The CLAO Journal 28(1): 12–27, 2002
Physiologic Changes of the Cornea with Contact
Lens Wear
Thomas J. Liesegang, M.D.
Purpose. This article reviews the corneal changes resulting from
the hypoxia that occurs during sleep and specifically during
contact lens wear. Methods. Discussion includes a literature re-
view and observations regarding the changes to the corneal epi-
thelium, stroma, and endothelium that take place during sleep and
wearing of contact lenses made from different materials. Results.
Hypoxia and hypercapnia cause significant changes to the corneal
epithelium, stroma, and endothelium. Some of these changes can
also be seen following the sleep cycle. Epithelial changes include
decreased metabolic rate, morphologic changes, microcysts,
changes in junctional integrity, decreased corneal sensation, and
pannus formation. Stromal changes include stromal edema, stro-
mal acidosis, neovascularization, and changes in corneal shape
and, ultimately, corneal thinning. Endothelial changes include bleb
formation, polymegethism, changes in endothelial cell density, and
possible changes in endothelial function. Conclusions. There are
multiple and significant corneal changes resulting from hypoxia
and hypercapnia. These changes vary with the specific lens style.
The high-oxygen-permeable contact lenses recently introduced
may overcome some of these problems.
Key Words: Blebs—Contact lenses—Endothelium—Hypercap-
nia—Hypoxia—Microcysts—Neovascularization—Polymegethism—
Stromal acidosis—Stromal edema.
Contact lenses interact mechanically with the cornea and modify
the physiologic processes of corneal tissue. These changes may
lead to reduced corneal function.1 It is necessary to differentiate
corneal changes that are physiologically acceptable from those that
are pathologic. Clinicians, biochemists, engineers, and vision sci-
entists have performed countless research studies to understand the
etiology of these changes in order to enhance the safety of contact
lens wear.
Changes in the cornea caused by contact lenses can be divided
according to the structures affected (tear film, epithelium, stroma,
endothelium) or according to the causes. The major consequence
of contact lens wear is chronic hypoxia, with corresponding
hypercapnia.2,3 Other consequences include tear film instability,
allergy and toxicity, mechanical effects, inflammation and infec-
tion, and desiccation, as outlined by Bruce and colleagues.4 Alter-
natively, these adverse events can be grouped into hypoxia-medi-
ated events, immune events, mechanical events, and osmotic
Accepted May 30, 2001.
From the Department of Ophthalmology, Mayo Clinic, Jacksonville,
Florida.
Address correspondence to Dr. Thomas J. Liesegang, Mayo Clinic, 4500
San Pablo Road, Jacksonville, FL 32224, U.S.A.
12
© 2002 Lippincott Williams & Wilkins, Inc.
events,5 but these categories are not mutually exclusive.
The physiologic changes differ among the various contact lens
materials (polymethylmethacrylate [PMMA], rigid gas-permeable
[RGP], soft hydrogel, silicone, and silicone hydrogel) and among
various patterns of wear (daily, conventional, extended, over-
night). Because individuals differ in susceptibility, these corneal
changes are not uniformly present, although patterns emerge.
This article reviews the normal consequences of the prolonged
closed-eye state and the superimposed consequences from contact
lens wear, particularly those due to hypoxia and hypercapnia. Tear
film instability, allergy and toxicity, or mechanical effects result-
ing from contact lens wear also contribute to some of these effects
but are difficult to separate and will not be specifically addressed.
The new silicone hydrogel contact lens may overcome some of
these complications.
PHYSIOLOGIC CHANGES DUE TO PROLONGED
EYELID CLOSURE
The preferred environment for the eye is created by an alternat-
ing period of opening and closing. Prolonged eyelid closure from
any cause triggers a cascade of biochemical, cellular, and micro-
bial events, culminating in inflammation, hypoxia, and dry-eye
states.6,7
In the closed-eye environment, the partial pressure of oxygen as
a percentage of oxygen in the atmosphere at the corneal surface is
reduced from 21% to approximately 8%. Prolonged eye closure
induces tear stasis, decreased tear volume, decreased oxygen
tension, increased carbon dioxide, a shift to an acidic pH, corneal
edema, corneal endothelial bleb response, increased corneal tem-
perature, decreased acetylcholine, and decreased corneal sensitiv-
ity.8 Analysis of the tear constituents in the closed eye confirms
that a subclinical inflammatory condition exists under an eyelid
during sleep.9 There are increases in total tear protein, secretory
IgA, and serum albumin; there is activation of complement and
plasminogen, production of chemokines, recruitment of polymor-
phonuclear cells (PMNs), and release of highly reactive substances
such as elastase and collagenase. Other major reflex tear compo-
nents, such as lysozyme, lactoferrin, and tear-specific prealbumin,
remain static.10 Eyelid closure also increases the microbial load on
the conjunctiva and lid margins.11
When the eye is open, the cornea is exposed to a partial pressure
of oxygen (Po2) of approximately 155 mm Hg and a partial
pressure of carbon dioxide (Pco2) of near zero mm Hg4 (Table 1).
In the anterior chamber, Po2 is estimated to be 55 mm Hg, and
Pco2 is estimated to be 40 mm Hg.4 There is normally a flow of
 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
TABLE 1. Ocular Environment in the Closed and Open Eye
Variable Closed Eye Open Eye
Cornea (pH) 7.39 7.55
Tears (pH) 7.25 7.45
Temperature (°C) 36.2 34.50
Tonicity (% NaCl) 0.89 0.97
O2 (mm Hg) 61.00 155.00
CO2 (mm Hg) 55.00 0.0
Modified from Vajdic CM, Holden BA. Extended-wear contact
lenses. In: Hamano H, Kaufman HE, eds. The Physiology of the
Cornea and Contact Lens Applications. New York, Churchill Living-
stone 1987:101–148; with permission.
oxygen onto the anterior corneal surface and an efflux of CO2 from
the surface.
When the eye is closed, the Po2 in the palpebral conjunctival
capillaries is approximately 60 mm Hg,12 one third that of the
pressure of the open eye. The Po2 decreases to approximately 40
mm Hg at the corneal surface because of corneal oxygen consump-
tion; this results in only a small oxygen flux onto the anterior
surface of the cornea. When the eye is closed, the palpebral
conjunctiva has a Pco2 similar to that of the aqueous humor, and
the resulting concentration gradient is negligible. Many investiga-
tors have observed significant individual variations in the levels of
open-eye and closed-eye responses to the hypoxia. Contributing
factors may include individual differences in corneal and crystal-
line lens oxygen requirements, endothelial structure and function,
tear chemistry, lid action, lens pumping, and physiologic lagoph-
thalmos. During sleep, the decrease in tear and stromal pH and the
increase in corneal temperature and tear osmolality may affect
corneal oxygen levels.
Mandell and Fatt13 were the first to report an increase in corneal
thickness (without contact lenses) during sleep, later measured to
be approximately 4%. Because of the osmotic stromal response to
the change in tear evaporation, the cornea returns to a baseline
thickness within 1 hour of eye opening and continues thinning
throughout the day.
Wearing soft contact lenses on an extended-wear basis mimics
prolonged and exaggerated eye closure. Corneal swelling during
continuous wear of hydrogel contact lens material also is cyclic,
reaching approximately 12% overnight and 4% during the day.
Zantos and Holden14 reported that the overnight swelling response
decreases with greater duration of continuous soft contact lens
wear.
Uncomplicated daily wear of soft contact lenses does not appear
to alter total protein or concentrations of secretory IgA and
complement. Sleeping in contact lenses, however, increases the
levels of total protein, secretory IgA, and complement to a greater
degree than sleeping without contact lenses.15
HYPOXIA AND HYPERCAPNIA FROM CONTACT
LENS WEAR
Fitting a contact lens on the eye leads to a significant reduction
in the oxygen supply to the cornea, in the range of 8% to 15%,
depending on the gas permeability of the lens material used. The
oxygen permeability of a contact lens is described in terms of the
rate of oxygen flow through a given area of the material. This rate
is given as Dk, where D is the diffusion coefficient of the material
and k is the solubility coefficient of the material, and it is generally
13
expressed as a whole number ⫻ 10⫺9 (cm ⫻ mL O2/s ⫻ mL ⫻
mm Hg). Oxygen transmissibility depends directly on this rate of
flow and is inversely related to the average thickness of the lens
(L).16 Thus, oxygen transmissibility is given as Dk/L, and the
higher the Dk value, the more permeable the lens is to oxygen.
The Po2 required by the human cornea for normal function is
considered to be at least 75 mm Hg,17,18 and therefore the oxygen
transmissibility necessary to avoid hypoxia in the closed eye is at
least 75 Dk/L. Extended-wear soft contact lenses need a Dk/L of
75 to 89 to avoid inducing edema.18,19 In open-eye conditions, the
corneal oxygen demand requires a Dk/L of at least 20, and
daily-wear soft contact lenses should have a Dk/L of 20 to 34 to
avoid inducing edema.18,19 Most thick or high-powered lenses or
extended-wear lenses do not meet these requirements. Another
way of looking at this is to define the minimum oxygen percentage
needed at the corneal surface to prevent corneal edema; this is
approximately 10% to 13%, compared with the normal 21%.18
Tear pumping is a supplementary route for providing oxygen to the
cornea. Investigators have found that there is a 10% to 20%
volume exchange per blink under an RGP contact lens, compared
with only a 1% volume exchange per blink under a soft contact
lens.20
CO2 transmissibility is directly related to O2 transmissibility.
