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Evaluating Corneal Oxygenation During Lens
Wear
Experts discuss current thinking on contact lens permeability and
transmissibility and the importance of corneal oxygenation to prevent
complications.
By Philip Morgan, PhD, and Noel Brennan, PhD
What are the five criteria for a contact lens to be successful in the
marketplace? A contact lens must support adequate corneal physiology, provide
satisfactory visual performance and acceptable comfort, and it must be easy to
handle and accessible to patients.
Adequate corneal physiology during contact lens wear has received the most
attention in the literature as a key measure of contact lens safety. Generally,
the various forms of ocular adverse events can be attributed to mechanical or
lens surface effects or hypoxia-related phenomena.
In this article, we will review oxygen transmissibility performance of contact
lenses currently available and evidence supporting the development of guidelines
to differentiate between lens types.
Importance of Oxygen
During contact lens wear, gas transport properties of the lens have a direct
impact on corneal oxygenation. Transmitting oxygen to the central and anterior
segments of the cornea is most important. The corneal periphery may derive some
of its oxygen supply from the local vasculature, while the posterior layers
receive oxygen from the aqueous humor. However, the central anterior cornea
depends on the atmosphere for oxygen. Thus, the oxygen transport characteristics
of a contact lens are of considerable importance.
It follows that we must develop a method to measure oxygenation of the eye
during contact lens wear. For more than 30 years, the best-known measures in
this area have included oxygen permeability of the materials from which lenses
are made and oxygen transmissibility, the oxygen performance of finished,
manufactured lenses.
Permeability And Transmissibility
In the materials science literature, gas permeability of a membrane is given as
the product of the diffusivity (D) of the material to the gas (the ease with
which the gas can move through the material) and the solubility (S) of the gas
within the membrane material (the amount of gas that is present in the material)1.
The formula appears as:
Permeability = DS
In the contact lens literature, we represent solubility as �k� so that the
formula appears as:
Permeability = Dk
It is important to know that permeability is a property of a material. The
oxygen performance of a manufactured contact lens is partly a function of the
permeability of the material from which the lens is made but also is related to
lens thickness. For example, if two lenses are made from the same material but
one lens is twice as thick as the other, then oxygen performance of the thicker
lens will be half that of the thinner lens. When thickness is taken into
account, we use the term oxygen transmissibility, which is shown as:
Transmissibility = Dk/t
The thickness of a finished contact lens can be a contentious issue, so any
report of lens transmissibility should include details on lens thickness. This
can be the thickness of the geometric center or of any part of the lens.2
Commonly, the thickness of the central zone (usually 6 mm in diameter) is used.
The rationale behind using the central zone as a value is both pragmatic and
clinical. Pragmatically, the 6-mm central zone falls within the optical zone of
the lens, which means that if the central thickness is measured as well as other
lens parameters (such as
lens power and water content), the average thickness of the central zone can be
calculated. Clinically, the central lens area is more likely to be of interest
because it covers the part of the cornea that relies on the atmosphere for
oxygen.
Dk and Dk/t for
Conventional Hydrogels
For conventional hydrogel materials, the factor that determines permeability is
simply water content. Oxygen reaching the ocular surface from the atmosphere
must pass through the water within the material. The first hydrogel lenses were
manufactured from poly hydroxy ethylmethacrylate (pHEMA), which has a
permeability of about 7 units.
As the importance of oxygen permeability became better understood, manufacturers
sought to increase the water content of their materials by adding other monomers
to the lens material. A common approach in contact lens manufacturing involves
adding methacrylic acid to increase water content of the polymer from 38% of
pHEMA to 50% to 60%. Another method is to use vinyl pyrrolidone or other
hydrophilic monomers to provide materials with water content values over 70%.
Increased water content causes an exponential increase in lens material
permeability. Figure 1 depicts the relationship between permeability and water
content (W) for conventional hydrogels found by Morgan and Efron.3
They demonstrated:
Dk = 1.67e0.0397W
Although clinicians are interested in the permeability of a contact lens
material, a much more relevant measure is transmissibility, which takes into
account the thickness of a lens as it relates to oxygen performance. If lens
thickness for any given power were similar for all material water contents, then
lenses made from materials with the greatest permeability would offer the best
transmissibility. However, this is not the case. Materials with very high water
content (over 70%) are rarely very thin because (a) such lenses are difficult to
manufacture and (b) thin, high water-content lenses cause central corneal
staining through a mechanism that is not well understood. However, it has been
suggested that the corneal staining might be related to local dehydration of the
corneal epithelium.4 In practice, this means that for conventional
hydrogel lenses in the mid-minus range, the oxygen transmissibility of a thin
mid-water lens is likely to be as good as or better than that of a thicker, high
water-content lens.
