Corneal physiology in relation to contact lens wear
Presenter
Hira Nath Dahal
3rd year OptometryResource personGauri Shankar Shrestha
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. Avascularity2. Uniform index of refraction3. Tight barrier of epithelium and endothelium4. 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 sourceEnergy in the form of ATP is generated by the breakdown of glucoseGlucose 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 cycleHexose -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 by-products of H20 and CO2
In the corneal epithelium, glucose is also metabolized through the HMP, but without the gain in ATPPurpose 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 hydrationMuch 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 conjunctivaBulbar conjunctivaAqueous humour
Stroma Aqueous humourAtmosphere
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°Ccorneal 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 requiredby the cornea to maintain normal metabolicactivity?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 ExtendedWear: 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 Embden-Meyerhof pathway converts:
• Glucose pyruvate lactateBecause 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 thinningHypoesthesiaSuperficial puncate keratitisEpithelial abrasionsStromal edemaEndothelial blebs
Chronic changes
Corneal neovascularisationStromal thinningCorneal shape alterationsEndothelial cell polymegathismPleomorphism (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 wearMaterial (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 aboutEpithelial acetylcholine is a neurotransmitter to corneal nerves and is decreased in hypoxiaDecreased 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 tissueIn 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 fragilityReduced 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 (0.91- 1.04%)
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 pHIn 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).
04/11/2023
Microcyst :Contd…
Pathologic examination of microcysts shows degenerated epithelial cells (apoptotic cells), probably from dysfunction of thebasal cells of the epithelium, with cellular degeneration and lysis.
Stromal changes
Stromal acidosisStromal edemaStromal thiningNeovascularisationCorneal 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 CO2Under 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 mid-peripheral, 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 blebsPolymegathismEndothelial cell changeEndothelial 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 slit-lamp 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 short-term 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: 2nd Edition A.K Khurana
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