1040-5488/01/7811-0783/0 VOL. 78, NO. 11, PP.

783–790
OPTOMETRY AND VISION SCIENCE
Copyright © 2001 American Academy of Optometry

2000 GLENN A. FRY AWARD LECTURE

Effects of Contact Lens-Induced Hypoxia on the

Physiology of the Corneal Endothelium
JOSEPH A. BONANNO, OD, PhD, FAAO
Indiana University, School of Optometry and Borish Center for Ophthalmic Research, Bloomington, Indiana

ABSTRACT: Contact lens wear can cause a number of physiological changes in the cornea. Two areas of interest in my
laboratory have been contact lens effects on the endothelium and, more recently, the role of metabolic activity in
predicting corneal swelling. The first part of this review focuses on the function of the corneal endothelium, the nature
of its fluid pump, and the effects of contact lens-induced hypoxia and corneal pH changes on corneal endothelial
function. In the second part, the etiology of hypoxia-induced corneal swelling is reviewed in relation to new studies on
the causes of intersubject corneal swelling variability. The results indicate that corneal swelling is influenced by both
corneal metabolic activity and endothelial function. (Optom Vis Sci 2001;78:783–790)

Key Words: corneal endothelium, contact lenses, hypoxia, intracellular pH, corneal swelling

T
he effect of contact lens wear on the cornea is a very broad
topic. Numerous morphologic, metabolic, and immuno-
logic changes can occur that may lead to alterations in vi-
sion, lens intolerance, inflammation, and infection. One heavily
studied topic area, which has been of interest to me, is the effect of
contact lens-induced hypoxia on corneal physiology. There are
many effects of hypoxia, however the one that probably most con-
cerns contact lens practitioners is the weakening of the corneal
epithelial barrier because this could lead to acute inflammation or
infection. Another major effect of hypoxia is corneal swelling. By
itself, corneal swelling is not a cause for alarm, but in some cases it
could produce annoying changes in refractive status due to alter-
ations in corneal topography. Because corneal swelling can be eas-
ily and accurately measured, it has been used as the primary test for
quantifying or ranking contact lens-induced hypoxia. Of course all
of the effects of hypoxia are exacerbated during continuous wear of
lenses, due to the deepening of hypoxia under the closed lid, and
lessened considerably if patients adhere to daily wear. With the
advent of hyper-oxygen permeable materials that have the comfort
and ease of use of standard hydrogels, hypoxia should no longer be
a major clinical concern, and continuous wear of contact lenses
could become more commonplace. Thus the focus of research on
contact lens-related clinical problems has already shifted to the
ocular surface. Trying to understand the stimuli for conjunctival
inflammation1–3 and dealing with tear deficiencies4, 5 are just two
examples of research areas that could have a large impact on the
contact lens-wearing population. Nevertheless, hypoxia has taught
us some interesting things about the cornea, and it is still useful as
a tool for measuring endothelial function6 and understanding vari-
ations in metabolic activity.7 Here, I will focus on two areas of
interest in my laboratory, the effects of lens wear on the physiology
of the corneal endothelium and the intersubject variability of hy-
poxia-induced corneal swelling.
MAINTENANCE OF CORNEAL HYDRATION
Stromal Fluid-Leak
The corneal endothelium is primarily responsible for maintain-
ing corneal hydration. To understand this function, some back-
ground information on the corneal stroma is necessary. The cor-
neal stroma is made up of many layers of lamellae that are primarily
composed of collagen fibers. Between the fibers and connected to
them is a stromal ground substance made up of very hydrophilic
glycosaminoglycans (GAGs). GAGs are a ubiquitous connective
tissue molecule whose job is to keep the tissue hydrated. At normal
corneal hydration (~3.5 mg H2O/mg dry tissue), the GAGs keep
the collagen fibers separated from each other (~30 nm) such that
the density of fibers is uniform. There is a significant difference in
refractive index between the ground substance and fibers, so the
potential for significant light scattering exists. The uniform density
of fibers, however, leads to destructive interference of scattered
light and a transparent stroma.8 Immersing the cornea in a bal-
anced saline solution after removal of either the corneal epithelium
or endothelium will lead to rapid swelling and an increase in light
scatter (loss of transparency) of the cornea relative to corneas that
have both layers intact. This swelling is due to the water-loving
GAGs that exert an imbibition pressure that is inversely propor-

