Special Edition 2007
Evaluating Corneal Oxygenation During Wear

Experts discuss current thinking on contact lens permeability and transmissibility and the importance of corneal oxygenation to prevent complications.

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.

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