The cornea is a transparent, avascular part of the eye that forms the anterior 1/6th of its outer fibrous coat and provides most of its refractive power. It consists of five layers and plays crucial roles in light entry, protection, and drug absorption, as well as wound healing. Maintaining corneal transparency and hydration is vital, relying on various anatomical and physiological factors including stromal arrangement, metabolic pathways, and nutrient supply.

1. PHYSIOLOGY OF
CORNEA
DR.MD.MAHABUB
MS(PHASE- A) STUDENT
DEPARTMENT OF OPHTHALMOLOGY
SSMC & MITFORD HOSPITAL

2. GROSS ANATOMY
Cornea is a transparent avascular structure.
Forms anterior 1/6th
of the outer fibrous coat
of eye ball.
It gives 70% refractive power of the eye
(+43D)
Principle optical surface of the eye

3. TOPOGRAPHY
Ant. Surface
Convex
Horizontal Diameter - 12mm.
Vertical Diameter – 11.5mm.
Post. Surface
Concave
Diameter - 11.5mm (average)

4. Radius of curvature of cornea
Central (1/3rd
): Ant. Surface
7.8mm, Post. Surface 6.5mm
Peripheral cornea is more
flattened.

5. Central corneal thickness
0.52mm.
Peripheral corneal thickness
0.67mm.
The central 5mm of the cornea
forms the most powerful
refractive surface of eye.

6. FUNCTIONS
Allows light to enter inside the eye.
Refraction.
Protects the intraocular contents from infective organisms, noxious
substances and ultra-violet rays.
Maintains structural integrity of the eye.
Cornea plays important role in absorption of topically applied
drugs.
Wound healing after anterior segment surgery or trauma.

7. HISTOLOGY
Cornea consists of 5 layers
from superficial to deep
Epithelium
Bowman’s Membrane
Stroma
Descemet’s Membrane
Endothelium

8. BIOCHEMICAL COMPOSITION
EPITHELIUM
Water 70%
Protein
Lipid-phospholipid & cholesterol.
Enzymes necessary for Glycolysis, Kreb’s cycle and ion
transport.
Electrolytes:. K+(High conc.) , Na+ and Cl-(Low conc.)

9. STROMA
 Water :75-80%
 Collagen : Predominant type I. 200-250 lamellae of collagen
fibrils are regularly arranged, between lamellae there is
Keratocytes and Fibroblast.
 Soluble proteins: Albumin, IgG IgA IgM, Glycoproteins.
 Enzymes: Glycolytic & Krebs cycle enzymes in stromal
keratocytes.
 Matrix metalloproteinase helps in remodeling after injury.

10.  Proteoglycans: GAG is present in interfibrillar space and accounts for
stromal swelling pressure which plays an important role in
transparency and hydration. 3types-
• Keratan Sulphate
• Dermatan Sulphate
• Chondroitin Sulphate
More Dermatan Sulphate is present anteriorly – so less water
absorptive property and greater water retentive property.
While Keratan Sulphate is located posteriorly – so greater water
absorptive property with little water retentive property.
 So clinically most oedema occur in posterior stroma
 Electrolytes: Conc. of Na+ is high & K+ is low.

11. DESCEMET’S MEMBRANE
Consists of collagen (73%) & glycoproteins.
High Hydroxyproline, Glycine and Hydroxyglycine content.
Does not contain GAG.
Collagen is insoluble except in strong acid or alkali.
Extremely resistant to chemical reagents and pathological
process.

12. ENDOTHELIUM
Single layer of hexagonal cell
No basement membrane
Abundant cellular organelles proves high metabolic
activity.
Plays vital role in corneal transparency by metabolic
pump

13. Nutrition supply of cornea
Mainly from 3 sources-
Aqueous humour
Pre corneal tear film
Perilimbal vessels

14. CORNEAL METABOLISM
Cornea requires energy for normal metabolic activities
as well as for maintaining transparency and dehydration.
Corneal epithelium uses primarily glucose and
glycogen for energy production.

15. Corneal epithelial cells store high level of
glycogen which is depleted under stress.
Energy is generated by the breakdown of glucose in
the form of ATP.
Most actively metabolizing layers are epithelium &
endothelium.

16. Sources of Nutrients
Oxygen – mainly from atmosphere through tear film, with
minor amounts supplied by the aqueous and limbal vasculature
Glucose, amino acid, vitamins, and other nutrients supplied to
cornea by aqueous humor, a lesser amounts from tears or
limbal vessels
Glucose also derived from glycogen stores in corneal
epithelium
Epithelium consumes O₂ 10 times faster than stroma.

