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By: Dr. Yajuvendra Singh Rathore
• Cornea is a transparent,
avascular, watchglass
like structure
• It forms anterior 1/6th
of the outer fibrous coat
of eyeball.
• Anterior surface of the cornea is
elliptical
• Horizontal diameter – 11.75mm
• Vertical diameter-11mm
• Posterior surface is spherical with
average diameter 11.5 mm.
• The radius of curvature of
cornea
– Anterior radius 7.8mm
– Posterior radius 6.5mm
• Thickness of cornea
– Center 0.52mm
– Periphery 0.67mm
• Central corneal thickness has
direct influence in IOP
measurement.
• The central 5 mm of the cornea forms the
most powerful refracting surface of the eye.
• The net refractive power of the cornea is
+43D which is 3/4th of the total refractive
power of eye.
• The refractive index of cornea is 1.37
Layers Thickness
(in µm)
Composition
Epithelium 50 Stratified Squamous Epithelium
Bowman's Membrane 8-14 Compact layer of collagen fibres
Stroma 500(0.5mm) Orderly arrangement of collagen
lamellae with keratocytes
Descemet's Membrane 10-12 Consists of collagen & glycoprotein
Endothelium 5 single layer of simple squamous
epithelium
Layers of Epithelium Description Mitoticactivity
Basal Cell Single layer of columnar cells
found adjacent to basal layer
+
Wing Cell 2-3 layers of polyhedral cells
-
Surface Cell 3 layers of flattened epithelial
cells with microvilli in contact
with the tear film.
-
It takes normally 7 days for replacement entire
corneal epithelium
• The surface corneal epithelial cells
has numerous microvilli and
microplicae and these cells secrete
glycocalyx which helps in adhesion
and stability of the tear film.
• The Basal cells are firmly joined
laterally to other basal cell &
anteriorly to the wing cell by
desmosomes & maculae occludent and
with the basal lamina with the help of
hemidesmosomes and other filaments.
• Corneal epithelium sheds at regular
interval & replaced by growth from its
basal cell
• It is an acellular tough membrane like zone situated in between
corneal epithelium and stroma.
• It is 8-14 µm thick
• composed of condensed collagen fibers.
• These collagen fibers are continuous with that of anterior
stroma.
• Because of the compact arrangement of collagen fibers, it is
comparatively resistant to trauma. However, once destroyed it
cannot be regenerated.
• The stroma or substantia propria, which occupies about 90% of the
total corneal thickness
• Composed of collagen fibrils, keratocytes and extracellular ground
substances
• Lamellae are arranged in many layers (200-250)
• Each layer is parallel to each other & with corneal surface and become
continuous with scleral plane
• Lamellae run from limbus to limbus
• Parallel arrangement of lamellae in the cornea allow an easy
intralamellar dissection during superficial keratectomy & lamellar
keratoplasty
• The peculiar arrangement of lamellae has also been implicated in the
corneal transparency
• Cells are embedded in hydrated
matrix of proteoglcans
• Amongst the cellular
components, keratocytes,
wandering macrophages,
histiocytes & few lymphocytes
(corneal fibroblasts) are the
major cell type of the stroma.
• They occupy 2-4% of the
stromal volume.
• They synthesize collagen and
proteoglycan and thus maintain
the stroma.
• It is strong homogenous layer which binds the stroma posterioly
• Represents the basement membrane of the endothelium from which
it is produced
• Elasticity is one of its physical characteristic
• It is made up of glycoprotein & collagen fibrils with no elastic fibers
• Thickness varies with age, at birth is 3 µm , young adults is 10-12
µm
• It is resistant to chemical agents, trauma and infection
• Even if whole stroma is sloughed off, Descemet’s
membrane can maintain the intergrity of the eyeball
for long
• In case of Descemet’s Membrane detachment or tear, the
membrane curls towards the stroma (inwards) because of
the elastic property of Descemet’s membrane.
• In periphery, it appears to end at the anterior limit of the
trabecular meshwork as schwalbe’s line(ring)
• It can regenerate
• Corneal endothelium is a simple squamous epithelium.
