Path Chapter 29: The Eye (pages 1346-1357)
Age-related macular degeneration (ARMD) is the most common cause of irreversible vision loss in the
US
The eye is a place where a doctor can easily visualize may different pathologies of the vascular system
Page 1346 – anatomy of the eye
Orbit – chamber that holds the eye, that is only open at its anterior
So diseases that increase things in the orbit, displace the eye forward, called proptosis
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In proptosis, the eye might not get covered completely by the eyelids, or get enough tears
across its cornea
Cornea exposure is painful, and can predispose to corneal ulceration or infection
In proptosis, where the thing that is enlarging is, will determine what direction the eye
protrudes to
o Things to the side of the eye, like the parotids, push they eye at an angle
o Masses in the cone formed by the rectus muscles, like the optic nerve, push the straight
out (axial proptosis)
Axial proptosis is an important manifestion of grave’s disease at the thyroid
o The proptosis is caused by accumulation of ECM proteins, & fibrosis in the rectus muscle
The floor of the orbit is the roof of the maxillary sinus, and the medial wall of the orbit separates it from
the ethmoidal sinuses
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So uncontrolled sinus infection can spread to the orbit as an acute infection (orbital cellulitis) or
from fungi (mucormycosis) in immunosuppressed people or diabetics
Idiopathic orbital inflammation (orbital inflammatory pseudotumor) – can be inflammation of the whole
orbit, or just localized in the lacrimal gland (sclerosing dacryoadenitis), extra-ocular muscles (orbital
myositis), or Tenon’s capsule (fascia that wraps around the eye, causes posterior scleritis)
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If you see vasculitis with necrotic collagen, it suggests Wegener granulomatosis
Most primary tumors of the orbit are vascular
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The most common primary tumors of the orbit are capillary hemangioma and lymphangiomas
of infancy, and cavernous hemangiomas of adulthood
The eyelid is made of skin externally, and then mucosa, called the conjunctiva, of the surface of the eye
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The eyelid protects and covers the eye, and also has things to generate tears – page 1348
If the drainage system of the sebaceous glands is obstructed by chronic inflammation at the
eyelid margin (called blepharitis), or by a tumor, lipids can leak into surrounding tissue and
provoke a granulomatous response to form a chalazion (lipogranuloma)
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Primary melonomas of the eyelid skin are rare
The most common cancer of the eyelid is basal cell carcinoma
Eyelid cancers can prevent the eyelids from closing completely, which hurts and predisposes
them to corneal ulceration
o Eyelid cancers don’t threaten their life, but you treat them quick to preserve vision
Sebaceous carcinoma can look like eye inflammation or a chalazion, and spreads first to the
parotid and submandibular nodes, with a higher mortality
o Sebaceous carcinoma will show vacuolization of the cytoplasm to help diagnose
In people with AIDs, Kaposi sarcoma can develop on the eyelid or conjunctiva
o Kaposi sarcoma of the eyelid looks purple from blood vessels in the dermis, but in the
conjunctiva it looks red
The conjunctiva is divided into 3 zones:
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Palpebral conjunctiva – conjunctiva lining the interior of the eyelid
o Palpebral conjunctiva is tethered to the tarsus
Conjunctiva in the fornix – pseudostratified columnar epithelium rich in goblet cells (tears)
o The fornix also has lacrimal tissue, and ductules from the main lacrimal gland
o Most of the lymph cells in the conjunctiva are in the fornix
 These lymph follicles can enlarge enough in viral conjunctivitis to be seen by
slit-lamp exam
 Granulomas from systemic sarcoidosis can be seen in the fornix
Bulbar conjunctiva – conjunctiva that covers the surface of the eye
o Bulbar conjunctiva is a nonkeratinizing stratified squamous epithelium
Conjunctival scarring:
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When chlamydia trachomatis infects the conjunctiva (trachoma), it can cause conjunctival
scarring
A decrease in the # of goblet cells from conjunctival scarring decreases surface mucin, which is
needed for adhering the aqueous part of tears to the corneal epithelium
o So even if the aqueous part of the tear film is adequate, the person will have dry eye
o Dry eye can hurt and predispose to corneal opacification and ulceration
o Dry eye is more often caused though by a deficiency in the aqueous part of the tear film
