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.
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%.
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
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
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