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Corneal physiology in relation
to contact lens wear

Resource person
Gauri Shankar Shrestha

Presenter
Hira Nath Dahal
3rd year Optometry
Corneal anatomy
Consists of 5 layers
• Epithelium
• Bowman’s

membrane
• Stroma (Substantia propria)
• Descemet’s membrane (Posterior elastic lamina)
• Endothelium
Blood supply to the cornea
Nerve supply to the cornea
Corneal physiology
Primarily concerned with
1. Source of energy of cornea that fuel the
cornea’s metabolic activity
2. Corneal transparency and its
maintenance
Corneal transparency
Attributable to
1. Avascularity
2. Uniform index of refraction
3. Tight barrier of epithelium and
endothelium
4. Lattice like arrangement of
collagen fibrils in the corneal stroma
Corneal metabolism
Structural integrity of the cornea is maintained by
an active fluid transport system which depends on
corneal metabolism.
Normal metabolic process are essential for cell
growth, replacement and in the case of the corneal
epithelium and endothelium, for the maintenance
of ionic pump mechanism, which is responsible for
maintaining the state of corneal hydration.
The main nutrient needed for corneal metabolic
activity is glucose, which is primarily sourced from
aqueous humour. Amino acids, vitamins and
minerals are also derived from this source
Energy in the form of ATP is generated by the
breakdown of glucose
Glucose is the main substrate in carbohydrate
metabolism, but a small supplementary
carbohydrate supply is stored in the cornea by
conversion of glucose to glycogen.
Aqueous: imp source for glucose also negligible
amount of glucose enters the cornea from the tear
film and by diffusion from the peri limbal
capillaries
Metabolism in the cornea involves three
alternative pathways:
Embden Meyerhof pathway(Glycolysis)
Kreb’s tricarboxylic acid cycle
Hexose -Monophosphate shunt (HMP)
Glycolysis is an oxygen free method of producing
energy, but the yield is low. Also, the by product
lactate is not so easily dispersed as the water and
carbon dioxide. The eye uses this pathway under
situations where oxygen availability is reduced
The Kreb’s tricarboxylic acid cycle produces a
comparatively high yield of energy and the byproducts of H20 and CO2
In the corneal epithelium, glucose is also
metabolized through the HMP, but without the
gain in ATP
Purpose is the production of NADPH which is
utilized in the biosynthesis of lipids by corneal
epithelium.
The ribose produced by the pentose shunt may be
used to build nucleic acids, DNA & RNA
Oxygen required for essential metabolism of the
cornea is primarily derived from the atmosphere via
the tears and diffusion across the cornea’s anterior
surface.
Each layer of the cornea consumes oxygen at its own
rate
Epithelium: 40%
• Stroma: 39%
• Endothelium: 21% of total oxygen consumption of the cornea
•

On the basis of volume of oxygen per unit volume of
tissue, epithelial oxygen utilisation is about ten times
that of the stroma and approx. 0.2 that of the
endothelium
Disturbance of corneal metabolism
Corneal Thickness

Corneal Transparency
 Corneal Vascularization


• Mechanical
•

or chemical damage
and causes metabolic stress in the cornea
Corneal Hydration
Water content of normal cornea is approx. 80% (highest water
content of any connective tissue in the body)
The health of a tissue depends upon the mechanical integrity of
its component cells. In the case of the cornea, when these cells
malfunction there is loss in transparency with the consequent
reduction in visual performance and an increase in corneal
thickness
Impaired function of epithelium and endothelium results in a n
increase in corneal hydration
Much greater corneal hydration will result from damage of the
endothelium, since this provides the facility of the ionic pump
mechanism and the mechanical barrier to the flow of fluid from
the aqueous to the cornea.
Sources of corneal oxygen
LAYER