Optometry and Vision Science, Vol. 78, No. 11, November 2001
784 Contact Lens-Induced Hypoxia—Bonanno
tional to the hydration of the stroma.9 Clinically, epithelial or
endothelial damage will produce corneal swelling. However, cor-
neas mounted and perfused in vitro that have had the epithelium
removed and coated with silicone oil can maintain corneal thick-
ness, whereas removal of the endothelium leads to swelling.10, 11
Furthermore, significant translocations of water can be ascribed to
the endothelium,12 whereas relatively smaller amounts of epithelial
water transport can only be demonstrated after pharmacological
stimulation.13 Thus, the endothelium is primarily responsible for
counteracting the stromal imbibition pressure or “fluid leak,”
whereas the epithelium serves as an important barrier or resistor to
stromal water influx.
Endothelial Fluid Pump
The stromal imbibition pressure has been called the “leak,” that
is, the driving force for water to move into the stroma, and the
endothelium has been called the “pump,” or driving force to move
water out of the stroma. This is illustrated in Fig. 1. The pump is
derived from the ion transport properties of the endothelium. Ions
are transported from the basolateral (stromal) side of the endothe-
lial cells to the apical (anterior chamber) side. This leads to small
osmotic pressure differences that drive water from the stroma to
the anterior chamber. In the steady-state, there is a balance be-
tween the leak and the pump so that corneal hydration and thus
thickness does not change. The nature of the ion transporters that
make up the endothelial pump is not completely understood.
However, early studies have shown that the endothelium requires
the bicarbonate ion and that it is sensitive to carbonic anhydrase
inhibitors.14 –17 Over the last 12 years, my laboratory has been
engaged in research to identify and characterize the bicarbonate-
dependent ion transporters in the corneal endothelium. Our goal is
FIGURE 1.
Pump-leak maintenance of corneal hydration. Schematic cross-section of
the cornea shows that the stroma glycosaminoglycans (GAGs) exert an
imbibition pressure that draws water into the stroma across the epithelium
and endothelium. The hydraulic conductivity of the epithelium is about
half of that of the endothelium, which is illustrated by the size of the
“Leak” arrows. Ion pumps, indicated by the letter P, located at the
endothelium, provide a small osmotic force to move water out of the
stroma. These pumps are essential for maintaining stromal hydration.
Optometry and Vision Science, Vol. 78, No. 11, November 2001
to understand the basic mechanisms that produce endothelial fluid
transport and, further, to discover possible regulatory mechanisms
(e.g., increasing intracellular cyclic AMP18) that could lead to
medical therapies for enhancing fluid transport in patients with a
dysfunctional endothelium. Our most recent studies19 have shown
that there is a robust Na⫹-dependent bicarbonate transporter lo-
cated on the basolateral membrane of endothelial cells. The
mRNA that codes for the protein responsible for this transport has
been cloned and sequenced and identified as the sodium bicarbon-
ate cotransporter or NBC.19 This transporter is responsible for
moving bicarbonate from the stroma into the endothelial cells. The
mechanism by which bicarbonate is then moved across the apical
membrane is less clear. We have proposed three possibilities: (1) a
membrane protein that pumps bicarbonate out of the cell in ex-
change for chloride (known as the anion exchanger), (2) an ion
channel that is permeable to bicarbonate, and/or (3) diffusion of
carbon dioxide across the apical membrane and its conversion to
bicarbonate catalyzed by the membrane-bound form of carbonic
anhydrase. These proposed mechanisms are illustrated in Fig. 2.
Recent molecular studies in our laboratory have shown that
corneal endothelial cells express an anion exchanger, an ion chan-
nel permeable to bicarbonate (known as CFTR), and carbonic
anhydrase IV.21 Immunoblot and immunofluorescence analyses
have confirmed the presence of these proteins on the apical mem-
brane of endothelial cells. CFTR is the cystic fibrosis transmem-
brane regulator, which is defective in patients with cystic fibrosis.
CFTR is primarily a chloride channel, but it is also permeable to
bicarbonate. Using endothelial function testing,6 it should be pos-
FIGURE 2.
Model for corneal endothelial HCO3⫺ transport. The division between
basolateral membranes (stromal side) and apical membranes (anterior
chamber side) is provided by the tight junction complexes shown by the
shaded rectangles between adjacent cells. (1) On the basolateral side,
HCO3⫺ is taken up by the Na⫹:HCO3⫺ cotransporter. Some of the
HCO3⫺ is converted to CO2, catalyzed by cytosolic carbonic anhydrase
(CA-II). Apical HCO3⫺ efflux, from the cells to the aqueous humor, is
either by (2) CO2 diffusion and conversion to HCO3⫺ at the apical
membrane catalyzed by CA-IV, (3) anion exchange, or (4) anion channels.
The Na⫹-K⫹ATPase, which is located on the lateral membranes, provides
the primary active transport for establishing the Na⫹ and K⫹ gradients
across the membrane. The Na⫹:K⫹:2Cl⫺ cotransporter on the basolateral
side regulates intracellular [Cl⫺],20 however its role in fluid transport is
uncertain.
 Contact Lens-Induced Hypoxia—Bonanno 785

