O2 Measurements And Needs
For long-term perspectives, higher permeability
We've discussed oxygen transmissibility at length. Is oxygen flux perhaps a more
meaningful metric than transmissibility? It's been said that if we use it, we can
effectively marginalize lenses above 87 x 10–9.
Dr. Holden: To create flux, there must be pressure
on one side, pressure on the opposite side and resistance in the middle. The higher
the partial pressure of oxygen under the lens, the lower the flux will be. So, if
we have a high-Dk/t lens say, 1,000 Dk/t there's no resistance to
oxygen flow. Flux across the lens is infinitesimal because there's no driving force.
So looking to flux to help assess corneal health doesn't tell us a whole lot with
In the literature,1–4 we've
seen studies of oxygen and partial pressures across corneas. They try to estimate
flow rates to determine which flow rates are beneficial to cells. In one publication,5
the graph of flux calculated based on a mathematical model vs. Dk/t went to Dk/t
18 and flat-lined, meaning flux into the cornea is the same at 18 Dk/t or 4 million
Dk/t. Of course, we know we need higher than 18 Dk/t to avoid corneal edema and
limbal hyperemia. It does make a difference whether the Dk/t is 20 or 125. So there's
a lot of confusion about calculated models of oxygen flux how the dynamic
circumstances of real-life lens wear, such as waking up after 8 hours of sleep,
require different oxygen transmission rates. To get meaningful data from flux numbers,
we need to state all the terms and conditions, and compartmentalize the lens, the
epithelium, the stroma and so forth.
Dr. Bonanno: Flux is a good metric to use,
but it's not any better than a lot of the other metrics we use. In the steady-state,
oxygen flux into the cornea is equal to flux across the contact lens. This can be
determined by knowing the Dk/t and the oxygen tension of the tears under the lens.
Flux = (Dk/t) x (155 – oxygen tension). So if we have a very high-Dk/t lens,
we'll have fairly high flux into the cornea. And as Dk/t goes down, there will be
less flux. For a "normal" cornea, knowing the flux into the cornea or knowing the
lens Dk/t or knowing the oxygen tension of the tears provides the same information.
HOW CAN WE USE OXYGEN
Dr. Holden: Most often,
oxygen flux is calculated based on a mathematical model with certain assumptions.
Dr. Bonanno, your group has actually measured the partial pressure of oxygen behind
a hydrogel lens.
Dr. Bonanno: We can measure
the difference in the mean oxygen tension, but if we take 30 subjects, we'll find
a lot of variability. There's this sort of logarithmic function: For patients in
high-Dk/t lenses, we measure the oxygen tension or flux between a lens that's 90
and a lens that's 110 or 130. It's my impression, although we haven't measured this
yet, that we'll need to have a huge difference in Dk/t to show any significant difference
Dr. Holden: Your data seem to indicate
significant acidosis a 0.34 increase in pH with very low Dk/t. And when you
got up to about 90 Dk/t, you had about a 0.15 increase in acidosis. You didn't have
any lenses beyond 90 at the time to test. It seemed you would hit the Dk/t axis
somewhere around 110 for open eye and 150 for closed eye. Has that work been done
Dr. Bonanno: No. That's even
harder to do. The differences are even smaller. It's harder to measure pH than it
is to measure oxygen. We can see what the threshold is by how far we can measure
Dr. Cavanagh: If we had a long-term,
well-adapted extended wearer in the group and the epithelium was 28 microns instead
of the baseline 52, the values would change. Have you ever baseline-corrected any
of your values for a patient's existing epithelial thickness?
Dr. Bonanno: No. That assumes
a thickness change will produce a linear change in metabolic activity. It might,
but we don't know if that actually happens. It would be difficult to study in a
human sample. We can measure the thickness change, but we don't know whether the
oxygen consumption per unit volume of tissue has changed as well.
In the steady-state, oxygen flux into the cornea
is equal to flux across the contact lens. This can be determined by knowing the
Dk/t and the oxygen tension of the tears under the lens. ... So if we have a very
high-Dk/t lens, we'll have a fairly high flux into the cornea.
HOW DO OXYGEN NEEDS CHANGE
IN REAL LIFE?
