# 25 - 34 Disorders of the Eye

### 34 Disorders of the Eye

■
■FURTHER READING
Aquino G et al: Towards the neurobiology of insomnia: A systematic 

review of neuroimaging studies. Sleep Med Rev 73:101878, 2024.
Cash RE et al: Association between sleep duration and ideal cardio­
vascular health among US adults, National Health and Nutrition 
Examination Survey. Prev Chronic Dis 17:E43, 2020.
Chinoy ED et al: Unrestricted evening use of light-emitting tablet 
computers delays self-selected bedtime and disrupts circadian timing 
and alertness. Physiol Rep 6:e13692, 2018.
Cribb L et al: Sleep regularity and mortality: A prospective analysis in 
the UK Biobank. Elife 12:RP88359, 2023.
Holth JK et al: The sleep-wake cycle regulates brain interstitial fluid 
PART 2
Cardinal Manifestations and Presentation of Diseases
tau in mice and CSF tau in humans. Science 363:880, 2019.
Landrigan CP et al: Effect on patient safety of a resident physician 
schedule without 24-hour shifts. N Engl J Med 382:2514, 2020.
Lee ML et al: High risk of near-crash driving events following nightshift work. Proc Natl Acad Sci USA 113:176, 2016.
Liblau RS et al: The immunopathogenesis of narcolepsy type 1. Nat 
Rev Immunol 24:33, 2024.
Scammell TE: Narcolepsy. N Engl J Med 373:2654, 2015.
Scammell TE et al: Neural circuitry of wakefulness and sleep. Neuron 
93:747, 2017.
Sletten TL et al: The importance of sleep regularity: A consensus 
statement of the National Sleep Foundation sleep timing and vari­
ability panel. Sleep Health 9:801, 2023.
VIDEO 33-1  A typical episode of severe cataplexy. The patient is joking and 
then falls to the ground with an abrupt loss of muscle tone. The electromyogram 
recordings (four lower traces on the right) show reductions in muscle activity 
during the period of paralysis. The electroencephalogram (top two traces) shows 
wakefulness throughout the episode. (Video courtesy of Giuseppe Plazzi, University 
of Bologna.)
VIDEO 33-2  Typical aggressive movements in rapid eye movement (REM) sleep 
behavior disorder. (Video courtesy of Dr. Carlos Schenck, University of Minnesota 
Medical School.)
Section 4	 Disorders of Eyes, Ears, Nose, 
and Throat
Jonathan C. Horton

Disorders of the Eye
THE HUMAN VISUAL SYSTEM
The visual system provides a supremely efficient means for the rapid 
assimilation of information from the environment to aid in the guid­
ance of behavior. The act of seeing begins with the capture of images 
focused by the cornea and lens on a light-sensitive membrane in 
the back of the eye called the retina. The retina is actually part of 
the brain, banished to the periphery to serve as a transducer for the 
conversion of patterns of light energy into neuronal signals. Light is 
absorbed by pigment in two types of photoreceptors: rods and cones. 
In the human retina, there are 100 million rods and 5 million cones. 
The rods operate in dim (scotopic) illumination. The cones function 
under daylight (photopic) conditions. The cone system is special­
ized for color perception and high spatial resolution. The majority 
of cones are within the macula, the portion of the retina that serves 
the central 10° of vision. In the middle of the macula, a small pit 

termed the fovea, packed exclusively with cones, provides the best 
visual acuity.
Photoreceptors hyperpolarize in response to light, activating bipolar, 
amacrine, and horizontal cells in the inner nuclear layer. After process­
ing of photoreceptor responses by this complex retinal circuit, the flow 
of sensory information ultimately converges on a final common path­
way: the ganglion cells. These cells translate the visual image impinging 
on the retina into a continuously varying barrage of action potentials 
that propagates along the primary optic pathway to visual centers 
within the brain. There are a million ganglion cells in each retina and 
hence a million fibers in each optic nerve.
Ganglion cell axons sweep along the inner surface of the retina in 
the nerve fiber layer, exit the eye at the optic disc, and travel through 
the optic nerve, optic chiasm, and optic tract to reach targets in the 
brain. The majority of fibers synapse on cells in the lateral geniculate 
nucleus, a thalamic relay station. Cells in the lateral geniculate nucleus 
project in turn to the primary visual cortex. This afferent retinoge­
niculocortical sensory pathway provides the neural substrate for visual 
perception. Separate classes of ganglion cells project to subcortical 
visual nuclei involved in other functions. Pupillary constriction and 
circadian rhythms are governed by ganglion cells that are intrinsically 
light sensitive, owing to a pigment named melanopsin. Pupil reflexes 
are mediated by a projection to the pretectal olivary nuclei. Their 
output is supplied to the Edinger-Westphal nuclei, which provide para­
sympathetic innervation to the iris sphincter via an interneuron in the 
ciliary ganglion. Circadian rhythms are timed by melanopsin ganglion 
cells that project to the suprachiasmatic nucleus. Visual orientation and 
eye movements are served by retinal input to the superior colliculus. 
Gaze stabilization and optokinetic reflexes are governed by a cluster 
of small retinal targets known collectively as the brainstem accessory 
optic system.
The eyes must be rotated constantly within their orbits to place 
and maintain targets of visual interest on the fovea. This activity, 
called foveation, or looking, is governed by an elaborate efferent 
motor system. Each eye is moved by six extraocular muscles that 
are supplied by cranial nerves from the oculomotor (III), trochlear 
(IV), and abducens (VI) nuclei. Activity in these ocular motor nuclei 
is coordinated by pontine and midbrain mechanisms for smooth 
pursuit, saccades, and gaze stabilization during head and body move­
ments. Large regions of the frontal and parietooccipital cortex con­
trol these brainstem eye movement centers by providing descending 
supranuclear input.
CLINICAL ASSESSMENT OF VISUAL 
FUNCTION
■
■REFRACTIVE STATE
In approaching a patient with reduced vision, the first step is to decide 
whether refractive error is responsible. In emmetropia, parallel rays 
from infinity are focused perfectly on the retina. Sadly, this condition 
is enjoyed by only a minority of the population. In myopia, the globe 
is too long, and light rays come to a focal point in front of the retina. 
Near objects can be seen clearly, but distant objects require a diverging 
lens in front of the eye. In hyperopia, the globe is too short, and hence, 
a converging lens is used to supplement the refractive power of the 
eye. In astigmatism, the corneal surface is not spherical, necessitating 
a cylindrical corrective lens. Most patients elect to wear eyeglasses or 
contact lenses to neutralize refractive error. An alternative is to perma­
nently alter the refractive properties of the cornea by performing laser 
in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK).
With the onset of middle age, presbyopia develops as the lens within 
the eye becomes unable to increase its refractive power to accommo­
date on near objects. To compensate for presbyopia, an emmetropic 
patient must use reading glasses. A patient already wearing glasses for 
distance correction usually switches to bifocals. The only exception is a 
myopic patient, who may achieve clear vision at near simply by remov­
ing glasses containing the distance prescription.
Refractive errors usually develop slowly and remain stable after ado­
lescence, except in unusual circumstances. For example, the acute onset

of diabetes mellitus can produce sudden myopia because of lens edema 
induced by hyperglycemia. Testing vision through a pinhole aperture is 
a useful way to screen quickly for refractive error. If acuity is improved 
by viewing through a pinhole, the patient needs a refraction to obtain 
best corrected visual acuity.
■
■VISUAL ACUITY
The Snellen chart is used to test acuity at a distance of 6 m (20 ft). 
A portable scale version of the Snellen chart called the Rosenbaum 
card is held at 36 cm (14 in.) from the patient (eFig. 34-1: available at 
accessmedicine.com/harrisons). All subjects should be able to read the 
6/6 m (20/20 ft) line with each eye using their refractive correction, 
if any. Patients who need reading glasses because of presbyopia must 
wear them for accurate testing with the Rosenbaum card. If 6/6 (20/20) 
acuity is not present in each eye, the deficiency in vision must be 
explained. If it is worse than 6/240 (20/800), acuity should be recorded 
in terms of counting fingers, hand motions, light perception, or no 
light perception. Legal blindness is defined by the Internal Revenue 
Service as a best corrected acuity of 6/60 (20/200) or less in the better 
eye or a binocular visual field subtending 20° or less. Loss of vision in 
one eye only does not constitute legal blindness. For driving, the laws 
vary by state, but most require a corrected acuity of 6/12 (20/40) in at 
least one eye for unrestricted privileges. Patients who develop a hom­
onymous hemianopia should not drive.
■
■PUPILS
The pupils should be tested individually in dim light with the patient 
fixating on a distant target. There is no need to check the near response 
if the pupils respond briskly to light, because isolated loss of constric­
tion (miosis) to accommodation does not occur. For this reason, the 
ubiquitous abbreviation PERRLA (pupils equal, round, and reactive to 
light and accommodation) implies a wasted effort with the last step. 
However, it is important to test the near response if the light response 
is poor or absent. Light-near dissociation occurs with neurosyphilis 
(Argyll Robertson pupil), with lesions of the dorsal midbrain (Parinaud’s 
syndrome), and after aberrant regeneration (oculomotor nerve palsy, 
Adie’s tonic pupil).
An eye with no light perception has no pupillary response to direct 
light stimulation. If the retina or optic nerve is only partially injured, 
the direct pupillary response will be weaker than the consensual pupil­
lary response evoked by shining a light into the healthy fellow eye. A 
relative afferent pupillary defect (Marcus Gunn pupil) is elicited with 
the swinging flashlight test. It is an extremely useful sign in retrobulbar 
optic neuritis and other optic nerve diseases, in which it may be the 
sole objective evidence for disease. In bilateral optic neuropathy, no 
afferent pupil defect is present if the optic nerves are affected equally.
Subtle inequality in pupil size, up to 0.5 mm, is a fairly common 
finding in normal persons. The diagnosis of essential or physiologic 
anisocoria is secure as long as the relative pupil asymmetry remains 
constant as ambient lighting varies. Anisocoria that increases in dim 
light indicates a sympathetic paresis of the iris dilator muscle. The triad 
of miosis with ipsilateral ptosis and anhidrosis constitutes Horner’s 
syndrome, although anhidrosis is an inconstant feature. A drop of 1% 
apraclonidine produces no effect on the normal pupil, but the miotic 
pupil dilates because of denervation hypersensitivity. Brainstem stroke, 
carotid dissection, and neoplasm impinging on the sympathetic chain 
occasionally are identified as the cause of Horner’s syndrome, but most 
cases are idiopathic.
Anisocoria that increases in bright light suggests a parasympathetic 
palsy. The first concern is an oculomotor nerve paresis. This possibility 
is excluded if the eye movements are full and the patient has no ptosis 
or diplopia. Acute pupillary dilation (mydriasis) can result from dam­
age to the ciliary ganglion in the orbit. Common mechanisms are infec­
tion (herpes zoster, influenza), trauma (blunt, penetrating, surgical), 
and ischemia (diabetes, temporal arteritis). After denervation of the 
iris sphincter, the pupil does not respond well to light, but the response 
to near is often relatively intact. When the near stimulus is removed, the 
pupil redilates very slowly compared with the normal pupil, hence the 
term tonic pupil. In Adie’s syndrome, a tonic pupil is present, sometimes 

in conjunction with weak or absent tendon reflexes in the lower 
extremities. This benign disorder, which occurs predominantly in 
healthy young women, is assumed to represent a mild dysautonomia. 
Tonic pupils are also associated with multiple system atrophy, segmen­
tal hypohidrosis, diabetes, and amyloidosis. Occasionally, a tonic pupil 
is discovered incidentally in an otherwise completely normal, asymp­
tomatic individual. The diagnosis is confirmed by placing a drop of 
dilute (0.125%) pilocarpine into each eye. Denervation hypersensitivity 
produces pupillary constriction in a tonic pupil, whereas the normal 
pupil shows no response. Pharmacologic dilatation from accidental or 
deliberate instillation of anticholinergic (atropine, scopolamine) drops 
can produce pupillary mydriasis. Gardener’s pupil refers to mydriasis 
induced by exposure to tropane alkaloids, contained in plants such as 
deadly nightshade, jimsonweed, or angel’s trumpet. When an anticho­
linergic agent is responsible for pupil dilation, 1% pilocarpine causes 
no constriction.

