5 layered structure
Horizontal diameter (11.7mm) greater than vertical (10.6mm)

And vertical meridian typically shorter radius of curvature than horizontal (more curved vertically)

Thinnest centrally (0.5mm) then peripherally at limbus (1.1mm)

In most people, the thinnest part is inferotemporal to the centre

Curvature steepest centrally and flattened peripherally

The radius of curvature is greater anteriorly than posteriorly

Refractive index 1.376 (cp 1.336 for aqueous)
Refractive power: 48.8 dioptres on anterior surface (RoC 7.7mm) and -5.8 dioptres on posterior surface (RoC 6.8mm): total is 43 dioptres

Provides 70% of eye’s refractive power

Cornea plana: rare anomaly of flat central cornea with power less than 43 dioptres. Associated with colobomas, Ehlers-Danlos, Finnish ancestry. The adjacent sclera has the same curvature.

Anatomical limbus: Schwalbe’s line and the corneoscleral junction
Surgical limbus:

Anterior to anatomical, a blueish transition zone. It lies between the anatomical limbus (Schwalbe’s line aka the termination of Descemet’s membrane) and and termination of Bowman’s layer (which is more anterior)
The white zone posterior to Schwalbe’s line extending to the scleral spur is the area overlying the trabecular meshwork

Conjunctival limbus: 1mm anterior to anatomical limbus
Collagen comprises 70% of dry weight
Proteoglycans comprise 10% of dry weight

## Embryology

Development begins at day 33
Epithelium and Bowman’s: surface ectoderm
Stroma: mesenchymal neural crest
Lamina propria (fibroblasts forming) and endothelium: neural crest (mesoderm)
Descemet’s: mesodermal and formed by endothelium
Corneal development induced by lens formation
Diameter determined by size of optic cup
Steps:

1. Bilayered epithelium formed from surface ectoderm
2. Waves of mesenchymal cells (from neural crest) pass over optic cup
3. Day 33: first wave forms double-layered endothelium
4. Day 49: second wave forms substantia propria/stroma
5. Weeks 9-10: epithelium stratifies to 3-4 layers and the eyelids form
6. Stroma infiltrated by fibroblasts (which become keratoblasts)
7. Endothelium synthesises DM
8. 5 months: Bowman’s is last to form
9. 5 months: corneal nerves reach epithelium
10. Adult form by 7 months (maturation progresses from deep to superficial)

Fetal cornea is opaque due to high hydration but transparency occurs before birth once the lamellae mature and the endothelial cells activity begins

Corneal opacification: failure of lamellar array of collagen (scleralisation of cornea)
Peter’s anomaly: posterior axial stromal defect with incarceration of pupillary iris. FOXE3 gene involved and PAX6 also implicated
Embryotoxon: displacement of Schwalbe's anterior to the limbus
Axenfeld’s anomaly: iridocorneal strands localised to Schwalbe’s line

Axenfeld-Rieger’s anomaly: the addition of iris hypoplasia, associated with juvenile glaucoma. PITX2 and FOXC1 genes involved

Neonatal cloudy cornea (STUMPED)

Sclerocornea: cornea is clear centrally (cp. Peters) and flatter than normal
Trauma or tears in Descemet’s
Ulcers
Metabolic disorder
Peters’ anomaly (dysgenesis of the anterior segment): cornea is opaque centrally (cp. sclerocornea)
Endothelial dystrophy
Dermoid

## Epithelium

Multilayered epithelium: 5 layers centrally, 10 peripherally
Squamous superficially and columnar in deeper layers
Microvilli on outer surface
Desmosomes between cells: tight junctions prevent access of tear electrolytes, therefore the epithelium is relatively impermeable

Zonulae adherens are a form of “belt” desmosome forming a ring around the cell apex
Desmosomal junctions are approx 20 nm in width

Hemidesmosomes with Bowman’s layer

Type VII (and type VI) collagen is an important part of hemidesmosomes

Note: desmosomes link cells together; hemidesmosomes link cells to the extracellular matrix.

