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.
|The 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. 1985;26:1354-1359.
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.