The Pco2 in the anterior cornea varies depending on the transmis-
sibility of the contact lens, increasing to a maximum of approxi-
mately 40 mm Hg with PMMA lenses. During eye closure, corneal
Pco2 is always approximately 40 mm Hg because this is the
tension at the palpebral vasculature.21
If the oxygen decreases below a critical level, the cornea shifts
to anaerobic glycolysis using the Embden-Meyerhof pathway, in
which glucose is broken down to pyruvate and then to lactate.
Because lactate does not diffuse rapidly out of the cornea, the
consequence of decreased aerobic metabolism is stromal lactate
accumulation. Hypoxia thus creates a lowered epithelial metabolic
rate, an increase in epithelial lactate production, and an acidic shift
in stromal pH. The degree of stromal acidosis varies, depending on
the O2 transmissibility of the lens (i.e., Dk/L) and the buildup of
CO2 under the lens.
Contact lens wear therefore produces corneal hypoxia and
accumulation of CO2, both of which cause acidosis.22 The pH of
the epithelium, stroma, and aqueous humor decreases significantly
with contact lens wear when the Dk/L is less than 100. Hypoxia
causes substantial effects on the epithelium and stroma but has
limited or no direct effects on the endothelium and aqueous humor.
Carbon dioxide accumulation causes significant acidosis in all
compartments measured. Most of the acidosis occurs in the ante-
rior layers of the cornea and results from retardation of the normal
carbon dioxide efflux. Corneal acidosis promotes endothelial poly-
megethism, epithelial microcysts, corneal edema, striate lines,
infiltrative keratitis, and microbial keratitis.
After prolonged corneal hypoxia, there is depletion of the
glycogen reserves of the cornea, diminished adenosine triphos-
phate (ATP), and ultimately a slowing of the water transport
system in the endothelium. The combined effects of the accumu-
lation of lactic acid in the stroma and a decrease in the pumping
action of the endothelium result in increased corneal edema.
Epithelial Effects of Hypoxia
The effects of hypoxia and hypercapnia on the epithelium
include a decreased epithelial metabolic rate with decreased oxy-
The CLAO Journal, Vol. 28, No. 1, 2002
14 T.J. LIESEGANG
TABLE 2. Epithelial Changes Due to Hypoxia and Hypercapnia
from Contact Lens Wear
Metabolic rate decreased
Morphologic changes
Microcysts
Compromised junctional integrity
Epithelial defects
Neovascularization
Decreased corneal sensation
gen uptake, lactate accumulation, acidic shift, decreased ion pump-
ing, reduction in cell synthesis with enzyme shifts, and possible
changes in DNA and RNA. The clinically observed correlates
include morphologic changes, microcysts, compromise in junc-
tional integrity, epithelial defects, neovascularization, and de-
creased corneal sensation (Table 2). The compromised junctional
integrity is accompanied by diminished electrical potential and
reduced adhesion.8 In the short term, this can manifest clinically as
epithelial erosions, edema, ulceration, and warpage; and long-term
manifestations include formation of microcysts, bullae, vacuoles,
thinning with vascularization, increased fragility, and decreased
sensitivity. Effects on epithelial function include abnormal metab-
olism and decreased sensation. The effects on epithelial structure
include reduced nerve density, edema, epithelial thinning, abnor-
mal cell shapes, and microcysts.
Epithelial Metabolic Rate Reduction
With extended-wear soft contact lenses, the epithelial metabo-
lism is reduced because of a 15% decrease in oxygen uptake. The
technique of redox fluorometry confirms the reduced epithelial
metabolic rate, and other studies confirm the reduced mitotic rate
of the basal epithelial cells. Short-term contact lens wear causes a
temporary decrease in corneal oxygen flux; long-term wear causes
a sustained reduction.23 The decreased metabolic rate affects the
epithelial physiology, the cellular junctional integrity, and the
cellular reserves of glycogen. Glycogen becomes depleted, cell
synthesis is reduced, and corneal sensation is decreased. Lactate
accumulates between basal cells, causing a decrease in pH, and
there is an increase in intercellular spaces manifest as “Sattler
veil.” There is no intracellular edema, and the epithelium actually
thins by approximately 6%. With decreased pumping ability,
increased permeability of the epithelial cells can result in dehy-
dration. The synthesis of cytochrome P-450 arachidonic metabo-
lites causes an inflammatory response.24 In the rabbit model of
extended-wear soft contact lenses, Ren and colleagues25 found
increased limbal epithelial stem-cell proliferation, with a concom-
itant decrease in the proliferation of basal epithelial cells. They
hypothesized that increased stem-cell activity is a compensatory
mechanism for decreased central basal cell activity and may lead
to a depletion of the stem-cell reservoir.
Epithelial Morphology Changes
Wide-field color specular microscopy has been used to monitor
surface epithelial morphology during extended wear of conven-
tional hydrogel lenses and to identify changes in epithelial barrier
function.26,27 Suppression of mitotic activity and of the exfoliation
rate in the corneal epithelium with soft contact lens wear results in
a decrease in the number of superficial cells and a flattening of the
underlying cells.28 A shift in size toward larger surface cells
occurs, also indicative of a reduced exfoliation rate and possibly
contributed to by the relatively stagnant post-lens tear film and the
The CLAO Journal, Vol. 28, No. 1, 2002
FIG. 1. Changes in corneal epithelial cell size over time, as mea-
sured by surface specular microscopy, in patients wearing soft
contact lenses on a daily-wear (DWSCL) versus an extended-wear
basis (EWSCL). (Modified from Tsubota K, Hata S, Toda I, et al.
Increase in corneal epithelial cell size with extended wear soft
contact lenses depends on continuous wearing time. Br J Ophthal-
mol 1996;80:144 –147; with permission.)
dampening effect of the lens on blink-mediated shear forces from
eyelid movement.
With extended-wear soft contact lenses,26 the mean corneal
epithelial cell size is affected most. Because these mature cells
have fewer microvilli and less mucin, more sites are available for
possible bacterial adhesion. This also results in epithelial thinning,
decreased corneal oxygen flux, epithelial microcysts, and in-
creased fragility of the epithelial layer. Because of the basal-cell
flattening and the decrease in the number and thickness of epithe-
lial cells with extended-wear soft contact lenses, the epithelium is
thinned by 6% on average. Hypoxia delays apoptosis, or pro-
grammed cell death, and results in the retention of the superficial
cells. The epithelial thickness is reduced to nearly one third its
normal thickness in areas of contact lens bearing. A layer of wing
cells is absent, and the basal cells are compressed.29 There is an
increase in rate of cell mitosis in these lens-bearing areas. The
thickness returns to normal within a short time after discontinua-
tion of contact lens wear.30 Tsubota and co-workers31 demon-
strated that corneal epithelial cell size increases linearly with
increasing overnight wear and overall duration of hydrogel lens
extended wear (Fig. 1).
Changes in tear film during overnight contact lens wear increase
epithelial permeability, leading to further increases in epithelial
dehydration. Although most tissues swell with hypoxia, the cor-
neal epithelium becomes thinner. Redistribution of cellular water
apparently occurs, leading to local changes in the refractive index
that give rise to the Sattler veil.32,33 The Sattler veil is a corneal
haze in which halos appear around lights. The condition occurs
without changes in epithelial thickness and without uptake of
water. It is caused by an increase in light scatter at the level of the
corneal epithelium. Epithelial edema causes more forward scatter-
ing of light than stromal edema and thus has a more profound
effect on vision—sometimes termed “epithelial bedewing.” Other
terms describing this hypoxia-induced corneal edema include “cor-
neal misting”34 and “central circular clouding.”35 The Sattler veil
seems to result from an increase in the intercellular spaces of the
epithelium during hypoxia, which may be due to an increase in
lactate concentration, with a corresponding decrease in pH, be-
tween basal cells. Sattler veil is distinct from microcysts. With
RGP or PMMA contact lenses, the change usually occurs under the
 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
area of the contact lens. With soft contact lenses, the edema is
more diffuse and usually less prominent, and a Sattler veil is not
visible.
Epithelial Microcysts
Epithelial microcysts do not occur immediately with either daily
or extended-wear contact lenses and usually take 2 to 3 months to
appear. Occasionally they appear after relatively short periods of
disposable contact lens wear. After cessation of lens wear, the
microcysts increase in number before they disappear within 2 to 3
months.30,36
Epithelial microcysts are another sign of altered epithelial me-
tabolism.23 Epithelial microcysts were first observed in PMMA
lens wearers but also occur frequently with soft contact lenses, and
especially with extended wear. The occurrence of intraepithelial
cysts is a useful and reliable clinical indicator of a disorder of
epithelial cell growth from chronic corneal hypoxic compromise.
Although, for unclear reasons, epithelial microcysts also occur in
persons who do not wear contact lenses, the number is small,
usually less than 10 microcysts.
Epithelial microcysts are usually asymptomatic. Zantos36 and
others proposed that hypoxia was the primary cause, although this
hypothesis does not explain microcyst location in the midperiph-
eral region of the cornea. Microcysts tend to conform to an arcuate
pattern in the lower pupillary margin. They are seen in areas of
contact lens bearing and also may be related to epithelial trauma
and inadequate lens movement, with pockets of cellular debris.
Staining is observed when microcysts break on the surface, al-
though this usually has no effect on vision. With extended-wear
contact lenses, epithelial microcysts usually increase in number
and size over a period of weeks, until they reach a steady state. The
increase in numbers of microcysts after discontinuing contact lens
wear is due to the return of normal epithelial metabolism, with
more encapsulated cellular matter brought to the surface before
being eliminated.30 The presence of microcysts correlates with a
reduced epithelial mitotic rate and an increase in the regeneration
time of the epithelium (Fig. 2). Impaired cellular synthesis and
waste removal are features related to this altered metabolism.
