Pathology of the

Eye

John R. Minarcik, M.D.

Outline and Introduction

SECTIONS 1. Orbit 2. Eyelid 3. Conjunctiva 4. Cornea 5. Uvea 6. Lens 7. Retina/Vitreous 8. Optic Nerve/Glaucoma

Intro - Basic Anatomy

THE ORBIT
Anatomy Thyroid Orbitopathy Tumors Inflammation/Infection Trauma

Orbit - Anatomy
Bones of the orbit
Sphenoid Maxillary Ethmoid Lacrimal Zygoma Palatine Frontal

Orbit - Osteology

Orbit Posterior Contents

The ANNULUS OF ZINN is the tendonring that encircles the ON and acts as an origin for the muscles.

Orbit Anterior Boundary

The ORBITAL SEPTUM is the anterior fascial boundary to the orbit

Thyroid-Related Orbitopathy (Graves Disease)

Autoimmune condition, triggered by TSH-R Antibodies, 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)

Orbit Thyroid-Related Orbitopathy

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

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

Orbit - Inflammation

Orbit - Trauma
Blowout fractures occur when blunt trauma to the eye causes the orbit to rupture Orbital Floor fractures can cause restricted upgaze if there is muscle entrapment

LIDS - Anatomy
LAYERS: Skin Orbicularis Tarsal plate Meibomian glands Palpebral conjunctiva

LIDS - Histology

LIDS - Tumors
Malignant
Basal cell carcinoma - most common Squamous Melanoma Sebaceous cell carcinoma

Benign
Chalazion vs. Hordeolum Papillomas/Verrucae Epidermal inclusion cysts Many others

LIDS - Tumors

Chalazion a cyst of the meibomian gland Hordeolum an inflammed cyst of the MG (foreign body granuloma)

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

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.

MALT, germinal centers

Conjunctivitis
A rare granulomatous variety

- Cat-scratch Fever! - Bartonella henselae

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

Conjunctiva - tumors
Conjunctival intraepithelial neoplasia (CIN) Squamous Cell Melanoma Lymphoid - arising from mucosa-associated lymphoid tissue (MALT)
Lymphoma

Conjunctiva

CIN (squamous cell), HPV 16/18

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.

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.

LASIK Traumatic Flap Dislocation

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

Cornea - HSV Keratitis

Epithelial dendritic Keratitis

Stromal Keratits (note the vessels and clouding)

Cornea - Bacterial Ulcer

Epithelial defect, infiltrate of white cells into the cornea, and a layered leukocyte collection in the AC (Hypopyon)

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.

Cornea Stromal Dystrophy

Granular Dystrophy

Hyaline material deposited in stroma

Cornea Stromal Dystrophy

Lattice Dystrophy

Amyloid deposition with apple-green birefringence. Stains with Congo Red

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

Cornea Transplant

THE UVEA

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

Each has a function

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)

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.

The Uvea Anterior Uveitis

Anterior uveitis/iritis

WBCs floating in the aqueous

Uvea Posterior Uveitis

Active Toxoplasmosis Choroiditis, and old scar (above)

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.

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

THE LENS

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

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

The Lens Cataract surgery

The dense, cloudy crystalline lens is removed, and replaced with an optical implant.

The Retina

The Retina
Anatomy Detachment Vascular disease/Ischemic retinopathy
Microvascular (Diabetes) Vascular occlusion (Vein occlusion/Arterial Occlusion)

Macular degeneration Tumors

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 2) 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 frequent causes of detachment (rhegmatogenous RD)

Tears can be spot welded with laser to prevent detachment

Retinal Detachment

The Retina Macular degeneration

Clinical appearance of drusen in Macular degeneration

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)

The Retina Diabetic Retinopathy

Microvascular dysfunction leads to tissue ischemia
Thickened and Leaky Capillary basement membranes Loss of pericytes Microaneurysms Nonperfusion

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

The Retina Diabetic Retinopathy

Microaneurysms!

Capillary dropout and Nonperfusion! Neovascularization!

The Retina Diabetic Retinopathy

Retinal neovascularization

The Retina MACROvascular Disease

CRVO/BRVO variety of anatomical prothrombotic predispositions
CRAO/BRAO watch out for carotid/cardiac embolic disease, or vasculitis.

The Retina Macrovascular disease

CRVO Hemorrhage, congestion, ischemia

The Retina Macrovascular disease

Ischemic CRVO led to VEGF production, which caused neovascularization of iris.

The Retina - Tumors

Retinoblastoma Classic pediatric tumor of retina Hereditary or Sporadic Requires two gene mutations (Knudsens two-hit hypothesis) Classic histologic features of FlexnerWintersteiner Rosettes, and fleurettes

OPTIC NERVE

Pathologic Conditions of the Optic Nerve

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

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

Optic Nerve - Glaucoma

Normal

Cupped

Advanced 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.

This Concludes Eye Pathology

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

Final discussion points?