Pathology of the Eye

Alemwosen T.(MD,pathologist)
 Eyes
Anatomy of Eye
Housed in a cone of fatty tissue
Eyeball
Three layers
External fibrous layer
Middle vascular layer
Inner layer of nerve tissue

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 Anatomy of the Eye

11/1/2011 3
 The Orbit
Thyroid ophthalmopathy ( Graves Disease )
Proptosis in patients with Graves disease
Development may not be dependent on the status of thyroid
function
Due to edema, infilteration by inflammatory cells &
adipocytes, the accumilation of extracellular matrix protein
and variable degree of fibrosis in the rectus muscles

A patient with hyperthyroidism. A wide-

eyed, staring gaze, caused by overactivity
of the sympathetic nervous system and a
protuberant appearance of the eyes.
The extraocular muscles are
greatly distended in a patient
with thyroid (Graves)
ophthalmopathy
 Orbital Inflammatory Conditions
Orbital cellulitis from uncontrolled sinus bacterial infection
Orbital Mucormycosis in immunosuppressed patients or in DKA
Wegener granulomatosis
Idiopathic Orbital Inflammation ( Orbital Inflammatory
pseudotumor )
unilateral or bilateral
all or portions of the orbital tissue will be involved
systemic vasculitis or other connective tissue disease
morphologically affected areas show chronic inflammation
and variable degree of fibrosis.
Orbit - Inflammation
The orbital fat is replaced by fibrosis. Note the
chronic inflammation, accompanied in this case by
eosinophils.
 Neoplasms of the orbit
The most frequently encountered primary neoplasms of the orbit
are vascular in origin and include
= Capillary hemangioma and lymphangioma of infants and
early childhood
= Cavernous hemangioma found typically in adults
Pleomorphic adenoma of lacrimal glands
Orbital Lymphomas
Metastasis : prostate, neuroblastoma and Wilms tumor
Children
rhabdomyosarcoma is the most common primary
malignancy of orbit
neuroblastoma is most common metastatic tumor
The Eyelid
Composite structure
Sebaceous gland pathology
Blepheritis chronic inflammation
Chalazion lipogranuloma due to obstruction of drainage
Sebaceous carcinoma
Basal cell carcinoma
 LIDS - Tumors

Chalazion a cyst of the meibomian gland

Hordeolum an inflammed cyst of the MG
(foreign body granuloma)
 Sebaceous carcinoma may form a mass or diffusely thicken
the eye lid
May also mimic inflammatory lesions like chalazion
Infiltrates to the parotid and submandibular glands
Morphologically the cells have vacoulated cytoplasm
Pagetoid spread is seen in some cases

Pagetoid spread of sebaceous

carcinoma. Neoplastic cells with
foamy cytoplasm are detected
within the epidermis
Conjunctival pathology

Conjuctival Scarring
Infection like by C. trachomatis ( trachoma )

Chemical irritation

Iatrogenic

Number of goblet cells is reduced decreased mucin (

which helps in the adherence of the aqueous component of
tear) dry eye with a risk of corneal opacification and
ulceration
 Conjunctiva

The bulbar layer is continous with the

palpebral layer
 Conjunctiva Pathologic conditions
Conjunctivitis (pink-eye) is an inflammation of the
conjunctiva due to a viral (Adenovirus), bacterial, or allergic
cause.
Ophthalmia neonatorum - Conjunctivitis in newborn
Pathogens: Neisseria gonorrhoeae (first week), Chlamydia
trachomatis (second week)

MALT, germinal centers

 Conjunctiva Degenerative
conditions
Pinguecula on the conj only
Pterygium encroaching onto cornea

Histologically identical
Both involve elastotic degeneration of the
conjunctiva, usually due to chronic ultraviolet
exposure
 Conjunctiva Degenerative
conditions

