THE CORNEA

Question 1

KNOW the OHTS (Ocular Hypertension Treatment Study) central corneal thickness measurements for African Americans and Caucasians

Answer 1

555 + 40 um in African Americans

579 + 37 um in Caucasians

Question 2

An intraocular pressure of 20 mmHg measured on a cornea that is 520 microns is most likely

Answer 2

Accurately estimating the IOP

Question 3

Which of the following corneal layers is being highlighted by the red arrow?

Answer 3

Endothelium

Question 4

Which of the following corneal junctions is responsible for preventing excess uptake from the tear film?

Answer 4

Zonula occludens

Question 5

Which of the following time frames is most consistent with the healing of a full thickness corneal abrasion with an intact basement membrane?

Answer 5

7-10 days

Question 6

An abnormality in which 2 of the following structures is generally the underlying cause for recurrent corneal erosions?

Answer 6

Basement membrane, Hemidesmosomes

Question 7

Which of the following cells are responsible for synthesizing the corneal stroma collagen?

Answer 7

Keratocytes

Question 8

Schwalbe’s line is the peripheral termination of which corneal layer?

Answer 8

Descemet’s

Question 9

The corneal endothelial cells allow passage of water into the stroma due to their interconnections by which of the following junctions?

Answer 9

Macula occludens

Question 10

The palisades of Vogt are directly supplied by which of the following arteries?

Answer 10

Corneal arcades

Question 11

Which of the following corneal nerve plexuses directly gives rise to the subepithelial plexus?

Answer 11

Midstromal plexus

Question 12

At the limbus, the corneal endothelium is directly continuous with (the)

Answer 12

Endothelium lining of the trabecular meshwork

Question 13

Which corneal layers regenerate? Which respond to injuries by scarring?

Answer 13

CORNEAL EPITHELIUM- regenerate
BOWMAN'S- scar
STROMA- scar 
DESCEMET'S- regenerates 
ENDOTHELIUM- scar (does not regenerate, does not proliferate if lost)

Question 14

How does the corneal endothelium respond to injury?

Answer 14

When corneal endothelial cells are lost due to aging or injury (i.e. are damaged), human corneal endothelial cells do not proliferate and they do not regenerate to replace the lost cells
– when endothelial cells are lost, in order to cover the entire posterior surface of the
cornea with fewer cells, neighboring cells spread out to cover a larger area, so the cells appear thinner when viewed in cross-section and there is decreased cell density.

Question 15

The cornea is flatter in the ______ (center or periphery).
The anterior surface of the cornea is ________ (smaller or larger) __________ (horizontally or vertically) than the posterior corneal surface.

Answer 15

The cornea is flatter in the periphery

Anterior surface of the cornea is smaller vertically compared to the back surface

Question 16

What are the 2 possible sources of new basal cells in the corneal epithelium?

Answer 16

1. Palisades of Vogt

2. Basal cells

Question 17

What is Bowman’s layer? What is Descemet’s membrane?

Answer 17

BOWMAN’S LAYER “anterior limiting membrane”

• acellular zone of corneal stroma absent of fibroblast cells
• randomly arranged collagen fibrils and ground substance (types 1 and 3), collagen smaller and more uniform than stroma
• somewhat resistant to shearing forces
• ends before limbus with no counterpart in sclera/bulbar conj. (clear zone)

DESCEMET’S MEMBRANE “posterior limiting membrane”
basal lamina of corneal endothelium
-easy to distinguish from endothelium; barrier preventing penetration of leukocytes and blood vessels into stroma
-mostly type 4 collagen fibrils in EC matrix
-thickens throughout life with part adjacent to endothelium being most recently formed
-replaced with fresh basal lamina if injured
-peripheral termination = internal landmark of corneal limbus (Schwalbe’s line)

Question 18

Where are the following junctions found in the cornea?

• zonula occludens
• macula occludens
• desmosomes

Answer 18

The squamous cells of the epithelium are interconnected by desmosomes & zonula occludens junctions. Zonula occludens are found at the apico-lateral borders between the most superficial squamous cells.

