pathology of the eye•conjunctival intraepithelial neoplasia (cin) •squamous cell •melanoma...
TRANSCRIPT
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Pathology of the Eye
John R. Minarcik, M.D.
LT MC USN
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Outline and Introduction
SECTIONS
1. Orbit
2. Eyelid
3. Conjunctiva
4. Cornea
5. Uvea
6. Lens
7. Retina/Vitreous
8. Optic Nerve/Glaucoma
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Intro - Basic Anatomy
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THE ORBIT
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Orbit
• Anatomy
• Thyroid Orbitopathy
• Tumors
• Inflammation/Infection
• Trauma
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Orbit - Anatomy
• Bones of the orbit
– Sphenoid
– Maxillary
– Ethmoid
– Lacrimal
– Zygoma
– Palatine
– Frontal
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Orbit - Osteology
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Orbit – Posterior Contents
• The ANNULUS OF ZINN is the tendon-ring that encircles the ON and acts as an origin for the muscles.
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Orbit – Anterior Boundary
• The ORBITAL SEPTUM is the anterior fascial boundary to the orbit
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Orbit – Thyroid-Related
(Graves’) Orbitopathy
• Autoimmune condition, triggered by ?Thyroid antigens, with lymphocytic infiltration, FIBROSIS, and ENLARGEMENT of extraocular muscles.
• Proptosis, strabismus/muscle-restriction, exposure problems (dry-eye), and compressive optic neuropathy.
• Treated with steroids, radiation therapy, or surgical decompression (opening the orbital walls into the sinuses)
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Orbit – Thyroid-Related
Orbitopathy
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Orbit - Tumors
• Wide variety of lacrimal, lymphoid, neural,
vascular, meningeal origin tumors, and
metastatic tumors
• Children
–rhabdomyosarcoma is the most common
primary malignancy of orbit.
– neuroblastoma is most common metastatic
tumor
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Orbit - Inflammation
• Orbital Cellulits frequently
extends from adjacent sinus
infections, or periocular trauma.
• A life and sight threatening
emergency! Can extend into
the cavernous sinus, and brain.
• “Pre-Septal” vs. “Post-Septal”
can be distinguished by
involvement of intraorbital
structures
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Orbit - Inflammation
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Orbit - Trauma
• “Blow–out” fractures occur when blunt
trauma to the eye causes the orbit to rupture
• Hemorrhages into the orbit can act like a
“compartment syndrome”
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Orbit - Trauma
Orbital Floor fractures can cause restricted upgaze if there is muscle entrapment
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LIDS
• Anatomy
• Tumors
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LIDS - Anatomy
LAYERS:
• Skin
• Orbicularis
• Tarsal plate
• Meibomian glands
• Palpebral
conjunctiva
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LIDS - Histology
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LIDS - Tumors
• Malignant
– Basal cell carcinoma - most common
– Squamous
– Melanoma
– Sebaceous cell carcinoma
• Benign
– Chalazion vs. Hordeolum
– Papillomas/Verrucae
– Epidermal inclusion cysts
– Many others…
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LIDS - Tumors
• Chalazion – a cyst of the meibomian gland
• Hordeolum – an inflammed cyst of the MG (foreign body granuloma)
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Conjunctiva
• Thin, non-keratinized skin covering the
sclera (bulbar) or the inner surface of the lid
(palpebral)
• Rich in goblet cells, which secret the
mucinous components of the tear film
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Conjunctiva
• The bulbar layer is continous with the
palpebral layer
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Conjunctiva – Pathologic
conditions
• Conjunctivitis (“pink-eye”) – is an
inflammation of the conjunctiva due to a
viral (Adenovirus), bacterial, or allergic
cause.
• Scarring – Can occur with serious
inflammatory conditions like Stevens-
Johnson syndrome and Ocular Cicatricial
Pemphigoid
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Conjunctivitis
• Cat-scratch
Fever!
• A rare granulomatous variety…
• Bartonella henselae
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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.
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Conjunctiva – Degenerative
conditions
• Small pinguecula • Pterygium
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Conjunctiva - tumors
• Conjunctival intraepithelial neoplasia (CIN)
• Squamous Cell
• Melanoma
• Lymphoid - arising from mucosa-associated
lymphoid tissue (MALT)
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Conjunctiva
• CIN (squamous cell), HPV 16/18
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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
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Cornea - Anatomy
5 Layers:
• Epithelium – Continuous with conj, richly innervated by CN-V1
• Bowman’s Membrane
• 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.
• Descemet’s membrane
• Endothelium – pumps the water out of the cornea and keeps it clear
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Cornea
The uniform spacing of the stromal collagen bundles at a
distance of approx ¼ wavelength light allows transparency.
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Cornea - Refractive Surgery
• Excimer Laser is applied to the stromal bed, underneath a reflected corneal flap (LASIK).
• The tissue is ablated precisely to counteract the refractive error of the eye.
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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
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Cornea - HSV Keratitis
• Epithelial “dendritic”
Keratitis
• Stromal Keratits (note the vessels and clouding)
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Cornea - Bacterial Ulcer
Epithelial defect, infiltrate of white cells into the cornea, and a layered leukocyte collection in the AC (Hypopyon)
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Cornea – Stromal Dystrophy
• Dystrophy – a heritable disorder resulting in
abnormal tissue morphology, function, or
abnormal depositions of material into the
cornea.
• MANY types, affecting each specific layer.
