This document provides information on the anatomy and physiology of the cornea. It describes the layers of the cornea including the epithelium, Bowman's membrane, stroma, Dua's layer, Descemet's membrane, and endothelium. It discusses the transparency of the cornea, metabolic processes, drug permeability, wound healing, and the effects of contact lens wear on corneal physiology. The cornea has several specialized functions including refracting light and protecting the interior of the eye.

1. ANATOMY & PHYSIOLOGY
OF CORNEA
Presented By – Dr. Om Patel
Moderator – Dr. Jyoti Puri

2. ANATOMY OF CORNEA
Cornea has the following physical characteristics:
• Transparent
• Avascular
• Watchglass like structure
• It forms anterior 1/6th of the
outer fibrous coat of the eyeball
2

3. DIMENSIONS
• Anterior surface
– Elliptical, 11.7 mm horizontally, 11
mm vertical
• Posterior surface
–Circular about 11.7mm in diameter,
1% wider in males
• Central Thickness – 0.52mm
• Peripheral Thickness – 0.67mm
• Anterior radius of curvature –
7.8mm
• Posterior radius of curvature –
6.5mm

4. • Optical zone - central third
• Refractive power
– 43 D (3/4th of total refractive power of eye)
• Refractive index – 1.37

5. Composed of 6 layers ( ant to post.) are
1. EPITHELIUM
2. BOWMANS MEMBRANE
3. SUBSTANTIA PROPRIA/STROMA
4. DUA’S LAYER
5. DESCEMENTS MEMBRANE
6. ENDOTHELIUM
HISTOLOGY

6. EPITHELIUM
• Stratified, Squamous, Non-keratinized
• 10% of total corneal thickness
• 50-90microns thick, 5-6 layers of nucleated cells namely
 Flattened surface cells ( superior 2 layers)
 Wing cells ( next 2 to 3 layers)
 Basal cell layer
 Basement Membrane

8. FLATTENED SURFACE CELLS
• Superficial 2 layers
• Flat and polygonal
• Surface covered with microvilli
• Plays important role in tear film stability

9. WING CELLS
• Polyhedral shape
• 2-3 layers
• Rich in intracellular tonofilaments composed of
keratin
• Numerous desmosomes and gap junctions are present
between the cells

10. BASAL CELL LAYER
• Tall columnar cells
• Forms the germinal layer of epithelium
• Secretes the basement membrane
• Basal cells are firmly joined laterally to other basal cells and
anteriorly to wing cells by desmosomes and maculae
occludentes – these tight intracellular junctions account for
epithelial transparency as well as its barrier function
• Absence of hemi-desmosomes of the basal epithelial cells is
responsible for recurrent corneal erosions

11. BASEMENT MEMBRANE
• Secreted by the basal cell layer
• PAS +ve
• Consist mainly of type IV collagen & laminin
• Blends indistinctly into bowman's membrane
• Responsible for maintainence of well organised corneal
epithelium
• Defective BM is associated with recurrent erosion and
epithelial defect

12. BOWMAN’S MEMBRANE
• 8-14 microns
• Also known as Anterior limiting lamina
• Acellular mass of condensed collagen fibrils
• Condensed superficial part of stroma
• Collagen fibrils are primarily type I and type III
• Shows considerable resistance to infection and injury
• Once destroyed it does not regenerate

13. STROMA/SUBSTANTIA PROPRIA
• 500 microns
• Forms the largest portion of cornea 90% of total thickness
• Consists of keratocytes and extracellular matrix
• Keratocytes are corneal fibroblasts, found throughout
stroma
• Keratocytes produce the extracellular matrix
• The extracellular matrix is made up of collagen fibrils and
GAG.