Disorders of the Eye
CHAPTER 34
Both pupils are affected equally by systemic medications. They are 
small with opiate use and large with anticholinergics (scopolamine). 
Parasympathetic agents (pilocarpine) used to treat glaucoma produce 
miosis. In any patient with an unexplained pupillary abnormality, a 
slit-lamp examination is helpful to exclude an occult foreign body, 
perforating injury, intraocular inflammation, adhesions (synechia), 
angle-closure glaucoma, and iris sphincter rupture from blunt trauma.
■
■EYE MOVEMENTS AND ALIGNMENT
Eye movements are tested by asking the patient, with both eyes open, 
to pursue a small target such as a pen tip into the cardinal fields of 
gaze. Normal ocular versions are smooth, symmetric, full, and main­
tained in all directions. Saccades, or quick refixation eye movements, 
are assessed by having the patient look back and forth between two 
stationary targets. The eyes should move rapidly and accurately in a 
single jump to their target. Ocular alignment can be judged by hold­
ing a penlight directly in front of the patient at about 1 m. If the eyes 
are straight, the corneal light reflex will be centered in the middle of 
each pupil. To test eye alignment more precisely, the cover test is use­
ful. The patient is instructed to look at a small fixation target in the 
distance. One eye is occluded with a paddle or hand, while the other 
eye is observed. If the viewing eye shifts position to take up fixation 
on the target, it was misaligned. If it remains motionless, the first eye 
is uncovered and the test is repeated on the second eye. If neither eye 
moves, the eyes are aligned orthotropically. If the eyes are orthotropic 
in primary gaze but the patient complains of diplopia, the cover test 
should be performed with the head tilted or turned in whatever direc­
tion elicits diplopia. With practice, the examiner can detect an ocular 
deviation (heterotropia) as small as 1° with the cover test. In a patient 
with vertical diplopia, a small deviation can be difficult to detect and 
easy to dismiss. The magnitude of the deviation can be measured by 
placing a prism in front of the misaligned eye to determine the power 
required to neutralize the fixation shift evoked by covering the other 
eye. Temporary press-on plastic Fresnel prisms, prism eyeglasses, or 
eye muscle surgery can be used to restore binocular alignment.
■
■STEREOPSIS
Stereoacuity is determined by presenting targets with retinal disparity 
separately to each eye by using polarized images. The most popular 
office tests measure a range of thresholds from 2000 to 40 s of arc. 
Normal stereoacuity is 40 s of arc. If a patient achieves this level of 
stereoacuity, one is assured that the eyes are aligned orthotropically and 
that vision is intact in each eye. Random dot stereograms have no mon­
ocular depth cues and provide an excellent screening test for strabismus.
■
■COLOR VISION
The retina contains three classes of cones, with visual pigments of 
differing peak spectral sensitivity: red (560 nm), green (530 nm), and 
blue (430 nm). The red and green cone pigments are encoded on the X 
chromosome, and the blue cone pigment on chromosome 7. Mutations 
of the blue cone pigment are exceedingly rare. Mutations of the red 
and green pigments cause congenital X-linked color blindness in 8% of 
males. Affected individuals are not truly color blind; rather, they differ

from normal subjects in the way they perceive color and how they 
combine primary monochromatic lights to match a particular color. 
Anomalous trichromats have three cone types, but a mutation in one 
cone pigment (usually red or green) causes a shift in peak spectral sen­
sitivity, altering the proportion of primary colors required to achieve a 
color match. Dichromats have only two cone types and therefore will 
accept a color match based on only two primary colors. Anomalous tri­
chromats and dichromats have 6/6 (20/20) visual acuity, but their hue 
discrimination is impaired. Ishihara color plates can be used to detect 
red-green color blindness. The test plates contain a hidden number 
that is visible only to subjects with color confusion from red-green 
color blindness. Because color blindness is almost exclusively X-linked, 
it is worthwhile screening only male children.

PART 2
Cardinal Manifestations and Presentation of Diseases
The Ishihara plates often are used to detect acquired defects in color 
vision, although they are intended as a screening test for congenital 
color blindness. Acquired defects in color vision frequently result 
from disease of the macula or optic nerve. For example, patients with 
a history of optic neuritis often complain of color desaturation long 
after their visual acuity has returned to normal. Color blindness also 
can result from bilateral strokes involving the ventral portion of the 
occipital lobe (cerebral achromatopsia). Such patients can perceive 
only shades of gray and also may have difficulty recognizing faces 
(prosopagnosia) (Chap. 32). Infarcts of the dominant occipital lobe 
sometimes give rise to color anomia. Affected patients can discriminate 
colors but cannot name them.
■
■VISUAL FIELDS
Vision can be impaired by damage to the visual system anywhere from 
the eyes to the occipital lobes. One can localize the site of the lesion 
with considerable accuracy by mapping the visual field deficit by finger 
confrontation and then correlating it with the topographic anatomy of 
the visual pathway (Fig. 34-1). Quantitative visual field mapping is per­
formed by computer-driven perimeters that present a target of variable 
intensity at fixed positions in the visual field (Fig. 34-1A). By generat­
ing an automated printout of light thresholds, these static perimeters 
provide a sensitive means of detecting scotomas in the visual field. 
They are exceedingly useful for serial assessment of visual function in 
chronic diseases such as glaucoma and pseudotumor cerebri.
The crux of visual field analysis is to decide whether a lesion is 
before, at, or behind the optic chiasm. If a scotoma is confined to one 
eye, it must be due to a lesion anterior to the chiasm, involving either 
the optic nerve or the retina. Retinal lesions produce scotomas that 
correspond optically to their location in the fundus. For example, a 
superior-nasal retinal detachment results in an inferior-temporal field 
cut. Damage to the macula causes a central scotoma (Fig. 34-1B).
Optic nerve disease produces characteristic patterns of visual field 
loss. Glaucoma selectively destroys axons that enter the superotempo­
ral or inferotemporal poles of the optic disc, resulting in arcuate scoto­
mas shaped like a Turkish scimitar, which emanate from the blind spot 
and curve around fixation to end flat against the horizontal meridian 
(Fig. 34-1C). This type of field defect mirrors the arrangement of the 
nerve fiber layer in the temporal retina. Arcuate or nerve fiber layer 
scotomas also result from optic neuritis, ischemic optic neuropathy, 
optic disc drusen, and branch retinal artery or vein occlusion.
Damage to the entire upper or lower pole of the optic disc causes an 
altitudinal field cut that follows the horizontal meridian (Fig. 34-1D). 
This pattern of visual field loss is typical of ischemic optic neuropathy 
but also results from retinal vascular occlusion, advanced glaucoma, 
and optic neuritis.
About half the fibers in the optic nerve originate from ganglion cells 
serving the macula. Damage to papillomacular fibers causes a cecocen­
tral scotoma that encompasses the blind spot and macula (Fig. 34-1E). 
If the damage is irreversible, pallor eventually appears in the temporal 
portion of the optic disc. Temporal pallor from a cecocentral scotoma 
may develop in optic neuritis, nutritional optic neuropathy, toxic optic 
neuropathy, Leber’s hereditary optic neuropathy, Kjer’s dominant optic 
atrophy, and compressive optic neuropathy. It is worth mentioning that 
the temporal side of the optic disc is slightly paler than the nasal side 
in most normal individuals. Therefore, it sometimes can be difficult to 

decide whether temporal pallor visible on fundus examination repre­
sents a pathologic change. Pallor of the nasal rim of the optic disc is a 
less equivocal sign of optic atrophy.
At the optic chiasm, fibers from nasal ganglion cells decussate into 
the contralateral optic tract. Crossed fibers are damaged more by 
compression than are uncrossed fibers. As a result, mass lesions of the 
sellar region cause a temporal hemianopia in each eye. Tumors ante­
rior to the optic chiasm, such as meningiomas of the tuberculum sella, 
produce a junctional scotoma characterized by an optic neuropathy in 
one eye and a superior-temporal field cut in the other eye (Fig. 34-1G). 
More symmetric compression of the optic chiasm by a pituitary ade­
noma (see Fig. 392-1), meningioma, craniopharyngioma, glioma, or 
aneurysm results in a bitemporal hemianopia (Fig. 34-1H). The insidi­
ous development of a bitemporal hemianopia often goes unnoticed by 
the patient and will escape detection by the physician unless each eye 
is tested separately.
It is difficult to localize a postchiasmal lesion accurately, because 
injury anywhere in the optic tract, lateral geniculate nucleus, optic 
radiations, or visual cortex can produce a homonymous hemianopia 
(i.e., a temporal hemifield defect in the contralateral eye and a match­
ing nasal hemifield defect in the ipsilateral eye) (Fig. 34-1I). A unilat­
eral postchiasmal lesion leaves the visual acuity in each eye unaffected, 
although the patient may read the letters on only the left or right half 
of the eye chart. Lesions of the optic radiations tend to cause poorly 
matched or incongruous field defects in each eye. Damage to the optic 
radiations in the temporal lobe (Meyer’s loop) produces a superior 
quadrantic homonymous hemianopia (Fig. 34-1J), whereas injury to 
the optic radiations in the parietal lobe results in an inferior quadrantic 
homonymous hemianopia (Fig. 34-1K). Lesions of the primary visual 
cortex give rise to dense, congruous hemianopic field defects. Occlu­
sion of the posterior cerebral artery supplying the occipital lobe is a 
common cause of total homonymous hemianopia. Some patients have 
macular sparing, because the central field representation at the tip of 
the occipital lobe is supplied by collaterals from the middle cerebral 
artery (Fig. 34-1L). Destruction of both occipital lobes produces 
cortical blindness. This condition can be distinguished from bilateral 
prechiasmal visual loss by noting that the pupil responses and optic 
fundi remain normal.
Partial recovery of homonymous hemianopia has been reported 
through computer-based rehabilitation therapy. During daily train­
ing sessions, patients fixate a central target while visual stimuli are 
presented within the blind region. The premise of vision restoration 
programs is that extra stimulation can promote recovery of partially 
damaged tissue located at the fringe of a cortical lesion. When fixation 
is controlled rigorously, however, no improvement of the visual fields 
can be demonstrated. No effective treatment exists for homonymous 
hemianopia caused by permanent brain damage.
DISORDERS
■
■RED OR PAINFUL EYE
Corneal Abrasions 
Corneal abrasions are seen best by placing a 
drop of fluorescein in the eye and looking with the slit lamp, using a 
cobalt-blue light. A penlight with a blue filter will suffice if a slit lamp 
is not available. Damage to the corneal epithelium is revealed by yellow 
fluorescence of the basement membrane exposed by loss of the overly­
ing epithelium. It is important to check for foreign bodies. To search 
the conjunctival fornices, the lower lid should be pulled down and the 
upper lid everted. A foreign body can be removed with a moistened 
cotton-tipped applicator after a drop of a topical anesthetic such as 
proparacaine has been placed in the eye. Alternatively, it may be pos­
sible to flush the foreign body from the eye by irrigating copiously with 
saline or artificial tears. If the corneal epithelium has been abraded, 
antibiotic ointment and a patch may be applied to the eye. A drop of an 
intermediate-acting cycloplegic such as cyclopentolate hydrochloride 
1% helps reduce pain by relaxing the ciliary body. The eye should be 
reexamined the next day. Minor abrasions may not require patching, 
antibiotics, or cycloplegia.

Monocular prechiasmal field defects:
C
D
E
F
A
B
30°
30°
Blind
spot Central scotoma
Normal field
right eye
Nerve-fiber bundle
(arcuate) scotoma
Altitudinal
scotoma
Cecocentral
scotoma
Enlarged blind-spot
with peripheral constriction
Binocular chiasmal or
postchiasmal field defects:
(Left eye)
(Right eye)
G
30°
100°
60°
Junctional scotoma
H
30°
Bitemporal hemianopia
I
30°
Optic
nerve
Homonymous hemianopia
J
Optic
chiasm
30°
Optic
tract
Superior quadrantanopia
K
Lateral
geniculate body
30°
Optic radiations
Inferior quadrantanopia
L
30°
Primary visual cortex
Homonymous hemianopia
with macular sparing
FIGURE 34-1  Ventral view of the brain, correlating patterns of visual field loss with the sites of lesions in the visual pathway. The visual fields overlap partially, creating 
120° of central binocular field flanked by a 40° monocular crescent on either side. The visual field maps in this figure were done with a computer-driven perimeter (Humphrey 
Instruments, Carl Zeiss, Inc.). It plots the retinal sensitivity to light in the central 30° by using a gray scale format. Areas of visual field loss are shown in black. The examples 
of common monocular, prechiasmal field defects are all shown for the right eye. By convention, the visual fields are always recorded with the left eye’s field on the left and 
the right eye’s field on the right, just as the patient sees the world.
Subconjunctival Hemorrhage 
This results from rupture of small 
vessels bridging the potential space between the episclera and the con­
junctiva. Blood dissecting into this space can produce an impressive 
red eye, but vision is not affected and the hemorrhage resolves without 
treatment. Subconjunctival hemorrhage is usually spontaneous but can 
result from blunt trauma, eye rubbing, or vigorous coughing. Occa­
sionally, it is a clue to an underlying bleeding disorder.
Pinguecula 
Pinguecula is a small, raised conjunctival nodule, 
usually at the nasal limbus. In adults such lesions are extremely 
common and have little significance unless they become inflamed 

30°
30°
30°
30°
Disorders of the Eye
CHAPTER 34
Right
Left
G
H
J
K
I
L
(pingueculitis). They are more apt to occur in workers with outdoor 
exposure. A pterygium resembles a pinguecula but has crossed the 
limbus to encroach on the corneal surface. Removal is justified when 
symptoms of irritation or blurring develop, but recurrence is common.
Blepharitis 
This refers to inflammation of the eyelids. The most 
common form occurs in association with acne rosacea or seborrheic 
dermatitis. The eyelid margins usually are colonized heavily by staphy­
lococci. Upon close inspection, they appear greasy, ulcerated, and 
crusted with scaling debris that clings to the lashes. Treatment consists 
of strict eyelid hygiene, applying warm compresses, and eyelash scrubs

with a cleansing agent. An external hordeolum (stye) is caused by 
staphylococcal infection of the superficial accessory glands of Zeis or 
Moll located in the eyelid margins. An internal hordeolum occurs after 
suppurative infection of the oil-secreting meibomian glands within 
the tarsal plate of the eyelid. Topical antibiotics such as bacitracin/
polymyxin B ophthalmic ointment can be applied. Systemic antibiot­
ics, usually tetracyclines or azithromycin, sometimes are necessary for 
treatment of meibomian gland inflammation (meibomitis) or chronic, 
severe blepharitis. A chalazion is a painless, chronic granulomatous 
inflammation of a meibomian gland that produces a pealike nodule 
within the eyelid. It can be incised and drained, but injection with 
glucocorticoids is equally effective. Basal cell, squamous cell, or mei­
bomian gland carcinoma should be suspected with any nonhealing 
ulcerative lesion of the eyelids.