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Cornea – Stromal Dystrophy
• Granular Dystrophy • Hyaline material
deposited in stroma
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Cornea – Stromal Dystrophy
• Lattice Dystrophy• Amyloid deposition with
“apple-green” birefringence, with Congo Red staining
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Cornea - Ectasia
• Progressive deformation of cornea is an ectasia. Keratoconus is the most common ectatic dystrophy. Ectasia can also be a complication of refractive surgery…
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THE UVEA
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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
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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)
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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.
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The Uvea – Anterior Uveitis
• Anterior uveitis/iritis • WBCs floating in the aqueous
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Uvea – Posterior Uveitis
• Active Toxoplasmosis Choroiditis, and old scar (above)
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The Uvea - Tumors
• The Choroid is a highly perfused vascular
“net” feeding the outer retina
• It is a potential target site for metastasis for
carcinoma, such as breast and lung.
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The Uvea - Tumors
• The uvea (especially choroid) is also richly pigmented, and primary melanocytic tumors are common.
• Nevi and malignant melanomas are both relatively common, and can be difficult to distinguish, clinically.
• Tumors with “spindle-B” or epithelioid histologic patterns are malignant
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THE LENS
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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.
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The Lens
• The deepest fibers are the oldest ones
• The lens continues to fatten throughout life
• Central fibers become sclerotic and opaque with time
• Entire structure
encapsulated
• Lens cells migrate and
elongate into fibers
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The Lens - Cataract
Opacities of the lens develop with time, or insult
• UV light, steroids, and inflammation are pathogenic factors
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The Lens – Cataract surgery
• A opening into the
lens capsule is
made
• The cataract is
emulsified with
ultrasound energy,
and aspirated out of
the eye
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The Lens – Cataract surgery
• The dense, cloudy crystalline lens is
removed, and replaced with an optical
implant.
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The Retina
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The Retina
• Anatomy
• Detachment
• Vascular disease/Ischemic retinopathy
– Microvascular (Diabetes)
– Vascular occlusion (Vein occlusion/Arterial Occlusion)
• Macular degeneration
• Tumors
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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…
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The Retina - AnatomyLayers (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. Bruch’s Membrane
(Choroid)
(Sclera)
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Retina – Anatomy
Pathologic conditions of layers
1) Retinal detachment: Separation between
RPE and photoreceptor segments
2) Macular degeneration: Bruch’s membrane
damaged by deposition of drusen,
allowing leaky choroidal vessels to grow
into retina (exudative type).
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The Retina - Detachment
Retinal tears are the most
frequent causes of detachment
(rhegmatogenous RD)
Tears can be “spot welded”
with laser to prevent
detachment
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The Retina – Macular degeneration
• Clinical appearance of drusen in Macular degeneration
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The Retina – Vasculopathy
• Microvascular (small vessel disease)
– Diabetes
– Sickle Cell
– Radiation
• Macrovascular (large vessel occlusions)
– Central retinal vein occlusion (CRVO)
– Branch retinal vein occlusion (BRVO)
– Central retinal artery occlusion (CRAO)
– Branch retinal artery occlusion (BRAO)
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The Retina – Diabetic Retinopathy
Microvascular dysfunction leads to tissue ischemia
– Thickened and Leaky Capillary basement membranes
– Loss of pericytes
– Microaneurysms
– Nonperfusion
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The Retina – Diabetic Retinopathy
Ischemia leads to vascular endothelial growth factor (VEGF) production from injured tissues
– Promotes Neovascularization (abnormal blood vessel growth) of the retina, optic nerve, or iris.
– Abnormal vessels can cause edema or tractional retinal detachments
– VEGF implicated in other ischemic eye diseases, like Retinopathy of Prematurity
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• Microaneurysms!• Capillary dropout and
Nonperfusion!
• Neovascularization!
The Retina – Diabetic Retinopathy
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• Retinal neovascularization
The Retina – Diabetic Retinopathy
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The Retina – MACROvascular Disease
• CRVO/BRVO – variety of anatomical
prothrombotic predispositions
• CRAO/BRAO – watch out for
carotid/cardiac embolic disease, or
vasculitis.
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The Retina – Macrovascular disease
CRVO – Hemorrhage, congestion, ischemia
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Ischemic CRVO led to VEGF production,
which caused neovascularization of iris.
The Retina – Macrovascular disease
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The Retina - Tumors
Retinoblastoma
• Classic pediatric tumor of retina
• Hereditary or Sporadic
• Requires two gene mutations (Knudsen’s
“two-hit” hypothesis)
• Classic histologic features of Flexner-
Wintersteiner Rosettes, and fleurettes
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OPTIC NERVE
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Optic nerve – Pathologic Conditions
of…• Ischemic Neuropathy – due to arteritic
(Giant Cell Arteritis) or non-arteritic causes.
• Optic Neuritis –Many causes, but
demyelinating (Multiple Sclerosis) causes
are most important
• Papilledema – swelling due to increased
intracranial pressure
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Optic Nerve – Pathologic conditions
of…
• Glaucoma – progressive injury of optic
nerve, frequently associated with elevated
intraocular pressure
- Characteristic “cupping” of nerve
- Loss of retinal nerve fiber layer
- Advancing peripheral visual field loss
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Optic Nerve - Glaucoma
• Loss of rim correlates to loss of axons from ganglion cells in
retina (Nerve fiber layer).
• Regions of lost ganglion cells/axons cause visual field loss.
Normal Cupped Advanced Glaucoma
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Final discussion points?
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Summary of *key* topics:
Thyroid orbitopathy
“Ditzels” on the front of the eye
Corneal layers
Uveitis as a manifestation of systemic disease
Lens and cataract
Diabetic Retinopathy
Retinal Detachment
Glaucoma
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This Concludes Eye Pathology