Dk and Dk/t for Silicone
Hydrogels
Although the polymers used in conventional hydrogel contact lenses are
inherently limited in permeability to oxygen (any permeability is via the water
contained within the material), many polymers can transmit oxygen. Polymers
containing siloxane groups, which are used to manufacture silicone hydrogel
contact lenses, are known to offer high levels of oxygen permeability. Six
contact lens brands are made of this type of material, with Dk values ranging
from 60 to 140 units1 (see Table 1).
Figure 2 shows the relationship between material
water content and oxygen permeability for silicone hydrogels. Clearly, the
intrinsic relationship seen in conventional hydrogels as shown in Figure 1 is
not evident for silicone hydrogels. While there is a general trend toward
decreasing water content associated with higher permeability values (as the
proportion of siloxane groups in the material increases), we cannot accurately
predict one parameter from the other.
Tighe5 has described families of silicone hydrogel materials in which
there is a reasonably predictable relationship between oxygen permeability and
water content. However, unlike the situation for conventional hydrogels, in
which the materials available are essentially from one family, the silicone
hydrogels on the market are derived from a number of material families, making
accurate associations between water content and other properties somewhat
difficult.
A vital question in understanding the issues relating to contact lens oxygen
performance is: How much oxygen does the cornea require to maintain normal
corneal physiology?
Researchers have addressed this question in many ways. For open-eye (daily wear)
conditions, Holden and Mertz6 presented the best known value,
suggesting that a lens with Dk/t of 24.1 units would not induce corneal swelling
during daily wear. At the time of their research, permeability values normally
were not edge-corrected. This is a calculated adjustment to laboratory measures
to account for artificially increased permeability values found during the
polarographic assessment of contact lenses.3 The edge-corrected equivalent value
is 21.8 units.
Other estimates of critical Dk/t levels include the work of Papas,7
who demonstrated that a peripheral Dk/t of 125 units was required to avoid
limbal hyperemia during open-eye wear of soft lenses. Harvitt and Bonanno8
proposed a value of 35 units to avoid hypoxia throughout the cornea.
The issues surrounding overnight wear are more complex. Holden and Mertz6 found
that a lens with a transmissibility of 87 units (73 units if edge-corrected
values are employed) would limit overnight corneal swelling to 4% � a value
considered equivalent to a non-lens wearer. They also suggested a compromise
threshold of 34 units, which might induce some additional corneal swelling after
overnight wear but that allowed the cornea to return to normal thickness soon
after waking. Subsequent researchers, using a variety of rationales, have
reported thresholds from 56 units9 to 300 units.10
To some extent, we can attribute these disparate values to the different
determination approaches. However, a more pertinent explanation is that the
difference in corneal oxygenation between an eye wearing a lens with a Dk/t of
56 units and another wearing a lens with a Dk/t of 300 units (to use the extreme
examples of Dk/t thresholds mentioned above) is surprisingly modest. Indeed, the
relationship between corneal oxygenation during contact lens wear and Dk/t is
such that trying to quantify thresholds for oxygen performance in terms of Dk/t
is not a trivial matter.
Alternative methods of describing corneal oxygenation include calculations of
oxygen volume reaching the cornea during contact lens wear (oxygen flux) and
corneal oxygen consumption. The latter has been proposed as a better index of
corneal physiology because it better reflects how much oxygen the cornea
metabolizes rather than simply the volume of oxygen available to the cornea, as
is the case in calculating oxygen flux.10
These
types of measures are potentially more desirable clinical indices because they
better indicate the physiological status of the cornea compared with Dk/t, which
is a laboratoryderived value. A number of authors have calculated the
relationship between Dk/t and corneal oxygenation (either oxygen flux or corneal
consumption). Figure 3 shows the relationship between these measures for the
closed eye (extended-wear) state. The main characteristic of this relationship
is a linear increase in oxygenation from a Dk/t of zero to about 50 units, after
which there is a marked flattening of the line representing the relationship
between the parameters. Put simply, we have a situation of diminishing returns
between increasing oxygen transmissibility of a contact lens and the amount of
oxygen provided to or used by the cornea.
This relationship explains why describing corneal oxygenation in terms of Dk/t
of a contact lens was appropriate in the era of low Dk lenses. If we only
consider values of Dk/t up to 30 units (about the maximum oxygen
transmissibility of most conventional hydrogels), then the near-linear
relationship between oxygenation and Dk/t would mean that doubling
transmissibility would account for approximately twice as much oxygen consumed
by the cornea. No such relationship exists for lenses of higher oxygen
transmissibility, and there is relatively little difference between the silicone
hydrogel lenses in terms of oxygen provision.