Regenerates via mitosis at the limbus
Subepithelial connective tissue creates folds (palisades of Vogt) at limbus to increase surface area
Glycocalyx coat contributes to mucin layer of tear film
Continuous with conjunctiva peripherally

## Bowman’s membrane

Acellular
Not a true basement membrane
10 microns thick
Consists of randomly arranged collagen fibrils
Posterior surface merges with stroma

Bowman’s membrane is not capable of regeneration: eg. corneal haze following PRK and LASEK

## Stroma

90% of corneal thickness
Organised lamellae obliquely li in the anterior 1/3rd and at right angles in the posterior 2/3rds
Principally type 1 collagen (50%)
Keratocytes arranged in corkscrew pattern

Produce GAGs: primarily keratan sulphate, chondroitin sulphate and dermatan sulphate (Note: not hyaluronic acid)
Gap junctions between cells

## Descemet’s membrane

Basement membrane of endothelium (a true basement membrane, cp Bowman’s)
10 microns thick in adulthood (3-4 at birth)
Collagen fibres (type IV mostly) arranged in hexagonal pattern
Acid-schiff positive
‘Banded’ anterior third and ‘non-banded’ posterior two-thirds

Anterior “fibrillar” layer is present at birth
Posterior layer is deposited after birth by the endothelium (as its BM) and thickens with age

Peripheral termination of DM is Schwalbe’s line (the anterior edge of the trabecular meshwork and the anatomical limbus)
Able to regenerate
More resistant to the flow of solvent than Bowman’s layer

Breaks in infant Descemet’s

Birth trauma: typically vertical with normal IOP
Congenital glaucoma: typically horizontal (Haab’s striae) with raised IOP

## Endothelium

Single layer of cuboidal endothelium
Microvilli extend into the aqueous humour
Lots of mitochondria:

Maintains corneal transparency by pumping water out into aqueous (active transport)
5 times as metabolically active as epithelium

Hexagonal array of cells resting on DM
Interdigitations between cells with tight junctions (ensure corneal hydration)

Endothelium is therefore relatively permeable

No regenerative capacity: defects closed by spreading of remaining cells
Number of endothelial cells decreases with age
Continuous with the passageways of the trabecular meshwork
Synthesises type VIII and type IV collagens

After injury, converts to fibroblast-type cells producing mainly type I collagen

Density is around 2500 cells/mm2 in healthy adults (3000-4000 cm/mm2 in children)

Age-related changes to cornea

Decreased translucency
Increased thickness of Bowman’s membrane
Increased thickness of Descemet’s membrane
Reduced endothelial density: compensated by cell enlargement (polymegathism)

## Specular microscopy

Reflections from the corneal endothelium can be viewed to assess its health
Coefficient of variation: how variable endothelial cell size is

Polymegathism: increased variation with higher risk of post-operative oedema

Hexagonality: lower percentages of hexagonal cells (pleomorphism) are associated with poor endothelial health and increased risk of post-operative oedema

## Nerve supply

Long ciliary nerves: branches of ophthalmic division of trigeminal
Course

1 Annular plexus of myelinated fibres form in stroma at limbus.

There are 50-90 main stromal nerve fibres at the limbus

2 Subepithelial plexus forms and fibres lose myelin approx 1-2mm from the limbus to preserve clarity

These axons travel in the anterior half of the stroma and from a mid-stromal plexus. This is densest at the periphery

3 Most mid-stromal fibres pass forward and form a subepithelial plexus beneath Bowman’s layer
4 Axons pierce Bowman’s layer
5 Intraepithelial plexus forms and sensory nerve endings supply the corneal surface

There are more sensory nerve endings per unit area than anywhere in the body

Cornea is sensitive to pain and cold only
Sympathetic supply too

Enlarged corneal nerves

Multiple endocrine neoplasia type 2b (MEN)
Leprosy
Neurofibromatosis
Acanthamoeba perineuritis