Corneal Structure And Development

• 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

• 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

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.&nbsp

• 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

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

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)

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

• Cornea is sensitive to pain and cold only
• Sympathetic supply too