PART 2
Cardinal Manifestations and Presentation of Diseases
Dacryocystitis 
An inflammation of the lacrimal drainage sys­
tem, dacryocystitis can produce epiphora (tearing) and ocular injec­
tion. Gentle pressure over the lacrimal sac evokes pain and reflux of 
mucus or pus from the tear puncta. Dacryocystitis usually occurs 
after obstruction of the lacrimal system. It is treated with topical and 
systemic antibiotics, followed by probing, silicone stent intubation, or 
surgery to reestablish patency. Entropion (inversion of the eyelid) or 
ectropion (sagging or eversion of the eyelid) can also lead to epiphora 
and ocular irritation.
Conjunctivitis 
Conjunctivitis is the most common cause of a red, 
irritated eye. Pain is minimal, and visual acuity is reduced only slightly. 
The most common viral etiology is adenovirus infection. It causes a 
watery discharge, a mild foreign-body sensation, and photophobia. 
Bacterial infection tends to produce a more mucopurulent exudate. 
Mild cases of infectious conjunctivitis usually are treated empirically 
with broad-spectrum topical ocular antibiotics such as sulfacetamide 
10%, polymyxin-bacitracin, or a trimethoprim-polymyxin combina­
tion. Smears and cultures usually are reserved for severe, resistant, or 
recurrent cases of conjunctivitis. To prevent contagion, patients should 
be admonished to wash their hands frequently, not to touch their eyes, 
and to avoid direct contact with others.
Allergic Conjunctivitis 
This condition is extremely common 
and often is mistaken for infectious conjunctivitis. Itching, redness, 
and epiphora are typical. The palpebral conjunctiva may become 
hypertropic with giant excrescences called cobblestone papillae. Irrita­
tion from contact lenses or any chronic foreign body also can induce 
formation of cobblestone papillae. Atopic conjunctivitis occurs in sub­
jects with atopic dermatitis or asthma. Symptoms caused by allergic 
conjunctivitis can be alleviated with cold compresses, topical vaso­
constrictors (naphazoline), antihistamines (olopatadine), and mast 
cell stabilizers (cromolyn). Topical glucocorticoid solutions provide 
dramatic relief of immune-mediated forms of conjunctivitis, but their 
long-term use is ill advised because of the complications of glaucoma, 
cataract, and secondary infection. Topical nonsteroidal anti-inflammatory 
drugs (NSAIDs; ketorolac) are better alternatives.
Keratoconjunctivitis Sicca 
Also known as dry eye, this produces 
a burning foreign-body sensation, injection, and photophobia. In mild 
cases, the eye appears surprisingly normal, but tear production mea­
sured by wetting of a filter paper (Schirmer strip) is deficient. A variety 
of systemic drugs, including antihistaminic, anticholinergic, and psy­
chotropic medications, result in dry eye by reducing lacrimal secretion. 
Disorders that involve the lacrimal gland directly, such as sarcoidosis 
and Sjögren’s syndrome, also cause dry eye. Patients may develop dry 
eye after radiation therapy if the treatment field includes the orbits. 
Ocular drying is also common after lesions affecting cranial nerve V or 
VII. Corneal anesthesia is particularly dangerous, because the absence 
of a normal blink reflex exposes the cornea to injury without pain to 
warn the patient. Dry eye is managed by frequent and liberal applica­
tion of artificial tears and ocular lubricants. In severe cases, the tear 
puncta can be plugged or cauterized to reduce lacrimal outflow.
Keratitis 
Keratitis is a threat to vision because of the risk of corneal 
clouding, scarring, and perforation. Worldwide, the two leading causes 

of blindness from keratitis are trachoma from chlamydial infection and 
vitamin A deficiency related to malnutrition. In the United States, con­
tact lenses play a major role in corneal infection and ulceration. They 
should not be worn by anyone with an active eye infection. In evaluat­
ing the cornea, it is important to differentiate between a superficial 
infection (keratoconjunctivitis) and a deeper, more serious ulcerative 
process. The latter is accompanied by greater visual loss, pain, photo­
phobia, redness, and discharge. Slit-lamp examination shows disrup­
tion of the corneal epithelium, a cloudy infiltrate or abscess in the 
stroma, and an inflammatory cellular reaction in the anterior chamber. 
In severe cases, pus settles at the bottom of the anterior chamber, giving 
rise to a hypopyon. Immediate empirical antibiotic therapy should be 
initiated after corneal scrapings are obtained for Gram’s stain, Giemsa 
stain, potassium hydroxide (KOH) prep, and cultures. Fortified topi­
cal antibiotics are most effective, supplemented with subconjunctival 
antibiotics as required. A fungal etiology should always be considered 
in a patient with keratitis. Fungal infection is common in warm humid 
climates, especially after penetration of the cornea by plant or vegetable 
material. Acanthamoeba keratitis is associated with improper disinfec­
tion of contact lenses.
Herpes Simplex 
The herpesviruses are a major cause of blindness 
from keratitis. Most adults in the United States have serum antibod­
ies to herpes simplex, indicating prior viral infection (Chap. 197). 
Primary ocular infection generally is caused by herpes simplex type 1 
rather than type 2. It manifests as a unilateral follicular blepharocon­
junctivitis that is easily confused with adenoviral conjunctivitis, unless 
telltale vesicles are present on the eyelids or conjunctiva. Recurrent 
ocular infection arises from reactivation of latent herpesvirus. A den­
dritic pattern of corneal epithelial ulceration revealed by fluorescein 
staining is pathognomonic for herpes infection but often not present. 
Involvement of both eyes is extremely rare. Corneal stromal inflamma­
tion produces edema, vascularization, and iridocyclitis. Herpes kerati­
tis is treated with cycloplegia and either a topical antiviral (trifluridine, 
ganciclovir) or an oral antiviral (acyclovir, valacyclovir) agent. Topical 
glucocorticoids are effective in mitigating corneal scarring but gener­
ally are reserved for cases involving stromal damage. Risks include 
corneal melting, perforation, prolonged infection, and glaucoma.
Herpes Zoster 
Herpes zoster from reactivation of latent varicella 
(chickenpox) virus causes a dermatomal pattern of painful vesicular 
dermatitis (Chap. 198). Ocular symptoms can occur after zoster 
eruption in any branch of the trigeminal nerve but are particularly 
common when vesicles form on the nose, reflecting nasociliary (V1) 
nerve involvement (Hutchinson’s sign). Herpes zoster ophthalmicus 
produces corneal dendrites, which can be difficult to distinguish from 
those seen in herpes simplex. Stromal keratitis, anterior uveitis, raised 
intraocular pressure, ocular motor nerve palsies, acute retinal necrosis, 
and postherpetic scarring and neuralgia are other common sequelae. 
Herpes zoster ophthalmicus is treated with antiviral agents and cyclo­
plegics. In severe cases, topical steroids may be added to reduce corneal 
scarring. Shingles should be prevented by vaccination of all healthy 
adults aged 50 years and older.
Episcleritis 
This is an inflammation of the episclera, a thin layer of 
connective tissue between the conjunctiva and the sclera. Episcleritis 
resembles conjunctivitis, but it is a more localized process and discharge 
is absent. Most cases of episcleritis are idiopathic, but some occur in 
the setting of an autoimmune disease. Scleritis refers to a deeper, more 
severe inflammatory process that frequently is associated with a connec­
tive tissue disease such as rheumatoid arthritis, lupus erythematosus, 
polyarteritis nodosa, granulomatosis with polyangiitis, or relapsing 
polychondritis. The inflammation and thickening of the sclera can be 
diffuse or nodular. In anterior forms of scleritis, the globe assumes a 
violet hue and the patient complains of severe ocular tenderness and 
pain. With posterior scleritis, the pain and redness may be less marked, 
but there is often proptosis, choroidal effusion, reduced motility, and 
visual loss. Episcleritis and scleritis should be treated with NSAIDs. If 
these agents fail, topical or even systemic glucocorticoid therapy may 
be necessary, especially if an underlying autoimmune process is active.

Anterior Uveitis 
Involving the anterior structures of the eye, uve­
itis was previously called iritis or iridocyclitis. The diagnosis requires 
slit-lamp examination to identify inflammatory cells floating in the 
aqueous humor or deposited on the corneal endothelium (keratic 
precipitates). Anterior uveitis develops in sarcoidosis, ankylosing spon­
dylitis, juvenile idiopathic arthritis, inflammatory bowel disease, pso­
riasis, reactive arthritis, and Behçet’s disease. It also is associated with 
herpes infections, syphilis, Lyme disease, onchocerciasis, tuberculosis, 
and leprosy. Although anterior uveitis can occur in conjunction with 
many diseases, no cause is found to explain the majority of cases. For 
this reason, laboratory evaluation usually is reserved for patients with 
recurrent or severe anterior uveitis. Treatment is aimed at reducing 
inflammation and scarring by judicious use of topical glucocorticoids. 
Dilatation of the pupil reduces pain and prevents the formation of 
synechiae.
Posterior Uveitis 
This diagnosis is made by observing inflam­
mation of the vitreous, retina, or choroid on fundus examination. It is 
more likely than anterior uveitis to be associated with an identifiable 
systemic disease. Some patients have panuveitis, or inflammation of 
both the anterior and posterior segments of the eye. Posterior uve­
itis is a manifestation of autoimmune diseases such as sarcoidosis, 
Behçet’s disease, Vogt-Koyanagi-Harada syndrome, and inflammatory 
bowel disease. It also accompanies diseases such as toxoplasmosis, 
onchocerciasis, cysticercosis, coccidioidomycosis, toxocariasis, and 
histoplasmosis; infections caused by organisms such as Candida, Pneu­
mocystis carinii, Cryptococcus, Aspergillus, herpes, and cytomegalovirus 
(see Fig. 200-1); and other diseases, such as syphilis, Lyme disease, 
tuberculosis, cat-scratch disease, Whipple’s disease, and brucellosis. In 
multiple sclerosis, chronic inflammatory changes can develop in the 
extreme periphery of the retina (pars planitis or intermediate uveitis). 
Glucocorticoids have been the mainstay of treatment for noninfectious 
uveitis. Biologic agents that target proinflammatory cytokines, such as 
the tumor necrosis factor alpha (TNF-α) inhibitor adalimumab, are 
effective at preventing vision loss in chronic uveitis.
Acute Angle-Closure Glaucoma 
This is an unusual but fre­
quently misdiagnosed cause of a red, painful eye. Asian populations 
have a particularly high risk of angle-closure glaucoma. Susceptible 
eyes have a shallow anterior chamber because the eye has either 
a short axial length (hyperopia) or a lens enlarged by the gradual 
development of cataract. When the pupil becomes mid-dilated, the 
peripheral iris blocks aqueous outflow via the anterior chamber 
angle and the intraocular pressure rises abruptly, producing pain, 
injection, corneal edema, obscurations, and blurred vision. In some 
patients, ocular symptoms are overshadowed by nausea, vomiting, or 
headache, prompting a fruitless workup for abdominal or neurologic 
disease. The diagnosis is made by measuring the intraocular pressure 
during an acute attack or by performing gonioscopy, a procedure 
that allows one to observe a narrow chamber angle with a mirrored 
contact lens. Acute angle closure is treated with acetazolamide (PO 
or IV), topical beta blockers, prostaglandin analogues, α2-adrenergic 
agonists, and pilocarpine to induce miosis. If these measures fail, 
a laser can be used to create a hole in the peripheral iris to relieve 
pupillary block. Many physicians are reluctant to dilate patients 
routinely for fundus examination because they fear precipitating an 
angle-closure glaucoma. The risk is actually remote and more than 
outweighed by the potential benefit to patients of discovering a hid­
den fundus lesion visible only through a fully dilated pupil. Moreover, 
a single attack of angle closure after pharmacologic dilatation rarely 
causes any permanent damage to the eye and serves as an inadvertent 
provocative test to identify patients with narrow angles who would 
benefit from prophylactic laser iridectomy.
Endophthalmitis 
This results from bacterial, viral, fungal, or 
parasitic infection of the internal structures of the eye. It usually is 
acquired by hematogenous seeding from a remote site. Chronically ill, 
diabetic, or immunosuppressed patients, especially those with a history 
of indwelling IV catheters or positive blood cultures, are at greatest risk 
for endogenous endophthalmitis. Although most patients have ocular 