sible to test in CF patients whether the defective CFTR also com-

promises endothelial fluid pumping.

Carbonic Anhydrase
Another interesting finding is that the rate that bicarbonate
enters the endothelial cells exceeds the rate that it exits.22 For this
to take place, the excess bicarbonate combines with a proton (H⫹)
and is converted to carbon dioxide, thereby raising intracellular pH
(pHi). This reaction, HCO3⫺ ⫹ H⫹ 7 H2CO3 7 CO2 ⫹ H2O,
is catalyzed by the cytosolic enzyme carbonic anhydrase-II (CAII).
Carbonic anhydrase inhibitors (CAI’s) applied directly to the en-
dothelium will slow endothelial pumping,15–17, 23 and because a
proton is consumed when bicarbonate is converted to carbon di-
oxide, the CAI’s will acidify endothelial cells and interfere with FIGURE 3.
pHi regulation.24 The CAI dorzolamide applied topically, which is Effect of contact lens wear on endothelial pH. Rabbit corneas were
used to lower intraocular pressure, has no apparent effect on nor- mounted in vitro on the stage of a fluorescence microscope. The endo-
thelial surface was perfused with bicarbonate ringer. Endothelial cells
mal cornea function,25, 26 however there are reports of endothelial
were loaded with a pH-sensitive fluorescent dye, and endothelial pH was
decompensation when dorzolamide is used in corneas with already continually measured. A rigid contact lens (Dk/t ⫽ 18) was placed on the
compromised endothelia.27 epithelial surface for a time shown by the box. For further information see
Giasson and Bonanno.31