Dr. Bonanno, I'm interested in the following phenomenon. For example, we might measure
or estimate the flux going into the epithelium without a contact lens and get a
base level number of, perhaps, 6 microliters/ cm2/hour. If we apply a
high-Dk/t lens and measure it, we'd measure the front 6 still going through the
epithelium. If we apply a low-Dk/t lens, drop the cornea's oxygen level and get
acidosis, we can measure a flux of 9 or 10 produced by this change in the cornea's
acid levels under stress. The flux into the cornea is higher than the resting flux.
Looking at the data, we might say, "Well, here's a lower flux."
Dr. Bonanno: When Dk/t is low,
there's a higher flux across the lens, but a lower flux into the cornea.
Dr. Holden: The eye never increases
its uptake in a normoxic environment unless the cornea is stressed.
Dr. Bonanno: No, because it's 155 in
the open eye with no lens, so you have high oxygen tension. There's a steep gradient
a lot of flux. As you apply lenses, lowering the Dk/t, the steady-state oxygen
tension at the tears will decrease, and then the gradient is shallower.
Dr. Holden: When we remove the lens
and restore oxygen at high levels, the uptake rate to the cornea is higher because
the cells have been under stress.
Dr. Bonanno: Right. But what's important,
I think, is the steady state. That's kind of the EOP. It's an indirect way of measuring
oxygen consumption, and it's a non-steady state.
Dr. Holden: In a real-world range of
situations, the eyes can respond more readily with high-Dk lenses than they can
with low-Dk lenses.
Dr. Bonanno: I agree. We should get
as much oxygen as possible. We just need to keep these numbers in perspective.
Dr. Holden: Right. The difference
between 90 and 180 Dk/t, for example, may not be remarkable in terms of flux when
one uses a mathematical model to calculate it. But it may have a major impact on
limbal redness, on decades of contact lens wear or on any other situations. The
fact that we can't double the flux isn't important for corneal health because that's
determined by long-term, high oxygen availability under all sorts of circumstances
or transient situations. But just from the perspective of long-term safety and minimizing
structural change to the cornea, we need to go for higher permeability.
Transmission Decreases Bacterial Binding
Dr. Fonn: Dr. Cavanagh, your group has repeatedly
found a relationship between oxygen transmission and bacterial binding to epithelial
cells. Is there a critical transmission level?
Dr. Cavanagh: Yes,
I think there is a critical level. Unlike the other biological outcome measures
that we've talked about so far, we're not quite there yet with silicone hydrogels.
We need to get as close to a gas permeable lens or no lens as possible.
Dr. Fonn: Why?
Dr. Cavanagh: As we sleep without lenses,
carbon dioxide goes up, oxygen goes down, and the cornea swells, but we don't wake
up with Pseudomonas ulcers. So hypoxia alone isn't the primary cause of susceptibility
to infection the lens is. Why? Because if the bug can't stick to the cornea,
it can't infect it. And we've found that in animal eyes, oxygen prevents sticking.
The quantity of bacteria sticking to the eye after 24 hours can be directly related
to the oxygen transmissibility value of a lens.1
CAN DIRECTLY RELATE THE OXYGEN TRANSMISSIBILITY VALUE OF A LENS TO
THE QUANTITY OF BACTERIA STICKING TO THE EYE AFTER 24 HOURS. DR. CAVANAGH
If we compare a soft lens and a gas
permeable lens with the same oxygen transmissibility value let's say 80 Dk/t
then twice as many bugs bind to the corneal surface of the soft-lens eyes
in rabbits.2 In humans, if we place a GP lens in the 200+ range on an
eye for 1 year, 30 nights at a time, there's no increased binding ability of Pseudomonas
.3,4 A 175 Dk/t soft lens, worn for 6 nights or 30, shows a small
but measurable increase.4 But even that increase is a lot less than conventional
disposable lenses with a Dk/t in the range of 24 to 60.5 The soft lenses
have a special need to transmit as much oxygen as possible.
Dr. Fonn: Even for daily wear lenses?