Small pinguecula Pterygium

Pinguecula Trachoma

Chlamydia trachomatisar
infects the conjunctival and
corneal epithelium
scarring and cicatization
Pterygium
 Conjunctiva - tumors
Conjunctival intraepithelial neoplasia (CIN)
Squamous Cell
Melanoma
Mucoepidermoid carcinoma
Lymphoid - arising from mucosa-associated
lymphoid tissue (MALT)

Lymphoma
 Cornea
The cornea is a unique transparent and
avascular tissue that is the most important
refractive structure of the eye

Anatomy
Inflammation/Infection
Dystrophy/Ectasia
 Cornea - Anatomy
5 Layers:
1. Epithelium Continuous with conj, richly innervated by
CN-V1
2. Bowmans Membrane
3. Stroma The thickest central portion (90%). This is where
LASIK/Refractive surgery happens! Primarily made up of
Type 1 Collagen in uniformly-spaced lamellar bundles.
4. Descemets membrane
5. Endothelium pumps the water out of the cornea and
keeps it clear
 Cornea

The uniform spacing of the stromal collagen bundles at a

distance of approx wavelength light allows transparency.
Normal corneal architecture
Pathology of the cornea
Keratitis and ulcers
Bacterial, fungal, viral ( esp. herps simplex & herps zoster )
and protozoa (Acanthamoeba) pathogens
Activation of collagenases dissolute the corneal stroma
Exudation may be seen to the anterior chamber ( hypopyon )
 Cornea Inflammation/Infection
Keratitis inflammation of cornea
Bacterial ulcer Frequent in contact lens users,
Pseudomonas most common
Viral Herpes (HSV) is a frequent etiology
Autoimmune, Syphilis, Fungal, ameobic, and
many other types
 The Lens
A transparent, avascular structure consisting of
concentric cellular fibers
Highest protein content of the body (Crystallins),
which account for a high refractive index
Interaction of the ciliary body muscle, through the
zonular fibers, cause dynamic shape changes.
In concert with the cornea, helps to focus light on
the retina.
 The Lens
Entire structure
encapsulated
Lens cells migrate and
elongate into fibers

The deepest fibers are the

oldest ones
The lens continues to fatten
throughout life
Central fibers become
sclerotic and opaque with
time
 The Lens - Cataract

Opacities of the lens develop with time, or insult

UV light, steroids, and inflammation are pathogenic factors
Cataract
Describes lenticular opacities
Can be congenital or acquired
Systemic diseases like DM
Age related cataract is due to opacification of the lens nucleus (
nuclear sclerosis )
Other changes that result in lens opacification include
liquefaction of the lens cortex and migration of lens epithelial
cells posteriorly ( posterior subcapsular cataract )
 The Uvea

The uvea is:

1. The Iris
2. The Ciliary body
3. The Choroid
Each has a function
1. Iris is a diaphragm for light
2. Ciliary body suspends and flexes the lens, and
makes the aqueous humor
3. The choroid helps nourish the outer retina
 The Uvea - Angle

The angle is a special region of the uvea where

the iris meets the cornea
Regulates the outflow of Aqueous humor through the
Canal of Schlem
Determines the Intraocular pressure (Important in
Glaucoma)
Glaucoma
Elevation in intraocular pressure ( can sometimes be normal)
Drainage of the aqueous humor is some how affected
Classified into open angle and angle closure glaucoma
 Both open angle and angle closure glaucoma are
subclassified in to primary and secondary
Primary open angle glaucoma is the commonest and is due
to genetic mutations
Neovascular glaucoma is when myofibroblastic components
are deposited on the surface of the iris
Gaucoma damages the optic nerve and characterstically
results in diffuse loss of ganglion cells and thinning of the
retinal fiber layer
 The Uvea - Inflammation