Basal cell layer of corneal epithelium:
Lateral borders of basal cells interdigitate (though less so than in the middle layer) & adjacent basal cells are interconnected by desmosomes, gap junctions and zonula adherens junctios. Interdigitations, desmosomes & gap junctions connect the basal cells to the overlying
wing cells.

The corneal endothelial cells are interconnected by discontinuous tight junctions at their apico-lateral borders (called macula occludens) and by gap junctions, which keep the cells electronically coupled

Question 19

With aging, what happens to the

• corneal endothelium
• Descemet’s membrane

Answer 19

With increased age, endothelial cells are lost

Descemet’s membrane continues to grow

Question 20

Which corneal layers contain nerves? Which nerves innervate the cornea?

Answer 20

Although some corneal nerves terminate in the stroma, the majority of the nerve endings are in the epithelium, very close to the corneal surface.

Cornea receives sensory innervation from long & short posterior ciliary nerves
– the LPCN (branches of the nasociliary nerve) & SPCN (branches of the ciliary ganglion) pierce
the sclera, travel through the suprachoroidal space (potential space between the sclera & choroid) & supraciliary space (potential space between the sclera & ciliary body) and a short distance posterior to the limbus, they form a circular plexus.

Question 21

Why are corneal nerves difficult to see clinically? Where would you look to most likely see them?

Answer 21

2-3 mm after entering the corneal stroma, the nerves lose their myelin sheath and perineurium but retain their Schwann cell coverings, form a midstromal plexus and subdivide into anterior and posterior branches. Loss of their myelin sheath makes these nerves difficult to see clinically but allows for corneal transparency.

The density of these nerve endings is greater centrally than peripherally which is consistent with the fact that the greatest sensitivity is known to exist in the central 5 mm of the cornea.

Question 22

Name and state where the corneal nerve plexuses are located in the cornea.

Answer 22

Cornea receives sensory innervation from long & short posterior ciliary nerves. The LPCN (branches of the nasociliary nerve) & SPCN (branches of the ciliary ganglion) pierce the sclera, travel through the suprachoroidal space (potential space between the sclera & choroid) & supraciliary space (potential space between the sclera & ciliary body) and a short distance posterior to the limbus, they form a circular plexus.

MIDSTROMAL PLEXUS
Radial branches from the circular plexus pass into the middle of the corneal stroma as 60-80 flattened, myelinated branches.
2-3 mm after entering the corneal stroma, the nerves lose their myelin sheath and perineurium but retain their Schwann cell coverings, form a&raquo_space;midstromal plexus&laquo_space;and subdivide into anterior and posterior branches. Loss of their myelin sheath makes these nerves difficult to see clinically but allows for
corneal transparency

SUB-EPITHELIAL PLEXUS
Anterior branches pass through the stroma and form a&raquo_space;sub-epithelial plexus&laquo_space;in the area of Bowman’s layer and the anterior stroma. As the nerves pass through Bowman’s layer they lose their Schwann cell covering
and the fibers proceed into the corneal epithelium as fine, free (naked), beaded nerve fibers where they will form an&raquo_space;intra-epithelial plexus

Question 23

Would the patient experience pain if the stromal edema was confined to the posterior portion of the stroma? Why?

Answer 23

No; because there are no nerves in the posterior stroma

Question 24

Would a patient experience pain if they had epithelial edema? Why?

Answer 24

Damage to the corneal epithelium, such as a corneal abrasion, would cause corneal edema
that usually is confined to the epithelium, but with more extensive damage the edema would spread into the stroma.
– Epithelial edema causes a hazy microcystic appearance in the epithelium, significantly
reducing vision and increasing glare. As the edematous process progresses, fluid-filled vesicles (bullae) develop in the corneal epithelium & just under the epithelium.
the bullae press on corneal nerves in the epithelium & sub-epithelium, leading to pain as the bullae enlarge, they may rupture onto the corneal surface, leading to severe pain.

Question 25

What are corneal guttata? How do they form and what is the clinical relevance if a patient has them?