Disorders of the Eye
CHAPTER 34
FIGURE 34-2  Roth’s spot, cotton-wool spot, and retinal hemorrhages in a 48-yearold liver transplant patient with candidemia from immunosuppression.
pain and injection, visual loss is sometimes the only symptom. Septic 
emboli from a diseased heart valve or a dental abscess that lodge in the 
retinal circulation can give rise to endophthalmitis. White-centered 
retinal hemorrhages known as Roth’s spots (Fig. 34-2) are considered 
pathognomonic for subacute bacterial endocarditis, but they also 
appear in leukemia, diabetes, and many other conditions. Endophthal­
mitis occurs as a complication of ocular surgery, especially glaucoma 
filtering, occasionally months or even years after the operation. An 
occult penetrating foreign body or unrecognized trauma to the globe 
should be considered in any patient with unexplained intraocular 
infection or inflammation.
■
■TRANSIENT OR SUDDEN VISUAL LOSS
Amaurosis Fugax 
This term refers to a transient ischemic attack 
of the retina (Chap. 438). Because neural tissue has a high rate of 
metabolism, interruption of blood flow to the retina for more than 
a few seconds results in transient monocular blindness, a term used 
interchangeably with amaurosis fugax. Patients describe a rapid fading 
of vision like a curtain descending, sometimes affecting only a portion 
of the visual field. Amaurosis fugax usually results from an embolus 
that becomes stuck within a retinal arteriole (Fig. 34-3). If the embolus 
breaks up or passes, flow is restored and vision returns quickly to nor­
mal without permanent damage. With prolonged interruption of blood 
flow, the inner retina suffers infarction. Ophthalmoscopy reveals zones 
of whitened, edematous retina following the distribution of branch 
retinal arterioles. Complete occlusion of the central retinal artery pro­
duces arrest of blood flow and a milky retina with a cherry-red fovea 
(Fig. 34-4). Emboli are composed of cholesterol (Hollenhorst plaque), 
calcium, or platelet-fibrin debris. The most common source is an ath­
erosclerotic plaque in the carotid artery or aorta, although emboli can 
also arise from the heart, especially in patients with diseased valves, 
atrial fibrillation, or wall motion abnormalities. Urgent evaluation is 
appropriate, because of the risk of stroke.
In rare instances, amaurosis fugax results from low central retinal 
artery perfusion pressure in a patient with a critical stenosis of the ipsi­
lateral carotid artery and poor collateral flow via the circle of Willis. In 
this situation, amaurosis fugax develops when there is a dip in systemic 
blood pressure or a slight worsening of the carotid stenosis. Sometimes 
there is contralateral motor or sensory loss, indicating concomitant 
hemispheric cerebral ischemia.
Retinal arterial occlusion also occurs rarely in association with 
retinal migraine, lupus erythematosus, anticardiolipin antibodies, 
anticoagulant deficiency states (protein S, protein C, and antithrombin

PART 2
Cardinal Manifestations and Presentation of Diseases
FIGURE 34-3  Hollenhorst plaque lodged at the bifurcation of a retinal arteriole 
proves that a patient is shedding emboli from the carotid artery, great vessels, or 
heart.
deficiency), Susac’s syndrome, pregnancy, IV drug abuse, blood dys­
crasias, dysproteinemias, and temporal arteritis.
Marked systemic hypertension causes sclerosis of retinal arteri­
oles, splinter hemorrhages, focal infarcts of the nerve fiber layer 
(cotton-wool spots), and leakage of lipid and fluid (hard exudate) 
into the macula (Fig. 34-5). In hypertensive crisis, sudden visual loss 
can result from ischemia induced by vasospasm of retinal arterioles. 
In addition, visual loss can occur from ischemic optic disc swelling. 
Patients with acute hypertensive retinopathy should be treated by low­
ering the blood pressure. However, the blood pressure should not be 
reduced precipitously, because there is a danger of optic disc infarction 
from sudden hypoperfusion.
Impending branch or central retinal vein occlusion can produce pro­
longed visual obscurations that resemble those described by patients 
with amaurosis fugax. The veins appear engorged and phlebitic, with 
numerous retinal hemorrhages (Fig. 34-6). In some patients, venous 
FIGURE 34-4  Central retinal artery occlusion in a 78-year-old man reducing acuity 
to counting fingers in the right eye. Note the splinter hemorrhage on the optic disc 
and the slightly milky appearance to the macula with a cherry-red fovea.

FIGURE 34-5  Hypertensive retinopathy with blurred optic disc, scattered 
hemorrhages, cotton-wool spots (nerve fiber layer infarcts), and foveal exudate in 
a 62-year-old man with chronic renal failure and a systolic blood pressure of 220.
blood flow recovers spontaneously, whereas others evolve a frank 
obstruction with extensive retinal bleeding (“blood and thunder” 
appearance), infarction, and visual loss. Venous occlusion of the 
retina is often idiopathic, but hypertension, diabetes, and glaucoma 
are prominent risk factors. Polycythemia, thrombocythemia, or other 
factors leading to an underlying hypercoagulable state should be cor­
rected; aspirin treatment may be beneficial.
Anterior Ischemic Optic Neuropathy (AION) 
This is caused 
by insufficient blood flow through the posterior ciliary arteries that 
supply the optic disc. It produces painless monocular visual loss that 
is sudden in onset, followed sometimes by stuttering progression. The 
optic disc is edematous and usually bordered by nerve fiber layer splin­
ter hemorrhages (Fig. 34-7). AION is divided into two forms: arteritic 
and nonarteritic. The nonarteritic form is most common. No specific 
cause is known, although diabetes, renal failure, and hypertension are 
FIGURE 34-6  Central retinal vein occlusion can produce massive retinal 
hemorrhage (“blood and thunder”), ischemia, and vision loss.

FIGURE 34-7  Anterior ischemic optic neuropathy from temporal arteritis in a 
64-year-old woman with acute disc swelling, splinter hemorrhages, visual loss, and 
an erythrocyte sedimentation rate of 60 mm/h.
common risk factors. Case reports have linked erectile dysfunction 
drugs to AION, but a causal association is doubtful. Evidence is strong 
that a crowded disc architecture and small optic cup predispose to the 
development of nonarteritic AION. In patients with such a “disc-at-risk,” 
the advent of AION in one eye increases the likelihood of the same 
event occurring in the other eye. No treatment is available for nonar­
teritic AION; glucocorticoids should not be prescribed.
About 5% of patients, especially Caucasian females aged >60, have 
the arteritic form of AION in conjunction with giant cell (temporal) 
arteritis (Chap. 375). It is urgent to recognize arteritic AION so that 
high doses of glucocorticoids can be instituted immediately to prevent 
blindness in the second eye. Tocilizumab, a monoclonal antibody 
against interleukin 6 receptor, is an effective alternative to glucocor­
ticoids for sustained suppression of giant cell arteritis. Symptoms of 
polymyalgia rheumatica may be present; the sedimentation rate and 
C-reactive protein level are usually elevated. In a patient with visual 
loss from suspected arteritic AION, temporal artery biopsy is manda­
tory to confirm the diagnosis. Administer glucocorticoids immediately, 
without waiting for the biopsy to be completed. The biopsy should be 
obtained as soon as practical, because prolonged glucocorticoid treat­
ment can hide inflammatory changes. It is important to harvest a long 
arterial segment and to examine a sufficient number of tissue sections. 
The histologic features of granulomatous inflammation are often quite 
subtle in temporal artery specimens. If an adequate biopsy is declared 
negative by an experienced pathologist, the diagnosis of arteritic AION 
is highly unlikely and glucocorticoids should usually be discontinued.
Posterior Ischemic Optic Neuropathy 
This is an uncommon 
cause of acute visual loss, induced by the combination of severe anemia 
and hypotension. Cases have been reported after major blood loss dur­
ing surgery (especially in patients undergoing cardiac or lumbar spine 
operation), shock, gastrointestinal bleeding, and renal dialysis. The 
fundus usually appears normal, although optic disc swelling develops 
if the process extends anteriorly far enough to reach the globe. Vision 
can be salvaged in some patients by immediate blood transfusion and 
reversal of hypotension.
Optic Neuritis 
This is a common inflammatory disease of the 
optic nerve. In the Optic Neuritis Treatment Trial (ONTT), the mean 
age of patients was 32 years, 77% were female, 92% had ocular pain 
(especially with eye movements), and 35% had optic disc swelling. In 
most patients, the demyelinating event was retrobulbar and the ocular 
fundus appeared normal on initial examination (Fig. 34-8), although 
optic disc pallor slowly developed over subsequent months.

Disorders of the Eye
CHAPTER 34
FIGURE 34-8  Retrobulbar optic neuritis is characterized by a normal fundus 
examination initially, hence the rubric “the doctor sees nothing, and the patient sees 
nothing.” Optic atrophy develops after severe or repeated attacks.
Virtually all patients experience a gradual recovery of vision after 
a single episode of optic neuritis, even without treatment. This rule is 
so reliable that failure of vision to improve after a first attack of optic 
neuritis casts doubt on the original diagnosis. Treatment with highdose IV methylprednisolone (250 mg every 6 h for 3 days) followed 
by oral prednisone (1 mg/kg per day for 11 days) makes no difference 
in ultimate acuity 6 months after the attack, but the recovery of visual 
function occurs more rapidly. Therefore, when visual loss is severe 
(worse than 20/100), IV followed by PO glucocorticoids are often 
recommended.
For some patients, optic neuritis remains an isolated event. How­
ever, the ONTT showed that the 15-year cumulative probability of 
developing clinically definite multiple sclerosis after optic neuritis 
is 50%. A brain magnetic resonance (MR) scan is advisable in every 
patient with a first attack of optic neuritis. If two or more plaques are 
present on initial imaging, treatment should be considered to prevent 
the development of additional demyelinating lesions (Chap. 455).
A particularly severe optic neuritis, often involving a long segment 
of nerve, occurs in neuromyelitis optica (NMO); it may be bilateral and 
associated with myelitis. NMO can occur as a primary disorder, in the 
setting of systemic autoimmune disease, or rarely, as a paraneoplastic 
condition. Detection of circulating antibodies directed against aqua­
porin-4 or myelin oligodendrocyte glycoprotein (MOG) is diagnostic. 
Treatment for acute episodes consists of glucocorticoids followed by 
satralizumab, eculizumab, or inebilizumab to prevent relapse. Neuro­
myelitis optica is discussed in detail in Chap. 456.
■
■LEBER’S HEREDITARY OPTIC NEUROPATHY
This disease usually affects young men, causing progressive, painless, 
severe central visual loss in one eye, followed weeks to years later by 
the same process in the other eye. Acutely, the optic disc appears mildly 
plethoric with surface capillary telangiectasias but no vascular leakage 
on fluorescein angiography. Eventually, optic atrophy ensues. Leber’s 
optic neuropathy is caused by a point mutation at codon 11778 in the 
mitochondrial gene encoding nicotinamide adenine dinucleotide dehy­
drogenase (NADH) subunit 4. Additional mutations responsible for the 
disease have been identified, most in mitochondrial genes that encode 
proteins involved in electron transport. Mitochondrial mutations that 
cause Leber’s neuropathy are maternally inherited by all children, but for 
unknown reasons, only 10% of cases occur in females. Clinical trials of 
gene therapy for this condition have been unsuccessful.
Toxic Optic Neuropathy 
This can result in acute visual loss with 
bilateral optic disc swelling and cecocentral scotomas. Cases have been