made by the lacrimal glands found in the eyelid and fornix
Surgery to remove a conjunctival cancer or lesion can leave the person with dry eye from
conjunctival scarring
Pinguecula and pterygium are both submucosal elevations on the conjunctiva
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They both result from actinic damage (sun), so they’re found in sun-exposed areas of the
conjunctiva, mainly the opening between the upper and lower eyelids (intrapalpebral fissure)
Pterygium usually originate in the conjunctiva next to the limbus
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Pterygium are formed by a submucosal growth of fibrovascular connective tissue that
migrates on the cornea
o Ptyergium don’t affect vision
Pinguecula are small yellowing submucosal elevations next to (astride?) the limbus
o Pinguecula don’t invade the cornea like the pterygium does, but it can cause uneven
distribution of the tear film over the cornea
 The dehydration can cause a “saucer-like” depression in the corneal tissue,
called a dellen
Conjunctival tumors:
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Both squamous and melanocytic cancers and their precursors, tend to develop at the limbus
Conjunctival intraepithelial neoplasia (precursor to invasive squamous carcinoma) and
squamous papillomas of the conjunctiva can both involve HPV’s 16 and 18
Pigmented lesions are most likely melanoma
Nevi of the conjunctiva characteristically have subepithelial cysts lined by surface epithelium –
page 1350
Conjunctival melanomas usually affect fair-skinned middle aged people – page 1350
o Conjunctival melanoma has a precursor lesion called primary acquired melanosis with
atypia
The sclera is made mainly of collagen, and has few blood vessels and fibroblasts
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So wounds to the sclera heal poorly
Immune complexes can deposit in the sclera in rheumoatoid arthritis, causing necrotizing
scleritis
“blue” sclera is seen in several problems:
o The sclera can get thin after an episode of scleritis, making it’s normal brown color look
blue
o High intraocular pressure can also thin the sclera, making it look blue
 This lesion is called a staphyloma
o The sclera can look blue in osteogenesis imperfecta (no collagen)
o A very pigmented congenital nevus under the uvea, can make the sclera look blue,
called congenital melanosis oculi
 When there’s also skin pigmentation around the eye, it’s called nevus of Ota
The cornea and its overlying tear film, make up the major refractive surface of the eye (not the lens!)
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Myopia (nearsighted) develops because the eye is too long for its refractive power
Hyperopia (farsighted) results from an eye that is too short for its refractive power
So cornea shape is very important in adding to the refractive power of the eye
Anteriorly, the cornea is covered by epithelium sitting on a basement membrane called
Descemet membrane
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Underneath the basement membrane is the Bowman layer, which doesn’t have cells,
and serves as a barrier against cancer from spreading from the epithelium to the
underlying stroma
The corneal stroma doesn’t have any blood vessels or lymphatics, which makes the cornea
transparent, and also makes the cornea good at getting transplants
Scarring and edema of the cornea both disrupt the alignment of the stroma collagen, adding to
corenal opacification
The corneal endothelium is derived from neural crest
A decrease in endothelial cells or an endothelial problem in the cornea will cause stromal edema
Descemet membrane gets thicker as you age, and is where the Kayser-Fleischer rings of
Wilson’s disease are found
Pathogens can cause corneal ulceration, leading to inflammation of the cornea, called keratitis
o In keratitis, dissolution of the corneal stroma can be accelerated by activation of
collagenases in the corneal epithelium and stromal fibroblasts (aka keratocytes)
o When exudate and cells leak from the iris and ciliary body vessels into the anterior
chamber, you can see it on slit-lamp exam, and it can accumulate into a hypopyon
o Although corneal ulcers can be infectious, the hypopyon rarely contains organisms,
showing how good the vascular response is here to acute inflammation
Cornea problems are divided into corneal disorders and corneal dystrophies
o Corneal degenerations can be either unilateral or bilateral, and are usually nonfamilial
o Corneal dystrophies are usually bilateral, and hereditary
Corneal degenerations:
o Keratoconus – common disorder with progressive thinning and dilation of the cornea
 There is no inflammation or vascularization
 Keratoconus thinning happens in abnormal eyes that have conical-shaped
corneas, instead of the normal spherical shape
