The document provides an outline and introduction for a lecture on eye pathology. It begins with an intro on basic eye anatomy and then outlines the main sections to be covered: Orbit, Eyelid, Conjunctiva, Cornea, Uvea, Lens, Retina/Vitreous, Optic Nerve/Glaucoma. Under each section, some key pathological conditions are briefly described, such as thyroid-related orbitopathy under Orbit, chalazion vs hordeolum under Eyelid, conjunctivitis types under Conjunctiva, and refractive surgery techniques under Cornea.

1. Today’s Quranic verse
‘Turn not your cheek away from people in scorn and pride, and
not on earth haughtily; for God does not love anyone who acts
proudly and boastfully. Be modest in your bearing and lower yo
voice; for the ugliest sound is the donkey’s braying.’
(Luqman 31: 18-19

3. Pathology of the
Eye - I
Dr. Khurshid Anwar
https://www.facebook.com/pages/Interactive-Neuroscience/160305064167505

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

7. Intro - Basic Anatomy

9. EYE PATHOLOGY-1

10. Orbit
• Functional Anatomy and Proptosis
– The orbit is a compartment that is closed medially, laterally,
and posteriorly. Any disease process that increases orbital
contents results in the forward displacement of the eye,
proptosis.
– Proptosis may be axial (directly forward) or positional.
• Axial proptosis
– Glioma and meningioma
• Positional (inferior and medial proptosis)
– Sarcoid or neoplasm (lymphoma or epithelial neoplasm such as
pleomorphic adenoma or adenoid cystic carcinoma)

11. Thyroid-Related Orbitopathy
(Graves’ Disease)
• Autoimmune condition, triggered by TSH-R Antibodies, with
lymphocytic infiltration, fibrosis and enlargement of extra-ocular
muscles.
• Proptosis, strabismus/muscle-restriction, exposure problems (dryeye), and compressive optic neuropathy.
• Treated with steroids, radiation therapy, or surgical decompression
(opening the orbital walls into the sinuses)

12. THYROID EYE DISEASE
Soft tissue involvement
• Periorbital and lid swelling
• Conjunctival hyperaemia
• Chemosis
• Superior limbic keratoconjunctivitis
Eyelid retraction
Proptosis
Optic neuropathy
Restrictive myopathy

13. Orbit – Thyroid-Related
Orbitopathy

14. Orbit - Trauma
• “Blow–out” 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

15. 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

16. Orbit - Inflammation

17. Orbit
• Other Orbital Inflammatory Conditions
– Orbital cellulitis
• Caused by fungal infection (Mucormycosis)
• Appears in systemic conditions such as Wegener granulomatosis
– Idiopathic orbital inflammation (orbital inflammatory
pseudotumor)
•
•
•
•
•
May be unilateral or bilateral
May be confined to the lacrimal gland (sclerosing dacryoadenitis)
Extraocular muscles (orbital myositis)
Tenon’s capsule (posterior scleritis)
In the long-term, patients may show evidence of systemic vasculitis
or other forms of connective tissue diseases

18. Orbital Neoplasms
– Most frequent primary neoplasms are vascular in origin
• capillary hemangioma (infancy and early childhood)
• lymphangioma
• encapsulated cavernous hemangioma (adults)
– Only a handful of orbital masses are encapsulated
• pleomorphic adenoma
• dermoid cyst
• neurilemmoma
– Malignant lymphoma
– In Children
• rhabdomyosarcoma is the most common primary malignancy of orbit.
• neuroblastomaa is the most common metastatic tumor.
– Metástasis: may produce characteristic periocular echymoses
• prostatic carcinoma
• metastatic neuroblastoma
• Wilms tumor

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

20. Anatomy of the conjunctiva and the eyelids

21. Eyelid
• Functional Anatomy
– The eyelid covers and protects the eye, and generates critical
components of the tear film
– The eyelid is a composite of skin externally and a mucosa (the
conjunctiva) on the surface apposed to the eye
– Eccrine and apocrine glands (glands of Moll) populate the eyelid.
– Blepharitis:
• Obstruction of the drainage system of the sebaceous glands by
chronic inflammation or by neoplasm
– Lipid extravasating into surrounding tissue and provoking a
granulomatose response is called a lipogranuloma or chalazion

22. LIDS - Histology

23. LIDS - Tumors
• Benign
–
–
–
–
Chalazion vs. Hordeolum
Papillomas/Verrucae
Epidermal inclusion cysts
Many others
• Malignant
– Basal cell carcinoma (most common, located in lower eyelid &
medial canthus)
–
–
–
–
Sebaceous cell carcinoma (D/D chalazion, belephritis)
Squamous cell carcinoma
Melanoma (rare)
Kaposi sarcoma in AIDS