OPEN EYE

CLOSED EYE

Epithelium

Atmosphere
Aqueous humour

Palpebral conjunctiva
Bulbar conjunctiva
Aqueous humour

Stroma

Aqueous humour
Atmosphere

Aqueous humour

endothelium

Aqueous humour

Aqueous humour
Oxygen tension levels vary across the cornea and
within the cornea. The highest level is at the
anterior surface.
Reduction in normal supply of oxygen to the corneal cells
will result in significant alteration to the physiology of the
cornea
If there is not enough oxygen available to convert the
glucose, by means of glycolysis, into sufficient energy and
allow the waste product, lactic acid, to diffuse quickly out of
the tissue, the less energy is available to the cellular activity.
This results in too much lactic acid being produced, which
builds up in the stroma, and so is implicated in the cause of
corneal oedema by causing an osmotic imbalance
Corneal Temperature
normal corneal temperature - 33-36 C
corneal temperature has been shown to rise
in the closed eye by about 3 C.
Elevated corneal temperatures have been
associated with increases in the anterior
cornea’s rate of metabolic activity (Freeman and
Fatt, 1973).
With SCLs, the lens’ anterior surface is about 0.5 C
cooler than the cornea underneath.
With an RGP lens, the anterior surface is slightly
cooler still as a result of the lens’ lower thermal
conductivity
What is EOP??
quantifies the corneal environment under a
contact lens by ascertaining what oxygen
concentration produces an identical corneal
response to that produced by the lens.
The oxygen pressure in the air corresponds
to about 20.9% (or about 159 mmHg; that
value is actually close to 155 mmHg because
of the presence of water vapour) and each
percentage point is equal to a pressure of
about 7.4 mmHg.
It is an in vivo measurement made on living tissue and
therefore provides a more accurate indication of corneal
function.
The results of the corneal oxygen consumption
measurement provide an accurate indication of the oxygen
need, or thirst, of the cornea.
Any type of lens can be fitted and an assessment made of
the effect on the corneal oxygen consumption rate. This
permits a direct comparison of SCL and RGP lenses.
P02 in open and closed eye
Open eye:
•
Under the lids:
33.7 to 61.4 mm Hg
•
Under contact lenses:
0 to 82.3 mm Hg
•
In the anterior chamber:
40 to 59.7 mm Hg
•
In the anterior chamber, contact lenses on:
25 to 75 mm Hg
Ruben, 1975, Benjamin, 1994, Thiel, 1967, Fatt and Ruben, 1993
Closed-eye:
•
At the central cornea:
50 to 67 mm Hg
•
In the anterior chamber:
55 mm Hg
•
Under contact lenses:
0 to 35 mm Hg
Ruben, 1975, O’Neal et al., 1983, Ichijima et al., 1998
To understand the effects of contact lenses on the
structure and function of the cornea, it is necessary
to consider its normal oxygen requirements under
a variety of conditions both with and without
lenses.
What is the minimum level of oxygen required
by the cornea to maintain normal metabolic
activity?
Holden and Mertz attempted to define the
minimum contact lens oxygen transmissibility
required to meet the needs of various modes of
contact lens wear.
Physiologically, the ideal SCL, when worn on a daily
wear (DW) basis, should cause zero corneal
oedema (swelling).
To minimize its impact on the average cornea, the
oxygen transmissibility of a SCL should be
24.1 2.7 x 10 -9 units
based on the study of Holden and Mertz

For a SCL to induce zero swelling during DW, the
EOP value should be
9.9% for the ‘average’ cornea
Oxygen Requirements During SCL Extended
Wear: zero residual swelling

Following overnight wear of an SCL, the cornea
swells by an amount which is related to the oxygen
transmissibility of the material.
After eye opening, the cornea begins to thin as its
metabolic activity increases due to the higher
availability of oxygen.
According to Holden and Mertz (1984), the oxygen
transmissibility of an SCL must be 34.3 x 10-9 units
or an EOP of 12.1%.
This Dk/t value limits the permissible overnight
corneal swelling to approximately 8.0%.
Corneal oxygen requirements
SCL Extended wear
For overnight oedema = 4.0%
•
Dk/t= 87.0 3.3 x 10-9
•
EOP of 17.9%
Minimum oxygen requirement
Criterion

Minimum 02 (%)

Corneal swelling

DW: 9.9%, EW: 17.9%

Epithelial mitosis

13.2%

Epithelial healing

10.4%

Corneal sensitivity

7.7%

Glycogen depletion

5%

Endothelial blebs

15-16.6%
Ocular environment in open and closed
eye
Variables

Closed eye

Open eye

Cornea (pH)

7.39

7.55

Tears (pH)

7.25

7.45

Temperature

36.20

34.50

Tonicity (% NaCl)

0.89

0.97

O2 (mmHg)

61.00

155.00

CO2 (mmHg)

55.00

0.00
Cornea and contact lens
Contact lens effectively occludes the cornea from
its surrounding environment of oxygen, tears and
ocular secretions.
The effect depends upon lens thickness, size,
method of fitting and material
Any reduction in the amount of oxygen available to
a metabolically active tissue can significantly alter
the physiological equilibrium of the component
cells and therefore, the tissue itself. The cornea is
no exception

An adequate supply of oxygen to the cornea is vital
to its metabolic processes and the maintenance of
its structural integrity. For successful contact lens
wear, the lenses fitted must supply at least the
minimum level of oxygen the cornea requires.
If the oxygen decreases below the critical
level anaerobic glycolysis using the EmbdenMeyerhof pathway converts:
• Glucose

pyruvate
lactate
Because lactate doesn’t diffuse rapidly out of the
cornea, the consequence of decreased aerobic
metabolism is stromal lactate accumulation
Hypoxia thus creates:
• Lowered

epithelial metabolic rate
• An increase in epithelial lactate production
• An acidic shift in pH

After prolonged hypoxia:

• Depletion of the glycogen reserves of the
cornea
• Diminished Adenosine Triphosphate (ATP)
& ultimately a slowing of water transport
system in the endothelium
A decrease in the pumping action of the
endothelium

leading to corneal edema
Acute physiological changes to the
cornea

Epithelial thinning
Hypoesthesia
Superficial puncate keratitis
Epithelial abrasions
Stromal edema
Endothelial blebs
Chronic changes
Corneal neovascularisation
Stromal thinning
Corneal shape alterations
Endothelial cell polymegathism
Pleomorphism (signs of endothelial cell stress)
Corneal Swelling with Soft Contact Lenses
All conventional soft contact lenses act as physical barriers
to the supply of oxygen from the atmosphere and reduce
the level of oxygen available to the cornea.
Higher the water content the greater the oxygen
permeability of the material. For a given water content, the
thinner the lens, the greater the transmission of oxygen to
the cornea.
There is only minimal exchange of tears behind an SCL with
each blink. This exchange therefore contributes a negligible
proportion of the oxygen supplied to the cornea during
SCL wear.
Contd....
As the thickness of a lens increases, its oxygen
transmissibility decreases and a higher level of corneal
swelling results.
Over an eight-hour period of wear, an ultra-thin HEMA lens
may induce only minimal swelling. A thicker lens such as a
toric or a plus power (typical tc = 0.13 mm) induces about
8% corneal swelling.
Centre thickness (tc)