PART 2
Cardinal Manifestations and Presentation of Diseases
FIGURE 34-9  Optic atrophy is not a specific diagnosis but refers to the combination 
of optic disc pallor, arteriolar narrowing, and nerve fiber layer destruction produced 
by a host of eye diseases, especially optic neuropathies.
FIGURE 34-10  Papilledema in a young, obese woman with idiopathic intracranial hypertension (top), showing resolution after placement of a lumboperitoneal shunt (bottom).
reported from exposure to methyl alcohol (moonshine) and ethylene 
glycol (antifreeze). More commonly, visual loss develops gradually and 
produces optic atrophy (Fig. 34-9) without a phase of acute optic disc 
edema. Ethambutol causes a dose-dependent toxic optic neuropathy 
in 2% of patients. Other agents have been implicated in toxic optic 
neuropathy, but supporting evidence is often weak. The following is 
a partial list of potential offending drugs or toxins: disulfiram, carbon 
monoxide, ethchlorvynol, chloramphenicol, amiodarone, monoclonal 
anti-CD3 antibody, ciprofloxacin, digitalis, streptomycin, lead, arse­
nic, thallium, d-penicillamine, isoniazid, emetine, and sulfonamides. 
Metallosis (chromium, cobalt, nickel) from hip implant failure is a rare 
cause of toxic optic neuropathy. Deficiency states induced by starva­
tion, malabsorption, alcoholism, or gastric bypass can lead to insidious 
visual loss. Thiamine, vitamin B12, and folate levels should be checked 
in any patient with unexplained bilateral central scotomas and optic 
pallor.
Papilledema 
This connotes bilateral optic disc swelling from raised 
intracranial pressure (Fig. 34-10). Headache is a common but not 
invariable accompaniment. All other forms of optic disc swelling (e.g., 
from optic neuritis or ischemic optic neuropathy) should be called 
“optic disc edema.” This convention is arbitrary but serves to avoid 
confusion. Often it is difficult to differentiate papilledema from other 
forms of optic disc edema by fundus examination alone. Transient

visual obscurations are a classic symptom of papilledema. They occur 
in only one eye or simultaneously in both eyes. They usually last 
seconds but can persist longer. Obscurations follow abrupt shifts in 
posture or happen spontaneously. When obscurations are prolonged 
or spontaneous, the papilledema is more threatening. Visual acuity 
is not affected by papilledema unless the papilledema is severe, longstanding, or accompanied by macular edema and hemorrhage. Visual 
field testing shows enlarged blind spots and peripheral constriction 
(Fig. 34-1F). With unremitting papilledema, peripheral visual field 
loss progresses in an insidious fashion while the optic nerve develops 
atrophy. In this setting, reduction of optic disc swelling is an ominous 
sign of a dying nerve rather than an encouraging indication of resolv­
ing papilledema.
Evaluation of papilledema requires neuroimaging to exclude an 
intracranial lesion. Noninvasive MR vascular imaging may be useful 
in selected cases to search for a dural venous sinus thrombosis or an 
arteriovenous shunt. If neuroradiologic studies are negative, the sub­
arachnoid opening pressure should be measured in the lateral decu­
bitus position by lumbar puncture. Inaccurate pressure readings are a 
common pitfall. An elevated pressure, with normal cerebrospinal fluid, 
points by exclusion to the diagnosis of pseudotumor cerebri (idiopathic 
intracranial hypertension). Almost all patients are female, and most 
are obese. Treatment with a carbonic anhydrase inhibitor such as acet­
azolamide lowers intracranial pressure by reducing the production of 
cerebrospinal fluid and improves the visual fields. Weight reduction is 
vital: treatment with a glucagon-like peptide-1 receptor agonist is rec­
ommended in patients who cannot lose weight by diet control. If vision 
loss is severe or progressive, a shunt (preferably lumboperitoneal) 
should be performed without delay to prevent blindness. Endovascular 
placement of a stent across the junction of the transverse and sigmoid 
dural sinuses, where stenosis is usually present, has emerged as a new 
treatment option. Optic nerve sheath fenestration is a less effective 
approach and does not address other neurologic symptoms, such as 
headache. Occasionally, fulminant papilledema produces rapid onset 
of blindness. In such patients, emergency surgery should be performed 
to install a shunt.
Optic Disc Drusen 
These are refractile, glittering particles within 
the substance of the optic nerve head (Fig. 34-11). They are unrelated 
to drusen of the retina, which occur in age-related macular degen­
eration. Optic disc drusen are most common in people of northern 
European descent. Their diagnosis is obvious when they are visible on 
the surface of the optic disc. However, in many patients, they are hid­
den beneath the surface, producing pseudopapilledema. It is important 
FIGURE 34-11  Optic disc drusen are calcified, mulberry-like deposits of unknown 
etiology within the optic disc, giving rise to “pseudopapilledema.”

to recognize optic disc drusen to avoid an unnecessary evaluation for 
papilledema. When optic disc drusen are buried, B-ultrasound is the 
most sensitive way to detect them. They appear hyperechoic because 
they contain calcium. They are also visible on computed tomography 
(CT) or optical coherence tomography (OCT), a technique for acquir­
ing cross-section images of the retina. In most patients, optic disc dru­
sen are an incidental, innocuous finding, but they can produce visual 
obscurations. On perimetry, they give rise to enlarged blind spots 
and arcuate scotomas from damage to the optic disc. With increasing 
age, drusen tend to become more exposed on the disc surface as optic 
atrophy develops. Hemorrhage, choroidal neovascular membrane, and 
AION are more likely to occur in patients with optic disc drusen. No 
treatment is available.

Disorders of the Eye
CHAPTER 34
Vitreous Degeneration 
This occurs in all individuals with 
advancing age, leading to visual symptoms. Opacities develop in the 
vitreous, casting annoying shadows on the retina. As the eye moves, 
these distracting “floaters” move synchronously, with a slight lag 
caused by inertia of the vitreous gel. Vitreous traction on the retina 
causes mechanical stimulation, resulting in perception of flashing 
lights. Photopsia is brief and is confined to one eye, in contrast to the 
bilateral, prolonged scintillations of cortical migraine. Contraction of 
the vitreous can result in sudden separation from the retina, heralded 
by an alarming shower of floaters and photopsia. This process, known 
as vitreous detachment, is a common involutional event in the elderly. 
It is not harmful unless it damages the retina. A careful examination of 
the dilated fundus is important in any patient complaining of floaters 
or photopsia to search for peripheral tears or holes. If such a lesion is 
found, laser application can forestall a retinal detachment. Occasion­
ally a tear ruptures a retinal blood vessel, causing vitreous hemorrhage 
and sudden loss of vision. On attempted ophthalmoscopy the fundus is 
hidden by a dark haze of blood. Ultrasound is required to examine the 
interior of the eye for a retinal tear or detachment. If the hemorrhage 
does not resolve spontaneously, the vitreous can be removed surgically. 
Vitreous hemorrhage also results from the fragile neovascular vessels 
that proliferate on the surface of the retina in diabetes, sickle cell ane­
mia, and other ischemic ocular diseases.
Retinal Detachment 
This produces symptoms of floaters, flashing 
lights, and a scotoma in the peripheral visual field corresponding to the 
detachment (Fig. 34-12). If the detachment includes the fovea, there is 
an afferent pupil defect and the visual acuity is reduced. In most eyes, 
retinal detachment starts with a hole, flap, or tear in the peripheral 
retina (rhegmatogenous retinal detachment). Patients with peripheral 
FIGURE 34-12  Retinal detachment appears as an elevated sheet of retinal tissue 
with folds. In this patient, the fovea was spared, so acuity was normal, but an 
inferior detachment produced a superior scotoma.

retinal thinning (lattice degeneration) are particularly vulnerable to 
this process. Once a break has developed in the retina, liquefied vit­
reous is free to enter the subretinal space, separating the retina from 
the pigment epithelium. The combination of vitreous traction on the 
retinal surface and passage of fluid behind the retina leads inexorably 
to detachment. Patients with a history of myopia, trauma, or prior cata­
ract extraction are at greatest risk for retinal detachment. The diagnosis 
is confirmed by ophthalmoscopic examination of the dilated eye.

Classic Migraine 
(See also Chap. 441) This usually occurs with 
a visual aura lasting about 20 min. In a typical attack, a small central 
disturbance in the field of vision marches toward the periphery, leav­
ing a transient scotoma in its wake. The expanding border of migraine 
scotoma has a scintillating, dancing, or zigzag edge, resembling the 
bastions of a fortified city, hence the term fortification spectra. Descrip­
tions of fortification spectra vary widely and can be confused with 
amaurosis fugax. Migraine patterns usually last longer and are per­
ceived in both eyes, whereas amaurosis fugax is briefer and occurs in 
only one eye. Migraine phenomena also remain visible in the dark or 
with the eyes closed. Generally, they are confined to either the right 
or the left visual hemifield, but sometimes, both fields are involved 
simultaneously. Patients often have a long history of stereotypic attacks. 
After the visual symptoms recede, headache develops in most patients.
PART 2
Cardinal Manifestations and Presentation of Diseases
Transient Ischemic Attacks 
Vertebrobasilar insufficiency may 
result in acute homonymous visual symptoms. Many patients mis­
takenly describe symptoms in the left or right eye when, in fact, 
symptoms are occurring in the left or right hemifield of both eyes. 
Interruption of blood supply to the visual cortex causes a sudden 
fogging or graying of vision, occasionally with flashing lights or 
other positive phenomena that mimic migraine. Cortical ischemic 
attacks are briefer in duration than migraine, occur in older patients, 
and are not followed by headache. There may be associated signs of 
brainstem ischemia, such as diplopia, vertigo, numbness, weakness, 
and dysarthria.
Stroke 
Permanent vision loss occurs when interruption of blood 
supply from the posterior cerebral artery to the visual cortex is pro­
longed. The only finding on examination is a homonymous visual field 
defect that stops abruptly at the vertical meridian. Occipital lobe stroke 
usually is due to thrombotic occlusion of the vertebrobasilar system, 
embolus, or dissection. Lobar hemorrhage, tumor, abscess, and arterio­
venous malformation are other common causes of hemianopic cortical 
visual loss.
Factitious (Functional, Nonorganic) Visual Loss 
This is 
claimed by hysterics or malingerers. The latter account for the vast 
majority, seeking sympathy, special treatment, or financial gain by 
feigning loss of sight. The diagnosis is suspected when the history is 
atypical, physical findings are lacking or contradictory, inconsisten­
cies emerge on testing, and a secondary motive can be identified. In 
our litigious society, the fraudulent pursuit of recompense often drives 
factitious visual symptoms.
■
■CHRONIC VISUAL LOSS
Cataract 
Cataract is a clouding of the lens sufficient to affect 
vision. Most cataracts develop slowly as a result of aging, leading to 
gradual impairment. The formation of cataract occurs more rapidly in 
patients with a history of uveitis, diabetes mellitus, ocular trauma, or 
vitrectomy. Cataracts are acquired in a variety of genetic diseases, such 
as myotonic dystrophy, neurofibromatosis type 2, and galactosemia. 
Radiation therapy and glucocorticoid treatment can induce cataract as 
a side effect. Such cataracts typically have a posterior subcapsular loca­
tion. Cataract can be detected by noting an impaired red reflex when 
viewing light reflected from the fundus with an ophthalmoscope or by 
examining the dilated eye with the slit lamp.
The only treatment for cataract is surgical extraction of the opaci­
fied lens. Thirty million cataract operations are performed each year 
around the globe. The operation generally is done under local anesthe­
sia on an outpatient basis. A plastic or silicone intraocular lens is placed 

within the empty lens capsule in the posterior chamber, substituting for 
the natural lens and leading to rapid recovery of sight. More than 95% 
of patients who undergo cataract extraction can expect an improve­
ment in vision. In some patients, the lens capsule remaining in the eye 
after cataract extraction eventually turns cloudy, causing secondary 
loss of vision. A small opening, called a posterior capsulotomy, is made 
in the lens capsule with a laser to restore clarity.
Glaucoma 
Glaucoma is a slowly progressive, insidious optic neu­
ropathy that usually is associated with chronic elevation of intraocu­
lar pressure. After cataract, it is the most common cause of blindness 
in the world. It is especially prevalent in people of African descent. 
The mechanism by which raised intraocular pressure injures the 
optic nerve is not understood. Axons entering the inferotemporal and 
superotemporal aspects of the optic disc are damaged first, producing 
typical nerve fiber bundle defects called arcuate scotomas. As fibers 
are destroyed, the neural rim of the optic disc shrinks and the physi­
ologic cup within the optic disc enlarges (Fig. 34-13). This process 
is referred to as pathologic “cupping.” The cup-to-disc diameter is 
expressed as a fraction (e.g., 0.2). The cup-to-disc ratio ranges widely 
in normal individuals, making it difficult to diagnose glaucoma 
reliably simply by observing an unusually large or deep optic cup. 
Careful documentation of serial examinations is helpful. In a patient 
with physiologic cupping, the large cup remains stable, whereas in a 
patient with glaucoma, it expands relentlessly over the years. Obser­
vation of progressive cupping and detection of an arcuate scotoma 
or a nasal step on computerized visual field testing is sufficient to 
establish the diagnosis of glaucoma. OCT reveals corresponding loss 
of fibers along the arcuate pathways in the nerve fiber layer and thin­
ning of the ganglion cell complex.
Most patients with glaucoma have open anterior chamber angles. 
The cause of elevated intraocular pressure is usually unknown. 
Although a positive family history is a risk factor, genetic mutations 
impairing aqueous filtration from the eye have been identified in only 
a minority of cases. Surprisingly, a third of patients with open-angle 
glaucoma have an intraocular pressure within the normal range of 
10–20 mmHg. Among patients with this normal-tension form of glau­
coma, high myopia is more common.
Chronic angle-closure glaucoma and chronic open-angle glaucoma 
are usually asymptomatic. Only acute angle-closure glaucoma causes 
a red or painful eye, from abrupt elevation of intraocular pressure. In 
all forms of glaucoma, foveal acuity is spared until end-stage disease is 
reached. For these reasons, severe and irreversible damage can occur 
FIGURE 34-13  Glaucoma results in “cupping” as the neural rim is destroyed and 
the central cup becomes enlarged and excavated. The cup-to-disc ratio is about 
0.8 in this patient.