24. LIDS - Tumors
• Chalazion – a cyst of the meibomian gland
• Hordeolum – an inflammed cyst of the MG (foreign body granuloma)

25. Conjunctiva
•
Thin (transparent), 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
The palpebral layer is continous with bulbar layer at fornix

26. Conjunctiva
• Functional Anatomy
The conjunctiva is divided into topologic zones, each with
distinctive histologic features and responses to disease:
• Palpebral conjunctiva
– The conjunctiva lining the interior of the eyelid (palpebral conjunctiva)
is trown into minute papillary folds in allergic conjunctivitis and bacterial
infectious conjunctivitis
• Fornix
– In viral conjunctivitis, lymphoid follicles may enlarge sufficiently to be
visualized clinically
– Granulomas (sarcoid)
– Primary lymphoma
• Bulbar conjunctiva

27. Conjunctivitis (pink eye)
It is an inflammation of the conjunctiva due to a viral
(Adenovirus), bacterial, or allergic cause
Most cases of conjunctivitis run a predictable course, and the
inflammation usually clears up in a few days.
Conjunctivitis is a common disease, especially in children. Although
conjunctivitis can be highly contagious (known to spread rapidly in
schools or daycare settings), it is rarely serious and will not damage
vision if detected and treated promptly.

28. Trachoma
Trachoma is the world’s leading cause of preventable blindness of infectious
origin.
Caused by the bacterium Chlamydia trachomatis.
It spreads through direct personal contact, shared towels and cloths, and flies
that have come in contact with the eyes or nose of an infected person.
If left untreated, repeated trachoma infections can cause severe scarring of the
inside of the eyelid and can cause the eyelashes to scratch the cornea
(trichiasis). In addition to causing pain, trichiasis permanently damages the
cornea and can lead to irreversible blindness.
It spreads in areas that lack adequate access to water and sanitation, affects the
most marginalized communities in the world. Globally, almost 8 million people
are visually impaired by trachoma; 500 million are at risk of blindness from the
disease throughout 57 endemic countries
http://www.cdc.gov/healthywater/hygiene/disease/trachoma.html

29. Conjunctivitis
A rare granulomatous variety…
Cat-scratch Fever!
(Bartonella henselae)

30. Conjunctiva
• Conjunctival Scarring
– Caused by:
•
•
•
•
Chlamydia trachomatis (trachoma)
Caustic alkalis
A sequela to ocular cicatricial pemphigoid
Iatrogenically through reaction to drugs or as a
concequence of surgery
– Painful, dry eye

31. Conjunctiva
Degenerative conditions
• Pinguecula – on the conjunctiva only
• Pterygium – encroaching onto cornea
• Histologically identical
• Both involve “elastotic degeneration” of the conjunctiva,
usually due to chronic ultraviolet exposure.

32. Conjunctiva
• Pterygium and Pinguecula
– Appear as submucosal elevations on the conjunctiva
– Result from actinic damage
Pterygium
•
•
•
•
•
In the conjunctiva astride the limbus
Formed by fibrovascular connective tissue that migrates onto the cornea
May possibly induce mild astigmatism
Commonly excised
Occasionally precursors of actinic-induced neoplasms (SCC, Melanoma)
Pinguecula
• Does not invade the cornea as pterygium does
• Focal dehydration (dellen: a saucer-like depression in the corneal tissue)
• Solar elastosis: sun-damaged collagen with elastic-like properties, that are
the reason why the pinguecula is yellow in color
• Actinic granuloma may develop secondary to a foreign body
granulomatous reaction against the elastotic collagen

33. Conjunctiva – Degenerative conditions
• Small pinguecula
• Pterygium

34. Conjunctival Neoplasm
– Squamous neoplasms (CIN – Conjunctival intraepithelial neoplasia & SCC)
• May be associated with the presence of human papillomavirus types 16 & 18
– Mucoepidermoid carcinoma (more aggressive course)
– Conjunctival nevi
– Conjunctival melanoma
• Tend to develop in the limbus
• Most cases develop through a phase of intraepithelial growth termed primary
acquired melanosis with atypia, which is analogous to melanoma in situ
• Spread first to the parotid or submandibular lymph nodes
• Mortality rate: 25%
– Lymphoma; Spread first to the parotid or submandibular lymph nodes