Pathologic examination of microcysts shows degenerated epi-
thelial cells (apoptotic cells), probably from dysfunction of the
basal cells of the epithelium, with cellular degeneration and ly-
sis.37 Microcysts probably form in the basal epithelium and are
transported anteriorly as the epithelium grows in that direction.
They appear to be caused by metabolic stress and the altered
growth pattern of the epithelium due to the direct and indirect
effects of hypoxia or hypercapnia.
Microcysts may resolve with an increase in the oxygen trans-
missibility of the contact lens, a decrease in overnight wear of an
extended-wear lens, or a change from a soft lens to a rigid lens.
Switching to a disposable extended-wear lens or changing solu-
tions is not likely to be effective.
Compromised Junctional Integrity and Epithelial Defects
The maintenance of the electrical potential between the tear film
and the aqueous humor depends in part on superficial epithelial
tight junctions between the corneal epithelial cells. Contact lens
wear may compromise junctional integrity by loosening the epi-
thelial tight junctions, thus separating the corneal epithelial cells.
The increase in epithelial fragility can be measured with the
Cochet-Bonnet esthesiometer; the minimum pressure required to
15
FIG. 2. Changes in epithelial oxygen uptake, thickness, and num-
ber of microcysts after cessation of long-term wear of high-water
content hydrogel contact lenses, compared with control eye data
(dashed line). (Modified from Holden BA, Sweeney DF, Vannas A, et
al. Effects of long-term extended contact lens wear on the human
cornea. Invest Ophthalmol Vis Sci 1985;26:1489 –1501; with permis-
sion).
produce epithelial damage is measured with the esthesiometer and
demonstrated by fluorescein staining.38 Fragility is also manifested
by decreases in corneal electrical potential, punctate staining,
epithelial abrasion, and an increased risk of microbial infection.
The reduction in epithelial adhesion correlates with a decrease in
hemidesmosome synthesis.39 Suggested mechanisms of the prob-
lems with epithelial adhesion include a mechanical deformation of
basal cell shape or a hypoxia-induced increase in intracellular
calcium. There is a reduction in epithelial healing rate, probably
from reduced ATP production. Contact lens wear induces corneal
swelling and an epithelial inflammatory response related to the
synthesis of the cytochrome P-450 arachidonic acid metabolites
12(R) hydroxyeicosatetraenoic acid (12 R HETE) and 8(R) hy-
droxy-hexadecatrienoic acid (8 R HHDTrE).24,40 Time-dependent
epithelial increases in the production of these metabolites correlate
directly with the corneal inflammatory response, and the inflam-
matory response can be reduced by their inhibition. 12 R HETE is
a sodium-potassium ATP inhibitor and is a vasodilatory, chemo-
tactic, and angiogenic factor.
Using rabbit corneas, Imayasu et al41 showed that the Dk/L of
extended-wear contact lenses correlates with increased surface cell
desquamation and increased binding of Pseudomonas aeruginosa.
This effect occurred regardless of whether soft or RGP contact
lenses were worn, implicating oxygen transmissibility rather than
other factors, such as lens fit, in compromising the cornea and
enhancing the risk of infection. Solomon42 found that higher
infection rates in rabbits correlated with the amount of corneal
edema, which is related to oxygen transmissibility. In humans,
Fleiszig et al43 reported that exfoliated cells from extended-wear
soft contact lens wear bind more P. aeruginosa than those from
daily-wear contact lens wearers; hypoxia was the suspected cause.
Chronic hypoxia alone, however, is not the sole explanation
because corneal infections do not commonly develop in patients
wearing PMMA lenses. The interaction with the closed eye during
contact lens wear is probably also an important mechanism. Early
studies with high-Dk materials suggested that such materials may
The CLAO Journal, Vol. 28, No. 1, 2002
16 T.J. LIESEGANG
reduce the epithelial barrier function defects and hold promise of
eliminating this problem.44
Epithelial abrasions are attributed to low oxygen transmissibility
of the contact lens, with loosening of intercellular tight junctions
and separation of corneal epithelial cells. Superficial punctate
keratitis is a common complication of contact lens wear attributed
to hypoxia that results in the desquamation of stressed surface
cells. Superficial punctate keratitis appears as pits in the epithelial
surface and leads to the premature shedding of small groups of
cells45; it is commonly seen in association with the corneal
hypoxia from overwear of PMMA or extended-wear soft contact
lenses. Although hypoxia is a frequent etiologic factor, superficial
punctate keratitis also may occur for many other reasons, including
solution toxicity, edema, lens deposits, lens care products, lens fit,
lens surface or edge irregularities, foreign bodies, improper lens
insertion or removal, tear film disruption, and accumulated meta-
bolic waste products. The compromised epithelial integrity related
to hypoxia and other osmotic or mechanical factors increases the
likelihood of bacterial adherence.
Vital stains can demonstrate the loss of the corneal epithelial
integrity. Rose bengal, trypan blue, methylene blue, fluorexon, and
bromthymol blue have been used, but fluorescein is the most
commonly used stain for contact lens evaluation.3 The defects can
be superficial, moderate, or deep (into the stroma). There are
punctate stains, diffuse stains, linear stains, and dimple stains
(indentations in the surface). Defects also may develop in individ-
uals who do not wear contact lenses (especially with age), but most
cases occur with RGP contact lenses and, to a lesser degree, with
soft contact lenses. Staining seen at the 3- and 9-o’clock positions
results from reduced or incomplete blinking habits. Arcuate stain-
ing occurs because of a poorly polished intermediate lens zone or
edge; and dimpling occurs in tight-fitting areas.
A classification of epithelial defects caused by contact lenses
has been proposed by Watanabe.46 Variations include (1) superfi-
cial punctate keratitis, which can be diffuse or involve the lower,
3- and 9-o’clock, or upper cornea; (2) linear (arcuate or
pseudodendritic) complications; and (3) plane complications (in-
filtration, epithelial edema, erosion, ulcer, and neovascularization).
Most of these epithelial complications occur with PMMA (73%)
and RGP (33%) lenses but can be seen with soft contact lenses
(15%–22%) or with disposable soft contact lenses (3%). The major
causes of these epithelial defects include insufficient oxygen
supply, mechanical stimulation, and local inadequate tear film.
Epithelial adhesion to the basement membrane is also reduced
with extended wear of contact lenses.47 Overwear can result in
sloughing of the epithelium adherent to the posterior surface of the
contact lens; this can cause a circular hole in the epithelium that
may take weeks to heal. RGP lenses have been demonstrated to
induce tear-film instability associated with damage to the ocular-
surface epithelium and mucin layer.48 In RGP wearers, abnormally
shortened conjunctiva break-up time produces ocular surface dam-
age, demonstrated as 3- and 9-o’clock staining.
Neovascularization
Neovascularization (angiogenesis) is produced as a response to
a metabolic or an angiogenic factor by mature existing blood
vessels. New vessels form from existing vascular endothelium that
retains the capacity to revert to primitive vascular mesenchyme.
Vasostimulatory factors initiate new growth by a direct effect on
The CLAO Journal, Vol. 28, No. 1, 2002
the endothelial vascular cells and determine the direction of
growth.
This response to contact lens wear has been described variously
as vascularization, neovascularization, limbal hyperemia, vessel
penetration, vasoproliferation, vascular pannus, or vascular re-
sponse. It is a normal (albeit undesirable) vascular response to
contact lens wear, and some vascular response occurs with almost
all contact lenses. There are several steps in the neovascularization
process: (1) Limbal hyperemia, a dilatation of existing limbal
capillaries, is reversible and is common with hydrogel soft contact
lenses worn overnight but can also occur with any tightly fitting
contact lens; (2) superficial neovascularization (pannus) is the
progression of limbal hyperemia and the penetration of vessels into
the superficial cornea; (3) deep stromal neovascularization results
from chronic hypoxia that may progress to an active inflammatory
or fibrovascular deep pannus; and (4) there may be an intracorneal
hemorrhage.
Limbal vessel dilatation has been identified as the initial clinical
sign in corneal vascularization. Chronic limbal vessel dilatation
could provide an active vascular plexus adjacent to the cornea on
which stimuli promoting vessel growth could act. Although cor-
neal vascularization has been reported during extended wear of
disposable and conventional lenses, quantitative and comparative
data are lacking. Because hypoxia is believed to be one of the
major causal factors of vascularization, the extent of corneal
vascularization with disposable and conventional contact lenses of
similar oxygen transmissibility would be expected to be similar.
New contact lenses with high oxygen transmissibility are promis-
ing developments for reducing these stimuli of vessel dilatation
and growth.
The prevalence of neovascularization is low with RGP or
PMMA contact lenses, more common with daily-wear soft contact
lenses, higher with extended-wear soft contact lenses, and very
high with aphakic extended-wear lenses. Neovascularization is
more common with soft contact lenses than with microcorneal
lenses because the soft contact lens covers the entire cornea.