before either the patient or the physician recognizes the diagnosis. 
Screening of patients for glaucoma by noting the cup-to-disc ratio on 
ophthalmoscopy and by measuring the intraocular pressure is vital. 
Glaucoma is treated with topical adrenergic agonists, cholinergic ago­
nists, beta blockers, prostaglandin analogues, and carbonic anhydrase 
inhibitors. Occasionally, systemic absorption of beta blocker from 
eyedrops can be sufficient to cause side effects of bradycardia, hypoten­
sion, heart block, bronchospasm, or depression. Laser treatment of the 
trabecular meshwork in the anterior chamber angle improves aqueous 
outflow from the eye. If medical or laser treatments fail to halt optic 
nerve damage from glaucoma, a filter must be constructed surgically 
(trabeculectomy) or a drainage device placed to release aqueous from 
the eye in a controlled fashion.
Macular Degeneration 
This is a major cause of gradual, painless, 
bilateral central visual loss in the elderly. It occurs in a nonexudative 
(dry) form and an exudative (wet) form. Inflammation may be impor­
tant in both forms of macular degeneration; susceptibility is associated 
with variants in the gene for complement factor H, an inhibitor of the 
alternative complement pathway. The nonexudative process begins 
with the accumulation of extracellular deposits called drusen under­
neath the retinal pigment epithelium. On ophthalmoscopy, they are 
pleomorphic but generally appear as small discrete yellow lesions clus­
tered in the macula (Fig. 34-14). With time, they become larger, more 
numerous, and confluent. The retinal pigment epithelium becomes 
focally detached and atrophic, causing visual loss by interfering with 
photoreceptor function. Treatment with vitamins C and E, beta-carotene, 
and zinc may slightly retard dry macular degeneration.
Exudative macular degeneration, which develops in only a minority 
of patients, occurs when neovascular vessels from the choroid grow 
through defects in Bruch’s membrane and proliferate underneath the 
retinal pigment epithelium or the retina. Leakage from these vessels 
produces elevation of the retina, with distortion (metamorphopsia) 
and blurring of vision. Although the onset of these symptoms is usually 
gradual, bleeding from a subretinal choroidal neovascular membrane 
sometimes causes acute visual loss. Neovascular membranes can be 
difficult to see on fundus examination because they are located beneath 
the retina. Fluorescein angiography and OCT are extremely useful for 
their detection. Major or repeated hemorrhage under the retina from 
neovascular membranes results in fibrosis, development of a round 
(disciform) macular scar, and permanent loss of central vision.
Exudative macular degeneration can be treated with intraocu­
lar injection of antagonists to vascular endothelial growth factor. 
FIGURE 34-14  Age-related macular degeneration consisting of scattered yellow 
drusen in the macula (dry form) and a crescent of fresh hemorrhage temporal to the 
fovea from a subretinal neovascular membrane (wet form).

Bevacizumab, ranibizumab, aflibercept, or brolucizumab is admin­
istered by direct injection into the vitreous cavity, beginning on a 
monthly basis. These antibodies cause the regression of neovascular 
membranes by blocking the action of vascular endothelial growth fac­
tor, thereby improving visual acuity.

Central Serous Chorioretinopathy 
This primarily affects males 
between the ages of 20 and 50 years. Leakage of serous fluid from the 
choroid causes small, localized detachment of the retinal pigment 
epithelium and the neurosensory retina. These detachments produce 
acute or chronic symptoms of metamorphopsia and blurred vision 
when the macula is involved. They are difficult to visualize with a 
direct ophthalmoscope because the detached retina is transparent and 
only slightly elevated. OCT shows fluid beneath the retina, and fluores­
cein angiography shows dye streaming into the subretinal space. The 
cause of central serous chorioretinopathy is unknown. Symptoms may 
resolve spontaneously if the retina reattaches, but recurrent detach­
ment is common. Laser photocoagulation has benefited some patients 
with this condition.
Disorders of the Eye
CHAPTER 34
Diabetic Retinopathy 
A rare disease until 1921, when the discov­
ery of insulin resulted in a dramatic improvement in life expectancy for 
patients with diabetes mellitus, diabetic retinopathy is now a leading 
cause of blindness in the United States. The retinopathy takes years 
to develop but eventually appears in nearly all cases. Regular surveil­
lance of the dilated fundus is crucial for any patient with diabetes. In 
advanced diabetic retinopathy, the proliferation of neovascular vessels 
leads to blindness from vitreous hemorrhage, retinal detachment, 
and glaucoma (Fig. 34-15). These complications can be avoided in 
most patients by administration of panretinal laser photocoagulation 
at the appropriate point in the evolution of the disease. Antivascular 
endothelial growth factor antibody treatment is equally effective, but 
intraocular injections must be given repeatedly. For further discussion 
of the manifestations and management of diabetic retinopathy, see 
Chaps. 415–417.
Retinitis Pigmentosa 
This is a general term for a disparate 
group of rod-cone dystrophies characterized by progressive night 
blindness, visual field constriction with a ring scotoma, loss of acuity, 
and an abnormal electroretinogram (ERG). It occurs sporadically or 
in an autosomal recessive, dominant, or X-linked pattern. Irregular 
black deposits of clumped pigment in the peripheral retina, called 
bone spicules because of their vague resemblance to the spicules of 
FIGURE 34-15  Proliferative diabetic retinopathy in a 25-year-old man with an 18-year 
history of diabetes, showing neovascular vessels emanating from the optic disc, 
retinal and vitreous hemorrhage, cotton-wool spots, and macular exudate. Round 
spots in the periphery represent recently applied panretinal photocoagulation.

PART 2
Cardinal Manifestations and Presentation of Diseases
FIGURE 34-16  Retinitis pigmentosa with black clumps of pigment known as “bone 
spicules.” The patient had peripheral visual field loss with sparing of central 
(macular) vision.
cancellous bone, give the disease its name (Fig. 34-16). The name is 
actually a misnomer because retinitis pigmentosa is not an inflamma­
tory process. Genetic testing usually identifies a mutation in the gene 
for rhodopsin, the rod photopigment, or in the gene for peripherin, a 
glycoprotein located in photoreceptor outer segments.
Leber’s congenital amaurosis, a rare cone dystrophy, has been treated 
by replacement of the missing RPE65 protein through gene therapy, 
resulting in slight improvement in visual function. Some forms of 
retinitis pigmentosa occur in association with rare, hereditary systemic 
diseases (olivopontocerebellar degeneration, Bassen-Kornzweig dis­
ease, Kearns-Sayre syndrome, Refsum’s disease). Chronic treatment 
with chloroquine, hydroxychloroquine, and phenothiazines (especially 
thioridazine) can produce visual loss from a toxic retinopathy that 
resembles retinitis pigmentosa. Patients receiving long-term treat­
ment with hydroxychloroquine require regular eye examinations and 
screening by OCT to monitor for potential development of a bull’s eye 
maculopathy.
Epiretinal Membrane 
This is a fibrocellular tissue that grows 
across the inner surface of the retina, causing metamorphopsia and 
reduced visual acuity from distortion of the macula. A crinkled, cello­
phane-like membrane is visible on the retinal examination. Epiretinal 
membrane is most common in patients aged >50 years and is usually 
unilateral. Most cases are idiopathic, but some occur as a result of 
hypertensive retinopathy, diabetes, retinal detachment, or trauma. 
When visual acuity is reduced to the level of about 6/24 (20/80), 
vitrectomy and surgical peeling of the membrane to relieve macular 
puckering are recommended. Contraction of an epiretinal membrane 
sometimes gives rise to a macular hole. Most macular holes, however, 
are caused by local vitreous traction within the fovea. Vitrectomy can 
improve acuity in selected cases.
Melanoma and Other Tumors 
Melanoma is the most common 
primary intraocular tumor (Fig. 34-17). Approximately 3500 cases 
occur annually in the United States. It causes photopsia, an enlarg­
ing scotoma, and loss of vision. A small melanoma is often difficult 
to differentiate from a benign choroidal nevus. Serial examinations 
are required to document a malignant pattern of growth. Risk factors 
include light skin, hair, and eyes. Uveal origin accounts for 85% of 
cases. GNAQ and GNA11 mutations are common. About half metas­
tasize, mainly to the liver. Small and medium-sized tumors may be 
treated with radiation therapy; enucleation is the best treatment for 
large tumors. Metastatic tumors to the eye outnumber primary tumors. 

FIGURE 34-17  Melanoma of the choroid, appearing as an elevated dark mass in the 
inferior fundus, with overlying hemorrhage. The black line denotes the plane of the 
optical coherence tomography scan (below) showing the subretinal tumor.
Breast and lung carcinomas have a special propensity to spread to the 
choroid or iris. Leukemia and lymphoma also commonly invade ocular 
tissues. Sometimes the only sign on eye examination is cellular debris 
in the vitreous, which can masquerade as a chronic posterior uveitis.
In a patient with vision loss, CT or MR scanning should be consid­
ered if the cause remains unknown after careful review of the history, 
visual fields, and thorough examination of the eye. Optic nerve sheath 
meningioma is a common retrobulbar tumor. It produces the classic 
triad of optociliary shunt vessels, optic atrophy, and progressive visual 
loss. Optic disc swelling and proptosis are also frequent signs. Optic 
nerve glioma in young patients is usually a pilocytic astrocytoma and 
has a good prognosis for preservation of vision, especially in neurofi­
bromatosis type 1 (Chap. 95). In adults, optic nerve glioma is rare and 
highly malignant. Chiasmal tumors (pituitary adenoma, meningioma, 
craniopharyngioma) produce visual loss with few objective findings 
except for optic disc pallor. Loss of the temporal visual field in each eye 
is typical, but usually patients complain of vision loss in just one eye. 
OCT shows loss of the retinal nerve fiber layer entering the nasal and 
temporal sides of the optic discs, as well as thinning of the ganglion cell 
complex in each nasal retina (Fig. 34-18). A high degree of vigilance 
is necessary to avoid missing chiasmal tumors. Although symptoms 
progress gradually, in rare instances, the sudden expansion of a pitu­
itary adenoma from infarction and bleeding (pituitary apoplexy) causes 
acute severe retrobulbar visual loss, with headache, nausea, and ocular 
motor nerve palsies.
■
■PROPTOSIS
When the globes appear asymmetric, the clinician must first decide 
which eye is abnormal. Is one eye recessed within the orbit (enophthal­
mos), or is the other eye protuberant (exophthalmos, or proptosis)? A 
small globe or Horner’s syndrome can give the appearance of enoph­
thalmos. True enophthalmos occurs commonly after trauma, from 
atrophy of retrobulbar fat, or from fracture of the orbital floor. The 
position of the eyes within the orbits is measured by using a Hertel 
exophthalmometer, a handheld instrument that records the position 
of the anterior corneal surface relative to the lateral orbital rim. If 
this instrument is not available, relative eye position can be judged by

FIGURE 34-18  Bitemporal hemianopia (top), with corresponding thinning of the 
ganglion cell complex in the nasal maculae bilaterally (middle) and reduced retinal 
nerve fiber layer thickness along the temporal and nasal edges of the optic discs (red 
zone <1%) from compression of the optic chiasm by a pituitary adenoma (bottom).
bending the patient’s head forward and looking down upon the orbits. 
A proptosis of only 2 mm in one eye is detectable from this perspective. 
The development of proptosis implies a space-occupying lesion in the 
orbit and may warrant CT or MR imaging.
Graves’ Ophthalmopathy 
This is the leading cause of proptosis 
in adults (Chap. 394). The proptosis is often asymmetric and can even 
appear to be unilateral. Orbital inflammation and engorgement of the 
extraocular muscles, particularly the medial rectus and the inferior 
rectus, account for protrusion of the globe. Corneal exposure, lid retrac­
tion, lid lag on downgaze, conjunctival injection, restriction of gaze, 
diplopia, and visual loss from optic nerve compression are cardinal 
symptoms. Graves’ eye disease is a clinical diagnosis, but laboratory 
testing can be useful. The serum level of thyroid-stimulating immu­
noglobulins is often elevated. Orbital imaging usually reveals enlarged 
extraocular eye muscles, but not always. Topical lubricants, taping the 
eyelids closed at night, and moisture chambers are helpful to limit 
exposure of ocular tissues. Graves’ ophthalmopathy can be treated with 
oral prednisone (60 mg/d) for 1 month, followed by a taper over several 
months, but worsening of symptoms upon glucocorticoid withdrawal 
is common. Infusions of teprotumumab, an inhibitor of the insulinlike growth factor I receptor, reduce proptosis and diplopia. Radiation 
therapy is not effective. Orbital decompression should be performed for 
severe, symptomatic exophthalmos or if visual function is reduced by 
optic nerve compression. In patients with diplopia, prisms or eye muscle 
surgery can be used to restore ocular alignment in primary gaze.
Orbital Pseudotumor 
Also known as idiopathic orbital inflam­
matory syndrome, orbital pseudotumor is distinguished from Graves’ 
ophthalmopathy by the prominent complaint of pain. Other symptoms 
include diplopia, ptosis, proptosis, and orbital congestion. Evaluation 
for sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease, 
and other types of orbital vasculitis or collagen-vascular pathology 
is negative. Imaging often shows swollen eye muscles (orbital myosi­
tis) with enlarged tendons. By contrast, in Graves’ ophthalmopathy, 
the tendons of the eye muscles usually are spared. The Tolosa-Hunt 
syndrome (Chap. 452) may be regarded as an extension of orbital 
pseudotumor through the superior orbital fissure into the cavernous 

sinus. The diagnosis of orbital pseudotumor is difficult. Biopsy of 
the orbit frequently yields nonspecific evidence of fat infiltration by 
lymphocytes, plasma cells, and eosinophils. A dramatic response to 
a therapeutic trial of systemic glucocorticoids indirectly provides the 
best confirmation of the diagnosis.