Swelling (%)

0.13

8

0.07

5

0.03

1
In the case of high water content material (75%)
High water content (75%), 8 hours wear

tc (mm)

Swelling (%)

0.3

2

0.15

0.5
Corneal swelling with SCL overnight wear
Material (8 hrs wear)

Swelling (%)

Low Water

12

Mid Water

10

High Water

11

Siloxane Elastomer

2.5
Corneal Swelling with RGP lenses
RGP lenses do not impede the supply of
oxygen to the cornea as significantly as do
conventional SCLs. This is due to:
• Higher oxygen permeability of RGP materials.
• Lens design features, such as a smaller total
diameter.
• Fitting characteristics, such as greater
movement over the eye.
Effects of Corneal Hypoxia
Any reduction in the supply of oxygen to the
cornea can have significant effects on normal
metabolic activity. The effects are numerous
and they range from mild to severe in their
impact on the cornea
•
Reduced aerobic glycolysis
•
•
•
•
•

Lactate accumulation (stroma)
Stromal acidosis
Osmotic imbalance
Oedema (swelling)
Structural changes
Other effects from reduced oxygen supply to
the cornea include changes to the:
•
•
•
•

Epithelial mitotic rate.
Density of nerve fibre endings.
Sensitivity of the cornea.
Corneal pH.
Corneal Sensitivity and Contact Lens
Wear
The cornea is the most densely innervated tissue in
the body. This innervations protects the eye by
making it highly sensitive and responsive to foreign
bodies, abrasion, etc.
A minimum of 8% oxygen is required to maintain
corneal sensitivity at or near a normal level for the
average person (Millodot and O’Leary, 1980)
Change in sensitivity d/t contact lens
wear
Corneal hypoesthesia is the first effect of hypoxia,
of which patient is unaware about
Epithelial acetylcholine is a neurotransmitter to
corneal nerves and is decreased in hypoxia
Decreased sensation is milder with soft contact
lenses and the return of sensation is more rapid,
compared with PMMA lenses.
Oxygen level required to maintain the nerve fibres in their
normal state is 9–10% Hamano (1985)
Corneal hypoesthesia is thought to be an
adaptation to chronic hypoxia, to decreased
corneal pH, or to mechanical stimulation and is
correlated with levels of acetycholine

Corneal sensation may be a more sensitive test
than refraction, keratometry, or pachometry for
monitoring the status of corneal health during
contact lens wear.
Corneal pH and Contact Lens Wear
Bonanno and Polse (1987) demonstrated that the
corneal stromal environment becomes more acidic
(lowered pH) in a range of circumstances including
contact lens wear.

It is postulated that a reduction (Holden et al., 1985) or
changes (Williams, 1986) in corneal pH cause the
endothelial bleb response.
Hypoxia and structural changes to the
cornea
Both short-term and chronic corneal hypoxia can result in
significant changes in the structure and function of
corneal tissue
In most cases, even subtle changes are visible with the
slit-lamp bio microscope.
•
Epithelial and stromal oedema
loss of transparency
•
Microcysts and vacuoles
•
Striae
•
Folds
•
Endothelial blebs
•
Endothelial polymegethism
•
Vascularization
Corneal tissue fragility
Reduced epithelial adhesion is found following contact lens
wear. It is related to the reduced numbers of
hemidesmosomes, which is due to loss of basal cell shape
and chronic corneal hypoxia following contact lens wear.
The hypoxia causes a decrease in the level of
metabolic activity including the rate of cell mitosis.
Cell life increases and those at anterior surface of
the epithelium may not retain normal functional
resistance.
This will have the effect of compromising the
epithelium with the increased likelihood of
microbial penetration and subsequent infection.
Tear Film Osmolality
Normal osmolality: 294-334 mOsm/litre (0.911.04%)