17. Metabolic pathways
Three processes or pathways –
1. Glycolytic pathway: (Embden-Myerhof pathway)
a) Glucose is primarily metabolized by anaerobic
glycolysis - converted to pyruvate yielding 2 ATP.
Under hypoxic condition, as in tight contact lens
pyruvate is converted to lactate.
b) Under aerobic condition pyruvate from glycolysis can
enter the Krebs's cycle (TCA cycle) and yields 36 ATP,
water & CO2.

18. 2. HMP shunt:
 converts hexoses to pentoses and produces
NADPH which are required for nucleic acid
synthesis
occurs both In hypoxic and normoxic condition
3. SORBITOL PATHWAY:
 Glucose is reduced to Sorbitol by aldose
reductase & to Fructose by Sorbitol
dehydrogenase

19. Fig: Pathways of glucose metabolism

20. Corneal transparency
Anatomical factors:
Uniform regular arrangement of the epithelium
Absence of blood vessels and
Non-myelinated fibers
Packed stromal lamellae of uniform size

21. Corneal transparency
Physiological factors:
Stromal swelling pressure
Metabolic pumps
Barrier function of both epithelium and endothelium
Evaporation from corneal surface
Intraocular pressure

22. Arrangement of the epithelium
Homogeneous refractive medium.
Basal cell are firmly joined laterally to other basal cells &
anteriorly to the wing cells by desmosomes & maculae
occludens.
Tight intercellular junction accounts for epithelial
transparency as well as its resistance to flow of water,
electrolytes & glucose i.e. barrier function.

23. Arrangement of the Stromal lamellae
Collagen fibrils of stroma are bundled together in form
of lamellae.
Arranged parallel to each other as to its surface.
Two theories

24. MAURICE THEORY
Uniform collagen fibrils are arranged in a regular
lattice.
As long as collagen fibrils are arranged regularly
in a lattice, having less diameter and separated by
less than a wave length of light cornea will remain
transparent.
Because of their small diameter and regularity of
distance, back scattered light is destroyed by
mutual interference
Interfibrillar distance is < wavelength of light
(4000A-7000A)

25. Hence rays travel in this plane would be
enhanced while those diffracted are
cancelled out, giving the transparency of
cornea

26. Goldman and Benedek’s Theory
Lattice arrangement is not a necessary factor for stromal
transparency .
Cornea is transparent because fibrils are small in relation to
light
Fibrils will not interfere transmission of light unless
they are larger than 1/3rd
of the wave length of
incident light.
Refractive elements with the dimensions < 2000A do
not scatter light.

27. CORNEAL AVASCULARITY
Cornea is avascular except for small loops which invade the
periphery for about 1mm
Some conditions of cornea is associated with vascularization
The purpose of this is to bring defense mechanisms into play against
the noxious agent
It facilitates nutrition, transport of antibiotics & drugs
Progressive vascularization is harmful as it interferes with corneal
transparency

28. Corneal Hydration
State of relative dehydration that is necessary for corneal
transparency.
Normal water content of cornea (80%) is kept constant by
balance of factors
that draw water in cornea (swelling pressure and IOP),
factor which prevent flow of water in cornea (epithelial
barrier)
that draw water out of cornea (Endothelial metabolic pump)

29. Fig: Factors maintaining Corneal hydration

30. IMBIBITION PRESSURE
•Negative pressure draining fluid inside cornea
•IP (imbibition pressure of corneal stroma)
=IOP- SP
•About -40mmHg
When IP >0mmHg, Corneal oedema occurs.

31. Stromal swelling pressure
Electrostatic repulsion of negatively charged stromal GAG
produce stromal swelling pressure (SP).
About 55mmHg which is inversely related to corneal
thickness
Prevent corneal edema and swelling of stroma;

33. INTRAOCULAR PRESSURE
 Normal cornea maintains a constant thickness in the presence
of IOP upto 50mmHg, because SSP is also in a similar range
 Corneal oedema may occur
 When IOP exceeds stromal swelling pressure
 In normal IOP when Stromal Pressure is decreased
As stromal pressure decreases precipitously by increase in
corneal thickness, mild corneal edema combined with increase in
IOP leads to high imbibition pressure.

34. Metabolic pump
In epithelium –
Apical – apical tight junction, Cl channel
ˉ
Basal –
Na+-K+ ATPase pump: maintain the inward sodium gradient
Na+-H+ exchanger: maintain the intracellular pH by extrusion of H
ions
H+-Lactate co-transporter: maintain the intracellular pH by
extrusion of lactate
Na+-Cl co-transporter:
ˉ influx of sodium down the concentration
gradient carrying chloride ions with it.

35. cAMP
increases
the
conductance
of apical
chloride
channels,
stimulating
chloride
transport.
Fig : Epithelial
Metabolic Pumps

36. Endothelial pump
Mechanism by which endothelium removes fluid from
stroma referred as endothelial pump.
Apical Tight Junction:
Consists of Macula occludens which doesn't completely
encircle the cell
As a result endothelium is “leaky” allowing free flow of
water and electrolyte.