Answer 25

Corneal guttata = focal, drop-like accumulations of abnormal basal lamina material deposited in Descemet’s membrane near the center of the cornea, produced by stressed or abnormal corneal endothelial cells. The corneal endothelial cells lying posterior to the guttata are stretched & thinned out over the guttata to the point where their “mechanic pumping” functions will be compromised and they will barely be able to provide even a thin cover on the posterior surface of the cornea, let alone be able to pump ions and water out of the corneal stroma. Loss of “metabolic pumping” functions by the thinned corneal endothelial cells leads to fluid accumulation in the corneal stroma corneal edema and thus rendering the cornea opaque rather than clear (as seen in Fuch’s endothelial dystrophy).

Question 26

Describe the transitions that occur at the limbus for the corneal layers: Corneal epithelium continuous with ________ Corneal stroma continuous with _________ Corneal endothelium continuous with __________ Bowman's layer _________ Descemet's membrane __________

Answer 26

> Corneal epithelium continuous with bulbar conjunctival epithelium > Bowman's layer ends and CT of Tenon's capsule and bulbar conjunctiva begins. > Corneal stroma continuous with scleral stroma > Descemet's membrane terminates peripherally as Schwalbe's line > Corneal endothelium becomes continuous with endothelium lining trabecular meshwork.

Question 27

(CO) 1. Describe corneal dimensions including: - the general difference between anterior and posterior surface diameters (i.e. front surface smaller vertically) - differences in thickness at center vs. periphery - changes in steepness from center to periphery

Answer 27

The anterior surface of the cornea has an oval appearance (i.e. it is wider than it is high). Horizontal diameter is ~ 12 mm and vertical diameter on average is ~ 11mm (10.6 mm on average). The posterior surface of the cornea is circular in shape when viewed from the back Horizontal diameter is ~ 12mm; vertical diameter on average is ~ 12mm. The front surface of the cornea is smaller vertically compared to back surface. The average thickness of the cornea varies, being thinnest at the center and thickest at periphery. OHTS found central thickness around 555+/- 40um in African Americans and 579 +/- 37 in Caucasians. The cornea is also steeper and thinner in the center, thicker and flatter in the periphery (greater flattening nasally).

Question 28

(CO) 2. Name the 5 layers of the cornea from anterior to posterior

Answer 28

The cornea has five layers: 1. Corneal epithelium (~50μm) outer layer adjacent to the tear film 2. Bowman’s layer(~12μm) 3. Corneal stroma(~450-500μm) 4. Descemet’smembrane(~10-15μm) 5. Corneal endothelium(~3-5μm)- innermost layer adjacent to anterior chamber & aqueous humor

Question 29

(CO) 3. Describe the layers of the cornea: For epithelium: -state epithelial classification -describe the different cell types in the different layers of the epithelium, including junctions -describe which layers have the following junctions: zonula occludens, desmosomes, hemidesmosomes, macula occludens -how and what it attaches to (don't forget the anchoring fibrils) -describe the turnover (renewal) of the corneal epithelium, including: location of source of new basal cells/location of stem cells -discuss the basement membrane (basal lamina) of the corneal epithelium in terms of: what cells produce it, how the epithelium attaches to it, how epithelium attaches to the corneal stroma