Orbital Cellulitis 
This causes pain, lid erythema, proptosis, con­
junctival chemosis, restricted motility, decreased acuity, afferent pupil­
lary defect, fever, and leukocytosis. It often arises from the paranasal 
sinuses, especially by contiguous spread of infection from the ethmoid 
sinus through the lamina papyracea of the medial orbit. A history of 
recent upper respiratory tract infection, chronic sinusitis, thick mucus 
secretions, or dental disease is significant in any patient with suspected 
orbital cellulitis. Blood cultures should be obtained, but they are usually 
negative. Most patients respond to empirical therapy with broadspectrum IV antibiotics. Occasionally, orbital cellulitis follows an over­
whelming course, with massive proptosis, blindness, septic cavernous 
sinus thrombosis, and meningitis. To avert this disaster, orbital celluli­
tis should be managed aggressively in the early stages, with immediate 
imaging of the orbits and antibiotic therapy that includes coverage of 
methicillin-resistant Staphylococcus aureus (MRSA). Prompt surgical 
drainage of an orbital abscess or paranasal sinusitis is indicated if optic 
nerve function deteriorates despite antibiotics.
Disorders of the Eye
CHAPTER 34
Tumors 
Tumors of the orbit cause painless, progressive propto­
sis. The most common primary tumors are cavernous hemangioma, 
lymphangioma, neurofibroma, schwannoma, dermoid cyst, adenoid 
cystic carcinoma, optic nerve glioma, optic nerve meningioma, and 
benign mixed tumor of the lacrimal gland. Metastatic tumor to the 
orbit occurs frequently in breast carcinoma, lung carcinoma, and lym­
phoma. Diagnosis by fine-needle aspiration followed by urgent radia­
tion therapy sometimes can preserve vision.
Carotid Cavernous Fistulas 
With anterior drainage through the 
orbit, these fistulas produce proptosis, diplopia, glaucoma, and cork­
screw, arterialized conjunctival vessels. Direct fistulas usually result 
from trauma. They are easily diagnosed because of the prominent signs 
produced by high-flow, high-pressure shunting. Indirect fistulas, or 
dural arteriovenous malformations, are more likely to occur spontane­
ously, especially in older women. The signs are more subtle, and the 
diagnosis frequently is missed. The combination of slight proptosis, 
diplopia, enlarged muscles, and an injected eye often is mistaken for 
thyroid ophthalmopathy. A bruit heard upon auscultation of the head 
or reported by the patient is a valuable diagnostic clue. Imaging shows 
an enlarged superior ophthalmic vein in the orbits. Carotid cavernous 
shunts can be eliminated by endovascular embolization.
■
■PTOSIS
Blepharoptosis 
This is an abnormal drooping of the eyelid. 
Unilateral or bilateral ptosis can be congenital, from dysgenesis of 
the levator palpebrae superioris, or from abnormal insertion of its 
aponeurosis into the eyelid. Acquired ptosis can develop so gradually 
that the patient is unaware of the problem. Inspection of old photo­
graphs is helpful in dating the onset. A history of prior trauma, eye 
surgery, contact lens use, diplopia, systemic symptoms (e.g., dysphagia 
or peripheral muscle weakness), or a family history of ptosis should 
be sought. Fluctuating ptosis that worsens late in the day is typical of 
myasthenia gravis. Ptosis evaluation should focus on evidence for pro­
ptosis, eyelid masses or deformities, inflammation, pupil inequality, or 
limitation of motility. The width of the palpebral fissures and distance 
from the upper eyelid margin to corneal light reflex are measured in 
primary gaze to determine the degree of ptosis. The ptosis will be 
underestimated if the patient compensates by lifting the brow with the 
frontalis muscle.
Mechanical Ptosis 
This occurs in many elderly patients from 
stretching and redundancy of eyelid skin and subcutaneous fat (dermato­
chalasis). The extra weight of these sagging tissues causes the lid to droop. 
Enlargement or deformation of the eyelid from infection, tumor, trauma, 
or inflammation also results in ptosis on a purely mechanical basis.

Aponeurotic Ptosis 
This is an acquired dehiscence or stretching 
of the aponeurotic tendon, which connects the levator muscle to the 
tarsal plate of the eyelid. It occurs commonly in older patients, presum­
ably from loss of connective tissue elasticity. Aponeurotic ptosis is also 
a common sequela of eyelid swelling from infection or blunt trauma to 
the orbit, cataract surgery, or contact lens use.

Myogenic Ptosis 
The causes of myogenic ptosis include myasthenia 
gravis (Chap. 459) and a number of rare myopathies that manifest with 
ptosis. The term chronic progressive external ophthalmoplegia refers to 
a spectrum of systemic diseases caused by mutations of mitochondrial 
DNA. As the name implies, the most prominent findings are symmet­
ric, slowly progressive ptosis and limitation of eye movements. In gen­
eral, diplopia is a late symptom because all eye movements are reduced 
equally. In the Kearns-Sayre variant, retinal pigmentary changes and 
abnormalities of cardiac conduction develop. Peripheral muscle biopsy 
shows characteristic “ragged-red fibers.” Oculopharyngeal dystrophy is a 
distinct autosomal dominant disease with onset in middle age, charac­
terized by ptosis, limited eye movements, and trouble swallowing. Myo­
tonic dystrophy, another autosomal dominant disorder, causes ptosis, 
ophthalmoparesis, cataract, and pigmentary retinopathy. Patients have 
muscle wasting, myotonia, frontal balding, and cardiac abnormalities.
PART 2
Cardinal Manifestations and Presentation of Diseases
Neurogenic Ptosis 
This results from a lesion affecting the inner­
vation to either of the two muscles that open the eyelid: Müller’s muscle 
or the levator palpebrae superioris. Examination of the pupil helps 
distinguish between these two possibilities. In Horner’s syndrome, the 
eye with ptosis has a smaller pupil and the eye movements are full. In 
an oculomotor nerve palsy, the eye with the ptosis has a larger or a 
normal pupil. If the pupil is normal but there is limitation of adduc­
tion, elevation, and depression, a pupil-sparing oculomotor nerve palsy 
is likely (see next section). Rarely, a lesion affecting the small, central 
subnucleus of the oculomotor complex will cause bilateral ptosis with 
normal eye movements and pupils.
■
■DOUBLE VISION (DIPLOPIA)
The first point to clarify is whether diplopia persists in either eye after 
the opposite eye is covered. If it does, the diagnosis is monocular dip­
lopia. The cause is usually intrinsic to the eye and therefore has no dire 
implications for the patient. Corneal aberrations (e.g., keratoconus, 
pterygium), uncorrected refractive error, cataract, or foveal traction 
may give rise to monocular diplopia. Occasionally, it is a symptom of 
malingering or psychiatric disease. Diplopia alleviated by covering one 
eye is binocular diplopia and is caused by disruption of ocular align­
ment. Inquiry should be made into the nature of the double vision 
(purely side-by-side vs partial vertical displacement of images), mode 
of onset, duration, intermittency, diurnal variation, and associated neu­
rologic or systemic symptoms. If the patient has diplopia while being 
examined, motility testing should reveal a deficiency corresponding 
to the patient’s symptoms. However, subtle limitation of ocular excur­
sions is often difficult to detect. For example, a patient with a slight left 
abducens nerve paresis may appear to have full eye movements despite 
a complaint of horizontal diplopia upon looking to the left. In this situ­
ation, the cover test provides a more sensitive method for demonstrat­
ing the ocular misalignment. It should be conducted in primary gaze 
and then with the head turned and tilted in each direction while the 
patient fixates a central, distant target. In the above example, a cover 
test with the head turned to the right bringing the eyes into left gaze 
will maximize the fixation shift evoked by the cover test.
Occasionally, a cover test performed in an asymptomatic patient 
during a routine examination will reveal an ocular deviation. If the eye 
movements are full and the ocular misalignment is equal in all direc­
tions of gaze (comitant deviation), the diagnosis is strabismus. In this 
condition, which affects about 1% of the population, fusion is disrupted 
in infancy or early childhood. To avoid diplopia, retinal input from the 
nonfixating eye may be partially suppressed. In some children, this leads 
to impaired vision (amblyopia, or “lazy” eye) in the deviated eye.
Binocular diplopia results from a wide range of processes: infec­
tious, neoplastic, metabolic, degenerative, inflammatory, and vascular. 
One must decide whether the diplopia is neurogenic in origin or is 

due to restriction of globe rotation by local disease in the orbit. Orbital 
pseudotumor, myositis, infection, tumor, thyroid disease, and muscle 
entrapment (e.g., from a blowout fracture) cause restrictive diplopia. 
The diagnosis of restriction is usually made by recognizing other 
associated signs and symptoms of local orbital disease. Dedicated, 
high-resolution orbital imaging with fat saturation and gadolinium 
enhancement is helpful when the cause of diplopia is not evident.
Myasthenia Gravis 
(See also Chap. 459) This is a major cause of 
painless diplopia. The diplopia is often intermittent, variable, and not 
confined to any single ocular motor nerve distribution. The pupils are 
always normal. Serial observation of a fatigable ptosis, often accompa­
nied by diplopia from fluctuating ocular misalignment, establishes the 
diagnosis. Many patients have a purely ocular form of the disease, with 
no evidence of systemic muscular weakness. Classically, the diagnosis 
was confirmed by an IV edrophonium injection, which produces a 
transient reversal of eyelid or eye muscle weakness, but this drug is 
discontinued in the United States. Blood tests for antibodies against 
the acetylcholine receptor or the MuSK protein are frequently negative 
in the purely ocular form of myasthenia gravis. Botulism from food or 
wound poisoning can mimic ocular myasthenia.
If restrictive orbital disease and myasthenia gravis are excluded, 
a lesion of a cranial nerve supplying innervation to the extraocular 
muscles is the most likely cause of binocular diplopia.
Oculomotor Nerve 
The third cranial nerve innervates the medial, 
inferior, and superior recti; inferior oblique; levator palpebrae superi­
oris; and the iris sphincter. Total palsy of the oculomotor nerve causes 
ptosis, a dilated pupil, and leaves the eye “down and out” because of 
the unopposed action of the lateral rectus and superior oblique. This 
combination of findings is obvious. More challenging is the diagnosis 
of early or partial oculomotor nerve palsy. In this setting, any com­
bination of ptosis, pupil dilation, and weakness of the eye muscles 
supplied by the oculomotor nerve may be encountered. Frequent 
serial examinations during the rapidly evolving phase of the palsy help 
ensure that the diagnosis is not missed. The advent of an oculomotor 
nerve palsy with pupil involvement, especially when accompanied by 
pain, suggests a compressive lesion, such as a tumor or circle of Willis 
aneurysm. Urgent neuroimaging should be obtained, along with a CT 
or MR angiogram. The resolution of these noninvasive techniques has 
advanced to the point that catheter angiography is rarely necessary to 
exclude an aneurysm.
A lesion of the oculomotor nucleus in the rostral midbrain produces 
signs that differ from those caused by a lesion of the nerve itself. There 
is bilateral ptosis because the levator muscle is innervated by a single 
central subnucleus. There is also weakness of the contralateral superior 
rectus, because it is supplied by the oculomotor nucleus on the other 
side. Occasionally both superior recti are weak. Isolated nuclear oculo­
motor palsy is rare. Usually, neurologic examination reveals additional 
signs that suggest brainstem damage from infarction, hemorrhage, 
tumor, or infection.
Injury to structures surrounding fascicles of the oculomotor nerve 
descending through the midbrain has given rise to a number of classic 
eponymic designations. In Nothnagel’s syndrome, injury to the superior 
cerebellar peduncle causes ipsilateral oculomotor palsy and contralat­
eral cerebellar ataxia. In Benedikt’s syndrome, injury to the red nucleus 
results in ipsilateral oculomotor palsy and contralateral tremor, chorea, 
and athetosis. Claude’s syndrome incorporates features of both of these 
syndromes, by injury to both the red nucleus and the superior cerebel­
lar peduncle. Finally, in Weber’s syndrome, injury to the cerebral pedun­
cle causes ipsilateral oculomotor palsy with contralateral hemiparesis.
In the subarachnoid space, the oculomotor nerve is vulnerable to 
aneurysm, meningitis, tumor, infarction, and compression. In cerebral 
herniation, the nerve becomes trapped between the edge of the tento­
rium and the uncus of the temporal lobe. Oculomotor palsy also can 
result from midbrain torsion and hemorrhage during herniation. In 
the cavernous sinus, oculomotor palsy arises from carotid aneurysm, 
carotid cavernous fistula, cavernous sinus thrombosis, tumor (pituitary 
adenoma, meningioma, metastasis), herpes zoster infection, and the 
Tolosa-Hunt syndrome.

