DK REALLY MATTERS
The Future of Contact Lenses: Dk Really Matters
Amid discussions of oxygen levels and calculated flux, the clinical imperative remains to maximize oxygen transmissibility for all lens wearers.
By Brien Holden BAppSc, LOSC, PhD, DSc, FAAO; Serina Stretton BSc, PhD; Percy Lazon de la Jara, BOptom, PhD, FIACLE; Klaus Ehrmann, BEng, MSc, PhD; and Donna LaHood, BOptom, MOptom
Recently, it's been suggested that the level of oxygen provided by any silicone hydrogel contact lens is sufficient for corneal health, and that providing the highest possible oxygen level does not matter to the cornea, the eye or the contact lens wearer.1,2 The implication is that the silicone hydrogel lens with the lowest oxygen transmissibility (Dk/t) is good enough, and that there's little value in completely eliminating hypoxia.
Dk (oxygen permeability) and Dk/t do matter. The eye has the greatest likelihood of good health if it receives the highest possible levels of oxygen. Of course, oxygen availability isn't the only important requisite for successful and safe contact lens wear. Adequate movement, deposit control, optical and physical design, ocular compatibility and surface wettability are also essential. And as a corollary, highly oxygen permeable lenses should be equal or superior to the conventional low-Dk hydrogel lenses in these and other important aspects of lens performance.
Wearers need the highest Dk possible for one simple reason: The cornea is designed for normoxia during the day and the (lower) levels of oxygen provided through the eyelid at night. Any reduction in oxygen availability requires some adjustment by the cornea, and long-term compromise will be deleterious in some way. Why compromise the cornea if it is not necessary?
As Efron and Brennan state,3 the real critical oxygen requirement for contact lens wear is 20.9% the concentration of oxygen in the atmosphere and any lens that delivers less than this concentration to the cornea ultimately will affect corneal physiology.
Some silicone hydrogel contact lenses
have local oxygen transmissibilities as low as 25 to 30 units
(with a unit measured as x 10-9 [cm/sec]/[mLO2/mL x mm Hg]), whereas others exceed 100 units across the entire lens. Even for the average wearer of daily wear lenses, it's unnecessarily challenging to the cornea to provide a lower-than-available oxygen level, since virtually all wearers nap for some period most days, and substantial numbers of wearers sleep in their daily-wear lenses, either occasionally or regularly.4 Why take the risk of hypoxic damage to the eyes if it can be avoided?
Effects of Contact Lens-induced Hypoxia
With the possible exception of silicone elastomer lenses under closed-eye conditions,5 contact lenses impede movement of oxygen to the anterior cornea, creating lens-induced hypoxia. Since the early days of contact lenses,6 chronic corneal hypoxia has been a major issue because it causes obvious corneal edema, variously described as Sattler's veil (haptic lenses),6 central corneal clouding (corneal lenses),7 and striae and folds (soft lenses).8 In the long term, hypoxia results in corneal exhaustion syndrome and discontinuation from contact lens wear.9
In recent decades, researchers have found that contact lenses that don't meet the cornea's oxygen requirements also cause impaired corneal metabolism and integrity, decreased epithelial thickness, stromal thinning, increased endothelial polymegethism and limbal redness, and corneal vascularization.10,11 Moreover, laboratory and clinical studies show that hypoxia causes increased bacterial adhesion to epithelial cells,12–15 and overnight corneal hypoxia increases the risk of infection.16
However, experience with silicone elastomer lenses17 and, more recently, silicone hydrogel lenses18 teaches us that eliminating hypoxia is not sufficient to prevent infection. Although hypoxia is a risk factor for microbial keratitis, overnight wear (eye closure) and bacterial contamination can be overwhelming factors.19–23
Estimating and Measuring Oxygen Supply
Researchers first recognized the need for contact lenses to transmit oxygen to the cornea almost 60 years ago.6 Debate and controversy continue to this day over the actual level of oxygen required by the cornea, partly because of the impracticalities of measuring oxygen supply in the normal clinical situation and partly because the wide variety of physiological and clinical indicators used in studies have different thresholds.