14. • Most abundant GAG is keratan sulfate (65%)
• The collagen fibrils are arranged in many layers with highly
uniform diameter (22.5 to 35 nm) & inter fibrillary distance (
41.5 nm)
• Fibrils are arranged parallel to each other and the corneal
plane
• Extends to periphery where the fibrils adopt a concentric
configuration to form weave at the limbus
• This imparts considerable strength to peripheral cornea &
permits it to maintain curvature & optical properties

16. DUA’S LAYER
• The existence of a new layer of cornea was suggested by
Harminder Singh Dua et al in 2013
• The existence of the layer was proved by injecting bubbles
in the specific pre-descement layer of cornea with the help
of surgical techniques
• The experimental results were studied by optical
and electron microscopy. The images showed a thin layer of
corneal collagen between the corneal stroma and Descemet's
membrane

17. • It is hypothetically 15 microns (0.00059 inches) thick, the
fourth caudal layer, and located between the corneal
stroma and Descemet's membrane
• Despite its thinness, the layer is very strong and impervious
to air

18. DESCEMENT’S MEMBRANE
• Appears at the second month of gestation.
• 3 microns at birth and 10-12 microns in young
adults
• Synthesis continues throughout adult life
• Basal lamina of the corneal endothelium
• Very resistant to chemical agents, trauma, infection,
pathological process and enzymatic degradation

19. • Has regenerative power unlike Bowman’s membrane
• It is sharply defined from the corneal stroma unlike Bowman’s
membrane. There is in fact a plane of separation between them
which is made use of in lamellar keratoplasty
• Peripherally it appears to end at the anterior limit of trabecular
meshwork as Schwalbe’s line
• Posterior surface shows rounded wart like excrescences
peripherally called Hassel Henle bodies which increase with
advancing age
• Similar central excrescenes are found in Fuch’s dystrophy known
as Guttate

20. ENDOTHELIUM
• Single layer of flat polygonal cells
• Cell density is about 6000 cells/mm sq. at birth which
goes on decreasing with age and comes around 2400-
3000 cells/mm sq. in young adults
• In adults these cells lose the ability to divide
• Defect left by dying cells is filled by enlargement of
remaining cells- POLYMEGATHISM
• Cell diameter varies from 18-20 microns in early life to
40 microns in aged

21. • Corneal decompensation – when more than 75% of adult age cells
lost ( <500 cells/mm sq)
• Cells are attached to each other & DM by tight junctional complexes
and hemidesmosomes which closes the intercelluar space from the
anterior chamber

22. BLOOD SUPPLY OF CORNEA
• Cornea is an avascular tissue
• The limbal region contains a vascular arcade which supplies the
cornea with blood components
• The vascular arcade is formed by the anastamoses b/w the
anterior ciliary artery (branch of ophthalmic artery) & branches
of external carotid artery
• It invades periphery for about 1 mm & provide nourishment to
cornea
• It is actually present in the sub - conjunctival tissue which
overlaps the cornea

23. NERVE SUPPLY OF CORNEA
• Cornea is one of the most heavily innervated tissues in the
body
• Innervational density is highest near the centre & gradually
decreases towards the periphery
• Trigeminal N.  Ophthalmic division  Nasociliary nerve
 Long ciliary nerves

25. Long ciliary nerve
↓
Enter the eyeball around the Optic nerve
↓
Run forward in suprachoroidal space
↓
Pierces the sclera close to the limbus
↓
Forms a PERICORNEAL PLEXUS OF NERVES with
conjuctival nerves
↓
Enters the cornea at various depths viz. sclera, episclera &
conjunctiva

26. ↓
Loses their myelin sheath after traversing 1-2 mm to form a
STROMAL PLEXUS
↓
Anteriorly forms a SUBEPITHELIAL PLEXUS
↓
Penetrates the pores in Bowman’s membrane,
divides into filaments under the basal layer of epithelium & extends
between the cells of all layers of epithelium to form
INTRAEPITHELIAL PLEXUS
↓
Ends in epithelium as fine beaded filaments

27. Subepithelial and Intraepithelial Plexus

28. CORNEAL PHYSIOLOGY
Physiological functions of cornea are :
• To act as a powerful refracting lens of fixed focus that
transmits light in an orderly fashion for proper image
formation
• To protect intraocular contents
• Absorption of topically applied drugs