37. Basolateral Surface:
◦Na+-K+ ATPase Pump: mediates the extrusion of
Na+ from tissue
◦HCo3 pump:
ˉ Transports bicarbonate out of the cell
which was generated intracellularly from CO2 and
water by carbonic anhydrase.
◦Na+-H+ exchange transporter: Moves sodium into
the cell ,water outward and acidifies ECF.

38. Fig: Endothelial Metabolic Pumps.

39. BARRIER FUNCTION
Leaky barrier- present in
endothelium
Complete barrier- present
in epithelium

40. EVAPORATION FROM CORNEAL
SURFACE
Increase in concentration of precorneal fluid(osmolarity)
Water from cornea is drawn into tear film
Relative state of corneal dehydration
•Water evaporates from the corneal surface at a rate of 2.5 uL/cm2
/hour.
•Evaporation accounts for 5% thinning of the cornea during the day time
compared to the thickness measured in the morning after night sleep.

41. CORNEAL WOUND HEALING
Injury to corneal epithelium:
It is constantly being regenerated by mitotic activity
Mitosis is limited to basal layer
After abrasion mitosis ceases, cells at wound edge retract,
thicken and lose hemidesmosomal attachment to
basement membrane produce various growth factors
The cells begin to move in an amoeboid movement to
cover the defect

42.  Migration process is halted by contact
inhibition
 Then they anchor and
 Mitosis resumes to re-establish
epithelial thickness
 Surface tight junctions re-established
 Adhesion with Bowman’s layer within
7 days (if basal lamina intact)
 The healing process occurs rapidly,
rate of cell migration is 60 – 80 μm/hr

43.  Within 2-6 hours PMN cells reach stromal wound from
limbal vasculature and start proteolytic debridement of
necrotic debris.
 Within 3 days there is increased number of keratinocytes.
 Increased ground substances & collagen fibril secreted by
keratinocytes. Newly formed collagens are larger than
normal.
 Collagens are not well organized & loss their normal tensile
strength.
Trauma to corneal stroma

44.  By the end of 8th
weeks there is numerous
fibroblastic cells
 Wound strength continues to increase for 3-6
months
 Scar tissue becomes more compact and blends into
the adjacent stroma.
 Tensile strength in corneal wounds increase
gradually up to 4th
postoperative year.

45.  Little or no mitosis occurs in human corneal
endothelium.
 When injury occurs cells from adjacent area spread to
the wound.
 When a single cell is lost - the cells in the surrounding
spread to fill the defect- over the time marked cell
enlargement occurs.
ENDOTHELIAL WOUND HEALING

46.  In large defect, extensive cell migration occurs at
80-100 µm/day initially elongating towards the
center
 finally wound closure and remodeling into more
hexagonal shape
 The pumps and tight junctions are re-established
so as the barrier
 After the barrier is established endothelial cells
increase the number of Na+
- K+
-ATPase pump

48.  Endothelial decompensation
will cause stromal edema,
reduced transparency and loss
of vision
 Endothelial decompensation
occurs when cells density falls
below 500 cells/mm²
 With advancing age the
endothelial cells become
polymorphic in shape due to
cell enlargement during repair

49. Drug permeability
Lipid & water solubility of drug
Molecular size, weight & concentration of drug
Ionic form of the drug
Ph of the solution
Tonicity of solution
Surface active agents
Pro-drug form

50. LIPID & WATER SOLUBILITY
◦A drug should be amphipathic i.e. both lipid & water
soluble to readily penetrate across cornea
MOLECULAR SIZE , WEIGHT, & CONCENTRATION
◦Molecular weight < 100 can pass easily & those with
>500 cannot pass easily
◦The rate of penetration through cornea of drug such as
pilocarpine, homatropine, atropine, steroids depend
upon their concentration in the solution.

51. Ionic Form of The Drug
◦The drug intended for topical use in eye must have
capacity to exist in both ionized & non–ionized form for
better penetration through the cornea since only non-
ionized drugs can penetrate through epithelium &
ionized drugs can pass through stroma.
Ph of the Solution
◦Varies from 4-10 without affecting the permeability of
the epithelium, but solution outside this range increases
the permeability

52.  Tonicity Of The Solution
• Hypotonicity of solution (those below 0.9% of sodium chloride)increases
the permeability of epithelium
 Surface Active Agents
• Agents that reduce surface tension ,increase corneal wetting & therefore
present more drug for absorption e.g. bezalkonium chloride used as
preservative also acts as wetting agent & thus increases the drug
absorption
 Pro-drug Form
• are lipophilic & after absorption through epithelium are converted into
proper drug which can easily pass through stroma e.g. dipiverfin is pro-drug
which is converted into epinephrine after its absorption into the eye

53. THANKS TO ALL