Contact lens effects:
• Initial

hard lens wear produces decreased
tear osmolality brought about by reflex
tearing. The cornea swells (mainly stromal)
some 2-4%.
• Initial soft contact lens wear increases tear
osmolality. This may be caused by changes
in the blink rate causing an increase in
evaporation.
Epithelial changes
Contact lenses predominantly affect the function of the
epithelium
Reduce the direct availability of oxygen to the epithelium,
thus shifting the balance from aerobic to anaerobic
metabolism
Lactate levels in the cornea are doubled with contact lens
wear and carbon dioxide production is increased thus
increasing pH
In severe cases, excessive use of contact lenses produces
epithelial oedema and keratopathy in the forms of punctate
epithelial erosions.
Epithelial Metabolic Rate Reduction
With extended-wear soft contact lenses, the
epithelial metabolism is reduced because of a 15%
decrease in oxygen uptake
With decreased pumping ability, increased
permeability of the epithelial cells can result in
dehydration.
Epithelial Morphology Changes
With extended-wear soft contact lenses, the mean
corneal epithelial cell size is affected most.
Mature cells have fewer microvilli and less mucin,
more sites are available for possible bacterial
adhesion
Epithelial Microcysts : Sign
appear as small (10 - 50 μm, average 20
μm), usually circular , translucent,
refractile dots’
sign of altered epithelial metabolism.
usually located in the central and
paracentral corneal regions
differentiated from other dot-like
corneal features by virtue of their
location, i.e. epithelial as opposed to
stromal or deeper locations).
Microcyst :Contd…
Pathologic examination of
microcysts shows
degenerated epithelial
cells (apoptotic cells),
probably from
dysfunction of the
basal cells of the
epithelium, with cellular
degeneration and lysis.
3/3/2014
Stromal changes
Stromal acidosis
Stromal edema
Stromal thining
Neovascularisation
Corneal shape alteration
Stromal Acidosis
hypercapnia accounts for about 30% of the total pH
drop d/t accumulation of stromal lactic acid during
anaerobic metabolism.
Respiratory acidosis is caused by the accumulation of
carbon dioxide (hypercapnia) because the gas
impermeable contact lens precludes normal efflux of
CO2
Under open-eye conditions, the human stromal pH
increases by 0.15 to 7.55.
decrease by as much as 0.25 during wear of soft
contact lens of nearly zero oxygen transmissibility.
Stromal Edema
break in epithelial or endothelial barriers, reduction
in pump function (mainly endothelial),
or
increase in osmotic activity (imbibition pressure) of
the stroma
Corneal swelling : Striae
striae appear as fine, whispy,
greyish, whitish or translucent
corneal lines in the central to midperipheral, posterior stroma
Striae were postulated to be the
result of stromal oedema (Wechsler,
1974)
Corneal swelling : striae
The level of corneal swelling required to produce
striae is of the order of 4-6% (Holden and Swarbrick, 1989).
They found that a count of 10 striae represented
11% 2% corneal swelling. (La Hood and Grant 1990)
The advent of siloxane hydrogels has lowered
further the incidence of striae in contact lens
wearers
Corneal Oedema: Folds and Black Lines
The level of corneal swelling
required to produce folds and
possibly black lines is 7% to 12%.
Black lines should be regarded as a
clear sign of oedema exceeding
clinically acceptable levels (Holden and
Swarbrick 1989).

significant stresses generated
within the cornea result in folds
appearing in the posterior stroma
adjacent to Descemet’s membrane
Stromal Thinning
Whereas stromal swelling is regarded as an acute
response to corneal oedema, stromal thinning is
regarded as an chronic response

Chronic oedema may lead to the dissolution of
polysaccharide (glycosaminoglycans) ground
substance in the stroma (Efron, 1999) causing thinning of
the stroma
Contd…
Holden et al. 1985 reported a thinning of 11µm
over an approximately 5 year period, i.e. about
2µm per year of lens wear
Thinning of the stroma has been demonstrated to
occur in long-term SCL, extended wear patients
Contd…
Thinning by 2% may be a sequelae of chronic
stromal edema correlated with degeneration and
possible death of stromal keratocytes
A study with the Orbscan topography system
showed that the mean corneal thickness in the
center and in eight peripheral areas was
significantly reduce by approximately 30 to 50µm
in long-term soft contact lens wearers compared
with noncontact lens wearing control subjects
Endothelial changes due to hypoxia
Endothelial blebs
Polymegathism
Endothelial cell change
Endothelial function change
Polymegathism
derivative of the Greek words
‘many’ (poly)
‘size’ (megethos)
Thus, literally means ‘many
sizes’
while some cells get smaller,
others enlarged to leave the
average largely unaltered
contd..
Polymegethism is one of the features of the
corneal exhaustion or fatigue syndrome
Recovery from contact lens-induced endothelial
polymegethism is slow, and the condition may be
irreversible, even after cessation of contact lens
wear

Endothelial polymegethism places the cornea at
greater risk for surgical complications
Endothelial Blebs
Blebs appear as very small, circumscribed,
irregularly-shaped, black zones obscuring
the cellular mosaic when viewed with a slitlamp using specular reflection
Blebs form within minutes (certainly within
10 minutes) of the application of a lens
(especially if it has a relatively low
transmissibility)

response peaks after about 20 to 30
minutes
contd..
Pathologic examination of blebs shows edema of
the nuclear endothelial cells, with intracellular
fluid vacuoles and fluid space between cells
blebs occur with conventional and disposable
contact lenses of similar oxygen transmissibility,
but their occurrence is minimal or absent with
silicone elastomer contact lenses.
blebs are asymptomatic and are thought to be of
little clinical significance; they represent a shortterm as well as long-term adaptation of the
endothelium
Conclusion
Very thin, high-water content hydrogel soft
contact lenses provide improved oxygen
transmissibility but not to the level required
to maintain normal epithelial aerobic
metabolism.
can induce corneal desiccation, have
inadequate durability, and are difficult to
handle
Contd...
Silicone elastomer contact lenses have yet to
attain successful clinical performance in
terms of surface chemistry, comfort, and
maintenance of lens movement for any
group of patients except aphakic infants and
children
Contd..
New lenses such as the silicone hydrogel and
fluorosilicone hydrogel hybrid lenses are in trial
and have the potential to overcome some of these
physiologic limitations

True daily-wear disposable contact lenses may also
overcome other issues with regard to contact lens
safety but will remain expensive for many patients
References:
The IACLE Contact Lens Course
•
•

MODULE 6 The Cornea in Contact Lens Wear
MODULE 7 Contact Lens-Related Complications

Adler’s Physiology of the Eye 11th edition
The Physiological causes of contact lens
complications: Judith Morris