29. Physiological processes concerned in carrying out
these functions are:
• BIOCHEMICAL COMPOSITION AND
METABOLISM OF CORNEA
• CORNEAL TRANSPARENCY
• DRUG PERMEABILITY THROUGH THE CORNEA
• CORNEAL WOUND HEALING

30. CORNEAL METABOLISM
• Cornea requires energy for normal metabolic activities as
well as for maintaining transparency & dehydration
• Energy is generated by the breakdown of glucose in form
of ATP
• Most actively metabolising layers – Epithelium &
Endothelium

31. Sources of Nutrients
1) Oxygen
 Epithelium
– Mainly from atmosphere through tear
film
- Limbal Capillaries
 Endothelium
- Through aqueous humour
• Minimum oxygen tension for normal corneal
hydration is 11-19 mm Hg. Below this range
cornea will hydrate and swell

32. 2) Glucose
• Mainly from the aqueous humour
• In case of deprivation stored glycogen or even fatty
acids are utilised as a source of glucose
3) Amino Acids
• Principal source is passive diffusion from aqueous
• Required for synthesis of protein needed for
epithelial turnover

33. METABOLIC PATHWAYS
• GLYCOLYSIS
- Many enzymes of the EMP or the TCA/Krebs cycle are
present in cornea
- There is accumulation of lactate even in aerobic
conditions due to high glycolytic activity but limited TCA
cycle activity
- Lactate is eliminated from the cornea by diffusion
through the epithelium

34. • HMP SHUNT
- This occurs without a net gain in the ATP
- Its purpose is to produce NADPH which is utilized for the
biosynthesis of lipids by corneal epithelium
- Ribose produced may be used to build DNA & RNA

35. CORNEAL TRANSPARENCY
Factors affecting corneal transparency are:
1. Corneal epithelium & tear film
2. Arrangement of stromal lamellae
3. Corneal vascularization
4. Corneal hydration
5. IOP

36. CORNEAL EPITHELIUM & TEAR FILM
• It has homogenous refractive index
• The various cells at different layers are firmly attached
with each other
• Tight intercellular junctions contribute to transparency

37. 2. ARRANGEMENT OF STROMAL
LAMELLAE
Two theories are proposed
1) MAURICE THEORY -(1957)
The regular lattice arrangement destroys the scattered
light by mutual interference. The collagen fibrils are separated
by less than a wavelength of light.

39. 2) Theory of GOLDMAN et al.
• Lattice arrangement not necessary
• Cornea is transparent because the fibrils are small in relation to
light & do not interfere with light transmission unless they are
larger than one half the wavelength of light
• However these theories fail to explain the occurrence of rapid
clouding of cornea associated with acute rise in IOP & the
rapid clearing of cornea with reduction of IOP

40. CORNEAL VASCULARIZATION
• Corneal vascularisation occurs as a defence mechanism in
response to noxious stimulus which interferes with the
transparency
• Various chemical and mechanical theories have been suggested
to explain the vascularisation of cornea in response to noxious
stimuli

41. CORNEAL HYDRATION
• The normal corneal water content is 80%
• Increase in the water content leads to increased central
corneal thickness and will compromise the corneal
transparency
• It is kept constant by balance of various factors

42. • Factor which draws water inside cornea
- Swelling pressure of stromal matrix
• Factor preventing the flow of water inside cornea
- Barrier function of epithelium &
endothelium
• Factor drawing water out of the cornea
- Active pump mechanisms of endothelium

43. STROMAL SWELLING PRESSURE
• Pressure (60 mm Hg) exerted by the GAGs of the corneal
stroma which act like a sponge
• Due to the electrostatic repulsion of the anionic charges on
the GAG molecule, a negative but equal pressure called
imbibition pressure is developed
• This is the negative pressure by which the level of
interfibrillar tension is maintained
• However in practice imbibition pressure
IP = ( IOP - SP )i.e. 17 - 60 = - 43 mm hg