Additionally, the tear film beneath the soft contact lens is mini-
mized because of the relatively tight fit required to keep the lens in
position. Vascularization is always greater in the superior limbus
and is directly related to lens oxygen transmissibility. It is espe-
cially common with large and thick contact lenses and results in
development of new corneal vessels in up to 20% of wearers.49
The vascularization associated with RGP lenses is caused by
continual 3- and 9-o’clock staining; the incidence of neovascular-
ization is low, related most often to limbal coverage by an
eccentrically riding contact lens or persistent overwear.50
Vascular regression occurs after lens removal, leaving “ghost
vessels” in the cornea. Occasionally, intrastromal opacities can
occur, consisting of lipid droplets and inflammatory cells adjacent
to the blood vessels in the deep stroma near the Descemet mem-
brane. Although these opacities are caused by inflammatory cells,
the cooperation of stromal keratocytes is necessary.
No single theory can account for corneal neovascularization;
rather, several factors may contribute.51 Proposed theories take the
following aspects into account: metabolic factors (hypoxia, lactic
acid, edema, stromal softening); angiogenic suppression (necessity
of substances that inactivate the normally present angiogenic
inhibitors); vasostimulation (locally generated or introduced vaso-
stimulatory factors such as free cellular elements, humoral com-
ponents, epithelial cell factors, or extrinsic factors); and neural
 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
FIG. 3. Proposed contributions of corneal epithelium-derived ei-
cosanoids to hypoxia-induced ocular inflammation. (From Mieyal
PA, Bonazzi A, Jiang H, et al. The effect of hypoxia on endogenous
corneal epithelial eicosanoids. Invest Opthalmol Vis Sci 2000;41:
2170 –2176; with permission.)
control (mediation of the vascular response to contact lens wear by
contact lens-induced changes to corneal neurology). Another way
of categorizing stimuli that can promote vessel penetration into the
normally avascular cornea includes nutritional, inflammatory, me-
chanical, traumatic, and toxic factors. One or all of these stimuli
are present during contact lens wear, particularly overnight wear.
Whatever classification system is used, the most important factor
is contact lens-induced tissue hypoxia, which induces corneal
edema and stromal softening. The additional mechanical injury to
the epithelium results in the release of enzymes, migration of
inflammatory cells into this site, and release of vasostimulatory
agents causing vessels to grow in that direction.
Soft contact lens-induced hypoxia has been shown to stimulate
the metabolism of arachidonic acid by a nicotinamide adenine
dinucleotide phosphate (NADPH)– cytochrome P-450 monooxy-
genase, hydroxyeicosatrienoic acid (12 R HETrE), a proinflamma-
tory and angiogenic factor (Fig. 3).52 Biologic actions of this factor
result in an increase in barrier permeability, vasodilatation, poly-
morphonuclear chemotaxis, and vascular endothelial cell mitogen-
esis. Routine contact lens wear is associated with inflammatory
reactions and, even in asymptomatic patients, can induce release of
some proinflammatory cytokines, including interleukins 6 and 8.
Hypoxia creates an environment in which epithelial cyclooxygen-
ase activity is severely suppressed, whereas metabolizing activity
of cytochrome P-450-arachidonic acid or 12-lipoxygenase is main-
tained or enhanced. The 12 R HETE produced by the corneal
epithelium acts intracellularly to promote corneal edema, whereas
12 R HETrE acts in a paracrine manner to initiate an inflammatory
cascade that can elicit neutrophil chemotaxis and neovasculariza-
tion of the cornea.52
Corneal Hypoesthesia
Contact lens wear is associated with a decrease in corneal
sensation, as measured by esthesiometry. Corneal touch thresholds
differ with the various types of contact lens (Fig. 4). Within 1 day,
those wearing PMMA contact lenses experience a 200% increase,
soft contact lens wearers experience a 50% increase, and those
wearing high-water content extended-wear soft contact lenses
experience a 10% increase of touch thresholds.
Decreased corneal sensation is not usually associated with RGP
or any high-oxygen transmissible contact lenses. Sensation returns
17
FIG. 4. Comparative rates of sensory loss among three types of
contact lenses during 12 hours of wear. (Modified from Millodot M.
Effect of the length of wear of contact lenses on corneal sensitivity.
Acta Ophthalmol 1976;54:721–730; with permission.)
to normal in a few hours after short-term contact lens wear.53,54
Eyelid closure during sleep also causes a reduction in corneal
sensitivity.55
Long-term wear of contact lenses causes a more pronounced
loss of sensation that is more persistent. There are individual
variations, and sensitivity tends to return with cessation of contact
lens wear. Decreased sensation is milder with soft contact lenses
and the return of sensation is more rapid, compared with PMMA
lenses. Extended wear results in pronounced decreases, but recov-
ery can occur. After 5 to 7 years of wear, sensation may be
permanently decreased with PMMA lenses, and the situation is
possibly similar with soft contact lens wear.
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.10 It does not appear
to be a consequence of edema. The specific end mechanism may
be related to acetycholine concentrations or choline acetyltrans-
ferase, the enzyme responsible for the synthesis of acetycholine.
Epithelial acetylcholine is a neurotransmitter to corneal nerves and
is decreased in hypoxia. There is also a suggestion of a lack of
trophic function for the ciliary nerves in the maintenance of
epithelial properties.49 A hypoxia-induced decrease in neural
transmission or neural damage or a sensory adaptation to mechan-
ical stimulation also may occur. Contact lenses appear less likely
to affect corneal sensation if oxygen transmissibility is high, and
most studies support the concept that hypoesthesia depends on the
epithelial oxygen tension level.56 Corneal sensation may be a more
sensitive test than refraction, keratometry, or pachometry for
monitoring the status of corneal health during contact lens
wear.10,56 Considerable individual variation exists, with many
unknown factors, however.
STROMAL EFFECTS OF HYPOXIA
The short-term effects of hypoxia and hypercapnia on the
stroma include stromal acidosis, edema, and striae. Long-term
effects include stromal thinning, infiltrates, neovascularization,
and corneal shape alterations8 (Table 3).
Stromal Acidosis
During contact lens wear, the stroma undergoes a decrease in pH
from the effects of metabolic and respiratory acidosis occurring in
The CLAO Journal, Vol. 28, No. 1, 2002
18 T.J. LIESEGANG

TABLE 3. Stromal Changes Due to Hypoxia and Hypercapnia
from Contact Lens Wear
Stromal acidosis
Stromal edema
Stromal thinning
Neovascularization
Corneal shape alterations
the epithelium and diffusing into the stroma (Fig. 5). Metabolic
acidosis is caused by the 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 carbon diox-
ide. Thus, both hypercapnia and hypoxia lead to stromal acidosis.4
Corneal epithelial and aqueous acidification during contact lens
wear in rabbits appears similar to the stromal acidification mech-
anism in humans, and this animal model has been used in several
studies.57
In closed-eye conditions, the normal pH of the human corneal
stroma is similar to that of blood (7.39) because of diffusion of
CO2 from the palpebral conjunctiva into the cornea.4 Under
open-eye conditions, the human stromal pH increases by 0.15 to
7.55. It may decrease by as much as 0.25 during wear of soft
contact lens of nearly zero oxygen transmissibility. Wearing thick,
low-water content soft contact lenses can produce a stromal pH of
7.15. Under closed-eye conditions, hypercapnia is always present,
with or without contact lens wear. Thus, the degree of corneal
hypoxia in contact lens wear is the only significant variable in
stromal acidosis.
The contact lens restricts oxygen at the anterior corneal surface.
Hypoxia decreases ATP production by the usual aerobic break-
down of glucose in the corneal epithelium. This causes a compen-
satory shift to the Embden-Meyerhof anaerobic glycolytic pathway
in epithelial cells. Smelser and Chen58 found increased corneal
lactate concentrations after corneal hypoxia. Klyce59 observed the
connection between increased corneal lactate values and the ob-
served swelling of the stroma during contact lens wear. Because
lactate cannot penetrate the superficial epithelium, all the newly
formed lactate accumulates between epithelial cells, subsequently
diffuses posteriorly into the stroma, across the endothelium, and
finally is washed out into the aqueous humor. Additionally, lactic
acid creates an osmotic load that is balanced by increased move-
ment of water into the stroma. The sudden influx of water cannot
be matched by the removal of water from the stroma by the
endothelial pump. Therefore, although the stromal edema appears
to be entirely due to lactate accumulation from hypoxia, the
decreased stromal pH (stromal acidosis) is a result of both hypoxia
and hypercapnia. This stromal acidosis also reduces the deswelling
response that occurs after corneal insult.
Contact lens hypoxia may correlate with the activity of lactate
dehydrogenase (LDH) in the cornea.60 With RGP wear, the LDH
isozyme appears to switch from the aerobic type to the anaerobic
type and return to normal over time. Tear LDH concentrations may
provide a method for ongoing assessment of the tolerance of the
ocular surface to contact lens wear.60
A contradictory study showed that chronic RGP contact lens
wear is associated with altered glucose-lactate metabolism in the

FIG. 5. Mechanism of pH reduction during contact lens wear. (A) Normal eye. Metabolic production
of lactate and hydrogen ions by the epithelium is at its basal rate because oxygen is readily available.
Carbon dioxide rapidly diffuses down a steep concentration gradient from aqueous to tears. (B) Open
eye with contact lens. Epithelial oxygen and possibly aqueous Po2 are reduced, which stimulates
lactate production (osmotically causing corneal swelling) and hydrogen ion production. Additionally,
CO2 efflux from the cornea is impeded, leading to higher stromal Pco2 which, when hydrated,
produces a hydrogen and a bicarbonate ion. Thus, the effects of hypoxia and hypercapnia on stromal
pH are additive. In the closed lens-wearing eye, epithelial Po2 is decreased and corneal Pco2 is
increased further because conjunctival Po2 ⬇ 55 mm Hg and Pco2 ⬇ 38 mm Hg. (From Bonanno JA,
Polse KA. Effect of rigid contact lens oxygen transmissibility on stromal pH in the living human eye.