Endothelial pHi and Function

with an end product of lactate. Lactate, produced in the hypoxic
Because of the relationship between carbon dioxide concentra- epithelial cells, is negatively charged and thus cannot easily diffuse
tion, bicarbonate concentration, and pH, it is plausible that any- across the cell membrane. A membrane protein that transports
thing that interferes with this relation or anything that disturbs lactate together with a proton facilitates its diffusion across the
pHi, (e.g., CAI’s) could inhibit endothelial pumping. For exam- membrane.34 This protein is called the lactate:H⫹ cotransporter.
ple, Cohen et al.28 have shown that corneas that are made acidic by Lactate then diffuses posteriorly across the stroma and then across
exposure to carbon dioxide have reduced endothelial function as the endothelium to be washed out in the aqueous humor.35 To
measured by the rate of corneal deswelling. Contact lens wear can cross the endothelium, lactate diffusion must again be facilitated,
acidify the corneal stroma.29, 30 The drop in stromal pH during and this could indirectly cause a change in endothelial pHi. Again,
contact lens wear is due to a modest increase in corneal carbon using an in vitro rabbit corneal model, Claude Giasson found that
dioxide levels, which is caused by the slowing of diffusion of CO2 indeed pHi was affected when stromal lactate was increased.36 Fig.
across the anterior surface of the cornea and the production of 4 shows that lactate caused a decrease in pHi, but this was quickly
metabolically derived acid due to hypoxia. Thus, we asked whether followed by an increase in pHi that reached a new steady-state
contact lens wear could affect endothelial pHi. Using an in vitro
rabbit corneal model, Claude Giasson, working in my laboratory,
found that lens wear could indeed produce a small decrease in
endothelial pHi (Fig. 3).31 Interestingly, anterior surface anoxia,
by application of 100% nitrogen-equilibrated solutions, had no
effect on endothelial pHi. On the other hand, increasing anterior
surface carbon dioxide produced decreases in pHi that were com-
parable to the contact lens. Thus, the decrease in endothelial pH
during lens wear was ascribed to an increase in corneal CO2 with
no significant contribution from metabolically derived acid. Al-
though contact lens wear reduces endothelial pHi and reduced pHi
(by CO2 exposure) inhibits corneal deswelling, attempts to show
that contact lens wearers have reduced endothelial function have
indicated little32 or no effect.33 This can be interpreted to mean
that reduced endothelial pH will interfere with fluid transport, but
this does not have a lasting or chronic effect on the endothelium.
FIGURE 4.
The effect of stromal lactate on endothelial pH. Rabbit corneas were
Lactate and Endothelial pHi mounted in vitro on the stage of a fluorescence microscope. The endo-
thelial surface was perfused with bicarbonate ringer. Endothelial cells
were loaded with a pH-sensitive fluorescent dye, and endothelial pH was
Another effect of hypoxia is the production of lactate. Because of continually measured. The epithelium was removed by scraping to expose
the reduced availability of oxygen, there is a decrease in oxidative the stroma. Lactate (50 mM) was added to the bare stroma for a time
metabolism and a commensurate increase in anaerobic glycolysis shown by the box. For further information, see Giasson and Bonanno.36

Optometry and Vision Science, Vol. 78, No. 11, November 2001
786 Contact Lens-Induced Hypoxia—Bonanno

above the baseline. The reason for this complex change in endo-
thelial pHi was that lactate entered the endothelial cells by two
mechanisms: lactate:H⫹ cotransport (contributes to the initial pHi
decrease) and Na⫹-dependent lactate cotransport, which has no
effect on pHi. However, exit of lactate across the apical membrane
and into the anterior chamber was exclusively by lactate:H⫹ co-
transport.36 Thus, more protons left the endothelial cells than
entered, so the steady-state pHi was higher than the baseline.
Therefore, if anything, anterior surface hypoxia alone should have
caused an increase in endothelial pHi. However, to detect these
lactate-induced pHi changes, a high concentration of lactate (50
mM) was added to the stroma.36 In the in vitro rabbit cornea,
anterior surface anoxia will cause the stromal lactate concentration
to increase from about 5 to 10 mM.35 At these small concentra-
tions of lactate, the endothelial pHi changes were too small to
separate from the measurement noise. Thus, these studies show
that contact lens wear can affect endothelial pHi by increasing
[CO2] and that hypoxia-induced lactate diffuses across the endo-
thelium by a two-step process that has little or no effect on steady-
state pHi.
FIGURE 6.
Endothelial cell swelling after exposure to carbon dioxide. Carbon dioxide
Endothelial Blebs, pHi, and Cell Volume diffuses into the cell and dissociates into H⫹ and HCO3⫺. The decrease in
endothelial pHi stimulates pHi ion transport regulatory proteins,
One of the first observations that contact lens wear can affect Na⫹:HCO3⫺ cotransport, and Na⫹/H⫹ exchange. Influx of solute causes
endothelial physiology was the description of the formation of an obligatory influx of water leading to cell swelling. The swelling is
endothelial blebs by Zantos and Holden.37 Fig. 5 shows that blebs shown on the apical surface because this is the area of least resistance to
membrane expansion.
are small black spots that appear as disruptions in the smooth
endothelial surface when observed in specular reflection. When a
contact lens is placed on the cornea, blebs will appear in about 20 blebs could be produced by lens wear, anterior surface hypoxia, or
to 30 min. With the lens remaining on the cornea the blebs will last 10% CO2 exposure. The largest response was produced by carbon
for about 20 to 30 min, and then the endothelial mosaic will return dioxide, and the smallest response was caused by hypoxia. The
to normal. Subsequent work from Holden et al.38 indicated that explanation for this transient phenomenon is probably a change in
cell volume induced by a decrease in endothelial pHi and/or lactate
entry. When cellular pH is reduced, ion transport mechanisms that
regulate pHi, (e.g., Na⫹/H⫹ exchange and Na⫹:HCO3⫺ cotrans-
port) are stimulated in an attempt to bring the pHi back to normal.
The movement of Na⫹ into the cell will also bring in water by
osmosis, and the cell swells. For example, exposing the corneal
surface to 10% CO2 probably causes the endothelial CO2 tension
to increase from ~4% to ~7% and thus is likely to significantly