• Endothelial cells are hexagonal which forms continuous
mosaic pattern, best seen in specular microscopy.
• Cell density
– Birth-6000cells/mm2
– Young adults-22500-3000cells/mm2
• The endothelial cells are interconnected with each other
with various junctional complexes like zonula occludans,
macula occludans and macula adherens.
• These cells possess ion transport system which is known
as endothelial pump. These endothelial pumps regulate
the water content of corneal stroma.
• Endothelial cells cannot divide or replicate.
With ageing, the cell density of the endothelium
decreases which is compensated by an increase
in cell size (Polymegathism) or shape
(Pleomorphism).
• As these endothelial cells are involved in
corneal hydration they help in maintenance of
corneal transparency
New Layer Discovered-DUA’S LAYER
• In a paper published
in 2013, the existence
of Dua's layer was
suggested by
Harminder Singh
Dua et al.
Implications of findings of Dua’s layer
• The layer may help surgeons improve
outcomes for patients undergoing corneal
grafts and transplants. During surgery, tiny air
bubbles are injected into the corneal stroma
in what is known as the "big bubble
technique". Sometimes the bubble bursts,
damaging the patient's eye. If the air bubble
is injected under Dua's layer instead of above
it, the layer's strength could reduce the risk of
tearing
• In normal condition, cornea does not contain any
blood vessel.
• Anterior ciliary artery, a branch of ophthalmic
artery forms a vascular arcade in the limbal
region invades its periphery for about 1mm
• helps in corneal metabolism and wound repair by
providing nourishment.
• Absence of blood vessel in cornea is one of the
contributing factors for its transparency.
• Cornea is primarily innervated through the ophthalmic branch
of the trigeminal nerve.
• The nasociliary nerve provides sensory innervation to the
cornea.
• The Long ciliary nerves after arising from nasociliary nerve
enter the eyeball around the optic nerve along with short
ciliary nerve & run forward in suprachoroidal space.
• A short distance from the limbus , these nerve pierce into sclera
to leave the eyeball
• Divide dichotomously & connect with each other &
conjunctival nerves to form a pericorneal plexus of nerve.
• About 60-80 myelinated trunks from the pericorneal
plexus enter into the cornea at various levels
– Sclera
– Episclera
– Conjunctiva
• After having gone for 1-2mm in the stroma the corneal
nerves loose their myelin sheath, branch dichotomously &
form stromal plexus
• Some nerves end in mid stroma. Most pass anteriorly &
form subepithelial plexus
• The fibers from here penetrate the pores in
bowman’s membrane ,lose their schwann’s sheath,
divide into filaments under basal layer of epithelium
which extend between the cells of all layers of
epithelium, & form intra epithelial plexus
• Thus nerve end in epithelium as fine beaded
filaments.
PHYSIOLOGICAL
• To act as powerful refracting lens.
• To protect the intraocular contents.
• Cornea plays imp. role in absorption
of topically applied drugs.
• Wound healing after anterior segment
Sx or trauma.
BIOCHEMICAL
• Biochemical composition
• Metabolism of cornea
• Corneal transparency
• Drug permeability
• Corneal wound healing
• Water: 70%
• Proteins: 5 times > stroma & 2 times > endothelium and
Descemets membrane.
• Lipids: phospholipids & cholesterol are components wich
constitue 5.4% of the dry wt of epithelium.
• Enzymes: Necessary for krebs, glycolysis are present in
high no.s
• Achetylcholine & cholinestrase play a role in cation
transport
• Electrolytes: HIGH K+ and LOW Na+ and Cl-
• Water :75-80%
• Collagen : Predominant type I. Type V, XII, XIV collagen also found
• In boiling water or acids collagen is converted to gelatin(acids
burns are less serious than alkali burns).
• Soluble proteins: albumin, immunoglobulins(G,A&M),
glycoproteins
• Proteoglcans: -keratin sulphate,chondrotin. Glycosamino glycans is
present in interfibrillar space and accounts for stromal swelling
pressure(N=60mmhg) plays imp role in transparency and
hydration.