 The abnormal shape causes an astigmatism that is hard to fix with glasses, but
contacts can help
 If glasses or contacts don’t work, you do a corneal transplant
 Despite being a corneal degeneration, keratoconus is often bilateral
 Keratoconus happens often in Down syndrome and Marfan syndrome
 The hallmark of keratoconus is thinning of the cornea, with breaks in the
Bowman layer
 Sometimes, the Descemet membrane can rupture, allowing aqueous humor
from the anterior chamber, into the corneal stroma, called a corneal hydrops
 Corneal hydrops can cause sudden worsening of vision
 Corneal hydrops can lead to corneal scarring, which makes vision loss
even worse
Corneal dystrophies:
o Band keratopathies:
 Calcific band keratopathy – calcium is deposited in the Bowman layer
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Often seen in chronic uveitis, especially with juvenile rheumatoid
arthritis
 Actinic band keratopathy – happens from chronic exposure to lots of UV light
from the sun
 The sunlight causes elastosis (accumulation of elastin) in the superficial
corneal collagen of the sun-exposed interpalpabral fissure, causing
horizontal bands
 The sun-damaged collagen looks yellow
Fuchs endothelial dystrophy
 Fuchs endothelial dystrophy is one of the main indications for corneal
transplants
 The 2 major manifestations of Fuchs endothelial dystrophy are edema and
bullous keratopathy, which are both caused by loss of endothelial cells
 Early, the endothelial cells make “drop-like” deposits of abnormal basement
membrane material (guttata)
 As it progresses, there’s a decrease in the # of endothelial cells, and the cells
that are left can’t maintain stromal deturgescence (state of normal dehydration
maintained by the cornea to keep it transparent)
 This causes the stroma to become edematous and thicken, giving it a groundglass appearance, and causing vision to blur
 If the # of endothelial cells decreases after cataract surgery, when they didn’t
have previous Fuchs dystrophy, it’s called pseudophakic bullous keratopathy
 As stromal edema increases, the epithelium causes “hydropic change” and
detaches the epithelium from the Bowman layer, causing a bullae that can
rupture
 Fibrous connective tissue can be deposited between the epithelium and
Bowman layer, called degenerative pannus
Stromal dystrophies – the stroma deposits cause opacities in the cornea, which can
decrease vision
 Macular corneal dystrophy – when macular deposits of keratin develop in the
corneal stroma
 Mutations to the TGFB1 gene, which codes for ECM protein keratoepithelin, can
cause deposition of different kinds of protein deposits in the cornea
 Lattice dystrophy – deposition of needle-shaped amyloid
 Granular dystrophy – deposition of chunky hyaline
Anterior segment:
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The borders of the anterior chamber:
o Anterior – cornea
o Lateral – trabecular meshwork
o Posterior – iris
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Aqueous humor is formed by the pars plicata of the ciliary body
o It then enters the posterior chamber, bathes the lens, and goes through the pupil to
enter the anterior chamber
The lens is a closed epithelial system, and its basement membrane (called the lens capsule)
totally envelops the lens
o So lens epithelium doesn’t exfoliate, like the skin epidermis would
 Instead, the lens epithelium and its fibers accumulate within the lens capsule,
called “infoliating”
 So as you age, the size of the lens increases
Cataract – lens opacity
o Cataracts can be congenital or acquired
o Things that can cause cataracts include galactosemia, diabetes, Wilson’s disease,
corticosteroids, radiation, and trauma
o Age can also cause cataracts, from nuclear sclerosis (opacification of the lens nucleus)
o Urochrome pigment can accumulate and make the lens nucleus brown, making it so you
can’t perceive blue color
o To treat cataracts, you can remove the lens contents but leave the lens capsule intact,
called extracapsular cataract extraction, or you can put in a prosthetic lens
o Morgagnian cataract – when the lens cortex almost entirely liquefies
 This can cause high molecular weight proteins to leak through the lens capsule,
called phacolysis, and then clog the trabecular meshwork, increasing intraocular pressure (glaucoma) and possible hurting the optic nerve
Glaucoma - diseases characterized by changes in the visual field, and in the cup and optic nerve
o Most glaucomas are associated with increased intra-ocular pressure
o Aqueous humor is made in the ciliary body, and passes from the posterior chamber
through the pupil into the anterior chamber – page 1354
 To get there, most of the aqueous humor drains through the trabecular
meshwork, found at the angle formed by the intersection between the cornea