FIGURE 5.
Corneal endothelial blebs. The left panel is before lens insertion and the
right panel is the same endothelial area during wear of a thick hydroxy-
ethyl methacrylate contact lens. Reprinted from Holden et al.38 with
permission from the Association for Research in Vision and
Ophthalmology.
FIGURE 7.
Endothelial cell swelling after exposure to stromal lactate. Lactate enters
the cells via Na⫹:lactate cotransport and lactate:H⫹ cotransport. The
increase in intracellular solute causes cell swelling. Swelling is probably
limited by the quick efflux of lactate via an apical lactate:H⫹
cotransporter.

Optometry and Vision Science, Vol. 78, No. 11, November 2001

FIGURE 8.
Regulatory volume decrease. When the cells swell, the membranes ex-
pand and pull on the actin cytoskeleton that lines the inside surface of the
cell membrane. This stimulates K⫹ and Cl⫺ channels to open, and KCl
together with water leaves the cell. The end result is that the cell recovers
its original volume.
reduce endothelial pHi and activate Na⫹ entry. This is illustrated
in Fig. 6. Similarly lactate diffusion into the endothelial cells will be
a stimulus for cell swelling. As mentioned above, lactate diffusing
from the stroma will enter the endothelial cells by Na⫹:lactate
cotransport and lactate:H⫹ cotransport, which is illustrated in Fig.
7. Cell swelling then induces a mechanical stretch in the membrane
that opens up ion channels, allowing K⫹ and Cl⫺ to leave the
cell, and thus the cell volume returns to normal. This is illus-
trated in Fig. 8. This process is called regulatory volume de-
crease, and it has been demonstrated to take place in the corneal
endothelium.39 Thus the cell swelling and deswelling is a tran-
sient phenomenon that roughly could have the time course of
the appearance and disappearance of endothelial blebs. Because
lactate concentration only doubles from 5 to 10 mM and be-
cause hypoxia alone does not affect endothelial pHi, together
with the fact that apical surface lactate:H⫹ efflux will combine
with the other regulatory volume decrease responses, probably
limits the bleb response during anterior surface anoxia. On the
other hand, contact lens wear leads to an increase in lactate
production and reduces endothelial pHi due to the small in-
crease in carbon dioxide (probably about 0.5%).31 Thus, the
bleb response appears to correlate with the size of the stimulus
that can reduce pHi and thereby change cell volume.
Optometry and Vision Science, Vol. 78, No. 11, November 2001
Contact Lens-Induced Hypoxia—Bonanno 787
FIGURE 9.
Variability in corneal swelling. Two-hour closed-eye corneal swelling
from 18 subjects wearing thick and thin 38% water hydrogel lenses; the
lines connect the same subject.
FIGURE 10.
Quenching of porphyrin dye phosphorescence by oxygen. After a 10-␮s
stimulatory flash, porphyrin dyes will emit phosphorescence, and the
decay time is inversely proportional to the oxygen concentration. The rate
of decay can be used to estimate oxygen tension in the surrounding
environment.
CORNEAL SWELLING
Hypoxia-Induced Swelling
Anterior surface corneal hypoxia causes corneal swelling.
Klyce35 found that the hypoxia-stimulated increase in stromal lac-
tate concentration could account for the hypoxia-induced swelling
in an in vitro rabbit model via lactate-induced osmotic water in-
flux. Further studies by Huff40, 41 were consistent with the lactate-
osmotic theory. Recently, it has been shown that the epithelium
produces inflammatory mediators (HETE’s) when made hy-
poxic42– 45 and that direct application of HETE’s to the endothe-
lium causes swelling by blocking Na⫹-K⫹ATPase,42 the mem-
brane protein responsible for primary active transport. However, it
has not been shown that HETE’s produced in the epithelium can
788 Contact Lens-Induced Hypoxia—Bonanno