The etiology of an isolated, pupil-sparing oculomotor palsy often 
remains an enigma even after neuroimaging and extensive laboratory 
testing. Most cases are thought to result from microvascular ischemia 
of the nerve somewhere along its course from the brainstem to the 
orbit. Usually, the patient complains of pain. Diabetes, hypertension, 
and vascular disease are major risk factors. Spontaneous recovery over 
a period of months is the rule. If this fails to occur or if new findings 
develop, the diagnosis of microvascular oculomotor nerve palsy should 
be reconsidered. Aberrant regeneration is common when the oculo­
motor nerve is injured by trauma or compression (tumor, aneurysm). 
Miswiring of sprouting fibers to the levator muscle and the rectus mus­
cles results in elevation of the eyelid upon downgaze or adduction. The 
pupil also constricts upon attempted adduction, elevation, or depres­
sion of the globe. Aberrant regeneration is not seen after oculomotor 
palsy from microvascular infarct and hence vitiates that diagnosis.
Trochlear Nerve 
The fourth cranial nerve originates in the mid­
brain, just caudal to the oculomotor nerve complex. Fibers exit the 
brainstem dorsally and cross to innervate the contralateral superior 
oblique. The principal actions of this muscle are to depress and intort 
the globe. A palsy therefore results in hypertropia and excyclotorsion. 
The cyclotorsion seldom is noticed by patients. Instead, they complain 
of vertical diplopia, especially upon reading or looking down. Vertical 
diplopia is exacerbated by tilting the head toward the side with the 
muscle palsy and alleviated by tilting it away. This “head tilt test” is a 
cardinal diagnostic feature. Review of old photographs will sometimes 
reveal a habitual head tilt, signifying a patient with a decompensated, 
congenital trochlear nerve palsy.
New, isolated trochlear nerve palsy results from all the causes listed 
above for the oculomotor nerve except aneurysm. The trochlear nerve 
is particularly apt to suffer injury after closed head trauma. The free 
edge of the tentorium impinges on the nerve during a concussive blow. 
Most isolated trochlear nerve palsies are idiopathic and hence are 
diagnosed by exclusion as “microvascular.” Spontaneous improvement 
occurs over a period of months in most patients. A base-down prism 
(conveniently applied to the patient’s glasses as a stick-on Fresnel lens) 
may serve as a temporary measure to alleviate diplopia. If the palsy 
does not resolve, the eyes can be realigned by weakening the inferior 
oblique muscle.
Abducens Nerve 
The sixth cranial nerve innervates the lateral 
rectus muscle. A palsy produces horizontal diplopia, worse on gaze 
to the side of the lesion. A nuclear lesion has different consequences, 
because the abducens nucleus contains interneurons that project via 
the medial longitudinal fasciculus to the medial rectus subnucleus of 
the contralateral oculomotor complex. Therefore, an abducens nuclear 
lesion produces a complete lateral gaze palsy from weakness of both 
the ipsilateral lateral rectus and the contralateral medial rectus. Foville’s 
syndrome after dorsal pontine injury includes lateral gaze palsy, ipsilat­
eral facial palsy, and contralateral hemiparesis incurred by damage to 
descending corticospinal fibers. Millard-Gubler syndrome from ventral 
pontine injury is similar except for the eye findings. There is lateral rec­
tus weakness only, instead of gaze palsy, because the abducens fascicle 
is injured rather than the nucleus. Infarct, tumor, hemorrhage, vascular 
malformation, and multiple sclerosis are the most common etiologies 
of brainstem abducens palsy.
After leaving the ventral pons, the abducens nerve runs forward 
along the clivus to pierce the dura at the petrous apex, where it enters 
the cavernous sinus. Along its subarachnoid course, it is susceptible to 
meningitis, tumor (meningioma, chordoma, carcinomatous meningitis), 
subarachnoid hemorrhage, trauma, and compression by aneurysm or 
dolichoectatic vessels. At the petrous apex, mastoiditis can produce deaf­
ness, pain, and ipsilateral abducens palsy (Gradenigo’s syndrome). In the 
cavernous sinus, the nerve can be affected by carotid aneurysm, carotid 
cavernous fistula, tumor (pituitary adenoma, meningioma, nasopharyn­
geal carcinoma), herpes infection, and Tolosa-Hunt syndrome.
Unilateral or bilateral abducens palsy is a classic sign of raised 
intracranial pressure. The diagnosis can be confirmed if papilledema is 
observed on fundus examination. The mechanism is still debated but 
probably is related to rostral-caudal displacement of the brainstem. The 

same phenomenon accounts for abducens palsy from Chiari malfor­
mation or low intracranial pressure (e.g., after lumbar puncture, spinal 
anesthesia, or spontaneous dural cerebrospinal fluid leak).

Treatment of abducens palsy is aimed at prompt correction of 
the underlying cause. However, the cause remains obscure in many 
instances despite diligent evaluation. As was mentioned above for 
isolated trochlear or oculomotor palsy, most cases are assumed to rep­
resent microvascular infarcts because they often occur in the setting 
of diabetes or other vascular risk factors. Some cases may develop as 
a postinfectious mononeuritis (e.g., after a viral flu). Patching one eye, 
occluding one eyeglass lens with tape, or applying a temporary prism 
will provide relief of diplopia until the palsy resolves. If recovery is 
incomplete, eye muscle surgery nearly always can realign the eyes, at 
least in primary position. A patient with an abducens palsy that fails to 
improve should be reevaluated for an occult etiology (e.g., chordoma, 
carcinomatous meningitis, carotid cavernous fistula, myasthenia gra­
vis). Skull base tumors are easily missed even on contrast-enhanced 
neuroimaging studies.
Disorders of the Eye
CHAPTER 34
Multiple Ocular Motor Nerve Palsies 
These should not be 
attributed to spontaneous microvascular events affecting more than 
one cranial nerve at a time. This remarkable coincidence does occur, 
especially in diabetic patients, but the diagnosis is made only in ret­
rospect after all other diagnostic alternatives have been exhausted. 
Neuroimaging should focus on the cavernous sinus, superior orbital 
fissure, and orbital apex, where all three ocular motor nerves are in 
close proximity. In a diabetic or immunocompromised host, fungal 
infection (Aspergillus, Mucorales, Cryptococcus) is a common cause of 
multiple nerve palsies. In a patient with systemic malignancy, carcino­
matous meningitis is a likely diagnosis. Cytologic examination may be 
negative despite repeated sampling of the cerebrospinal fluid. The can­
cer-associated Lambert-Eaton myasthenic syndrome also can produce 
ophthalmoplegia. Giant cell (temporal) arteritis occasionally manifests 
as diplopia from ischemic palsies of extraocular muscles. Fisher’s syn­
drome, an ocular variant of Guillain-Barré, produces ophthalmoplegia 
with areflexia and ataxia. Often the ataxia is mild, and the reflexes are 
normal. Antiganglioside antibodies (GQ1b) can be detected in about 
50% of cases.
Supranuclear Disorders of Gaze 
These are often mistaken for 
multiple ocular motor nerve palsies. For example, Wernicke’s encepha­
lopathy can produce nystagmus and a partial deficit of horizontal and 
vertical gaze that mimics a combined abducens and oculomotor nerve 
palsy. The disorder occurs in patients who are malnourished, alco­
holic, or following bariatric surgery, and can be reversed by thiamine. 
Infarct, hemorrhage, tumor, multiple sclerosis, encephalitis, vasculitis, 
and Whipple’s disease are other important causes of supranuclear gaze 
palsy. Disorders of vertical gaze, especially downward saccades, are 
an early feature of progressive supranuclear palsy. Smooth pursuit is 
affected later in the course of the disease. Parkinson’s disease, 
Huntington’s disease, and olivopontocerebellar degeneration also can 
affect vertical gaze.
The frontal eye field of the cerebral cortex is involved in generation 
of saccades to the contralateral side. After hemispheric stroke, the eyes 
usually deviate toward the lesioned side because of the unopposed 
action of the frontal eye field in the normal hemisphere. With time, 
this deficit resolves. Seizures generally have the opposite effect: the 
eyes deviate conjugately away from the irritative focus. Parietal lesions 
disrupt smooth pursuit of targets moving toward the side of the lesion. 
Bilateral parietal lesions produce Bálint’s syndrome, which is charac­
terized by impaired eye-hand coordination (optic ataxia), difficulty 
initiating voluntary eye movements (ocular apraxia), and visuospatial 
disorientation (simultanagnosia).
Horizontal Gaze 
Descending cortical inputs mediating horizon­
tal gaze ultimately converge at the level of the pons. Neurons in the 
paramedian pontine reticular formation are responsible for control­
ling conjugate gaze toward the same side. They project directly to the 
ipsilateral abducens nucleus. A lesion of either the paramedian pon­
tine reticular formation or the abducens nucleus causes an ipsilateral

conjugate gaze palsy. Lesions at either locus produce nearly identical 
clinical syndromes, with the following exception: vestibular stimula­
tion (oculocephalic maneuver or caloric irrigation) will succeed in 
driving the eyes conjugately to the side in a patient with a lesion of 
the paramedian pontine reticular formation but not in a patient with a 
lesion of the abducens nucleus.

INTERNUCLEAR OPHTHALMOPLEGIA  This results from damage to the 
medial longitudinal fasciculus ascending from the abducens nucleus 
in the pons to the oculomotor nucleus in the midbrain (hence, “inter­
nuclear”). Damage to fibers carrying the conjugate signal from abducens 
interneurons to the contralateral medial rectus motoneurons results in 
a failure of adduction on attempted lateral gaze. For example, a patient 
with a left internuclear ophthalmoplegia (INO) will have slowed or 
absent adducting movements of the left eye (Fig. 34-19). A patient with 
bilateral injury to the medial longitudinal fasciculus will have bilateral 
INO. Multiple sclerosis is the most common cause, although tumor, 
stroke, trauma, or any brainstem process may be responsible. One-anda-half syndrome is due to a lesion of the medial longitudinal fasciculus 
combined with a lesion of either the abducens nucleus or the paramedian 
pontine reticular formation on the same side. The patient’s only horizon­
tal eye movement is abduction of the eye on the other side.
PART 2
Cardinal Manifestations and Presentation of Diseases
Vertical Gaze 
Midbrain lesions of the rostral interstitial nucleus of 
the medial longitudinal fasciculus and the interstitial nucleus of Cajal 
cause supranuclear paresis of upgaze, downgaze, or all vertical eye 
movements. Distal basilar artery ischemia is the most common etiol­
ogy. Skew deviation refers to a vertical misalignment of the eyes, usually 
constant in all positions of gaze. The finding has poor localizing value 
because skew deviation has been reported after lesions in widespread 
regions of the brainstem and cerebellum.
PARINAUD’S SYNDROME  Also known as dorsal midbrain syndrome, 
this is a distinct supranuclear vertical gaze disorder caused by damage 
to the posterior commissure. It is a classic sign of hydrocephalus from 
aqueductal stenosis. Pineal region or midbrain tumors, cysticercosis, 
and stroke also cause Parinaud’s syndrome. Features include loss of 
upgaze (and sometimes downgaze), convergence-retraction nystagmus 
on attempted upgaze, downward ocular deviation (“setting sun” sign), 
lid retraction (Collier’s sign), skew deviation, pseudoabducens palsy, 
and light-near dissociation of the pupils.
Nystagmus 
This is a rhythmic oscillation of the eyes, occurring 
physiologically from vestibular and optokinetic stimulation or pathologi­
cally in a wide variety of diseases (Chap. 24). Abnormalities of the eyes 
or optic nerves, present at birth or acquired in childhood, can produce a 
complex, searching nystagmus with irregular pendular (sinusoidal) and 
jerk features. Examples are albinism, Leber’s congenital amaurosis, and 
bilateral cataract. This nystagmus is commonly referred to as congenital 
sensory nystagmus. This is a poor term because even in children with 
congenital lesions, the nystagmus does not appear until weeks after birth. 
Congenital motor nystagmus, which looks similar to congenital sensory 
nystagmus, develops in the absence of any abnormality of the sensory 
visual system. Visual acuity usually is also reduced, probably by the nys­
tagmus itself, but seldom below a level of 20/200.
JERK NYSTAGMUS  This is characterized by a slow drift off the target, 
followed by a fast corrective saccade. By convention, the nystagmus is 
named after the quick phase. Jerk nystagmus can be downbeat, upbeat, 
horizontal (left or right), and torsional. The pattern of nystagmus may 
vary with gaze position. Some patients will be oblivious to their nystag­
mus. Others will complain of blurred vision or a subjective to-and-fro 
movement of the environment (oscillopsia) corresponding to the nys­
tagmus. Fine nystagmus may be difficult to see on gross examination 
of the eyes. Observation of nystagmoid movements of the optic disc on 
ophthalmoscopy is a sensitive way to detect subtle nystagmus.
GAZE-EVOKED NYSTAGMUS  This is the most common form of jerk 
nystagmus. When the eyes are held eccentrically in the orbits, they 
have a natural tendency to drift back to primary position. The subject 
compensates by making a corrective saccade to maintain the deviated 
eye position. Many normal patients have mild gaze-evoked nystagmus. 

A
B
C
D
FIGURE 34-19  Left internuclear ophthalmoplegia (INO). A. In primary position of 
gaze, the eyes appear normal. B. Horizontal gaze to the left is intact. C. On attempted 
horizontal gaze to the right, the left eye fails to adduct. In mildly affected patients, 
the eye may adduct partially or more slowly than normal. Nystagmus is usually 
present in the abducted eye. D. T2-weighted axial magnetic resonance image 
through the pons showing a demyelinating plaque in the left medial longitudinal 
fasciculus (arrow).