Variations in the way oxygen flow is measured or calculated and inconsistent use of terminology has caused great confusion among practitioners and, through advertising, their patients. Practitioners need reliable and practical measures of the oxygen performance of a lens. In addition, rather than rely on spurious and inaccurate statements, such as "all silicone hydrogel lenses supply essentially the same high levels of oxygen to the cornea," practitioners need to understand how well lenses of different Dks, powers and thickness profiles supply oxygen to the cornea.
Figure 1: Lens thickness profiles for a range of –3.00D silicone hydrogel lenses.
Practitioners have come to rely on two ways to estimate oxygen supply:
1. In-vitro measurements of lens material permeability (Dk) and the calculations and models necessary to derive clinically meaningful numbers from these in-vitro measurements
2. In-vivo clinical assessment and measurement of the effects on the cornea with such techniques as pachymetry of lenses of different oxygen transmissibility (Dk/t).
The advantage of an in-vitro measure such as Dk (D being diffusivity and k, solubility of oxygen) is that it's relatively simple to standardize techniques and obtain reliable data. Dk is a material property; Dk/t (where t is thickness and can be central or average) is the local or average estimate of ease of flow through a lens (the inverse of resistance).
Dk, the material property, is calculated from laboratory measurements of t/Dk (resistance to flow) and describes the permeability of a lens material, regardless of material thickness (barrier and edge effects having been considered). Once the Dk of a lens material is known, then the Dk/t of all lenses made from the same material can be calculated. Therefore, Dk allows the practitioner to consider and estimate oxygen supply for lenses of various thicknesses, powers and shapes.
Figure 2: Color-coded views of the oxygen transmissibilities (Dk/t) of –3.00D (top) and –6.00D (bottom) silicone hydrogel lenses. Plane view shows Dk/t over the area of each lens. Raised areas in the 3-D view show areas of highest Dk/t for each lens.
To understand part of the "Dk/t – oxygen flux" story, it's important to know that t/Dk is measured with a lens positioned between an air-rich and an oxygen-depleted chamber. Dk/t is a measure of the maximum potential of a lens to deliver oxygen to the eye over a given area when the front surface of the lens is in contact with air and the back surface is anoxic. This situation approximates when, for example, wearers just open their eyes after wearing a very thick, low-Dk/t lens. What Dk and Dk/t allow practitioners to do is estimate the oxygen performance of lenses across a wide variety of lens shapes, lens powers and environmental conditions (aphakic and thick-edge lenses in high altitudes, planes, sleep, and so on).
A misleading problem is created for the practitioner in that Dk/t is often quoted for lenses (or even implied for a lens type), using the central Dk/t, calculated using the instantaneous center thickness of a -3.00D lens. This Dk/t (at the thinnest point of a -3.00D lens) has also been used to calculate oxygen flux. Such reporting oversimplifies oxygen transmissibility and is misleading because it ignores both central thickness differences between lenses of different powers and differences across lenses of different power profiles. These differences have a significant impact on oxygen supply to the cornea and the limbus. After all, people don't wear lens centers they wear whole lenses that affect the entire cornea, including the limbus and the limbal conjunctiva. Comparing thickness profiles of some of the currently available silicone hydrogel lenses (Figure 1) clearly illustrates the considerable variation.
When we convert these profiles to Dk/t, we can see that, as expected, the Dk/t of minus-power lenses is greater in the center than it is in the periphery (Figure 2), and the opposite is true of plus-powered lenses (Figure 3). Contact lenses made from the same material in different shapes supply different amounts of oxygen to the cornea.
In an attempt to predict how much oxygen actually reaches the cornea over a given area and time (oxygen flux) and assess the impact of corneal oxygen consumption on oxygen flow during lens wear, Hill and Fatt27 modeled the distribution of oxygen across the cornea using Fick's law of diffusion (Figure 4). Fick's law is used to predict steady-state oxygen flux, and it states that flux depends on the difference in oxygen tension between the front and the back surfaces, e.g. of the lens, and the oxygen transmissibility of that lens.