Dr. Cavanagh: Going to lower-Dk/t lenses
for convenience can compromise the patient's safety. Lower Dk/t lenses can have
higher water content and better comfort, but they're not as safe. This is true even
for daily wear, where 50% or more Pseudomonas infections occur.4
1. Compan V, San Roman J, Riande E,
et al. Oxygen transport through methylmethacrylate-based hydrogels with potential
biological capability. Biomaterials. 1996;17:1243-1249.
2. Imayasu M, Petroll WM, Jester JV,
et al. The relation between contact lens oxygen transmissibility and binding of
Pseudomonas aeruginosa to the cornea after overnight wear. Ophthalmology. 1994;101:371-388.
3. Yamamoto N, Yamamoto N, Petroll
MW, et al. Internalization of Pseudomonas aeruginosa is mediated by lipid rafts
in contact lens-wearing rabbit and cultured human corneal epithelial cells. Invest
Ophthalmol Vis Sci. 2005;46:1348-1355.
4. Cavanagh HD, Ladage PM, Li SL, et
al. Effects of daily and overnight wear of a novel hyper oxygen-transmissible soft
contact lens on bacterial binding and corneal epithelium: a 13-month clinical trial.
5. Lin MC, Graham AD, Polse KA, McNamara
NA, Tieu TG. The effects of one-hour wear of high-Dk soft contact lenses on corneal
pH and epithelial permeability. CLAO J. 2000;26:130-133.
The "Too Much Oxygen" Myth
MOST OXYGEN REACHES THE
EYE'S SURFACE FAIRLY SLOWLY BY DIFFUSION, RATHER
THAN QUICKLY BY PUMPING THROUGH TEARS.
Dr. Fonn: We've talked a lot about the eye's
need to receive oxygen through contact lenses the more, the better. In a
natural environment, can the eye get too much oxygen?
Dr. Wilson: Most oxygen reaches the eye's
surface fairly slowly by diffusion, rather than quickly by pumping through tears.
Because diffusion means moving from a higher to a lower concentration, the eye has
no way to reach a higher oxygen level than its environment, the surrounding air.
Dr. Hill: The cornea is naturally at
an atmospheric oxygen level to start with. We're just returning it to its normal
level when we increase the Dk/t, so I don't see any kind of risk for the cornea.
WHO ARE "HAPPY" IN THEIR PMMA OR GP LENSES STILL
GIVE THEM VERY LOW OVERALL COMFORT RATINGS.
... HIGHER-DK/T LENSES CAN REDUCE THE REDNESS AND
DISCOMFORT, AND ENHANCE LONG-TERM EYE HEATH.
Dr. Holden: In the past, when we refitted
people with high-oxygen GP lenses, people said, "Don't go too far. The patient will
complain!" Now we know we get corneal sensitivity back, which can mean greater initial
awareness and discomfort, but overwhelmingly, patients are far happier. At meetings,
some colleagues even tried to convince me I was doing a disservice by promoting
GPs over PMMA lenses. The supporting data is there, and myths often tend to come
from hesitation among colleagues. Dr. Sweeney did a terrific piece on switching
people from low-Dk/t to high-Dk/t lenses "cold turkey" that debunked the idea of
"breaking in patients gently."
Sweeney: Yes, we fit patients straight from low- to high-Dk/t lenses, and they did
extremely well. In terms of comfort, patients who are "happy" in their PMMA or GP
lenses still give them very low overall comfort ratings. They're chronically uncomfortable,
but they stay with their lenses for the advantages they offer. Higher-Dk/t lenses
can reduce redness and discomfort, and enhance long-term eye health.
1. Efron N, Brennan N. How much oxygen? In search
of the oxygen requirement of the cornea. Contax. 5-18, July 1987.
2. Benjamin WJ. Corneal oxygen philosophies.
Int Eyecare. 1986;2:106.
3. Benjamin WJ, Hill R. Human cornea:
Oxygen uptake immediately following deprivation. Graefe's Arch Clin Exp Ophthalmol.
4. Fatt I, Chaston J. Measurement of
oxygen transmissibility and permeability of hydrogel lenses and materials. Int Cont
Lens Clin. 1982;9:76-88.
5. Brennan NA. A model of oxygen flux
through contact lenses. Cornea. 2001;20:104-108.
Contact Lens Spectrum, Issue: August 2005