Anatomy and Physiology of eye: 2

nd

A.K Khurana

Edition
Corneal physiology in relation to contact lens wear

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Corneal physiology in relation to contact lens wear

  • 1.
  • 2. Corneal physiology in relation to contact lens wear Resource person Gauri Shankar Shrestha Presenter Hira Nath Dahal 3rd year Optometry
  • 3. Corneal anatomy Consists of 5 layers • Epithelium • Bowman’s membrane • Stroma (Substantia propria) • Descemet’s membrane (Posterior elastic lamina) • Endothelium
  • 4.
  • 5. Blood supply to the cornea
  • 6. Nerve supply to the cornea
  • 7. Corneal physiology Primarily concerned with 1. Source of energy of cornea that fuel the cornea’s metabolic activity 2. Corneal transparency and its maintenance
  • 8. Corneal transparency Attributable to 1. Avascularity 2. Uniform index of refraction 3. Tight barrier of epithelium and endothelium 4. Lattice like arrangement of collagen fibrils in the corneal stroma
  • 9. Corneal metabolism Structural integrity of the cornea is maintained by an active fluid transport system which depends on corneal metabolism. Normal metabolic process are essential for cell growth, replacement and in the case of the corneal epithelium and endothelium, for the maintenance of ionic pump mechanism, which is responsible for maintaining the state of corneal hydration.
  • 10. The main nutrient needed for corneal metabolic activity is glucose, which is primarily sourced from aqueous humour. Amino acids, vitamins and minerals are also derived from this source Energy in the form of ATP is generated by the breakdown of glucose Glucose is the main substrate in carbohydrate metabolism, but a small supplementary carbohydrate supply is stored in the cornea by conversion of glucose to glycogen.
  • 11. Aqueous: imp source for glucose also negligible amount of glucose enters the cornea from the tear film and by diffusion from the peri limbal capillaries Metabolism in the cornea involves three alternative pathways: Embden Meyerhof pathway(Glycolysis) Kreb’s tricarboxylic acid cycle Hexose -Monophosphate shunt (HMP)
  • 12. Glycolysis is an oxygen free method of producing energy, but the yield is low. Also, the by product lactate is not so easily dispersed as the water and carbon dioxide. The eye uses this pathway under situations where oxygen availability is reduced The Kreb’s tricarboxylic acid cycle produces a comparatively high yield of energy and the byproducts of H20 and CO2
  • 13. In the corneal epithelium, glucose is also metabolized through the HMP, but without the gain in ATP Purpose is the production of NADPH which is utilized in the biosynthesis of lipids by corneal epithelium. The ribose produced by the pentose shunt may be used to build nucleic acids, DNA & RNA
  • 14. Oxygen required for essential metabolism of the cornea is primarily derived from the atmosphere via the tears and diffusion across the cornea’s anterior surface. Each layer of the cornea consumes oxygen at its own rate Epithelium: 40% • Stroma: 39% • Endothelium: 21% of total oxygen consumption of the cornea • On the basis of volume of oxygen per unit volume of tissue, epithelial oxygen utilisation is about ten times that of the stroma and approx. 0.2 that of the endothelium
  • 15.
  • 16. Disturbance of corneal metabolism Corneal Thickness  Corneal Transparency  Corneal Vascularization  • Mechanical • or chemical damage and causes metabolic stress in the cornea
  • 17. Corneal Hydration Water content of normal cornea is approx. 80% (highest water content of any connective tissue in the body) The health of a tissue depends upon the mechanical integrity of its component cells. In the case of the cornea, when these cells malfunction there is loss in transparency with the consequent reduction in visual performance and an increase in corneal thickness Impaired function of epithelium and endothelium results in a n increase in corneal hydration Much greater corneal hydration will result from damage of the endothelium, since this provides the facility of the ionic pump mechanism and the mechanical barrier to the flow of fluid from the aqueous to the cornea.
  • 18. Sources of corneal oxygen LAYER OPEN EYE CLOSED EYE Epithelium Atmosphere Aqueous humour Palpebral conjunctiva Bulbar conjunctiva Aqueous humour Stroma Aqueous humour Atmosphere Aqueous humour endothelium Aqueous humour Aqueous humour
  • 19. Oxygen tension levels vary across the cornea and within the cornea. The highest level is at the anterior surface.
  • 20. Reduction in normal supply of oxygen to the corneal cells will result in significant alteration to the physiology of the cornea If there is not enough oxygen available to convert the glucose, by means of glycolysis, into sufficient energy and allow the waste product, lactic acid, to diffuse quickly out of the tissue, the less energy is available to the cellular activity. This results in too much lactic acid being produced, which builds up in the stroma, and so is implicated in the cause of corneal oedema by causing an osmotic imbalance
  • 21. Corneal Temperature normal corneal temperature - 33-36 C corneal temperature has been shown to rise in the closed eye by about 3 C. Elevated corneal temperatures have been associated with increases in the anterior cornea’s rate of metabolic activity (Freeman and Fatt, 1973).
  • 22. With SCLs, the lens’ anterior surface is about 0.5 C cooler than the cornea underneath. With an RGP lens, the anterior surface is slightly cooler still as a result of the lens’ lower thermal conductivity