Uveitis is inflamation of any combination of the

iris, ciliary body, or choroid.
Many etiologies (autoimmune, syphilis, sacrcoid,
TB, HLA-B27, infectious, idiopathic, etc)
Many names (iritis, anterior uveitis, iridocylitis,
choroiditis, etc) depending on the location
Sometimes associated with SERIOUS systemic
inflamatory diseases (eg. arthritic diseases),
inflamatory bowel disease, and vasculitis.
Neoplasms of the uvea
Metastasis is the most common adult intraoccular
malignancy, especially to the choroid
Uveal Nevi
Melanoma
The most common primary adult intraoccular malignancy
Incidence is now increasing
Association with uv-light is not clear
Metastatic spread is first to the liver
Tumor dormancy
Melanomas of the iris are less aggressive than those of the
choroid and ciliary body
 The Retina - Anatomy
Cell types (overview)
Photoreceptors (detect
light signal)
Bipolars
transmit/modulate signal
to ganglion cells
Ganglion cells send signal
by long axons through
optic nerve and into visual
pathways of the brain
Other cell types
 The Retina - Anatomy
Layers (inside to out):
1. Inner limiting membrane
2. Nerve Fiber Layer
3. Ganglion Cell Layer
4. Inner plexiform layer
5. Inner nuclear layer
6. Outer plexiform layer
7. Outer nuclear layer
8. Photoreceptor segments
9. Retinal Pigment Epithelium
10. Bruchs Membrane
(Choroid)
(Sclera)
 Retina Anatomy
Pathologic conditions of layers
1) Retinal detachment: Separation between
RPE and photoreceptor segments
-separation of the neurosensory retina
from the retinal pigment epithelium
1) Macular degeneration: Bruchs membrane
damaged by deposition of drusen, allowing
leaky choroidal vessels to grow into retina
(exudative type).
 The Retina - Detachment

Retinal tears are the most Tears can be spot welded

frequent causes of detachment with laser to prevent
(rhegmatogenous RD) detachment
 Age-Related Macular Degeneration
Irreversible visual impairment
Cause is unclear but factors like smoking, nutritional factors ,
atherosclerosis and hypertension were attributed
Hereditary inheritance is seen esp. when it occurs in young
patients
Atrophic (dry) ARMD or Exudative (wet) ARMD

Retinal inflammation (retinitis)

variety of pathogens such as candida and CMV in immunocompromised
patients
 DIABETIC
RETINOPATHY
MECHANISM
* constriction of ocular blood vessels &
leakage of blood into retina
(microaneurysms, neovascularization = new
blood vessels)
* leakage of blood into vitreous humor
* scar tissue
ETIOLOGY
diabetics with uncontrolled glucose levels

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 The Retina - Tumors
Retinoblastoma
Classic pediatric tumor of retina
Hereditary or Sporadic
Requires two gene mutations (Knudsens
two-hit hypothesis)
Classic histologic features of Flexner-
Wintersteiner Rosettes, and fleurettes
Retinal neoplasms
Retinoblastoma
The most common primary intraoccular malignancy in
children
Cell of origin is neuronal
Prognosis depends on extraoccular extension and optic nerve
invasion
Germ line mutation of RB allel ( 40% of cases, which are
bilateral )
 RETINOBLASTOMA

Is the most common malignant eye tumor of

childhood.
Unique aspects - frequently occurs as a congenital
tumor, it can be multifocal and bilateral, it undergoes
spontaneous regression and patients have a high
incidence of second primary tumors.
most cases being diagnosed before the age of 4 years
Retinoblastomas occur in both familial and sporadic
patterns.
 Approximately 60% to 70% of the tumors are associated
with a germline mutation in the RB1 gene and are hence
heritable.
The remaining occurs sporadically hence they are
associated with somatic RB1 gene mutation
Retinoblastoma is believed to arise from a cell of
neuroepithelial origin, usually in the posterior retina
Clinical Features. The median age at presentation is 2
years, although the tumor may be present at birth. The
presenting findings include poor vision, strabismus, a
whitish hue to the pupil ("cat's eye reflex"), and pain and
tenderness in the eye.
Rb is either sporadic or familial
- Sporadic cancer in 55-65% of all cases
- Sporadic cancers are unilateral

