How much oxygen?

Contact lenses impede the movement of oxygen from the atmosphere, which contains 20.9% oxygen, to the anterior corneal surface. This is particularly significant during overnight wear, because even less oxygen is available from the palpebral conjunctival vessels compared to the atmosphere. Circulation of oxygen-rich tears behind a lens only occurs when the eye is open, therefore diffusion of oxygen through a contact lens is the major factor impacting oxygen supply during overnight wear. The need for contact lenses that transmit high levels of oxygen to the cornea was first recognised almost 60 years ago (Goodlaw 1946; Smelser & Ozanics 1952). However it wasn’t until the 1970s that attempts to quantify the actual level of oxygen needed were published. Using gas-goggles Polse and Mandell (Polse & Mandell 1970) found up to 2.5% oxygen was necessary to prevent corneal swelling but later clinical experience indicated that this underestimated the needs of the cornea during contact lens wear. Indeed several studies have since shown that between 10 and 15% oxygen is required for the majority of patients to prevent stromal swelling and that the individual variation in the need for oxygen can be as high as 21% (Holden et al. 1984; Mizutani et al. 1983). When the eye is deprived of oxygen from the atmosphere, there are a range of short-term effects such as reduced visual acuity and discomfort, as well as long-term adverse effects impacting all layers of the cornea. For patients with higher than average requirements for oxygen, even small reductions in the availability of oxygen may be detrimental to corneal health.

Efron and Brennan succinctly captured the controversy over measurements of the critical oxygen requrement of the cornea in their review entitled “How much oxygen? In search of the critical oxygen requirement of the cornea” published in July 1987 in Contax pp 5-18. Accurate definition of the amount of oxygen the cornea needs during lens wear is useful not only for predicting how wearers may respond to different lens types but is a baseline from which to design lens materials that maximise the transfer of oxygen from the atmosphere to the cornea.

In their review Efron and Brennan described and compared the numerous methods for measuring oxygen requirements that have been applied to each layer of the cornea. For the epithelium, studies have focussed on assessing biochemical or structural/functional changes in response to varying levels of oxygen. Biochemical studies measure the metabolic response of the epithelium to oxygen depletion; principally the reactions involved the breakdown of glucose. The first steps in glucose metabolism involve conversion of glucose to pyruvate (an intermediate of glycolysis). Under aerobic conditions, pyruvate is then completely converted to carbon dioxide, water and energy through the citric acid cycle. One of the oxygen dependent enzymes of the citric acid cycle, succinic dehydrogenase has been used as a measure of the level of oxygen required by the cornea. Under anaerobic conditions, pyruvate is reduced to lactate by lactate dehydrogenase. Lactate then diffuses into the stroma causing oedema and continues across the endothelium into the aqueous. Accumulation of lactate in the anterior chamber and changes in the distribution and level of lactate dehydrogenase therefore are also useful measures of hypoxia at the epithelium. In addition, depletion of glycogen, which is an alternate energy source stored in the epithelium has also been used as a marker of hypoxia. Overall the studies using these techniques in Efron and Brennans’ review were conducted in rabbit eyes and indicate between 5 and 13% oxygen is needed for normal metabolic function. This range of oxygen concentration is in agreement with the studies examining the structural and functional changes of the epithelium using epithelial thickness, corneal sensitivity, rate of mitosis or mitochondrial function as indicators of hypoxia. The variability in the results from these studies reflects the differences in experimental design, techniques and statistical analyses, as well as the variation in oxygen needs of individual corneas making it difficult to determine what the actual critical oxygen requirements of the human cornea may be.

Benjamin and Hill (Benjamin 1986; Benjamin & Hill 1985) found even higher levels of oxygen may be needed in their study of oxygen consumption of human cornea. In this study, Benjamin and Hill measured the flux of oxygen into the cornea across the tear-epithelium interface with a polarographic oxygen sensor following exposure to eight oxygen concentrations ranging from 0% to 20.9%. Oxygen uptake increased linearly as oxygen supply decreased and by comparing the changes in oxygen uptake with changes in corneal function Benjamin (1985) inferred that the critical oxygen requirement of the cornea could be as much as 15.6%.