and the iris
o 2 categories of glaucoma:
 Open-angle glaucoma – the aqueous humor has complete access to the
trabecular meshwork, and the increase in intra-ocular pressure results from an
increased resistance to aqueous outflow in the open angle
 Angle-closure glaucoma – the iris adheres to the trabecular meshwork and
physically impedes the movement of aqueous humor from the eye
o Both types of glaucoma can be primary or secondary
o Primary open-angle glaucoma – most common form of glaucoma
 The angle is open, and few changes are seen
 Primary open-angle glaucoma can be caused by mutations to MYOC
o Secondary open-angle glaucoma – when things clog the trabecular meshwork in the
presence of an open angle
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Elevations in pressure on the surface of the eye when there’s an open angle, can
also cause open-angle glaucoma
 Happens in Sturge-Weber syndrome
o Primary angle-closure glaucoma – usually develops in eyes with shallow anterior
chambers, often in people with hyperopia (farsightedness)
 When the pupil margin of the iris connects to the anterior surface of the lens, it
can obstruct flow of aqueous humor through the pupillary aperature, called a
pupillary block
 Continued making of aqueous humor by the ciliary body then increases pressure
in the posterior chamber, and can bow the iris periphery forward, connecting it
to the trabecular meshwork, causing increased intra-ocular pressure
 You’ll see subcapsular opacities, called glaukomflecken
o Secondary angle-closure glaucoma:
 Contraction of many kinds of pathologic membranes that formed over the
surface of the iris, can draw the iris over the trabecular meshwork, occluding
aqueous outflow
 Chronic retinal ischemia increases VEGF for angiogenesis, which forms a
transparent membrane over the surface of the iris, which can contract to cause
occlusion of the trabecular meshwork by the iris
 This is called neovascular glaucoma
 Tumors in the ciliary body can compress the iris onto the trabecular meshwork,
closing off the major pathway of aqueous outflow
In intra-ocular inflammation, vessels in the ciliary body and iris get leaky, allowing exudate to
accumulate in the anterior chamber
o The inflammatory cells can sometimes adhere to the corneal endothelium, forming
keratic precipitates
o Exudate can cause adhesions between the iris and the trabecular meshwork of the
cornea, called an anterior synechiae, or between the iris and anterior surface of the
lens, called a posterior synechiae
 Anterior synechiae can increase intra-ocular pressure
 Prolonged contact between the iris and lens can deprive the lens of aqueous
humor, causing fibrous metaplasia of the lens epithelium ,called anterior
subcapsular cataract
 You use drugs to induce pupil dilation in people with intra-ocular inflammation,
in order to prevent formation of synechiae
o Endophthalmitis – inflammation within the vitreous humor
 The vitreous humor is next to the retina, so endophthalmitis hurts the retina
o Panophthalmitis – inflammation within the eye that involves the retina, choroid, and
sclera, and extends into the orbit
Uvea – the iris, choroid, and ciliary body
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The uvea is one of the most vascularized parts of the body, but has no lymphatics
Uveitis – inflammation in any of the tissues that make up the uvea
o Uveitis can involve either just the anterior segment, or both the anterior and posterior
o Uveitis usually hurts the retina
o Granulomatous uveitis is a common complication of sarcoidosis
 There’s an exudate in the anterior segment that evolves into “mutton-fat”
keratic precipitates
 In the retina, there can be perivascular inflammation, showing characteristic
“candle wax drippings”
o Toxoplasmosis often causes uveitis
o People with AIDS often get CMV caused retinitis and uveitis
o Injured eyes can develop sympathetic opthalmia, which is a noninfectious endogenous
cause of uveitis that is bilateral
 The injury exposed retinal antigens the body doesn’t normally see, which got
into the lymph and caused a hypersensitivity rxn that involves both eyes
 Can develop weeks to years after the injury
 Shows diffuse granulomatous inflammation of the uvea, sometimes with
eosinophils
The most common eye malignancy of adults is metastasis to the uvea, usually the choroid
o It is very fatal very quick
Uveal melanoma is the most common primary intra-ocular malignancy in adults
o The nevi is common (10% of people) but it’s more rare for it to progress to melanoma
o Since there’s no lymph in the eye, uveal melonmas spread by the blood, first ot the liver
o It has spindle and epitheliod cells
 The more epitheliod cells, the worse the prognosis
o Uveal melonomas can cause retinal detachment or glaucoma, affecting vision