FIGURE 11.
FIGURE 12.
Tear oxygen tension beneath contact lenses. A standard hydrogel lens was
Corneal swelling is proportional to tear oxygen levels. Linear regressions
coated with a porphyrin dye bound to bovine serum albumin. The lens
(LReg) of thin lens corneal swelling are shown as a function of open and
was placed on a subject’s eye, and the eye was closed for 5 min.
closed eye oxygen tension.
Phosphorescence decay times were then measured immediately after eye
opening. By fitting the data to a single exponential rise, the initial oxygen
tension under the lid (3.9 torr) could be estimated. SS, steady-state open
eye oxygen tension; R, correlation coefficient.

lead to sufficient increase in HETE’s at the endothelium to pro-

duce corneal swelling. Furthermore, one study has shown that use
of the topical anti-inflammatory drug Voltaren, which should re-
duce HETE formation, had no effect on corneal swelling.46 An-
other possible cause of corneal swelling is reduced endothelial pHi.
Recent studies with rabbits showed decreased lactate production
after a number of weeks of lens wear in the face of continuing
corneal swelling, which has been interpreted to suggest that a drop
in pH and not increased lactate during lens wear is enough to slow
endothelial function. This is consistent with the results from
Cohen et al.28 showing that increased corneal [CO2] slows the FIGURE 13.
corneal deswelling rate, suggesting that lowering endothelial Corneal swelling is affected by endothelial function. Linear regression of
thin lens swelling is shown as a function of percent recovery per hour
pHi can reduce fluid pumping. On the other hand, corneal
(PRPH).
swelling produced by nitrogen goggle hypoxia was reduced
when 5% CO2 was added,47 suggesting that the acid environ-
ment slowed glycolysis and the production of lactate.48 Fur-
Intersubject Variability of Corneal Swelling
thermore, direct reduction of pH in the solution bathing the in
vitro rabbit endothelium, which will cause a drop in endothelial Given the oxygen transmissibility of a contact lens, it is possible
pHi, had no effect on corneal thickness and thus no apparent to predict the average amount of corneal swelling that the lens will
effect on endothelial fluid transport.49 Together, these studies cause in a group of subjects. On the other hand, it is much more
suggest that acute swelling is driven primarily by lactate, but difficult to predict the amount of corneal swelling that the lens will
that chronic swelling is influenced more by endothelial pHi. cause in a single individual. This is because there is significant
Finally, it is possible that anterior surface hypoxia also leads to intersubject variability in corneal swelling. Fig. 9 shows the vari-
endothelial hypoxia. This notion has not been considered be- able corneal swelling response induced by closed eye wear of two
cause it has been assumed that anterior chamber oxygen, deliv- different hydrogel lenses in a group of normal non-contact lens
ered by the iris, represents a large stable reservoir of oxygen. On wearers. These results are similar to those shown earlier by Sarver et
the other hand, recent measurements of anterior chamber oxy- al.,51 where they demonstrated that thirty subjects who wore the
gen tension using a phosphorescent probe indicate that lens same contact lens for the same amount of time produced increases
wear can reduce anterior chamber oxygen.50 Regardless of the in corneal thickness that ranged from 22 to 55 ␮m. Similarly,
exact cause(s) of hypoxia-induced corneal swelling, it is clear Efron52 showed that this intersubject variability could also be dem-
that it ultimately depends on a metabolic mechanism. onstrated by producing anterior surface hypoxia without lens wear