• Enzymes: glycolsis & krebs cycle enzymes in stromal keratocytes
• Matrix metalloprotinase help in remodelling after injury
• Electrolytes: Na+ is high & K+ is low
o Collagen : 75%
o Glycoproteins
o The collagen of this layer is insoluble and
extremely resistant to chemical and enzymatic
action.
• Cornea requires energy for maintenance of
transparency & dehydration.
• Most actively metabolising layers are
epithelium & endothelium.
• Nutrients: Oxygen, glucose and aminoacids
– Glycolysis
– Hexose monophosphate shunt
CORNEAL TRANSPARENCY
• Optically smooth tear film.
• Role of corneal epithelium
• Arrangement of stromal fibers
• Corneal avascularity.
• Absence of myelin sheath around
corneal nerves.
• Corneal dehydration
• Forms a homogeneous layer over ant surface of cornea.
• Acts as a lubricant.
• Fills up the small surface irregularity on the cornea
• Condition associated with abnormalities of tear is associated
with loss of corneal transparency.
• Homogeneous refractive medium.
• Basal cell are firmly joined
laterally to other basal cells &
anteriorly to the wing cells by
desmosomes & maculae
occludents.
• Tight intercellular junction
accounts for epithelial
transparency as well as its
resistance to flow of water,
electrolytes & glucose i.e barrier
function.
• Collagen fibrils of
stroma are bundled
together in form of
lamellae.
• Arranged parallel to
each other as to its
surface.
• Two theories
– Maurice theory
– Goldman et al theory
• Uniform collagen fibrils
are arranged in a regular
lattice
• Scattered light is
destroyed by destructive
interferance
• Interfibrillar distance is <
wavelength of light
(4000A-7000A)
• Diffraction theory.
• Lattice arrangement is not required
• 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.
• Cornea is asvascular 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
– Role of Vaso-inhibiting factor: (Meyer & Chafre )
• Presence of sulfate ester of hyaluronic acid in the stroma
glycosaminoglycan acts as VIF
– Role of Vaso-stimulatory factor: (Campbell &
Michaelson)
• Experimental corneal burns, release of VSF at the of lesion
which diffuses through the stroma to limbus & stimulates new
vessel growth from limbal plexus.
• VSF is thought be low molecular weight amine
• Corneal hypoxia also induces neovascularization by activation
of VSF
: (Cogan)
– Blood vessels cannot invade normal cornea because of its
compact structural nature & that of loosening of compactness
of corneal tissue due to edema was mandatory for
neovascularization
: ( Maurice et al)
• Role of both VIF & compactness of cornea
• Leucocytes perform an essential role in stimulating
vascularization
• Corneal nerves loose their
myelin sheath at 1-2mm
away from the limbus.
• Cornea maintains itself in a state of relative
dehydration
• Water content of normal cornea is around 80%,
which is highest water content of any connective
tissue in the body.
• Factors which draw water in cornea
Imbibition Pressure
• Factors which prevent the flow of water in the cornea
Barrier Mechanism Of Epithelium
• Factors which pump out water from the cornea
Endothelial Metabolic Pump
• Factors which draw water in cornea
• Stromal swelling pressure
• Pressure is 60mm of Hg which is exerted by
glycoaminoglycans(GAGs)of corneal stroma which acts like
sponge
• The electrostatic repulsion of anionic charges on the GAGs
molecule expands the tissue ,sucking in the fluid with equal
but negative pressure called IMBIBITION PRESSURE
• Imbibition pressure=Stromal pressure in vitro
• IP is reduced equivalent to IOP in vivo i.e IP =IOP-SP
• SP generates a level of inter-fibillar tension
• SP may reciprocally activate chloride channels.
• Factors which prevents the flow of water
• Both epithelium & endothelium function as
barrier to excessive flow of water
• Diffusion of electrolytes into the stroma due its
semi-permeable nature
• Corneal epithelium offers twice the resistance to
flow of water than endothelium
• Perfect semi-permeable membrane for small
solutes such as NaCl+ & urea when they are
used to produce hypertonicity of the solution
bathing the cornea.