Hereditary childhood cancer:

- bilateral tumors in ~75% of cases
- unilateral tumors in ~25% of cases
The Knudsons two hit hypothesis for the
generation of RB
 Retinoblastoma is inherited as a dominant
trait, but it is recessive at the cellular level

People with familial Retinoblastoma

carry one mutated copy in ALL their
cells. Cells that would get a second
hit will develop Rb or later, other
cancers
 Implications

Early diagnosis is critical

If left untreated cancer can spread

Over 95% of children in US survive and

lead normal lives
Follow up appointments are important to
detect possible secondary cancers
Morphology of retinoblastoma
Sheets of small undifferentiated hyperchromatic cells are seen
with areas of differentiation ( i.e formation of rossetts and
fleurettes )
Perivascular location of tumor cells and necrosis are seen
Dystrophic calcification may be seen
Papilledema
Edema and hyperemia of the head of the optic nerve
Due either to compression of the nerve ( neoplasm ) or
elevations of CSF pressure surrounding the nerve
That caused by raised intracranial pressure is bilateral

Optic neuritis
Loss of vision secondary to demyelinization of the optic nerve
Multiple sclerosis is an important cause and can be its first
manifestation
The End-Stage Eye : Phthisis Bulbi
Trauma, intraocular inflammation, chronic retinal
detachment result in small (atrophic) and internally
disorganized eye.
Endophthalmitis -suppurative inflammation in the vitreous
humor
panophthalmitis - is applied to inflammation within the eye
that involves the retina, choroid, and sclera and extends into
the orbit
The Ear
 3 Parts of the Ear
Outer, Middle, and Inner Ear
Part 1 OUTER EAR- Pinna to Tympanic Membrane
The pre amp makes sound waves stronger
 What Causes Outer Ear
Hearing Loss ?
Wax pushed up against eardrum
(tympanic membrane)- from q-tip use
Sharp objects that puncture tympanic
membrane
Born with damaged ear canal or without
pinna
Swimmers Ear -
 disorders
examples of foreign bodies
 disorders

impacted cerumen
 Part 2 - Middle Ear
Sound waves change to
mechanical energy in
the middle ear
 What are the parts of the Middle Ear?

Back of tympanic membrane

3 small bones
Eustachian tube
Eustachian Tube
What is the
purpose?

Drain cells/tissue
Equalize air
pressure
 What Causes Hearing Loss in the
Middle Ear ?
Calcium deposits on bones
Loud sudden noises- firecracker, gunshot
Trauma to the head- fall, car accident
Otitis media
 CONDUCTIVE HEARING LOSS
Any hearing loss occurring in the
OUTER or MIDDLE EAR
Malformed pinna
too much wax
swimmers ear (or water stuck in ear)
torn tympamic membrane
Otitis media
calcium deposits on ossicles
torn muscles that control the ossicles
 The Inner Ear
Cochlea
semi- circular canals
auditory nerve (8th cranial
nerve)

Note the changes of

energy as the sound waves
come through each part of
the ear
Entrance to the Inner ear
The COCHLEA
Size of a pea
Fluid filled
Contains up to 20,000
cilia or hair-like nerve
endings
Auditory nerve- carries electrical impulses
from cilia (in cochlea and semicircular
canals) to the brain for interpretation
 Sensorineural Hearing Loss
(Hearing loss in the Inner Ear)
Known etiologies-
Multiple Sclerosis
Leukemia
Sickle cell
syphilis
Bacterial infection( meningitis)
Mumps
ototoxic drugs (aspirin)
unknown
 Review--Pathway of Sound
Sound waves enter pinna travel through auditory canal
Sound waves strike tympanic membrane causing vibrations
(mechanical energy)
Vibrating TM causes ossicles to vibrate
Vibrating stapes bone at oval window generates movement of
cochlear fluid (Hydralics)
Fluid movement stimulates cilia- lined cochlea
Cilia sends electrical impulses along auditory nerve to brain for
interpretation