  • 23. What is EOP?? quantifies the corneal environment under a contact lens by ascertaining what oxygen concentration produces an identical corneal response to that produced by the lens. The oxygen pressure in the air corresponds to about 20.9% (or about 159 mmHg; that value is actually close to 155 mmHg because of the presence of water vapour) and each percentage point is equal to a pressure of about 7.4 mmHg.
  • 24. It is an in vivo measurement made on living tissue and therefore provides a more accurate indication of corneal function. The results of the corneal oxygen consumption measurement provide an accurate indication of the oxygen need, or thirst, of the cornea. Any type of lens can be fitted and an assessment made of the effect on the corneal oxygen consumption rate. This permits a direct comparison of SCL and RGP lenses.
  • 25. P02 in open and closed eye Open eye: • Under the lids: 33.7 to 61.4 mm Hg • Under contact lenses: 0 to 82.3 mm Hg • In the anterior chamber: 40 to 59.7 mm Hg • In the anterior chamber, contact lenses on: 25 to 75 mm Hg Ruben, 1975, Benjamin, 1994, Thiel, 1967, Fatt and Ruben, 1993
  • 26. Closed-eye: • At the central cornea: 50 to 67 mm Hg • In the anterior chamber: 55 mm Hg • Under contact lenses: 0 to 35 mm Hg Ruben, 1975, O’Neal et al., 1983, Ichijima et al., 1998
  • 27. To understand the effects of contact lenses on the structure and function of the cornea, it is necessary to consider its normal oxygen requirements under a variety of conditions both with and without lenses.
  • 28. What is the minimum level of oxygen required by the cornea to maintain normal metabolic activity? Holden and Mertz attempted to define the minimum contact lens oxygen transmissibility required to meet the needs of various modes of contact lens wear. Physiologically, the ideal SCL, when worn on a daily wear (DW) basis, should cause zero corneal oedema (swelling).
  • 29. To minimize its impact on the average cornea, the oxygen transmissibility of a SCL should be 24.1 2.7 x 10 -9 units based on the study of Holden and Mertz For a SCL to induce zero swelling during DW, the EOP value should be 9.9% for the ‘average’ cornea
  • 30.
  • 31. Oxygen Requirements During SCL Extended Wear: zero residual swelling Following overnight wear of an SCL, the cornea swells by an amount which is related to the oxygen transmissibility of the material. After eye opening, the cornea begins to thin as its metabolic activity increases due to the higher availability of oxygen.
  • 32. According to Holden and Mertz (1984), the oxygen transmissibility of an SCL must be 34.3 x 10-9 units or an EOP of 12.1%. This Dk/t value limits the permissible overnight corneal swelling to approximately 8.0%.
  • 33. Corneal oxygen requirements SCL Extended wear For overnight oedema = 4.0% • Dk/t= 87.0 3.3 x 10-9 • EOP of 17.9%
  • 34.
  • 35. Minimum oxygen requirement Criterion Minimum 02 (%) Corneal swelling DW: 9.9%, EW: 17.9% Epithelial mitosis 13.2% Epithelial healing 10.4% Corneal sensitivity 7.7% Glycogen depletion 5% Endothelial blebs 15-16.6%
  • 36. Ocular environment in open and closed eye Variables Closed eye Open eye Cornea (pH) 7.39 7.55 Tears (pH) 7.25 7.45 Temperature 36.20 34.50 Tonicity (% NaCl) 0.89 0.97 O2 (mmHg) 61.00 155.00 CO2 (mmHg) 55.00 0.00
  • 37. Cornea and contact lens Contact lens effectively occludes the cornea from its surrounding environment of oxygen, tears and ocular secretions. The effect depends upon lens thickness, size, method of fitting and material
  • 38. Any reduction in the amount of oxygen available to a metabolically active tissue can significantly alter the physiological equilibrium of the component cells and therefore, the tissue itself. The cornea is no exception An adequate supply of oxygen to the cornea is vital to its metabolic processes and the maintenance of its structural integrity. For successful contact lens wear, the lenses fitted must supply at least the minimum level of oxygen the cornea requires.
  • 39. If the oxygen decreases below the critical level anaerobic glycolysis using the EmbdenMeyerhof pathway converts: • Glucose pyruvate lactate Because lactate doesn’t diffuse rapidly out of the cornea, the consequence of decreased aerobic metabolism is stromal lactate accumulation
  • 40. Hypoxia thus creates: • Lowered epithelial metabolic rate • An increase in epithelial lactate production • An acidic shift in pH After prolonged hypoxia: • Depletion of the glycogen reserves of the cornea • Diminished Adenosine Triphosphate (ATP) & ultimately a slowing of water transport system in the endothelium
  • 41. A decrease in the pumping action of the endothelium leading to corneal edema
  • 42. Acute physiological changes to the cornea Epithelial thinning Hypoesthesia Superficial puncate keratitis Epithelial abrasions Stromal edema Endothelial blebs
  • 43. Chronic changes Corneal neovascularisation Stromal thinning Corneal shape alterations Endothelial cell polymegathism Pleomorphism (signs of endothelial cell stress)
  • 44. Corneal Swelling with Soft Contact Lenses All conventional soft contact lenses act as physical barriers to the supply of oxygen from the atmosphere and reduce the level of oxygen available to the cornea. Higher the water content the greater the oxygen permeability of the material. For a given water content, the thinner the lens, the greater the transmission of oxygen to the cornea. There is only minimal exchange of tears behind an SCL with each blink. This exchange therefore contributes a negligible proportion of the oxygen supplied to the cornea during SCL wear.