• Factors which draw water out of cornea
• Solutes diffuse across the layer ,water is extracted osmotically
• Barrier function of endothelium is calcium dependent
• Corneal transparency is decreased & corneal thickness is
increased when endothelium is damaged and to lesser extent
when the epithelium is damaged
• Na+/K+ATPase Pump System
– Enzyme Na+/K+ACTIVATED ATPase mediates the extrusion of Na+ from tissue
– Oubain, a specific ATPase inhibitor, when applied topically to eye blocks
endothelial fluid transport & results in corneal over hydration
• Bicarbonate Dependent ATPase
– Depletion of bicarbonate from incubation/perfusion induces swelling
• Carbonic Anhydrase Enzyme
– Implicated in regulation of fluid transport ,
– Carbonic anhydrase inhibitor decreases flow of fluid from stroma to aqueous
humour
• Na+/H+ Pump
• Passive ion movement also occur,K+, Cl-& HCO3- ions diffuse into the aqueous
humour,
• In contralateral direction, Na+, Cl- & HCO3 passively diffuse from the aqueous to
cornea.
– Evaporation of precorneal tear film results in increased
osmolarity
– Hypertonicity of the tear film draw water from the cornea,
loss of fluid is replaced by aqueous
– Edema may occur
o When IOP exceeds stromal pressure
o In normal IOP when Stromal Pressure is decreased
• 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
– A drug should be amphipathic i.e both lipid & water
soluble to readily penetrate across cornea
– 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.
– 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
– Varies from 4-10 without affecting the permeability of the
epithelium, but solution outside this range increases the
permeability
• Hypotonicity of solution (those below 0.9% of sodium
chloride)increases the permeability of epithelium
• Agents that reduce surface tension ,increase corneal wetting &
therefore present more drug for absorption e.g. bezalkonium chloride
used as perservative also acts as wetting agent & thus increases the
drug asorption
• 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
THANK YOU

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Anatomy of cornea & corneal tranparency dr.ysr

  • 1. By: Dr. Yajuvendra Singh Rathore
  • 2. • Cornea is a transparent, avascular, watchglass like structure • It forms anterior 1/6th of the outer fibrous coat of eyeball.
  • 3. • Anterior surface of the cornea is elliptical • Horizontal diameter – 11.75mm • Vertical diameter-11mm • Posterior surface is spherical with average diameter 11.5 mm.
  • 4. • The radius of curvature of cornea – Anterior radius 7.8mm – Posterior radius 6.5mm • Thickness of cornea – Center 0.52mm – Periphery 0.67mm • Central corneal thickness has direct influence in IOP measurement.
  • 5. • The central 5 mm of the cornea forms the most powerful refracting surface of the eye. • The net refractive power of the cornea is +43D which is 3/4th of the total refractive power of eye. • The refractive index of cornea is 1.37
  • 6. Layers Thickness (in µm) Composition Epithelium 50 Stratified Squamous Epithelium Bowman's Membrane 8-14 Compact layer of collagen fibres Stroma 500(0.5mm) Orderly arrangement of collagen lamellae with keratocytes Descemet's Membrane 10-12 Consists of collagen & glycoprotein Endothelium 5 single layer of simple squamous epithelium
  • 7. Layers of Epithelium Description Mitoticactivity Basal Cell Single layer of columnar cells found adjacent to basal layer + Wing Cell 2-3 layers of polyhedral cells - Surface Cell 3 layers of flattened epithelial cells with microvilli in contact with the tear film. - It takes normally 7 days for replacement entire corneal epithelium
  • 8.
