O_{2} Measurements And Needs
For longterm perspectives, higher permeability
is important.
Dr. Fonn: We've discussed oxygen transmissibility at length. Is oxygen flux perhaps a more meaningful metric than transmissibility? It's been said that if we use it, we can effectively marginalize lenses above 87 x 10^{–9}.
Dr. Holden: To create flux, there must be pressure on one side, pressure on the opposite side and resistance in the middle. The higher the partial pressure of oxygen under the lens, the lower the flux will be. So, if we have a highDk/t lens — say, 1,000 Dk/t — there's no resistance to oxygen flow. Flux across the lens is infinitesimal because there's no driving force. So looking to flux to help assess corneal health doesn't tell us a whole lot with these lenses.
In the literature,^{1–4} we've seen studies of oxygen and partial pressures across corneas. They try to estimate flow rates to determine which flow rates are beneficial to cells. In one publication,^{5} the graph of flux calculated based on a mathematical model vs. Dk/t went to Dk/t 18 and flatlined, meaning flux into the cornea is the same at 18 Dk/t or 4 million Dk/t. Of course, we know we need higher than 18 Dk/t to avoid corneal edema and limbal hyperemia. It does make a difference whether the Dk/t is 20 or 125. So there's a lot of confusion about calculated models of oxygen flux — how the dynamic circumstances of reallife lens wear, such as waking up after 8 hours of sleep, require different oxygen transmission rates. To get meaningful data from flux numbers, we need to state all the terms and conditions, and compartmentalize the lens, the epithelium, the stroma and so forth.
Dr. Bonanno: Flux is a good metric to use, but it's not any better than a lot of the other metrics we use. In the steadystate, oxygen flux into the cornea is equal to flux across the contact lens. This can be determined by knowing the Dk/t and the oxygen tension of the tears under the lens. Flux = (Dk/t) x (155 – oxygen tension). So if we have a very highDk/t lens, we'll have fairly high flux into the cornea. And as Dk/t goes down, there will be less flux. For a "normal" cornea, knowing the flux into the cornea or knowing the lens Dk/t or knowing the oxygen tension of the tears provides the same information.
HOW CAN WE USE OXYGEN FLUX?
Dr. Holden: Most often, oxygen flux is calculated based on a mathematical model with certain assumptions. Dr. Bonanno, your group has actually measured the partial pressure of oxygen behind a hydrogel lens.
Dr. Bonanno: We can measure the difference in the mean oxygen tension, but if we take 30 subjects, we'll find a lot of variability. There's this sort of logarithmic function: For patients in highDk/t lenses, we measure the oxygen tension or flux between a lens that's 90 and a lens that's 110 or 130. It's my impression, although we haven't measured this yet, that we'll need to have a huge difference in Dk/t to show any significant difference between lenses.
Dr. Holden: Your data seem to indicate significant acidosis — a 0.34 increase in pH with very low Dk/t. And when you got up to about 90 Dk/t, you had about a 0.15 increase in acidosis. You didn't have any lenses beyond 90 at the time to test. It seemed you would hit the Dk/t axis somewhere around 110 for open eye and 150 for closed eye. Has that work been done yet?
Dr. Bonanno: No. That's even harder to do. The differences are even smaller. It's harder to measure pH than it is to measure oxygen. We can see what the threshold is by how far we can measure it.
Dr. Cavanagh: If we had a longterm, welladapted extended wearer in the group and the epithelium was 28 microns instead of the baseline 52, the values would change. Have you ever baselinecorrected any of your values for a patient's existing epithelial thickness?
Dr. Bonanno: No. That assumes a thickness change will produce a linear change in metabolic activity. It might, but we don't know if that actually happens. It would be difficult to study in a human sample. We can measure the thickness change, but we don't know whether the oxygen consumption per unit volume of tissue has changed as well.


In the steadystate, oxygen flux into the cornea is equal to flux across the contact lens. This can be determined by knowing the Dk/t and the oxygen tension of the tears under the lens. ... So if we have a very highDk/t lens, we'll have a fairly high flux into the cornea. –Dr. Bonanno 

HOW DO OXYGEN NEEDS CHANGE IN REAL LIFE?
Dr. Holden: Dr. Bonanno, I'm interested in the following phenomenon. For example, we might measure or estimate the flux going into the epithelium without a contact lens and get a base level number of, perhaps, 6 microliters/ cm^{2}/hour. If we apply a highDk/t lens and measure it, we'd measure the front 6 still going through the epithelium. If we apply a lowDk/t lens, drop the cornea's oxygen level and get acidosis, we can measure a flux of 9 or 10 produced by this change in the cornea's acid levels under stress. The flux into the cornea is higher than the resting flux. Looking at the data, we might say, "Well, here's a lower flux."
Dr. Bonanno: When Dk/t is low, there's a higher flux across the lens, but a lower flux into the cornea.
Dr. Holden: The eye never increases its uptake in a normoxic environment unless the cornea is stressed.
Dr. Bonanno: No, because it's 155 in the open eye with no lens, so you have high oxygen tension. There's a steep gradient — a lot of flux. As you apply lenses, lowering the Dk/t, the steadystate oxygen tension at the tears will decrease, and then the gradient is shallower.
Dr. Holden: When we remove the lens and restore oxygen at high levels, the uptake rate to the cornea is higher because the cells have been under stress.
Dr. Bonanno: Right. But what's important, I think, is the steady state. That's kind of the EOP. It's an indirect way of measuring oxygen consumption, and it's a nonsteady state.
Dr. Holden: In a realworld range of situations, the eyes can respond more readily with highDk lenses than they can with lowDk lenses.
Dr. Bonanno: I agree. We should get as much oxygen as possible. We just need to keep these numbers in perspective.
Dr. Holden: Right. The difference between 90 and 180 Dk/t, for example, may not be remarkable in terms of flux when one uses a mathematical model to calculate it. But it may have a major impact on limbal redness, on decades of contact lens wear or on any other situations. The fact that we can't double the flux isn't important for corneal health because that's determined by longterm, high oxygen availability under all sorts of circumstances or transient situations. But just from the perspective of longterm safety and minimizing structural change to the cornea, we need to go for higher permeability.