35. Conjunctiva Neoplasm
CIN (squamous cell), HPV 16/18

36. Sclera
• May appear “blue” in a variety of conditions:
– high intraocular pressure (staphyloma)
– osteogenesis imperfecta
– congenital melanosis oculi
• Heavily pigmented congenital nevus of the underlying uvea
• Together with periocular cutaneous pigmentation
– Nevus of Ota

37. Cornea
• Functional Anatomy
– The cornea and its overlying tear film – and not the lens –
make up the major refractive surface of the eye
– Corneal stroma lacks blood vessels and lymphatics (is very
transparent; corneal transplantation is usually successful)
– Scars can exist due to inflammation or trauma

38. Cornea - Histology
5 Layers:
1. Epithelium – Continuous with
conj, richly innervated by CN-V1
2. Bowman’s Membrane
3. Stroma – The thickest central
portion (90%). This is where
LASIK/Refractive surgery
happens! Primarily made up of
Type 1 Collagen in uniformlyspaced lamellar bundles.
4. Descemet’s membrane
5. Endothelium – pumps the water
out of the cornea and keeps it
clear

39. Cornea
The uniform spacing of the stromal collagen bundles at a
distance of approx ¼ wavelength light allows transparency .

40. Normal corneal microarchitecture

41. Cornea - Refractive Surgery
•
•
Excimer Laser is applied to the stromal bed, underneath a reflected
corneal flap (LASIK= Laser-Assisted Stromal In-situ Keratomileusis).
The tissue is ablated precisely to counteract the refractive error of the eye.

42. LASIK – Traumatic Flap Dislocation

43. Cornea-Pathology
• Functional Anatomy
– Descemet membrane increases in thickness with age
• It is the site of copper deposition in the Kayser-Fleischer ring of
Wilson disease
• Keratitis (inflammation of cornea) and Ulcers
– Bacterial (frequent in contact lens users, pseudomonas most common)
– Fungal
– Viral (especially herpes simplex and herpes zoster)
• Chronic herpes simplex keratitis may be associated with a
granulomatous reaction to Descemet’s membrane
– Protozoal (Acanthoamoeba)
– Autoimmune, Syphilis etc

44. Cornea - Bacterial Ulcer
Epithelial defect, infiltrate of white cells into the cornea, and a layered
leukocyte collection in the AC (Hypopyon)

45. Cornea - HSV Keratitis
Epithelial “dendritic” Keratitis
Stromal Keratits (note the
vessels and clouding)
chronic herpes simplex keratitis may be associated with a granulomatous reaction involving the
Descemet membrane

46. Corneal degenerations
May be either unilateral or bilateral & typically non-familial.
Calcific band keratopathy is characterized by deposition of calcium in the Bowman layer. This
condition may complicate chronic uveitis, especially in individuals with chronic juvenile
rheumatoid arthritis.
Actinic band keratopathy develops in individuals who are exposed chronically to high levels of
ultraviolet light. In this condition, extensive solar elastosis develops in the superficial layers of
corneal collagen in the sun-exposed interpalpebral fissure, hence the horizontally distributed
band of pathology. ("oil-droplet keratopathy.“)
Keratoconus is fairly common disorder characterized by progressive thinning and ectasia of the
cornea without evidence of inflammation or vascularization and leads to irregular astigmatism
that is difficult to correct with spectacles. Activation of collagenases, gelatinases, and matrix
metalloproteinases has been implicated in the pathogenesis of this condition

47. Cornea - Ectasia
Progressive deformation of cornea is an ectasia. Keratoconus is the most
common ectatic degenerative change. Ectasia can also be a complication
of refractive surgery.

48. Cornea – Dystrophy
Group of progressive, usually bilateral mostly genetically determined, noninflammatory opacifying disorders characterized by abnormal tissue
morphology, function, or abnormal depositions of material into the cornea.
MANY types, affecting each specific layer (epithelial, Bowmans membrane,
stroma or endothelium).
Fuchs Dystrophy
Affecting the endothelium, is one of the principal indications for corneal transplantation in the
United States. The two major clinical manifestations of Fuchs endothelial dystrophy-stromal
edema and bullous keratopathy-are both related to a primary loss of endothelial cells.
Macular Dystrophy
Least common, autosomal recessive, most severe, characterized by multiple, gray-white
opacities that are present in the corneal stroma and that extend out into the peripheral cornea)
Crystalline Dystrophy
Granular Dystrophy
Lattice Dystrophy
Map-Dot-Fingerprint Dystrophy

49. Cornea – Stromal Dystrophy
Granular Dystrophy
Hyaline material deposited in stroma
Diverse mutations in TGFB1 disrupt the folding of keratoepithelin, and depending on the exact
mutation, lead to the deposition of various types of proteinaceous deposits in the cornea.