If you take into account the various thresholds for Dk/t for both daily wear and
extended-wear contact lenses and convert these values into measures of corneal
oxygen consumption, it appears the cornea will need to consume at least 90% of
natural oxygen levels to behave in a normal physiological manner. This can be
translated to minimum Dk/t values of about 20 and 50 units across the entire
lens, not just the lens center, for daily wear and extended wear, respectively.
Table 2 shows calculated Dk/t values as measured in our laboratory for the
geometric center and the thickest point of the lens periphery for a range of �
3.00DS conventional and silicone hydrogels. Of course, central lens thickness
will vary with lens power. Peripheral thickness, however, varies much less
across a range of powers.
Clinical
Signs
While the mathematical diffusion model provides comprehensive, versatile
information about corneal oxygenation, it is important to amalgamate such
analysis with clinical observation. To achieve this, we can consider the
presence or absence of hypoxiarelated clinical signs across a range of lenses;
an appropriate sign to consider is limbal hyperemia, which is an early response
to corneal hypoxia.11 In a masked, controlled study of neophyte
subjects, Maldonado-Codina and colleagues12 found that limbal redness
increased during daily wear of Acuvue 2 (Vistakon) lenses (peripheral Dk/t 9
units) by about half a clinical grade compared with baseline. Researchers
observed no change in limbal redness in patients who wore Acuvue Advance (Vistakon)
lenses (peripheral Dk/t 29 units) or Night & Day (CIBA Vision) lenses
(peripheral Dk/t 130 units)12 (Figure 4). This finding supports the
corneal oxygen consumption-derived threshold of about 20 units for
hypoxia-related changes during daily wear. Note that the four-fold difference in
peripheral Dk/t between the two silicone hydrogel lenses studied did not result
in a difference in limbal redness, presumably because both lenses fall on the
flat part of the corneal oxygenation vs. Dk/t curve.
Researchers have performed similar studies of extended wear contact lenses.
Brennan and colleagues13 reported greater limbal redness when
subjects slept in Acuvue 2 lenses compared with PureVision (Bausch & Lomb)
lenses (peripheral Dk/t 52 units) for 1 year. Morgan and Efron14
reported no difference in limbal redness in a study comparing PureVision lenses
and Night & Day lenses, each worn for 8 weeks on an extended-wear basis. The
research supports the notions that a threshold of about 50 Dk/t units exists for
extended wear across all lenses, and that the clinical performance of silicone
hydrogel lenses is similar in terms of hypoxia-related signs.
Oxygen at All Costs?
Although the relationship between Dk/t and corneal oxygenation during contact
lens wear reaches a virtual plateau in the silicone hydrogel region of the graph
(Figure 3), there remains a slight gradient to the relationship line. In other
words, increasing Dk/t for silicone hydrogel lenses offers a small oxygen
benefit to the wearer, and some may argue that we should provide maximum levels
of oxygen to contact lens wearers at all costs. We disagree with this view.
Although corneal physiology is an extremely important aspect of wearing contact
lenses, it is just one of five criteria for successful lens wear. We do believe
it is the most important criterion of those listed and, therefore, deserves a
heavy weighting factor when assessing the overall performance of a contact lens
brand. However, there needs to be a balance across all listed criteria. In the
absence of clear clinical benefits with ever-increasing Dk/t values, we must
take into account other considerations, such as contact lens wearer comfort and
vision.
REFERENCES
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measurement systems and application of contact lens oxygen permeability.
Ophthalmic Physiol Opt. 1987;7:485-490.
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calculations. Am J Optom Physiol Opt. 1984;61:627-635.
3. Morgan PB, Efron N. The oxygen performance of contemporary hydrogel contact
lenses. Contact Lens Ant Eye. 1997;21:3-6.
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water content lenses. Clin Exp Optom. 1986;69:103-107.
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Optom Vis Sci. 1999;76:712-719.
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contact lens extended wear on rabbit corneal epithelium using confocal micro-scopy.
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10. Brennan NA. Beyond flux: total corneal oxygen consumption as an index of
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11. Efron N. Contact Lens Complications. 2nd edition. Oxford, UK:
Butterworth-Heinemann, 2004.
12. Maldonado-Codina C, Morgan PB, Schnider CM, et al. Short-term physiologic
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30-day continuous wear schedule. Ophthalmol. 2002;109:1172-1177.
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Contact Lens Spectrum, Issue: May 2007