Oxygen Transmission Decreases Bacterial Binding  
Dr. Fonn: Dr. Cavanagh, your group has repeatedly found a relationship between oxygen transmission and bacterial binding to epithelial cells. Is there a critical transmission level? Dr. Cavanagh: Yes, I think there is a critical level. Unlike the other biological outcome measures that we've talked about so far, we're not quite there yet with silicone hydrogels. We need to get as close to a gas permeable lens or no lens as possible. Dr. Fonn: Why? Dr. Cavanagh: As we sleep without lenses, carbon dioxide goes up, oxygen goes down, and the cornea swells, but we don't wake up with Pseudomonas ulcers. So hypoxia alone isn't the primary cause of susceptibility to infection — the lens is. Why? Because if the bug can't stick to the cornea, it can't infect it. And we've found that in animal eyes, oxygen prevents sticking. The quantity of bacteria sticking to the eye after 24 hours can be directly related to the oxygen transmissibility value of a lens.^{1}
If we compare a soft lens and a gas permeable lens with the same oxygen transmissibility value — let's say 80 Dk/t — then twice as many bugs bind to the corneal surface of the softlens eyes in rabbits.^{2} In humans, if we place a GP lens in the 200+ range on an eye for 1 year, 30 nights at a time, there's no increased binding ability of Pseudomonas .^{3,4} A 175 Dk/t soft lens, worn for 6 nights or 30, shows a small but measurable increase.^{4} But even that increase is a lot less than conventional disposable lenses with a Dk/t in the range of 24 to 60.^{5} The soft lenses have a special need to transmit as much oxygen as possible. Dr. Fonn: Even for daily wear lenses? Dr. Cavanagh: Going to lowerDk/t lenses for convenience can compromise the patient's safety. Lower Dk/t lenses can have higher water content and better comfort, but they're not as safe. This is true even for daily wear, where 50% or more Pseudomonas infections occur.^{4} Oxygen matters. REFERENCES 1. Compan V, San Roman J, Riande E, et al. Oxygen transport through methylmethacrylatebased hydrogels with potential biological capability. Biomaterials. 1996;17:12431249. 2. Imayasu M, Petroll WM, Jester JV, et al. The relation between contact lens oxygen transmissibility and binding of Pseudomonas aeruginosa to the cornea after overnight wear. Ophthalmology. 1994;101:371388. 3. Yamamoto N, Yamamoto N, Petroll MW, et al. Internalization of Pseudomonas aeruginosa is mediated by lipid rafts in contact lenswearing rabbit and cultured human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2005;46:13481355. 4. Cavanagh HD, Ladage PM, Li SL, et al. Effects of daily and overnight wear of a novel hyper oxygentransmissible soft contact lens on bacterial binding and corneal epithelium: a 13month clinical trial. Ophthalmology. 2002;109:19571969. 5. Lin MC, Graham AD, Polse KA, McNamara NA, Tieu TG. The effects of onehour wear of highDk soft contact lenses on corneal pH and epithelial permeability. CLAO J. 2000;26:130133. 


The "Too Much Oxygen" Myth  
Dr. Fonn: We've talked a lot about the eye's need to receive oxygen through contact lenses — the more, the better. In a natural environment, can the eye get too much oxygen? Dr. Wilson: Most oxygen reaches the eye's surface fairly slowly by diffusion, rather than quickly by pumping through tears. Because diffusion means moving from a higher to a lower concentration, the eye has no way to reach a higher oxygen level than its environment, the surrounding air. Dr. Hill: The cornea is naturally at an atmospheric oxygen level to start with. We're just returning it to its normal level when we increase the Dk/t, so I don't see any kind of risk for the cornea.
Dr. Holden: In the past, when we refitted people with highoxygen GP lenses, people said, "Don't go too far. The patient will complain!" Now we know we get corneal sensitivity back, which can mean greater initial awareness and discomfort, but overwhelmingly, patients are far happier. At meetings, some colleagues even tried to convince me I was doing a disservice by promoting GPs over PMMA lenses. The supporting data is there, and myths often tend to come from hesitation among colleagues. Dr. Sweeney did a terrific piece on switching people from lowDk/t to highDk/t lenses "cold turkey" that debunked the idea of "breaking in patients gently." Dr. Sweeney: Yes, we fit patients straight from low to highDk/t lenses, and they did extremely well. In terms of comfort, patients who are "happy" in their PMMA or GP lenses still give them very low overall comfort ratings. They're chronically uncomfortable, but they stay with their lenses for the advantages they offer. HigherDk/t lenses can reduce redness and discomfort, and enhance longterm eye health. 

REFERENCES
1. Efron N, Brennan N. How much oxygen? In search of the oxygen requirement of the cornea. Contax. 518, July 1987.
2. Benjamin WJ. Corneal oxygen philosophies. Int Eyecare. 1986;2:106.
3. Benjamin WJ, Hill R. Human cornea: Oxygen uptake immediately following deprivation. Graefe's Arch Clin Exp Ophthalmol. 1985;223:4749.
4. Fatt I, Chaston J. Measurement of oxygen transmissibility and permeability of hydrogel lenses and materials. Int Cont Lens Clin. 1982;9:7688.
5. Brennan NA. A model of oxygen flux through contact lenses. Cornea. 2001;20:104108.