50. Cornea – Stromal Dystrophy
Lattice Dystrophy
Amyloid deposition with “applegreen” birefringence. Stains with
Congo Red

51. Cornea Transplant

52. The Uvea
“The uvea” is:
1.
2.
3.
The Iris
The Ciliary body
The Choroid
Each has a function
1.
2.
3.
Iris is a diaphragm for light
Ciliary body suspends & flexes the lens, & makes the aqueous
humor
The choroid helps nourish the outer retina
The choroid is among the most richly vascularized sites in the body
As in the retina, there are no lymphatics within the uvea

53. 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)

54. 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, posterior uveitis
etc.) depending on the location
•
Sometimes associated with SERIOUS systemic inflamatory diseases (eg.
arthritic diseases), inflamatory bowel disease, and vasculitis.

55. Uveitis
Causes:
• Infectious agents
– e.g.: pneumocystis carinii
• Idiopathic
– e.g.: sarcoidosis
• Autoimmune
Sympathetic ophthalmia
Sympathetic ophthalmia, an example of noninfectious autoimmune uveitis
Characterized by bilateral granulomatous inflammation typically affecting all components of the
uvea: a panuveitis.
May complicate a penetrating injury of the eye. In the injured eye, retinal antigens sequestered
from the immune system may gain access to lymphatics in the conjunctiva and thus set up a
delayed hypersensitivity reaction that affects not only the injured eye but also the contralateral,
noninjured eye.
Condition may develop from 2 weeks to many years after injury. Enucleation of a blind eye
(which can be the sympathizing eye rather than the directly injured eye) may yield diagnostic
findings.
Treated by the administration of systemic immunosuppressive agents.

56. The Uvea – Anterior Uveitis
• Anterior uveitis/iritis
• WBCs floating in the aqueous

57. Uvea – Posterior Uveitis
• Active Toxoplasmosis Choroiditis, and old scar (above)

58. The cherry-red spot in Tay-Sachs disease. A, Fundus photograph of the cherry-red
spot in Tay-Sachs disease. B, Photomicrograph of the macula in a patient with TaySachs disease, stained with periodic acid-Schiff to highlight the accumulation of
ganglioside material in the retinal ganglion cells. The presence of ganglion cells filled
with gangliosides outside the fovea blocks the transmission of the normal orange-red
color of the choroid, but absence of ganglion cells within the fovea (to the right of the
vertical bar) permits the normal orange-red color to be visualized, accounting for the
so-called cherry-red spot.

59. Uveal Neoplasm
– Most common intraocular malignancy of adults:
metastasis, typically to the choroid from breast and lung
• Suggestive of extremely short survival
– Nevi and Melanomas
• Uveal melanoma
–
–
–
–
–
Most common primary intraocular malignancy of adults (7-20/million)
Histologically spindle & epitheloid type
SIZE OF TUMOR/CELL TYPE/PROLIFERATIVE INDEX
Melanomas of the ciliary body and choroid are more aggressive
Most spread first to the liver; metastases appear many years after
treatment (dormancy).
– Mortality: 40% at ten years
• Uveal nevi
– Especially choroidal nevi, are common, affecting 10% of the
Caucasian population.

60. 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

61. Anterior Segment
Functional Anatomy
The anterior chamber is bounded anteriorly
by the cornea, laterally by the trabecular
meshwork, and posteriorly by the iris.
Aqueous humor, formed by the pars plicata
of the ciliary body, enters the posterior
chamber, bathes the lens, and circulates
through the pupil to gain access to the
anterior chamber.
The lens is a closed epithelial system; the basement membrane of the lens
epitheliuim (known as the lens capsule) totally envelops the lens.
With aging, the size of the lens increases.
Neoplasms of the lens have not been described.

62. 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.