Answer 29

Classification = non-keratinized stratified squamous epithelium -5-7 layers nucleated cells: single basal layer (columnar), 2-3 layers "wing cells"(polygonal; wider and flatter), 2-3 layers non-keratinized squamous cells (most anterior; nucleated+flat) > Desmosomes allow cell-cell adhesion within and between layers of corneal epithelium > Hemidesmosomes attach corneal epithelium and basal cell layer to underlying basement membrane > Basal cell layer interdigitate and are interconnected by desmosomes, gap junctions, zonula adherens junctions > Wing cells are interconnected (and connect to superficial squamous/basal cell) by desmosomes and gap junctions > Superficial squamous cells are interconnected by desmosomes and zonula occludens junctions (occludens found at apico-lateral border between most superficial squamous cells (layers below develop zonula occludens, microvilli, and microplicae just before they move to outermost layer) Basal cells of the epithelium are attached to underlying basement membrane by hemidesmosomes. When the basal cells migrate, the attachments must be broken to allow movement and are reformed after cells stop migrating. Anchoring plaques remain in corneal stroma for re-attachment. Renewal: Complete turnover happens every 7-10 days (faster than other parts of the body); as a result of mitotic division in basal cell layer -> differentiate into wing cells-> superficial squamous then shed in tear film Corneal basal cells are continually replenished by stem cells at the limbus which are undifferentiated (at palisades of Vogt); cells migrate centripetally as they move upward Basement membrane: The basal cells of the corneal epithelium rest on a basement membrane (basal lamina) which they secrete and which helps to attach the corneal epithelial basal cells to the underlying corneal layers. The basal cells are attached to underlying basement membrane by hemidesmosomes. Anchoring fibrils are type 7 collagen linked to hemidesmosomes by basal lamina components. They form complex branching network from basal lamina through Bowman's layer into corneal stroma where they insert into anchoring plaques. This allows for tight adherence of epithelium to underlying stroma.

Question 30

Discuss Bowman's layer including: - what it is (anterior part of stroma) - describe its general composition - describe how it differs in composition from the corneal stroma - describe how it responds to injury - describe its function - state which layer of the cornea corneal arcus and band keratopathy deposits lie in and why they have a peripheral "clear zone" associated with them

Answer 30

- Acellular zone (absent of fibroblast cells); composed of randomly arranged collagen fibrils + ground substance (type 1 and 3 collagen in irregular pattern; collagen fibrils uniform in size and smaller in diameter compared to stroma) - Relatively resistant to damage by shearing forces, penetration, infection but if affected it will scar and turn opaque since it does not regenerate after injury. - Bowman's layer ends 0.5mm before the limbus and has no counterpart in sclera/bulbar conjunctiva, resulting in a "clear zone" in this layer from the periphery of Bowman's to the limbus. Corneal arcus: begins in Descemet's and proceeds to Bowman's Band keratopathy: calcium deposits into Bowman's layer

Question 31

Describe corneal stroma including: - lamellar organization - cell types - how fibrils and cells are organized in the stroma - connective tissue type it is - how the stroma responds to injury = scar formation - what cells produce it

Answer 31

Made of dense regular connective tissue; contains collagen fibrils, keratocytes (fibroblasts), ground substance Collagen fibrils bundled in "lamellae" = layers of corneal stroma which run straight, parallel to cornea and have uniform diameter. They are regularly spaced to form "lattice-type" network -all the collagen fibrils in a single lamella run in the same direction, but adjacent lamellae lie at angles to one another – each lamella runs across the entire diameter of the cornea - flattened fibroblasts with branched processes liw between each lamellae Densely packed with glycosaminoglycans (GAGs) in ground substance. Ground substance made by the fibroblasts (keratocytes) between the lamellae. When injured, stroma forms a scar (by keratocytes); collagen not uniformly spaced, fibrils larger, proteoglycans differ in size, sulfation, distribution- all this affects transparency.

Question 32

Describe Descemet's membrane including: - its location - what it is (basal lamina of endothelium) - collagen type it contains - what cells produces it - how it responds to injury - location of newly formed Descemet's membrane - how it changes with age - what Schwalbe's line is - what guttata are and how guttata affect corneal endothelial cell function

Answer 32

Barrier to prevent penetration of leukocytes and blood vessels into corneal stroma. Composed mainly of fine type 4 collagen. When injured, Descemet's membrane can be regenerated by underlying corneal endothelial cells. Fresh basal lamina structurally identical to normal. It is produced by the corneal endothelial cells and thickens throughout life. The part of Descemet's membrane lying adjacent to the endothelium is most recent. The peripheral termination of Descemet's membrane is the internal landmark of the corneal limbus called Schwalbe's line (anterior limit of anterior chamber angle and peripheral termination of Descemet's membrane. Visible in gonio as circular white band superior to trabecular meshwork. see previous question on guttata