  • 45. Contd.... As the thickness of a lens increases, its oxygen transmissibility decreases and a higher level of corneal swelling results. Over an eight-hour period of wear, an ultra-thin HEMA lens may induce only minimal swelling. A thicker lens such as a toric or a plus power (typical tc = 0.13 mm) induces about 8% corneal swelling. Centre thickness (tc) Swelling (%) 0.13 8 0.07 5 0.03 1
  • 46. In the case of high water content material (75%) High water content (75%), 8 hours wear tc (mm) Swelling (%) 0.3 2 0.15 0.5
  • 47. Corneal swelling with SCL overnight wear Material (8 hrs wear) Swelling (%) Low Water 12 Mid Water 10 High Water 11 Siloxane Elastomer 2.5
  • 48. Corneal Swelling with RGP lenses RGP lenses do not impede the supply of oxygen to the cornea as significantly as do conventional SCLs. This is due to: • Higher oxygen permeability of RGP materials. • Lens design features, such as a smaller total diameter. • Fitting characteristics, such as greater movement over the eye.
  • 49. Effects of Corneal Hypoxia Any reduction in the supply of oxygen to the cornea can have significant effects on normal metabolic activity. The effects are numerous and they range from mild to severe in their impact on the cornea • Reduced aerobic glycolysis • • • • • Lactate accumulation (stroma) Stromal acidosis Osmotic imbalance Oedema (swelling) Structural changes
  • 50. Other effects from reduced oxygen supply to the cornea include changes to the: • • • • Epithelial mitotic rate. Density of nerve fibre endings. Sensitivity of the cornea. Corneal pH.
  • 51. Corneal Sensitivity and Contact Lens Wear The cornea is the most densely innervated tissue in the body. This innervations protects the eye by making it highly sensitive and responsive to foreign bodies, abrasion, etc. A minimum of 8% oxygen is required to maintain corneal sensitivity at or near a normal level for the average person (Millodot and O’Leary, 1980)
  • 52. Change in sensitivity d/t contact lens wear Corneal hypoesthesia is the first effect of hypoxia, of which patient is unaware about Epithelial acetylcholine is a neurotransmitter to corneal nerves and is decreased in hypoxia Decreased sensation is milder with soft contact lenses and the return of sensation is more rapid, compared with PMMA lenses. Oxygen level required to maintain the nerve fibres in their normal state is 9–10% Hamano (1985)
  • 53. Corneal hypoesthesia is thought to be an adaptation to chronic hypoxia, to decreased corneal pH, or to mechanical stimulation and is correlated with levels of acetycholine Corneal sensation may be a more sensitive test than refraction, keratometry, or pachometry for monitoring the status of corneal health during contact lens wear.
  • 54. Corneal pH and Contact Lens Wear Bonanno and Polse (1987) demonstrated that the corneal stromal environment becomes more acidic (lowered pH) in a range of circumstances including contact lens wear. It is postulated that a reduction (Holden et al., 1985) or changes (Williams, 1986) in corneal pH cause the endothelial bleb response.
  • 55. Hypoxia and structural changes to the cornea Both short-term and chronic corneal hypoxia can result in significant changes in the structure and function of corneal tissue In most cases, even subtle changes are visible with the slit-lamp bio microscope. • Epithelial and stromal oedema loss of transparency • Microcysts and vacuoles • Striae • Folds • Endothelial blebs • Endothelial polymegethism • Vascularization
  • 56. Corneal tissue fragility Reduced epithelial adhesion is found following contact lens wear. It is related to the reduced numbers of hemidesmosomes, which is due to loss of basal cell shape and chronic corneal hypoxia following contact lens wear.
  • 57. The hypoxia causes a decrease in the level of metabolic activity including the rate of cell mitosis. Cell life increases and those at anterior surface of the epithelium may not retain normal functional resistance. This will have the effect of compromising the epithelium with the increased likelihood of microbial penetration and subsequent infection.
  • 58. Tear Film Osmolality Normal osmolality: 294-334 mOsm/litre (0.911.04%) Contact lens effects: • Initial hard lens wear produces decreased tear osmolality brought about by reflex tearing. The cornea swells (mainly stromal) some 2-4%. • Initial soft contact lens wear increases tear osmolality. This may be caused by changes in the blink rate causing an increase in evaporation.
  • 59. Epithelial changes Contact lenses predominantly affect the function of the epithelium Reduce the direct availability of oxygen to the epithelium, thus shifting the balance from aerobic to anaerobic metabolism Lactate levels in the cornea are doubled with contact lens wear and carbon dioxide production is increased thus increasing pH In severe cases, excessive use of contact lenses produces epithelial oedema and keratopathy in the forms of punctate epithelial erosions.
  • 60.
  • 61. Epithelial Metabolic Rate Reduction With extended-wear soft contact lenses, the epithelial metabolism is reduced because of a 15% decrease in oxygen uptake With decreased pumping ability, increased permeability of the epithelial cells can result in dehydration.
  • 62. Epithelial Morphology Changes With extended-wear soft contact lenses, the mean corneal epithelial cell size is affected most. Mature cells have fewer microvilli and less mucin, more sites are available for possible bacterial adhesion
  • 63. Epithelial Microcysts : Sign appear as small (10 - 50 μm, average 20 μm), usually circular , translucent, refractile dots’ sign of altered epithelial metabolism. usually located in the central and paracentral corneal regions differentiated from other dot-like corneal features by virtue of their location, i.e. epithelial as opposed to stromal or deeper locations).