Ophthalmology 1987;94:1305–1309; with permission.)

The CLAO Journal, Vol. 28, No. 1, 2002

 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
cornea and the aqueous humor. Increased concentrations of lactate
were found in the epithelium, but decreased lactate concentrations
were found in the stroma and aqueous humor, for lenses with a low
Dk/L.61 No increase in epithelial lactate concentration, however,
was observed in a study of a hyper-oxygen transmissible test lens
(Dk/L ⫽ 125); thus, these lenses remain promising.44 These
authors suggest that increased stromal lactate accumulation cannot
account for persistent stromal edema in chronic extended wear of
RGP lenses. They suggest that this effect appears to be indepen-
dent of lens-oxygen transmissibility and may thus represent a
prolonged mechanical effect of contact lens wear itself.
Stromal Edema
The cornea is 78% water, and the stroma constitutes 90% of the
thickness of the cornea, with a tendency to imbibe water. In the
pump-leak model of the endothelium, water is moved out of the
stroma by a sodium-potassium-ATPase and bicarbonate ion pump.
Both an endothelial pump-leak and a minor epithelial pump-leak
occur. During sleep, edema occurs in every human cornea, with an
increase in thickness of 4%, whereas on waking, a reduction in
thickness occurs. Superimposing a contact lens adds to this fluc-
tuation in corneal thickness, which is related to hypoxia. Stromal
edema occurs because of a break in epithelial or endothelial
barriers, a reduction in pump function (mainly endothelial), or an
increase in osmotic activity (imbibition pressure) of the stromal
compartment.
Measurement of central corneal swelling is the most commonly
used short-term index of the physiologic compatibility of a contact
lens, because a change in corneal thickness is inversely related to
the average oxygen transmissibility of the contact lens.62 The
response begins within half an hour after contact lens insertion and
generally peaks within 3 hours. The degree of corneal edema
associated with long-term contact lens wear appears to decrease
with time. The swelling response to contact lens wear is generally
presented as a population mean; however, there is significant
variation among individuals.
When the oxygen tension of the anterior part of the eye is
restricted by contact lens wear, this provokes a change in epithelial
cellular lactate production rate. The principal drainage route for
lactate is across the stroma through the endothelium into the
aqueous humor. Lactate is a well-dissociated acid; thus, it is
principally present in the stroma as its sodium salt. The presence
of stromal sodium lactate has an osmotic effect. The change in
stromal water content due to the osmotic (imbibition) pressure of
the lactic acid in turn determines the thickness of the stroma. The
degree of stromal thickness observed in anoxia can be wholly
accounted for theoretically by the changes in lactate levels. Factors
other than hypoxia contribute to corneal edema, including temper-
ature, humidity, osmolality, carbon dioxide of the tears and cornea,
mechanical effects, and inflammation, but these effects are prob-
ably minimal.8 Klyce59 proved by complex mathematical models
and by laboratory techniques that anoxia provokes stromal swell-
ing. The combination of hypoxia and excess carbon dioxide may
be the most significant contribution.8 Alternatively, however,
studies on RGP extended wear and stromal swelling in rabbits61
found that increased stromal lactate accumulation from contact
lens wear could not account for persistent stromal edema with
chronic extended wear of RGP lenses. These authors thought that
stromal edema may be independent of oxygen transmissibility of
19
FIG. 6. The relationship between corneal edema and lens oxygen
performance showing the Holden-Mertz criterion of 87 Dk/L units
for avoiding edema during overnight lens wear. (From Brennan N,
Efron N. What to expect with new high-Dk soft extended wear
lenses. Contact Lens Spectrum Suppl 1999;August:4s– 8s; with
permission.)
the lens and may represent the prolonged mechanical effect of lens
wear itself.
With extended-wear soft contact lenses, the increase in stromal
thickness occurs significantly more in the center than in the
periphery because of hypoxia. With current soft contact lenses and
RGP lenses, unadapted patients usually have daytime corneal
edema of 1% to 6% and nighttime edema of 10% to 15%, as
measured on awakening. With extended-wear lenses, overnight
edema averages 10% to 12%. If the soft contact lens water content
is increased to the maximum, it is possible to maintain normal
corneal thickness, at least during the day. After weeks of soft
contact lens wear, the pattern of daytime thinning of the cornea is
also reduced, possibly from adaptation.
Extended wear of RGP lenses usually induces less central
edema than extended wear of soft hydrogel contact lenses. Other
factors that influence corneal thickness, such as reflex hypotonic
tearing or a long-term physical thinning of the stroma, however,
can introduce an artifact into measurements of corneal thickness,
in long-term contact lens wearers. The degree of corneal swelling
induced by contact lenses varies markedly among individuals, and
adaptation is a confounding variable. With RGP lenses, as the
oxygen transmissibility is increased to 90 to 100 Dk/L units, the
increased thickness becomes difficult to detect, and there is no
detectable clinical gain with Dk/L values in excess of these values
(Fig. 6).
Striae and folds that appear during overnight contact lens wear
are a function of the oxygen transmissibility of the lens and the
oxygen uptake rate of the cornea. Grades of edema can be
assigned.2 Posterior striae indicate an acute change in corneal
thickness. Striae occur at 5% to 7% stromal edema and represent
fluid separation of vertically arranged collagen fibrils in the pos-
terior stroma. Zantos and Holden63 measured the average critical
level of stromal swelling for the appearance of striae at 4.5% for
vertical and 3.8% for horizontal striae. The folds appear as black
lines in the posterior stroma, observed if 10% to 15% stromal
swelling is present, and represent physical buckling of the poste-
rior stromal layers of the Descemet membrane. There is an alter-
ation to the topography of the endothelial layer as seen in specular
reflection. Haze appears at 15% stromal edema and represents an
The CLAO Journal, Vol. 28, No. 1, 2002
20 T.J. LIESEGANG
advanced form of striae, with gross separation of collagen fibers
through the full thickness of the stroma.
Holden and Mertz18 reported that an oxygen value of 12%
(compared with the normal 21% at sea level) is required to avoid
stromal edema for daily wear of contact lenses; and 18% is
required for extended-wear lenses.64 Therefore, a Dk/L of approx-
imately 70 to 90 was required for extended wear, and a Dk/L of 34
was required for daily wear.
Corneal acidosis also reduces corneal hydration control as
measured by the rate at which the thickness of the cornea decreases
exponentially after an increased hydration load.65 The relation
between recovery and corneal pH is relatively unchanged for pH in
the physiologic range but decreases notably when pH is below the
physiologic range (7.4 –7.65). The deswelling rate is different for
soft and RGP contact lenses and for patients with no previous
contact lens wear. Years of contact lens wear could possibly result
in a 12% loss of ability to recover.
A corneal stress test for extended wear42 has been suggested.
Measuring corneal swelling after 1 night of wearing extended-
wear soft contact lenses may identify those patients whose corneas
are at risk for significant oxygen deprivation during overnight
contact lens wear. Corneal swelling of 5% or less seems to indicate
that the cornea can tolerate 7 nights of extended wear.
The corneal edema varies with the material and design of the
contact lens. PMMA causes swelling in the area covered by the
contact lens (steeper in that area), whereas the soft contact lens
affects the entire cornea (with less effect on corneal topography or
power),66 and the Sattler veil is generally absent in soft contact
lens wearers. The anoxic swelling may subside over time, although
the reasons are unknown. Wearers of PMMA contact lenses show
three types of response67: (1) Some individuals may demonstrate
maximum stromal swelling of 2% to 4% during the first day of
wear but no swelling after 2 weeks of wear; these individuals have
adequate levels of tear exchange and corneal oxygenation and
suffer only from changes in tear osmolarity. (2) Other PMMA
wearers may have a maximum swelling of 5% to 8% during the
first days of wear, with a decrease to a lower level after 2 weeks
of wear; these individuals are usually able to wear contact lenses,
but any further problem is superimposed on the initial problem of
swelling, and contact lens wear becomes intolerable. (3) Some
individuals may have greater than 8% stromal swelling and are
unable to wear the contact lenses beyond 6 hours the first day. In
the third group, oxygenation is inadequate, and this level of
response is usually provoked by a grossly tight fit; wearing time is
restricted, and problems are more common in this group because
they are always at risk for overwear syndrome.
Because swelling is a function of the ability of the lens material
to transmit gases, lens thickness and water content are important
criteria in soft contact lens wear. Large variability in patients
exists, although the following observations have been made: (1)
thick hydrogen lenses provoke more stromal swelling than thin
lenses; (2) the extent of swelling declines with time; (3) the extent
of swelling rarely exceeds the maximum amount that can be
provoked by anoxia alone (8%); (4) the use of thin lenses causes,
on average, less than 1% stromal swelling; and (5) swelling is
much greater with extended wear of soft contact lenses, which
results in increased levels of corneal thickness during periods of
sleep.
The CLAO Journal, Vol. 28, No. 1, 2002
FIG. 7. Decrease in stromal thickness of the lens-wearing eye after
cessation of lens wear, indicating true edema, apparent edema, and
stromal thinning versus control eye data (dashed line). (Modified
from Holden BA, Sweeney DF, Vannas A, et al. Effects of long-term
extended contact lens wear on the human cornea. Invest Ophthal-
mol Vis Sci 1985;26:1489 –1501; with permission.)