64. CATARACT
– The term cataract describes lenticular opacities that may be
congenital or acquired.
– Causes:
• Systemic diseases:
–
–
–
–
Galactosemia
Diabetes mellitus
Wilson disease
Atopic dermatitis
• Drugs:
– Corticosteroids
•
•
•
•
•
Radiation
Trauma
Many intraocular disorders
Age-related cataract (nuclear sclerosis)
Smoking

65. 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

66. The Lens - Cataract
Opacities of the lens develop with time, or insult
• UV light, steroids, and inflammation are pathogenic factors

68. 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

69. The Lens – Cataract surgery
The dense, cloudy crystalline lens is removed, and replaced with an optical implant.
Inflammatory reactions to lens material may develop following exposure of the intact
lens cortex caused by rupture of the capsule due to trauma or as a result of cataract
extraction. It has been suggested that antigen-antibody complexes containing lens
cortical material develop especially in the presence of Propionibacterium acnes (which
acts as an adjuvant), generating a lens-induced uveitis

70. Rubella syndrome, or congenital rubella, is a group of physical abnormalities that
have developed in an infant as a result of maternal infection and subsequent fetal
infection with rubella virus. It is characterized by rash at birth, low birth weight, small
head size, heart abnormalities, visual problems and bulging fontanelle.

71. Hypermature Cataract & Glaucoma
Occasionally, the lens cortex may liquefy nearly entirely, a condition known
as hypermature or morgagnian cataract.
High-molecular-weight proteins from liquefied lens cortex may leak through
the lens capsule(phacolysis). This phacolytic protein-either free or
contained within macrophages-may clog the trabecular meshwork and
contribute to elevation in intra-ocular pressure and optic nerve damage;
phacolytic glaucoma is an example of secondary open-angle glaucoma.

72. GLAUCOMA
• The Anterior Segment and Glaucoma
The term glaucoma refers to a collection of diseases characterized by
distinctive changes in the visual field and in the cup of the optic nerve. Most
of the glaucomas are associated with elevated intraocular pressure, although
some patients with normal intraocular pressure may develop characteristic
optic nerve and visual field changes (normal or low-tension glaucoma).
It is the third most common cause of blindness in world
Risk Factors
Diagnosis of Glaucoma
Intraocular pressure ( IOP ) and its measurement. (tonometry)
Optic disc examination.
Visual Field examination ( perimetry )
Age
Race
Family
Diabetese
Eye injuries
Drugs

74. Classification of Glaucoma
– Glaucoma may be classified as:
• Open angle glaucoma
– Increased resistance to aqueous outflow in the open angle
– Primary
– Secondary
• Angle closure glaucoma
– The peripheral zone of the iris adheres to the trabecular meshwork and
impedes the egress of aqueous from the eye.
– Primary
– Secondary

75. Open angle glaucoma
• Primary
– The most common form of glaucoma
– Few changes are apparent
– Mutations in the GLC1A gene which encodes the protein myocilin
located on chromosome 1 have been associated with a subset of
individuals with juvenile and adult primary open-angle glaucoma.
• Secondary
–
–
–
–
–
–
Phacolysis (liquefied lens cortex, leaking through the lens capsule)
Senescent red blood cells after trauma (ghost cell glaucoma)
iris epithelial pigment granules (pigmentary glaucoma),
fragments of oxytalan fibers (exfoliation glaucoma), and
necrotic tumors (melanomalytic glaucoma) .
Anything that contributes to elevate the pressure on the surface of the
eye (episcleral venous pressure) in the presence of an open angle can
contribute to other types of secondary open angle glaucoma

76. Angle closure glaucoma
Primary
– Typically develops in eyes with shallow anterior chambers
– Often found in patients with hyperopia (hypermetropia)
– Consequences:
» Pupillary block
» Iris bombé apposing it to the trabecular mesh work
» Corneal edema
» Bullous keratopathy
Secondary (causes)
– Contraction of various types of pathologic membranes that form over
the surface of the iris (chronic retinal ischemia is associated with the
up-regulation of VEGF)
– Necrotic tumors
– Iridocorneal endothelial syndrome
– Following intraocular surgery or penetrating trauma
– Tumors in the ciliary body

79. ENDOPHTHALAMITIS & PANOPHTHALAMITIS
Causes:
• Blunt trauma
• Corneal infections
• Uveitis
The term endophthalmitis is not applied clinically unless there is
suppurative inflammation within the vitreous humor is poorly tolerated by
the retina; after only a few hours of exposure to acute inflammation, the
retina may be irreversibly damaged
Exogenous (originating in the environment and gaining access to the
interior of the eye through a wound)
Endogenous (delivered to the eye hematogenously).
Panophthalmitis: inflammation within the eye that involves the
retina, choroid, and sclera and extends into the orbit may produce
proptosis

80. Acknowledgements
•Books:
Robbins and Cortran, Pathologic Basis of Disease
•Images:
RC-PBD, Elsevier
Various public internet sources