  • 64. Microcyst :Contd… Pathologic examination of microcysts shows degenerated epithelial cells (apoptotic cells), probably from dysfunction of the basal cells of the epithelium, with cellular degeneration and lysis. 3/3/2014
  • 65. Stromal changes Stromal acidosis Stromal edema Stromal thining Neovascularisation Corneal shape alteration
  • 66. Stromal Acidosis hypercapnia accounts for about 30% of the total pH drop d/t accumulation of stromal lactic acid during anaerobic metabolism. Respiratory acidosis is caused by the accumulation of carbon dioxide (hypercapnia) because the gas impermeable contact lens precludes normal efflux of CO2 Under open-eye conditions, the human stromal pH increases by 0.15 to 7.55. decrease by as much as 0.25 during wear of soft contact lens of nearly zero oxygen transmissibility.
  • 67. Stromal Edema break in epithelial or endothelial barriers, reduction in pump function (mainly endothelial), or increase in osmotic activity (imbibition pressure) of the stroma
  • 68. Corneal swelling : Striae striae appear as fine, whispy, greyish, whitish or translucent corneal lines in the central to midperipheral, posterior stroma Striae were postulated to be the result of stromal oedema (Wechsler, 1974)
  • 69. Corneal swelling : striae The level of corneal swelling required to produce striae is of the order of 4-6% (Holden and Swarbrick, 1989). They found that a count of 10 striae represented 11% 2% corneal swelling. (La Hood and Grant 1990) The advent of siloxane hydrogels has lowered further the incidence of striae in contact lens wearers
  • 70. Corneal Oedema: Folds and Black Lines The level of corneal swelling required to produce folds and possibly black lines is 7% to 12%. Black lines should be regarded as a clear sign of oedema exceeding clinically acceptable levels (Holden and Swarbrick 1989). significant stresses generated within the cornea result in folds appearing in the posterior stroma adjacent to Descemet’s membrane
  • 71. Stromal Thinning Whereas stromal swelling is regarded as an acute response to corneal oedema, stromal thinning is regarded as an chronic response Chronic oedema may lead to the dissolution of polysaccharide (glycosaminoglycans) ground substance in the stroma (Efron, 1999) causing thinning of the stroma
  • 72. Contd… Holden et al. 1985 reported a thinning of 11µm over an approximately 5 year period, i.e. about 2µm per year of lens wear Thinning of the stroma has been demonstrated to occur in long-term SCL, extended wear patients
  • 73. Contd… Thinning by 2% may be a sequelae of chronic stromal edema correlated with degeneration and possible death of stromal keratocytes A study with the Orbscan topography system showed that the mean corneal thickness in the center and in eight peripheral areas was significantly reduce by approximately 30 to 50µm in long-term soft contact lens wearers compared with noncontact lens wearing control subjects
  • 74. Endothelial changes due to hypoxia Endothelial blebs Polymegathism Endothelial cell change Endothelial function change
  • 75. Polymegathism derivative of the Greek words ‘many’ (poly) ‘size’ (megethos) Thus, literally means ‘many sizes’ while some cells get smaller, others enlarged to leave the average largely unaltered
  • 76. contd.. Polymegethism is one of the features of the corneal exhaustion or fatigue syndrome Recovery from contact lens-induced endothelial polymegethism is slow, and the condition may be irreversible, even after cessation of contact lens wear Endothelial polymegethism places the cornea at greater risk for surgical complications
  • 77. Endothelial Blebs Blebs appear as very small, circumscribed, irregularly-shaped, black zones obscuring the cellular mosaic when viewed with a slitlamp using specular reflection Blebs form within minutes (certainly within 10 minutes) of the application of a lens (especially if it has a relatively low transmissibility) response peaks after about 20 to 30 minutes
  • 78. contd.. Pathologic examination of blebs shows edema of the nuclear endothelial cells, with intracellular fluid vacuoles and fluid space between cells
  • 79. blebs occur with conventional and disposable contact lenses of similar oxygen transmissibility, but their occurrence is minimal or absent with silicone elastomer contact lenses. blebs are asymptomatic and are thought to be of little clinical significance; they represent a shortterm as well as long-term adaptation of the endothelium
  • 80. Conclusion Very thin, high-water content hydrogel soft contact lenses provide improved oxygen transmissibility but not to the level required to maintain normal epithelial aerobic metabolism. can induce corneal desiccation, have inadequate durability, and are difficult to handle
  • 81. Contd... Silicone elastomer contact lenses have yet to attain successful clinical performance in terms of surface chemistry, comfort, and maintenance of lens movement for any group of patients except aphakic infants and children
  • 82. Contd.. New lenses such as the silicone hydrogel and fluorosilicone hydrogel hybrid lenses are in trial and have the potential to overcome some of these physiologic limitations True daily-wear disposable contact lenses may also overcome other issues with regard to contact lens safety but will remain expensive for many patients
  • 83. References: The IACLE Contact Lens Course • • MODULE 6 The Cornea in Contact Lens Wear MODULE 7 Contact Lens-Related Complications Adler’s Physiology of the Eye 11th edition The Physiological causes of contact lens complications: Judith Morris Anatomy and Physiology of eye: 2 nd A.K Khurana Edition