Stromal Thinning
Whereas stromal edema is an acute response to contact lens
wear, stromal thinning is a chronic pathophysiologic change in
patients who have worn contact lenses for years. Thinning by 2%
may be a sequela of chronic stromal edema correlated with
degeneration and possible death of stromal keratocytes.68 Imme-
diately after contact lens removal, the stromal thinning is masked
by superimposed edema; the thinning becomes apparent only 2
days after cessation of contact lens wear (Fig. 7). Less stromal
thinning is associated with a thinner initial stroma, lower epithelial
oxygen uptake rate, and less endothelial polymegethism before
lens wear. Unlike the recovery of the epithelium, recovery of the
stroma from chronic edema is slow. Both stromal edema and a
subsequent 4.8% reduction in stromal thickness were recorded
with long-term extended wear of hydrogel lenses.30 Continuation
of stromal thinning was reported up to 6 months after cessation of
contact lens wear.
The causes of corneal thinning probably involve the losses of
stromal keratocytes and mucopolysaccharide.68 Chronic edema
induces morphologic changes in the stromal keratocytes, manifest-
ing as functional changes in the ability of these cells to synthesize
collagen, glycoproteins, and proteoglycans. Another possible
cause is dissolution of stromal tissue, perhaps due to the effects of
lactic acid on the stromal mucopolysaccharide ground substance.8
Stromal keratocytes lose their ability to synthesize new stromal
tissue because of hypoxia and the indirect effects of chronic
induced-tissue acidosis due to accumulation of lactic acid and
carbonic acid. Confocal microscopic examination of extended-
wear soft contact lens patients showed reduced stromal keratocyte
density.69 Additive mechanisms include hypoxic, cytokine-medi-
ated, or mechanical effects. Hyper-reflective keratocyte nuclei
were also reported.70 With confocal microscopy, a new type of
chronic stromal change also was observed, with highly reflective
panstromal microdot deposits in the corneal stroma.71 This depo-
sition is more common with long-term wear of contact lenses and
more common with soft lenses than with RGP lenses. This con-
dition may be an early stage of corneal disease, but its clinical
significance is unknown. No data are yet available comparing the
 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
effects of conventional and disposable contact lenses on stromal
thickness during long-term wear.72
A study with the Orbscan (Orbscan Inc., Salt Lake City, UT)
topography system73 showed that the mean corneal thickness in
the center and in eight peripheral areas was significantly reduced
by approximately 30 to 50 ␮m in long-term soft contact lens
wearers compared with noncontact lens wearing control subjects.
Corneal Shape Alterations
Contact lens wear can result in corneal distortion or warpage.
Multiple other terms have been used in the literature to describe
these changes, including “indentation,” “steepening,” “flattening,”
“sphericalization,” “imprinting,” and “wrinkling.” These changes
are predictable to the extent that contact lenses can be used to
reduce the cone protrusion in keratoconus and in orthokeratology,
which is the controversial practice of fitting progressively flatter,
reversed-geometry tight-fitting RGP lenses, with the aim of flat-
tening the cornea to reduce myopia.
Videokeratopographic mapping techniques reveal that all forms
of contact lens wear are capable of inducing changes in corneal
topography. Topographic abnormalities were detected in 75% of
corneas with PMMA lens wear, 57% with RGP lens wear, 31%
with daily-wear soft lenses, and 23% with extended-wear soft
lenses, compared with 8% of normal corneas without contact lens
wear.74 These changes can cause spectacle blur or contact lens
decentration. Generally, contact lenses with high oxygen transmis-
sibility induce little warpage.75 Corneal topographic changes with
contact lenses have been reviewed by Ruiz-Montenegro et al.74
Significant changes occur with RGP contact lenses and occasion-
ally with daily-wear or extended-wear soft contact lenses. Many
different topographic patterns can result from contact lens wear,
but most involve flattening in areas of lens bearing. The changes
correlate with the resting position of the RGP or PMMA lenses and
entail flattening beneath the decentered contact lens and possible
adjacent steepening, usually detectable only with computer-as-
sisted topographic analysis. Changes also occur in the overall
curvature; and central clouding occurs initially with PMMA
lenses, with induced central steeping and myopia.76 With PMMA
lenses, a central flattening occurs later, with reduction in myopia.
RGP lenses have the same effect but to a lesser extent, which is
proportional to the oxygen transmissibility of the contact lens.
Changes in corneal asymmetry also take place with contact lens
wear. The surface asymmetry index (SAI), a quantitative measure
of the radial symmetry of the four central videokeratoscope mires
surrounding the vertex of the cornea, is higher with PMMA, RGP,
and extended-wear soft contact lenses. In addition, there are
changes in corneal regularity. The surface regularity index (SRI) is
a measure of central and paracentral corneal irregularity derived
from the summation of fluctuations in corneal power that occur
along semimeridians of the 10 central videokeratoscope mires. The
SRI is high with PMMA and RGP lenses, and occasionally also
with soft lenses.
Corneal wrinkling may manifest with the appearance of a series
of deep parallel grooves in the cornea that give the impression of
a wrinkled cornea.77 There may be signs of corneal indentation, in
which the impression of the contact lens edge is evident on the
cornea. Other patterns can occur, including central irregular astig-
matism, radial asymmetry, changes in the axis of astigmatism, and
reversal of the normal pattern of progressive flattening from the
center to the periphery.
21
When PMMA lenses first became available, the main problems
encountered were central corneal clouding, 3- and 9-o’clock stain-
ing, and corneal distortion.8 Approximately 30% of PMMA lens
wearers manifest corneal distortion that can be clinically signifi-
cant.78 Distortion (warpage) with PMMA lenses is caused by a
combination of central corneal edema (due to hypoxia) plus
superimposed mechanical pressure from the contact lens or the
eyelid on the softened cornea, and also by mucus binding beneath
the rigid lens. Metabolic factors such as oxygen tension may also
contribute. The central cornea steepens with PMMA wear. Such
steepening may be more than the circadian changes that have been
observed,79 in which the cornea flattens again during periods of
sleep after PMMA lens wear, although baseline curvature is not
achieved before the next period of lens wear. Over the first year of
PMMA lens wear, the induced corneal steepening gradually de-
creases and the cornea may eventually become flatter than its prefit
value.49 The curvature changes are more apparent in the horizontal
than in the vertical meridian.80,81 Changes are less marked with
soft contact lenses, which induce a slight corneal flattening in the
first 2 or 3 weeks, followed by a period of relative steepening.
Although changes in corneal shape and reduction of refractive
error are touted as permanent effects in the practice of orthokera-
tology, cessation of PMMA lens wearing is followed by large
fluctuations in corneal shape and refractive error. The myopia of
most subjects eventually returns to prelens-wear levels.82 The
induced changes in corneal topography and refractive state may
remain unpredictable, and with long-term wear, this molding effect
may lead to loss of regularity, resolving power, and visual func-
tion. The prognosis varies and depends on magnitude and duration
of lens-induced deformation forces. The cornea usually returns to
its original shape over months, but sometimes the changes are
irreversible. Changes in shape are less common with soft contact
lenses and usually require corneal topography examination to
detect or monitor.
The Orbscan topography system73 demonstrated that the mean
corneal thickness was significantly reduced in long-term soft
contact lens wear by 30 to 50 ␮m, compared with normal eyes
without contact lenses. There was no correlation between central
thickness and the degree of myopia detected. Corneal curvature
was significantly steeper in the eyes wearing soft contact lenses
than in normal eyes. No difference in mean corneal astigmatism
was noted. The SRI and SAI were significantly greater in the
contact lens wearers than in the control group. The authors con-
cluded that long-term soft contact lens wear (average of 13 years)
appears to decrease the entire corneal thickness and to increase the
corneal curvature and surface irregularity. This may be caused by
thinning of the epithelium and stroma due to chronic edema of the
stroma and biochemical changes. Alternatively, it may be related
to chronic exposure to a hyperosmotic tear film or to increased
apoptosis of keratocytes and epithelial cells from chronic micro-
trauma and hypoxia. The increased curvature could be a contact
lens-induced ectasia (similar to forme fruste keratoconus).
ENDOTHELIAL EFFECTS OF HYPOXIA
The additive effects of hypoxia and hypercapnia alter the
stroma. This induction of stromal acidosis has both short-term and
long-term ramifications for endothelial function. Initial contact
lens wear causes transient endothelial blebs and folds. Chronic
hypoxia disturbs endothelial cell stability and produces poly-
The CLAO Journal, Vol. 28, No. 1, 2002
22 T.J. LIESEGANG
TABLE 4. Endothelial Changes Due to Hypoxia and Hypercapnia
from Contact Lens Wear
Endothelial blebs
Polymegethism
Endothelial cell density change
Endothelial function change
megethism, pleomorphism, bedewing, guttata, and possibly cell
death (Table 4). Endothelial polymegethism is a relatively perma-
nent effect of inadequate oxygen permeability8 and is prevalent
with all contact lenses. The coefficient of variation for cell size is
high with all types except RGP lenses. The effect on endothelial
function appears to be minimal, although the functional reserve at
times of stress may be reduced.