  • 9. • The surface corneal epithelial cells has numerous microvilli and microplicae and these cells secrete glycocalyx which helps in adhesion and stability of the tear film. • The Basal cells are firmly joined laterally to other basal cell & anteriorly to the wing cell by desmosomes & maculae occludent and with the basal lamina with the help of hemidesmosomes and other filaments. • Corneal epithelium sheds at regular interval & replaced by growth from its basal cell
  • 10. • It is an acellular tough membrane like zone situated in between corneal epithelium and stroma. • It is 8-14 µm thick • composed of condensed collagen fibers. • These collagen fibers are continuous with that of anterior stroma. • Because of the compact arrangement of collagen fibers, it is comparatively resistant to trauma. However, once destroyed it cannot be regenerated.
  • 11. • The stroma or substantia propria, which occupies about 90% of the total corneal thickness • Composed of collagen fibrils, keratocytes and extracellular ground substances • Lamellae are arranged in many layers (200-250) • Each layer is parallel to each other & with corneal surface and become continuous with scleral plane • Lamellae run from limbus to limbus • Parallel arrangement of lamellae in the cornea allow an easy intralamellar dissection during superficial keratectomy & lamellar keratoplasty • The peculiar arrangement of lamellae has also been implicated in the corneal transparency
  • 12. • Cells are embedded in hydrated matrix of proteoglcans • Amongst the cellular components, keratocytes, wandering macrophages, histiocytes & few lymphocytes (corneal fibroblasts) are the major cell type of the stroma. • They occupy 2-4% of the stromal volume. • They synthesize collagen and proteoglycan and thus maintain the stroma.
  • 13.
  • 14. • It is strong homogenous layer which binds the stroma posterioly • Represents the basement membrane of the endothelium from which it is produced • Elasticity is one of its physical characteristic • It is made up of glycoprotein & collagen fibrils with no elastic fibers • Thickness varies with age, at birth is 3 µm , young adults is 10-12 µm • It is resistant to chemical agents, trauma and infection • Even if whole stroma is sloughed off, Descemet’s membrane can maintain the intergrity of the eyeball for long
  • 15. • In case of Descemet’s Membrane detachment or tear, the membrane curls towards the stroma (inwards) because of the elastic property of Descemet’s membrane. • In periphery, it appears to end at the anterior limit of the trabecular meshwork as schwalbe’s line(ring) • It can regenerate
  • 16. • Corneal endothelium is a simple squamous epithelium. • Endothelial cells are hexagonal which forms continuous mosaic pattern, best seen in specular microscopy. • Cell density – Birth-6000cells/mm2 – Young adults-22500-3000cells/mm2 • The endothelial cells are interconnected with each other with various junctional complexes like zonula occludans, macula occludans and macula adherens. • These cells possess ion transport system which is known as endothelial pump. These endothelial pumps regulate the water content of corneal stroma.
  • 17. • Endothelial cells cannot divide or replicate. With ageing, the cell density of the endothelium decreases which is compensated by an increase in cell size (Polymegathism) or shape (Pleomorphism). • As these endothelial cells are involved in corneal hydration they help in maintenance of corneal transparency
  • 18. New Layer Discovered-DUA’S LAYER • In a paper published in 2013, the existence of Dua's layer was suggested by Harminder Singh Dua et al.
  • 19. Implications of findings of Dua’s layer • The layer may help surgeons improve outcomes for patients undergoing corneal grafts and transplants. During surgery, tiny air bubbles are injected into the corneal stroma in what is known as the "big bubble technique". Sometimes the bubble bursts, damaging the patient's eye. If the air bubble is injected under Dua's layer instead of above it, the layer's strength could reduce the risk of tearing
  • 20. • In normal condition, cornea does not contain any blood vessel. • Anterior ciliary artery, a branch of ophthalmic artery forms a vascular arcade in the limbal region invades its periphery for about 1mm • helps in corneal metabolism and wound repair by providing nourishment. • Absence of blood vessel in cornea is one of the contributing factors for its transparency.
