Measuring Oxygen Uptake
Equivalent oxygen percentage measurements reveal
the short-term effects of various lenses and how the eye responds.
Dr. Fonn: As researchers, we now have several
methods to help determine how much oxygen reaches the cornea through a contact lens.
It's a challenge to define each technique's capabilities and choose what's best
for our purposes. Oxygen consumption is one index that measures how much oxygen
is reaching the cornea. Do you find it effective?
Dr. Sweeney: Generally, we measure equivalent
oxygen percentage (EOP) after very short exposure to a lens, so the response is
useful in a way that corneal swelling is not. We need many methods for assessing
how the cornea responds to the lens. EOP tells us how the eye responds and helps
us discriminate some differences.
Dr. Holden: EOP is a very good test
to see how the cornea responds to a challenge. Done correctly, it can help distinguish
between the high-level oxygen transmissibility lenses, which is difficult to determine
from some other measures. This means we can measure the cellular response to a lens
that provides 21% oxygen, like silicone elastomer, and a lens that provides 19%
to 20%, like a Dk/t 175 or 200. We want to know what lens will make a difference
in 20 years, not just the short-term response. In one study,1 Cornea
and Contact Lens Research Unit (CCLRU) researchers looked at the eyes of 60 people:
20 who'd removed GP lenses the day before; 20 who'd removed 24- to 30-Dk/t soft
lenses; and 20 who'd never worn lenses. Researchers identified the soft
lens wearers 85% to 90% of the time because they had limbal vascularization and
redness associated with chronic hypoxia. If we look at the EOP numbers, we have
to validate any decrease and think about what it means for the cornea.
Dr. Hill: When distinguishing between
high-transmissibility lenses, we're talking primary effects, or the direct need
for oxygen. But EOP may pick up some secondary effects over longer and subtler applications.
For example, the mechanical effects of a lens on the cornea may shave, slough or
swell the epithelium, or neovascularization may occur. An EOP done 2 or 3 weeks
later or for a longer period might reflect these things in some way. These are dimensions
of EOP we haven't really explored. In the future, we could see these options, as
well as tests that show levels of substances other than oxygen, such as acetylcholine,
which will help us assess sensations like touch, pressure, warmth and coolness.
HOW DOES EPITHELIAL
DAMAGE IMPACT OXYGEN UPTAKE?
Dr. Papas: What do we actually
measure with an oxygen consumption rate the uptake rate of epithelial cells
or an average value for the whole cornea?
Dr. Hill: Primarily, it's influenced
by the local epithelial cells, but the longer you constrain the cornea say,
in a PMMA contact lens the more you'll drain the secondary reservoirs. The
stroma is pulled down, and the epithelium gets first shot at any oxygen and reaches
some fairly high rates. After a while, as the epithelium gets enough oxygen and
the reservoir begins to come back, the rate slows.
Dr. Fonn: Epithelial thinning occurs
as a result of wearing low-Dk lenses. Does that change oxygen consumption?
Dr. Hill: If you remove the epithelium,
the oxygen consumption drops dramatically, and the same will happen if it swells
badly. The effects of smaller changes to the epithelium are tougher to quantify
one layer out of six, or two or three layers. And we don't know whether cuboidal
and columnar cells have different uptake rates. But these are subtleties we have
to look at in fine measurements.
Dr. Holden: In the Gothenburg study,2
we looked at patients who'd worn a 30 Dk/t contact lens on one eye only for 5 years.
The oxygen uptake rate was lower in the eye with the contact lens, and the epithelium
had thinned. It took about 1 month for the oxygen consumption to recover and 6 months
for the corneal thickness to recover. I don't consider this "adaptation." I call
it chronic damage to the epithelium. There's no doubt that long-term, the lenses
compromised the epithelium.
Dr. Cavanagh: Ladage and associates3
showed that you don't get epithelial thinning in a rabbit model in a 72-hour wear.
But we know that the mitotic rates and cell-shearing rates go down,3
and terminal differentiation or upward movement of cells is decreased. In other
words, when we think about not having enough oxygen, we have to think in terms of
hypoxia plus a lens. Hypoxia alone won't be the culprit. The lens will take the
oxygen below natural and create adverse conditions for the cornea to survive.
Dr. Fonn: Epithelial damage is a consideration
not only for oxygen consumption but for other issues, including infection. EOP tells
us about short-term effects, but in the future, it may tell us more about some
long-term effects of contact lens wear.
Benefit of CO2 Transmission
Dr. Fonn: A high-Dk/t silicone hydrogel lens
has a high rate of oxygen transmission, and it's probably a good transmitter of
carbon dioxide. Is CO2
transmission as important as oxygen transmission?
Dr. Bonanno: Having
5% carbon dioxide is like having your eyes closed all the time, and we know that
can cause some long-term problems.
Dr. Hill: So maybe we should look at
carbon dioxide transmission as a beneficial feature of high-Dk/t lenses that will
help us avoid acidosis and maintain metabolism.
Dr. Holden: We published a paper1
on HEMA lenses, which accumulate carbon dioxide in open-eye conditions. This actually
drives the endothelial bleb response, which in turn, shows endothelial contour changes
within 30 seconds. Carbon dioxide drove the process.
Dr. Fonn: Do you think endothelial
bleb response could discriminate between 90 and 175 Dk/t?
Dr. Holden: Yes. In fact, Hamano published
a study2 showing a definitive difference in bleb response profiles with
low, moderate and high-Dk/t lenses. Higher carbon dioxide transmissibility does
make a difference in eye health.
1. Holden BA, Williams L, Zantos SG. The etiology
of transient endothelial changes in the human cornea. Invest Ophthalmol Vis Sci.
2. Hamano H, Jacob JT, Senft C, et al. Differences
in contact lens induced responses in the corneas of Asian and non-Asian subjects.
CLAO J. 2002;28:101-104.
1. Covey M, Sweeney DF, Terry R, et al. Hypoxic
effects on the anterior eye of high Dk soft contact lens wearers are negligible.
Optom Vis Sci. 2001;78:95-99.
2. Holden BA, Sweeney DF, Vannas A,
et al. Effects of long-term extended wear contact lens wear on the human cornea.
Invest Ophthalmol Vis Sci. 1995;11:1489-1501.
3. Ladage PM, Yamamoto K, Ren DH, et
al. Proliferation rate of rabbit corneal epithelium during overnight rigid contact
lens wear. Invest Ophthalmol Vis Sci. 2001;42:2804-2812.
Contact Lens Spectrum, Issue: August 2005