44. BARRIER FUNCTION OF EPITHELIUM
AND ENDOTHELIUM
• Functions as barriers to excessive flow of water and diffusion of
electrolytes into the stroma due to their semipermeable nature
• Corneal transparency decreases and thickness increases when
the corneal endothelium is damaged and to a lesser extent when
the epithelium is damaged

45. ACTIVE PUMP MECHANISM OF
ENDOTHELIUM
The corneal endothelium plays an important role in
controlling fluid transport across itself due to the presence of
several enzyme pump mechanisms namely
• Na+/K+ ATPase Pump
• Bicarbonate dependant ATPase
• Na+/H+ exchanger
• Carbonic Anhydrase enzyme system

47. INTRAOCULAR PRESSURE
• Epithelial edema occurs when IOP increases more than
stromal swelling pressure
• Clinically detectable corneal edema can be seen with IOP
more than 50 mm Hg
• However in endothelial dystrophy corneal oedema can
occur with normal IOP also due to decreased swelling
pressure

48. DRUG PERMEABILITY ACROSS
THE CORNEA
Factors affecting this are:
1) Lipid & water solubility of drug
– Drug should be amphipathic to readily penetrate
cornea as epithelium & endothelium are lipophilic while the
stroma is hydrophilic
2) Molecular size, weight & concentration of drug –
- Lipophilic molecules can easily cross epithelium
while hydrophilic molecules only smaller than 0.4 nm
can cross through the pores in the cell membrane
48

49. - Substances with molecular weight of less than 100
daltons can easily pass through the cell membrane while
those with more than 500 cannot
- Drugs with large molecular size in high concentration
can cross the cornea following laws of mass action
3) Ionic forms of the drug
– Drug must have the capacity to exist in both ionized &
non-ionized forms for a better penetration through cornea
49

50. KINSEY MODEL FOR DRUG IONIZATION AND
PERMEABILITY

51. 4) pH of the solution
– Within a range of pH 4-10, epithelial permeability is
not affected but beyond this range, the permeability
increases
5) Tonicity of the solution
– Hypotonic solutions greatly increase the permeability
of the epithelium
6) Surface active agents
– Agents that reduce surface tension, increase corneal
wetting & thus present more drug for absorption

52. 7) Pro-drug
– Prodrug forms are lipophilic & after absorption
through epithelium are converted into proper drugs that can
easily pass through stroma. E.g.. Dipivefrin- Epinephrine

53. EFFECT OF CONTACT LENS WEAR
ON CORNEAL PHYSIOLOGY
• CL affect the function of epithelium
• Epithelium gets oxygen from tears &
glucose from aqueous & limbal vessels
• CL shifts the balance from aerobic 
anaerobic metabolism  increases lactate
& CO2 production
• Leads to acidosis  Stromal hydration

54. • CL types are based on their oxygen flux defined as the DK
value
• Oxygen flux = DK/L * DP
D = Diffusion Coefficient
K = Solubility
L = Thickness of lens
DP = Change in the partial pressure
of oxygen across the material
• HEMA and PMMA have low oxygen flux
• Hydrogen and Silicon lenses have high flux
• Both DK value and thickness of lens determines the
suitability for use

55. • Rigid CL (PMMA)
• Reduces O2 availability
• Deplete glycogen stores
• Reduces direct glucose utilization by the cornea
• Affect corneal transparency
• Tear film instability
• Soft CL permits extended wear due to their permeability
to O2 & CO2
• RGP combines the reduced toxicity of PMMA and high
gas transfer capability

56. • Deleterious effects of CL  Due to low O2 permeability
• Epithelial thinning
• Reduction in the hemidesmosome density
• Reduction in anchoring fibrils
• Reduce adhesion of the epithelium to the basement
membrane
• Severe cases produce epithelial edema and punctate epithelial
erosions

57. CORNEAL WOUND HEALING

58. 58