Optometry and Vision Science, Vol. 78, No. 11, November 2001

by using the nitrogen goggle technique. Thus, there must be inter-
subject differences in corneal metabolic activity or endothelial
function. That is, individuals with greater corneal metabolic activ-
ity, i.e., greater oxygen consumption, would become more hypoxic
and produce more lactate (and H⫹), and thus their corneas would
swell the most. On the other hand, it has been shown that there is
a substantial range of endothelial function in a young normal pop-
ulation,6 so it is possible that variability in endothelial function
could determine the extent of swelling.
To address these possibilities, we have started a study that at-
tempts to determine whether the variability in corneal swelling can
be explained by variability in tear oxygen tension while wearing a
soft contact lens (i.e., variability in corneal oxygen consumption).
Tear oxygen levels are measured using a noninvasive phosphores-
cence technique53 that has been adapted for use in human subjects.
Fig. 10 shows the relationship between phosphorescence decay and
oxygen tension, and Fig. 11 shows sample data from a subject
wearing a standard hydrogel lens after eye closure. Furthermore,
we measured the change in stromal pH due to the lens-induced
hypoxia using the pH-sensitive properties of the fluorescent dye
fluorescein.54 We predicted that those individuals with the greatest
swelling would show the most corneal oxygen consumption and
should show the greatest pH change. After corneal swelling, we
measured the rate of deswelling to calculate the percent recovery
per hour (PRPH) of corneal thickness, which was used as an assay
of endothelial function.6
Figs. 12 and 13 show preliminary results from this study.7 We
are finding that both oxygen consumption and PRPH may con-
tribute to predicting corneal swelling. Fig. 12 indicates that there is
a significant (p ⬍ 0.05) negative correlation between corneal swell-
ing and tear oxygen tension. Similarly, Fig. 13 shows that there is
a significant (p ⬍ 0.05) negative correlation between swelling and
PRPH. Corneal swelling directly correlated with the drop in stro-
mal pH to about the same extent as with oxygen tension, which is
consistent with metabolic activity as a significant predictor of
swelling. Thus, our preliminary conclusion is that variability in
corneal metabolic activity and endothelial function may be respon-
sible for the observed variability in corneal swelling.
SUMMARY
Contact lens wear can cause a number of changes in corneal
physiology. I have just touched on three of those changes here:
corneal swelling, endothelial cell pH changes, and the formation of
endothelial blebs. The studies that I have summarized indicate that
contact lens-induced corneal swelling, while initially induced by
increased lactate concentration, may also be influenced by endo-
thelial function, which may be compromised by the acidic state of
the cornea during lens wear. Thus, other conditions that could
acidify the endothelium, e.g., diabetes, anterior chamber inflam-
mation, or use of dorzolamide, may also contribute to corneal
swelling or reduced endothelial function.
ACKNOWLEDGMENTS
I acknowledge all of the hard work of the students and postdoctoral researchers
who have contributed to the studies from my laboratory that were reported
here, including Claude Giasson, Dan Harvitt, S. P. Srinivas, and Xingcai
Optometry and Vision Science, Vol. 78, No. 11, November 2001
Contact Lens-Induced Hypoxia—Bonanno 789
Sun. This work was supported by the National Eye Institute, National Insti-
tutes of Health grants EY08834 and EY12934, The Morton D. Sarver Center
for Cornea and Contact Lens Research, Vistakon, and Polymer Technology.
Received June 6, 2001.
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20. Bonanno JA, Srinivas SP. Cyclic AMP activates anion channels in
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790 Contact Lens-Induced Hypoxia—Bonanno
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24. Bonanno JA, Srinivas SP, Brown M. Effect of acetazolamide on in-
tracellular pH and bicarbonate transport in bovine corneal endothe-
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25. Egan CA, Hodge DO, McLaren JW, Bourne WM. Effect of dorzol-
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Joseph A. Bonanno
Indiana University
School of Optometry and Borish Center for Ophthalmic Research
800 E. Atwater Ave.
Bloomington, Indiana 47405
e-mail: jbonanno@indiana.edu