Endothelial Blebs
Before 1977, the endothelium was thought to be immune to the
effects of contact lenses because it received its nourishment from
the aqueous. Zantos and Holden,83 however, noted that the endo-
thelial mosaic undergoes a dramatic alteration within minutes of
insertion of a contact lens, especially when the oxygen transmis-
sibility of the lens is low. Endothelial blebs appear as black,
nonreflecting areas in the endothelial mosaic and as an increase in
separation between cells. Blebs consist of endothelial swelling,
with subsequent changes in the contours of cell membranes.72
Initially, this appears as if cells had fallen off the posterior surface
of the cornea. The phenomenon is observed within minutes after
insertion of the lens, peaks at 20 to 30 minutes, and subsides to low
levels after 45 to 60 minutes, with only a few blebs visible at other
times. Due to adaptation, the response is reduced with continual
contact lens wear.
Blebs can be produced by contact lens wear combined with
anoxia or by passing a nitrogen gas mixture containing 10%
carbon dioxide and 21% oxygen through a goggle. Because the gas
mixture does not produce stromal swelling (there is no hypoxia),
the common factor is the production of stromal acidosis. Thus,
blebs resulting from contact lens wear appear to be a consequence
of hypoxic acidosis and an accumulation of carbon dioxide be-
cause of a diffusion barrier, rather than because of hypoxia per
se.84 The carbonic and lactic acids may alter the physiologic status
of the environment surrounding the endothelial cells; this induces
changes in membrane permeability or pump activity, resulting in
net movement of water into endothelial cells, with resultant de-
velopment of blebs. Both endothelial blebs and stromal acidosis
occur faster with hypercapnia than with hypoxia. The intracellular
endothelial pH is the common factor.
Pathologic examination of blebs shows edema of the nuclear
endothelial cells, with intracellular fluid vacuoles and fluid space
between cells.85 There is localized edema of groups of endothelial
cells, which bulge toward the aqueous.
The bleb response is universal among contact lens wearers
within 10 minutes after insertion, but there is variation in response.
The blebs also occur during sleep and can be observed on awak-
ening.86 To a similar extent, blebs occur with conventional and
disposable contact lenses of similar oxygen transmissibility, but
their occurrence is minimal or absent with silicone elastomer
contact lenses. There is also an increase in the number of blebs in
the late evening in patients with extended-wear soft contact lenses.
The overall number of blebs can be seen to decrease over the initial
8 days of extended wear. Despite their dramatic clinical appear-
The CLAO Journal, Vol. 28, No. 1, 2002
ance, 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.87
Polymegethism
Polymegethism refers to a greater-than-normal variation of
corneal endothelial cell size, resulting in a layer of large and small
cells. The degree of endothelial polymegethism is measured by the
coefficient of variation of endothelial cell size, a dimensionless
ratio calculated by dividing the standard deviation of the areas of
the cells in a defined field by the arithmetic mean of the areas of
all cells in that field. For endothelial cells, polymorphism (or
pleomorphism) refers to variations in cell shape distinct from the
classical, uniform six-sided endothelial cell appearance. Pleomor-
phism can be defined as an increase in the proportion of nonhex-
agonal cells on the monolayer and usually accompanies poly-
megethism.
Polymegethism is a normal phenomenon of aging but is accel-
erated with contact lens wear correlates with hypoxia. MacRae et
al88 and, recently, Lee et al89 reported an association between
significant increases in endothelial polymegethism and pleomor-
phism and reduction in endothelial cell density. MacRae and
colleagues hypothesized that polymegethism and pleomorphism
precede reduced cell density because all three features were ob-
served in long-term wearers. Polymegethism has been observed
and quantified with daily- and extended-wear soft, RGP, and
PMMA contact lenses and with age. Only the silicone elastomer
contact lens, which has high gas permeability, does not lead to
significant endothelial polymegethism. The degree of polymegeth-
ism was shown to correlate with duration of contact lens wear and
degree of hypoxia by many but not all investigators. Extended
wear of contact lenses appears to produce a more rapid increase in
the coefficient of variation of endothelial cell size than daily wear.
Recovery from contact lens-induced endothelial polymegethism is
slow, and the condition may be irreversible, even after cessation of
contact lens wear. This condition is unique because other corneal
changes induced by contact lenses usually disappear with cessation
of wear. Sibug et al,90 however, reported a trend toward reduced
polymegethism 5 years after cessation of contact lens wear. In
another study,91 the endothelial polymegethism was still present
even 7 years after cessation of PMMA contact lens wear.
The cause of polymegethism is not yet clear. Connor and
Zagrod92 theorized that the causes of polymegethism involve a
hypoxia-induced reduction in ATP levels and changes in the
concentration of extracellular and intracellular calcium. Alterna-
tively, corneal stromal acidosis may be an etiologic factor.22
Polymegethism is one of the features of the corneal exhaustion or
fatigue syndrome.93,94 This syndrome is thought to represent
endothelial dysfunction brought on by chronic contact lens-in-
duced hypoxia and acidosis. Whether the morphologic changes in
the endothelium in polymegethism are a result of changes in cell
size or a redistribution of cell mass is in dispute.95,96 Regardless of
the cause, an irregular mosaic is inherently unstable, because
adjacent cells with similar dimensions best maintain the barrier
function of the endothelium.97
When the cornea is exposed to 12 R HETE and 8 R HHDTrE,
changes similar to those seen with contact lens-induced hypoxia
occur, including edema, neovascularization, and endothelial poly-
megethism.40 An underlying mechanism of polymegethism is
related to the ability of 12 R HETE to inhibit the sodium-
 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
FIG. 8. Bergmanson’s theory of the development of endothelial
polymegethism. Normal endothelium has interdigitated lateral sides
and minimal separations between cells. Chronic anterior hypoxia
results in an oblique reorientation of the lateral wall of the endothe-
lial cell. Thus, a cell with a large anterior surface may have a small
posterior surface and vice versa. Consequently, cellular volume may
remain constant. (From Efron N. Contact Lens Complications. Ox-
ford, Butterworth-Heinemann 1999:193; with permission.)
potassium ATPase of the endothelial pump. Repeated endothelial
exposure to 12 R HETE and 8 R HHDTrE due to the diffusion of
these eicosanoids (which results from the corneal epithelial inflam-
matory response to contact lens wear) causes endothelial cell
swelling and a permanent change in the cellular cytoskeleton,
leading to endothelial polymegethism.
The consequences of endothelial polymegethism are unclear.
The condition may be benign, although polymegethism appears to
be linked to corneal hydration control. Hydration control can be
tested by inducing corneal edema and then recording the exponen-
tial rate of corneal deswelling.98 Deswelling after induced edema
is considerably slower in PMMA contact lens wearers than in
non-contact lens wearers. An impaired functional reserve was
demonstrated in a study that showed increased endothelial perme-
ability and an increased endothelial pump rate in patients with
polymegethism associated with wearing extended-wear soft con-
tact lenses.99 Endothelial polymegethism may adversely affect the
ability of the cornea to reduce edema after surgical stress, a
concern specifically for surgical patients.97,100,101 Rao et al97
showed that patients with polymegethism take longer to recover
from corneal edema induced by cataract surgery. Slow corneal
deswelling has been associated with polymegethism in the young
and the elderly.102
The pathologic basis of polymegethism is debated. Although the
endothelial cells have clearly changed in shape, the volume of each
cell may remain constant because the cells have become reoriented
in three-dimensional space96 (Fig. 8). An oblique reorientation of
the lateral walls of endothelial cells occurs in contact lens wearers
with some intercellular and intracellular edema. Endothelial cy-
toskeletal F-actin has abnormal patterns that may contribute to
polymegethism and may be the result of constant stress in cell
volume regulation.103 No damage was evident on examination of
the ultrastructure of the organelles of endothelial cells.96
Endothelial Cell Density
Although polymorphism and pleomorphism are well-known
consequences of contact lens wear, most studies have been unable
to confirm a change in endothelial cell density with contact lens
23
wear18,30,88,101,104 –111; however, there have been a few isolated
reports of endothelial cell loss.112 MacRae et al88 reported low
endothelial cell density in a subgroup of PMMA lens wearers.
PMMA wearers showed advanced polymegethism and pleomor-
phism compared with controls. Although their endothelial cell
density was not significantly different from that of controls, a
significantly greater percentage of contact lens wearers had low
endothelial cell density and were more likely to have severe
polymegethism and pleomorphism. The authors suggested that
polymegethism and pleomorphism lead to a reduced physiologic
reserve and are precursors to accelerated corneal endothelial cell
death. MacRae and associates used the term “contact lens-induced
endotheliopathy,” because these changes may represent pathologic
processes that may result in premature cell death and reduced
endothelial cell density. A subset of approximately 10% of PMMA
lens wearers show these changes.
Using age-matched controls (not following individual patients),
Setala and co-workers113 also noted a lower endothelial cell
density. In this study, mean endothelial cell density in contact lens
wearers was minimally lower, and the mean coefficient of varia-
tion differed significantly from normal in all contact lens wearers.
Very low mean endothelial cell density was observed in some
patient populations of contact lens wearers and was seen only in
contact lens wearers. A recent study by Lee et al89 also found a
significant change in the coefficient of variation of cell size and a
decrease in cell density among long-term soft contact lens wearers.
Thus, some studies suggest that there may be a subset of PMMA
and soft contact lens wearers who react with high pleomorphism
and polymegethism and also a decrease in endothelial cell density.
The morphologic change in endothelial cell density is specu-
lated to be an indicator of cell stress due to chronic hypoxia;
therefore, polymegethism and pleomorphism may be signs of
premature cell death. This appears related to the type of contact
lens. For example, Setala et al113 found minimal or no endothelial
morphologic changes with RGP and silicone lenses. These authors
suggested that long duration of contact lens wear affects cell
densities, especially after 25 years. Corneas with low cell density
may remain clear unless stressed by conditions such as contact lens
wear, surgical procedures, or age. Although these endothelial
changes have not been shown to be reversible after cessation of
contact lens wear, Sibug et al90 believed that the changes might be
slowly reversible.