  • 21. • Cornea is primarily innervated through the ophthalmic branch of the trigeminal nerve. • The nasociliary nerve provides sensory innervation to the cornea. • The Long ciliary nerves after arising from nasociliary nerve enter the eyeball around the optic nerve along with short ciliary nerve & run forward in suprachoroidal space. • A short distance from the limbus , these nerve pierce into sclera to leave the eyeball
  • 22. • Divide dichotomously & connect with each other & conjunctival nerves to form a pericorneal plexus of nerve. • About 60-80 myelinated trunks from the pericorneal plexus enter into the cornea at various levels – Sclera – Episclera – Conjunctiva • After having gone for 1-2mm in the stroma the corneal nerves loose their myelin sheath, branch dichotomously & form stromal plexus • Some nerves end in mid stroma. Most pass anteriorly & form subepithelial plexus
  • 23. • The fibers from here penetrate the pores in bowman’s membrane ,lose their schwann’s sheath, divide into filaments under basal layer of epithelium which extend between the cells of all layers of epithelium, & form intra epithelial plexus • Thus nerve end in epithelium as fine beaded filaments.
  • 24. PHYSIOLOGICAL • To act as powerful refracting lens. • To protect the intraocular contents. • Cornea plays imp. role in absorption of topically applied drugs. • Wound healing after anterior segment Sx or trauma. BIOCHEMICAL • Biochemical composition • Metabolism of cornea • Corneal transparency • Drug permeability • Corneal wound healing
  • 25. • Water: 70% • Proteins: 5 times > stroma & 2 times > endothelium and Descemets membrane. • Lipids: phospholipids & cholesterol are components wich constitue 5.4% of the dry wt of epithelium. • Enzymes: Necessary for krebs, glycolysis are present in high no.s • Achetylcholine & cholinestrase play a role in cation transport • Electrolytes: HIGH K+ and LOW Na+ and Cl-
  • 26. • Water :75-80% • Collagen : Predominant type I. Type V, XII, XIV collagen also found • In boiling water or acids collagen is converted to gelatin(acids burns are less serious than alkali burns). • Soluble proteins: albumin, immunoglobulins(G,A&M), glycoproteins • Proteoglcans: -keratin sulphate,chondrotin. Glycosamino glycans is present in interfibrillar space and accounts for stromal swelling pressure(N=60mmhg) plays imp role in transparency and hydration. • Enzymes: glycolsis & krebs cycle enzymes in stromal keratocytes • Matrix metalloprotinase help in remodelling after injury • Electrolytes: Na+ is high & K+ is low
  • 27. o Collagen : 75% o Glycoproteins o The collagen of this layer is insoluble and extremely resistant to chemical and enzymatic action.
  • 28. • Cornea requires energy for maintenance of transparency & dehydration. • Most actively metabolising layers are epithelium & endothelium. • Nutrients: Oxygen, glucose and aminoacids – Glycolysis – Hexose monophosphate shunt
  • 29. CORNEAL TRANSPARENCY • Optically smooth tear film. • Role of corneal epithelium • Arrangement of stromal fibers • Corneal avascularity. • Absence of myelin sheath around corneal nerves. • Corneal dehydration
  • 30. • Forms a homogeneous layer over ant surface of cornea. • Acts as a lubricant. • Fills up the small surface irregularity on the cornea • Condition associated with abnormalities of tear is associated with loss of corneal transparency.
  • 31. • Homogeneous refractive medium. • Basal cell are firmly joined laterally to other basal cells & anteriorly to the wing cells by desmosomes & maculae occludents. • Tight intercellular junction accounts for epithelial transparency as well as its resistance to flow of water, electrolytes & glucose i.e barrier function.
  • 32. • Collagen fibrils of stroma are bundled together in form of lamellae. • Arranged parallel to each other as to its surface. • Two theories – Maurice theory – Goldman et al theory
  • 33. • Uniform collagen fibrils are arranged in a regular lattice • Scattered light is destroyed by destructive interferance • Interfibrillar distance is < wavelength of light (4000A-7000A)
  • 34.
  • 35. • Diffraction theory. • Lattice arrangement is not required • 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.