In contrast to the broad range of techniques applied to the epithelium, the single overriding measure of hypoxia in the stroma has been the swelling response. A great advantage of this indicator is that it can be measured in vivo and can be applied to the centre and peripheral regions. Efron and Brennan’s review clearly shows that as our ability to measure the swelling response has improved, estimates of the oxygen needs of the cornea have increased. In parallel work Mizutani et al. (1983) and Holden et al. (1984) found that 15 and 10.1% oxygen, respectively are required to prevent stromal swelling and these are in agreement with Brennan et al. (1987) data showing 9.8% and 12.3% are required at the central and peripheral cornea.

Endothelial blebs are small, dark, non-reflective areas that appear scattered over the endothelial mosaic minutes after low-Dk lenses are inserted and disappear rapidly after lenses are removed. Intially it was thought that blebs occur in direct response to oxygen deprivation at the anterior surface of the cornea but it appears they form more in response to an acid shift during hypoxa rather than to low oxygen concentrations per se (Williams & Holden 1986). Williams and Holden (1986) found 16.6% oxygen is required to prevent the formation of endothelial blebs.

Many of the studies described in Efron and Brennan’s review focus on measuring the oxygen needs of the cornea in the absence of lens wear and may underestimate the actual levels of oxygen required during wear. By comparing the relationship between corneal swelling and equivalent oxygen percentage (EOP) during lens wear with corneal swelling and gaseous concentrations of oxygen in the absence of lens wear Brennan et al. (1988) found that the critical oxygen requirement to avoid swelling was 18% with contact lens wear and 10.9% without lens wear. Although these differences may be attributed to differences in the techniques themselves these data highlight the impact of contact lens-induced hypoxia on the cornea and the contribution of other factors such as changes in temperature, tear pH and tear osmolarity to overnight corneal swelling.

Conclusions

Efron and Brennan conclude that although some of the early differences in estimates of the critical oxygen needs of the cornea came about because of lack of experimental and statistical rigour, measurement of the critical oxygen requirement of the cornea is useful for predicting the corneal response to contact lens-induced hypoxic stress. When comparing critical oxygen requirements, practitioners should keep in mind how these estimates are derived and particularly should remember that research studies such as these represent the average of sometimes small groups of subjects, giving no indication of the large variation in critical oxygen requirements that can exist across individuals. Efron and Brennan propose that the real critical oxygen requirement is 20.9%, the concentration of oxygen in the atmosphere, and that any contact lens that delivers less than this concentration to the cornea ultimately will affect corneal physiology. The decision practitioners must make is what is the minimum level of change in corneal physiology that is acceptable for each of their patients.

References

Benjamin, W. J. 1986 Corneal oxygen philosophies. Int Eyecare 2, 106.

Benjamin, W. J. & Hill, R. 1985 Human cornea: oxygen uptake immediately following graded deprivation. Graefe's Arch Clin Exp Ophthalmol 223, 47-49.

Brennan, N., Efron, N. & Carney, L. 1988 Corneal oxygen availability during contact lens wear: a comparison of methodologies. Am J Optom Physiol Opt 65, 19-24.

Brennan, N. A., Efron, N. & Carney, L. G. 1987 Critical oxygen requirements to avoid oedema of the central and peripheral cornea. Acta Ophthalmol (Copenh) 65, 556-564.

Goodlaw, E. 1946 Contact lens solutions and their wearing time. Optom Weekly 37, 1675-1679.

Holden, B. A., Sweeney, D. F. & Sanderson, G. 1984 The minimum precorneal oxygen tension to avoid corneal edema. Invest Ophthalmol Vis Sci 25, 476-480.

Mizutani, Y., Matsunaka, H., Takemoto, N. & Mizutani, Y. 1983 The effect of anoxia on the human cornea [Japanese]. Acta Soc Ophthalmol Jpn 87, 644-649.

Polse, K. A. & Mandell, R. M. 1970 Critical oxygen tension at the corneal surface. Arch Ophthalmol 84, 505-508.

Smelser, G. K. & Ozanics, V. 1952 Importance of atmospheric oxygen for maintenance of the optical properties of the human cornea. Science 115, 140.

Williams, L. & Holden, B. A. 1986 The bleb response of the endothelium decreases with extended wear of contact lenses. Clin Exp Optom 69, 90-92.