Wiffen and colleagues114 showed that endothelial cell density
was significantly higher centrally than peripherally in normal
subjects without contact lenses but not in contact lens wearers. The
coefficient of variation of cell area was higher peripherally than
centrally for both normal controls and contact lens wearers, but
contact lens wearers had significantly higher coefficients of vari-
ation than controls in both the center and the periphery. The central
cornea has more hexagonal cells than the peripheral cornea in both
normals and contact lens wearers: the percentage of hexagonal
cells is less in both the center and periphery in contact lens wearers
compared with normals. These authors conclude that contact lens
wear causes a mild redistribution in endothelial cell density from
the central to the peripheral cornea. Other authors have found
increased central endothelial cell density with RGP lens wear.115
In patients newly fitted with fluorocarbon RGP contact lenses,
the coefficient of variation of cell area increased within 2 months
and continued to increase over the next 3 years,116 and this
correlated with the oxygen transmissibility of the lenses. The
The CLAO Journal, Vol. 28, No. 1, 2002
24 T.J. LIESEGANG
endothelial cell density was decreased at 2 and 3 years, but corneal
thickness did not change. In older contact lens wearers who
switched to RGP fluorocarbon contact lenses, after 3 years there
were no significant changes in any morphologic values, except that
corneal thickness was decreased significantly. The authors con-
cluded that, although oxygen transmissibility was improved with
the fluorocarbon lens, polymegethism was still induced within 2
months by these contact lenses, and morphologic changes stem-
ming from previous contact lens wear did not improve during 3
years of daily wear of these RGP lenses. These contact lens
changes do not occur in patients wearing silicone lenses, which are
highly permeable to oxygen.
Endothelial Function
To date, no direct link has been established between contact
lens-induced acidosis and corneal function, although there is some
indirect evidence. Long-term contact lens wear reduces endothelial
functional reserve, as measured by the rate of corneal deswelling
following lens-induced edema. This correlates with the duration
and transmissibility of the contact lens worn. Other studies confirm
that acute corneal swelling and deswelling rates are slowed in an
acidic environment, implying that an acid environment may affect
endothelial pumping or endothelial hydraulic activity.
Vannas et al85 have suggested that monitoring the rate of
decrease of corneal thickness after the induction of hypoxic cor-
neal edema provides an assessment of endothelial pump function.
Polse et al,1 using the term “open-eye steady state,” developed a
clinical method to measure overall endothelial function or corneal
hydration control by inducing hypoxic corneal swelling with a
contact lens and then measuring the rate of deswelling. Preliminary
data7 suggested that hypoxic exposure alters endothelial structure
and reduces corneal function. Nieuwendaal et al,98 using a similar
method, found abnormally low rates of deswelling in long-term
contact lens wearers.
Another approach was used by Carlson and co-workers,104 who
evaluated barrier function by measuring endothelial permeability
to fluorescein. They found no difference between contact lens
wearers and controls in corneal clarity, central corneal thickness,
or endothelial response to fluorescein. Oxygen transmissibility,
estimated underlying oxygen tension, and duration of contact lens
wear did not correlate with any morphologic or functional endo-
thelial variables. These authors concluded that long-term contact
lens wear induces morphologic changes in the endothelium that
may progress over time, but no functional abnormality was de-
tected by the methods of anterior-segment fluorophotometry. In
further studies Bourne et al116 again found no statistically signif-
icant differences between contact lens wearers and controls in
endothelial permeability, corneal deswelling, endothelial pump
rate, or endothelial cell density, although contact lens wearers had
significantly higher aqueous flow rate, coefficient of variation of
cell area, and corneal autofluorescence than non-contact lens
wearers.
Corneal Exhaustion Syndrome
Sweeney94 coined the term “corneal exhaustion syndrome” to
characterize the sudden intolerance to contact lens wear with
photophobia associated with a distorted endothelial mosaic and
moderate to severe polymegethism. The condition involves contact
lens intolerance with blurred vision, mire distortion, fluctuating
changes in corneal curvature, and spectacle refraction after cessa-
The CLAO Journal, Vol. 28, No. 1, 2002
tion of contact lens wear, as well as excessive open-eye edema
response and moderate to severe endothelial changes. The effects
on the endothelium appear to be long-term and possibly perma-
nent.
Corneal exhaustion syndrome (contact lens failure after long-
term wear) may be caused by endothelial dysfunction due to
long-term hypoxia and acidosis. After years of contact lens wear,
the endothelial function of regulating corneal hydration may be
compromised to the point that the endothelium is no longer able to
cope with the stresses imposed by contact lenses with low oxygen
transmissibility. There must be an individual susceptibility to this
rare syndrome.
LESSONS FROM VARIOUS TYPES OF CONTACT
LENS WEAR AND DIRECTIONS FOR THE FUTURE
Biochemical, cellular, and microbial changes occur in the
closed-eye environment. The closed eye is a state of subclinical
inflammation with an increase in tear protein, secretory IgA, serum
albumin, complement and plasminogen, chemokines, and poly-
morphonuclear cells. This state may be beneficial against infec-
tion, but the addition of a contact lens may facilitate infection.
PMMA lenses present some unique problems. Daily wear of
PMMA lenses induces approximately 6% central corneal edema117
and frequent corneal warpage. This corneal stress may cause many
unacceptable changes in corneal structure and function. Although
some regression of endothelial polymegethism may occur after
lens wear is discontinued, most changes appear to be irreversible.
Endothelial polymegethism places the cornea at greater risk for
surgical complications.97,118 The corneal exhaustion syndrome is a
rare problem that may occur in some patients with PMMA lens-
es.93
Soft contact lenses initially were believed to supply enough
oxygen to the cornea,119 since Polse and Mandell120 determined
that only 2% oxygen was required to prevent corneal edema.
Carney and Bailey121 published the first paper questioning the
adequacy of oxygen level supplied by a soft contact lens. The use
of thick, soft lenses of low water content produced corneal edema,
polymegethism,107 myopic creep,122 vascularization,123 and occa-
sionally the corneal exhaustion syndrome.93,124
Extended-wear soft contact lenses generally do not provide
sufficient oxygen to the eye.14,125–128 In the Gothenberg (Sweden)
study,30 chronic hypoxia induced by extended wear of soft hydro-
gel lenses resulted in a 15% decrease in oxygen uptake rate, with
85% of patients producing microcysts. The epithelium thinned by
6%. The stroma was slightly edematous (2.5% of stromal thick-
ness) while the patients were wearing the contact lenses, but when
patients removed their contact lenses, the stroma was significantly
thinner (2.3%) than before the contact lens wear. There was
increased polymegethism in 95% of lens wearers, with a mean
increase of 22%.30 Sterile peripheral ulcers occurred in 1% in a
2-year prospective study.8 Reduced oxygen with the closed lid plus
extended wear of soft contact lenses caused problems of corneal
swelling, epithelial microcysts, stromal and epithelial thinning,
reduced epithelial mitosis rate, decreased damage threshold, stro-
mal acidosis, endothelial polymegethism, decreased epithelial ad-
hesion, increased epithelial cell size, and increased inflammatory
activity in the epithelium.
The availability of disposable contact lenses led to a resurgence
of the popularity of extended wear. Hypoxic, inflammatory, and
 PHYSIOLOGIC CHANGES OF THE CORNEA WITH CONTACT LENS WEAR
infectious complications were soon documented, however, dispel-
ling the belief that these lenses were the ultimate solution. Hypoxia
still underlies most of the complications associated with hydrogel
extended-wear soft contact lenses, and regular lens replacement of
conventional or disposable contact lenses has no effect on this
problem. All current hydrogel contact lenses create hypoxic stress,
resulting in significant morphologic and functional corneal com-
promise. The hypoxia leads to increased anaerobic metabolism
with stromal acidosis, overnight corneal swelling, residual daytime
corneal edema, microcysts, vacuoles, striae, folds, blebs, and
polymegethism. Controversy remains as to the relative incidence
of corneal staining, neovascularization, sterile infiltrates, and in-
fectious keratitis with disposable versus conventional extended-
wear soft contact lenses.
Very thin, high-water content hydrogel soft contact lenses pro-
vide improved oxygen transmissibility but not to the level required
to maintain normal epithelial aerobic metabolism. Additionally,
these lenses can induce corneal desiccation, have inadequate du-
rability, and are difficult to handle. 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.
Other non-hydrogel materials with high oxygen permeability are
currently being tested in clinical trials; however, corneal compro-
mise is a function of both impaired oxygen supply and carbon
dioxide accumulation in tissue. Therefore, adequate carbon diox-
ide transmissibility is another requirement. Maximizing contact
lens oxygen transmissibility will not eradicate all the inflammatory
and infectious events during overnight wear because the closed-
eye environment cannot be overcome. Extended wear of current
hydrogel polymers causes subtle long-term tissue changes that can
have serious implications.
Newer soft materials with high oxygen transmissibility, anti-
inflammatory and anti-infective components, and improved wet-
tability ultimately are required to provide both safety and comfort
during extended wear.72 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. They
have very high oxygen transmissibility and, in early studies, did
not raise the same issues of hypoxia.44 True daily-wear disposable
contact lenses may also overcome other issues with regard to
contact lens safety but will remain expensive for many patients.
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The CLAO Journal, Vol. 28, No. 1, 2002