Question 33

Discuss the corneal endothelium including: - epithelial type - density of corneal endothelial cells in normal human cornea at birth vs. adulthood - associated cell junctions - functions - what happens to the endothelium as the cornea ages - what happens when endothelial cells are lost due to injury, etc. - what the difference is between polymegathism and pleomorphism - describe what corneal guttata are (composition, what cells produce them, where deposited in the cornea) and how they affect the corneal endothelial cells

Answer 33

Flattened polygonal cells lining posterior surface of cornea with basal surface on Descemet's membrane and apical surface facing anterior chamber. Microvilli extend from apical. Cell type = simple squamous epithelium; cytoplasm contains needed organelles for synthesis/active transport of fluids. Endothelial cell density in a normal human cornea is much greater at birth, then reduces gradually as a person ages. When endothelial cells are lost, in order to cover the entire posterior surface of the cornea with fewer cells, neighboring cells spread out to cover a larger area, so the cells appear thinner when viewed in cross-section and there is decreased cell density. Endothelial cell size tends to be greater in areas of endothelial disease or trauma, and although the original cells were all similar in size and shape (homogeneous), with aging, disease and/or trauma, they become more variable (heterogeneous) in size (polymegathism) and shape (pleomorphism). The corneal endothelial cells lying posterior to the guttata are stretched & thinned out over the guttata to the point where their “mechanic pumping” functions will be compromised and they will barely be able to provide even a thin cover on the posterior surface of the cornea, let alone be able to pump ions and water out of the corneal stroma. Loss of “metabolic pumping” functions by the thinned corneal endothelial cells leads to fluid accumulation in the corneal stroma corneal edema and thus rendering the cornea opaque rather than clear (as seen in Fuch’s endothelial dystrophy).

Question 34

Describe the innervation of the cornea including: - What nerves innervate the cornea - the location of the three plexuses in the cornea - what layers of the cornea do not have nerves - whether there would be associated pain with epithelial vs. posterior stromal edema and why or why not?

Answer 34

see previous question

Question 35

(CO) 5. State the three ways the cornea gets nutrients

Answer 35

1. Tears- provide oxygen (dissolved in tears) to all layers of the cornea 2. Aqueous humor- provides glucose and most other nutritional substances 3. Capillaries at the limbus- peripheral cornea receives oxygen by diffusion from the capillaries of the corneal arcades (derived from conjunctival vessels at the episcleral arteries)

Question 36

(CO) 6. Describe the blood supply to the cornea including what blood vessels supply it and their origin

Answer 36

The anterior ciliary arteries divide into the major perforating branch and episcleral arteries supplying episclera/sclera then anastomosing to form episcleral arterial circle. This circle continues to the cornea where it is called the conjunctival arteries. Conjunctival vessels further anastomose-> superficial marginal plexus Marginal plexus divides into two branches->> anterior conj. arteries and corneal arcades "corneal arcades near the termination of Bowman's membrane; these arcades give off fine vascular loops into the palisades of Vogt to help supply the peripheral cornea – these vascular loops can be readily seen on a patient at the limbus – recall that the palisades of Vogt are radial folds in the bulbar conjunctiva at its junction with the cornea and these folds increase the surface area at the limbus"

Question 37

(CO) 7. Describe the transitions that occur at the limbus

Answer 37

> Gradual transition from corneal epithelium to the bulbar conjunctival epithelium > Bowman’ layer ends and connective tissue of Tenon’s capsule & bulbar conjunctiva begins > Gradual transition from corneal stroma (with orderly, uniform diameter collagen fibrils) to the scleral stroma (with coarse, interwoven collagen fibrils of variable diameter) > Descemet’s membrane terminates peripherally as Schwalbe’s line > Corneal endothelium becomes continuous with the endothelium lining the trabecular meshwork of the anterior chamber angle

Question 38

(CO) 8. Describe which layers of the cornea can regenerate

Answer 38

see previous question

Question 39

(CO) 9. Describe where you would find zonula occludens, macula occludens, desmosomes, and hemidesmosomes in the cornea

Answer 39

zonula occludens - macula occludens - desmosomes - hemidesmosomes -