc

Common causes
Long standing papilledema
Inflammation (optic neuritis)
Ischemia
Glaucoma

Thank You!