  • 36. • Cornea is asvascular 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
  • 37. – Role of Vaso-inhibiting factor: (Meyer & Chafre ) • Presence of sulfate ester of hyaluronic acid in the stroma glycosaminoglycan acts as VIF – Role of Vaso-stimulatory factor: (Campbell & Michaelson) • Experimental corneal burns, release of VSF at the of lesion which diffuses through the stroma to limbus & stimulates new vessel growth from limbal plexus. • VSF is thought be low molecular weight amine • Corneal hypoxia also induces neovascularization by activation of VSF
  • 38. : (Cogan) – Blood vessels cannot invade normal cornea because of its compact structural nature & that of loosening of compactness of corneal tissue due to edema was mandatory for neovascularization : ( Maurice et al) • Role of both VIF & compactness of cornea • Leucocytes perform an essential role in stimulating vascularization
  • 39. • Corneal nerves loose their myelin sheath at 1-2mm away from the limbus.
  • 40. • Cornea maintains itself in a state of relative dehydration • Water content of normal cornea is around 80%, which is highest water content of any connective tissue in the body.
  • 41. • Factors which draw water in cornea Imbibition Pressure • Factors which prevent the flow of water in the cornea Barrier Mechanism Of Epithelium • Factors which pump out water from the cornea Endothelial Metabolic Pump
  • 42. • Factors which draw water in cornea • Stromal swelling pressure • Pressure is 60mm of Hg which is exerted by glycoaminoglycans(GAGs)of corneal stroma which acts like sponge • The electrostatic repulsion of anionic charges on the GAGs molecule expands the tissue ,sucking in the fluid with equal but negative pressure called IMBIBITION PRESSURE • Imbibition pressure=Stromal pressure in vitro • IP is reduced equivalent to IOP in vivo i.e IP =IOP-SP • SP generates a level of inter-fibillar tension • SP may reciprocally activate chloride channels.
  • 43. • Factors which prevents the flow of water • Both epithelium & endothelium function as barrier to excessive flow of water • Diffusion of electrolytes into the stroma due its semi-permeable nature • Corneal epithelium offers twice the resistance to flow of water than endothelium • Perfect semi-permeable membrane for small solutes such as NaCl+ & urea when they are used to produce hypertonicity of the solution bathing the cornea.
  • 44. • Factors which draw water out of cornea • Solutes diffuse across the layer ,water is extracted osmotically • Barrier function of endothelium is calcium dependent • Corneal transparency is decreased & corneal thickness is increased when endothelium is damaged and to lesser extent when the epithelium is damaged
  • 45. • Na+/K+ATPase Pump System – Enzyme Na+/K+ACTIVATED ATPase mediates the extrusion of Na+ from tissue – Oubain, a specific ATPase inhibitor, when applied topically to eye blocks endothelial fluid transport & results in corneal over hydration • Bicarbonate Dependent ATPase – Depletion of bicarbonate from incubation/perfusion induces swelling • Carbonic Anhydrase Enzyme – Implicated in regulation of fluid transport , – Carbonic anhydrase inhibitor decreases flow of fluid from stroma to aqueous humour • Na+/H+ Pump • Passive ion movement also occur,K+, Cl-& HCO3- ions diffuse into the aqueous humour, • In contralateral direction, Na+, Cl- & HCO3 passively diffuse from the aqueous to cornea.
  • 46. – Evaporation of precorneal tear film results in increased osmolarity – Hypertonicity of the tear film draw water from the cornea, loss of fluid is replaced by aqueous – Edema may occur o When IOP exceeds stromal pressure o In normal IOP when Stromal Pressure is decreased
  • 47. • 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
  • 48. – A drug should be amphipathic i.e both lipid & water soluble to readily penetrate across cornea – 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.
  • 49. – 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 – Varies from 4-10 without affecting the permeability of the epithelium, but solution outside this range increases the permeability
  • 50. • Hypotonicity of solution (those below 0.9% of sodium chloride)increases the permeability of epithelium • Agents that reduce surface tension ,increase corneal wetting & therefore present more drug for absorption e.g. bezalkonium chloride used as perservative also acts as wetting agent & thus increases the drug asorption • 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