Figure 3: Color-coded views of the oxygen transmissibilities (Dk/t) of +6.00D silicone hydrogel lenses. Plane view shows Dk/t over the area of each lens. Raised areas in the 3-D view show areas of highest Dk/t for each lens.
Measurement of the oxygen pressure (P0) behind a contact lens is difficult. Hamano24 achieved it using a thin-wire oxygen probe; Bonanno25 used oxygen-sensitive phosphorescent dyes; and Hill26, 27 measured P0 indirectly using equivalent oxygen percentage (EOP). EOP is obtained by sliding a lens off an eye, immediately measuring the oxygen uptake rate and then referring the value obtained to corneal responses calibrated to known gases.
Brennan1 proposed that total corneal oxygen consumption should replace Dk/t and oxygen flux as benchmarks for practitioners comparing lens performance because it better reflects corneal oxygen metabolism during lens wear. However, difficulties arise from the theoretical nature of the calculations and their reliance on various assumptions and immeasurable variations in conditions throughout a wearer's daily cycle and with a variety of lenses.
Brennan's first flux model predicted that oxygen transmissibilities of 15 units for daily wear and 50 units for extended wear were sufficient to sustain normal oxygen supply. Clearly, from daily and overnight edema measurements,28 these levels do not avoid even a crude sign of poor physiology, such as the onset of visible edema.
One major problem is that flux is a calculated entity, based on a certain set of assumptions, which in the initial Brennan model1 included the assumption of fixed corneal oxygen consumption. However, corneal oxygen consumption varies with the ambient oxygen conditions, corneal pH, temperature, physical pressure, the layer of cells, the number of cells and their state of health.
As Brennan points out, his model is a theoretical exercise only. It does not take into account the dynamic nature of corneal metabolism or the effects of environmental variations such as acidosis, as the model by Radke and Chhabra29 has done. Their work confirmed that 125 units should be the minimum to avoid significant impedance to oxygen supply under closed-eye conditions. These problems should not deter the development of models, which are useful for theoretical analysis. However, because they rely on a fixed set of circumstances, they have limited applicability in clinical situations.
In essence, the problems with using flux to make predictions about overall corneal health are 1) its susceptibility to the assumed model conditions and 2) the assumption that equal (calculated) fluxes mean the same consequences for corneal health.
|Figure 4. Fick's law of diffusion applied to a contact lens.|
j = Dk/t X (P1 – P0)
J is oxygen flux,
The second issue assuming that all fluxes are equal can be best understood if we take two different situations with the same apparent flux. Flux is the mathematical product of Dk/t multiplied by the partial pressure difference across the lens (Figure 4). It follows, therefore, that the same flux will be calculated through a lens with a Dk/t of 100 units and a driving force, P1 – P0, of 10 mm Hg (e.g. 155 mm Hg to 145 mm Hg), as is obtained with a lens with a Dk/t of 10 units and a driving force of 100 mm Hg (e.g. 155 mm Hg to 55 mm Hg). Because the calculated fluxes are the same, the two conditions a high-Dk/t lens and a low driving force (because of high levels of oxygen behind the lens) and a low-Dk/t lens and a high driving force (because of poor levels of oxygen behind the lens) are implied to be equivalent. Clearly, this is misleading, because these are very different circumstances physiologically. One cornea would be subject to a partial pressure of oxygen of 55 mm Hg (7% oxygen), and the other would have 145 mm Hg (19% oxygen).
Correlating Dk/t and Corneal Effects
Recent evidence from the work of both Ren and Wilson30 and Cavanagh31 on corneal homeostasis has revealed some of the reasons for the dramatic and long-lasting effects of lens-induced hypoxia on ocular physiology. Their work has shown that all contact lens types and wear modalities influence maintenance and turnover of the corneal epithelium to some degree, and the impact of lens wear on these processes is mediated in part by lens-induced hypoxia.14,32–36 Furthermore, the impact of high-Dk silicone hydrogels on epithelial turnover is less pronounced compared to other lens types, and wearers show more evidence of adaptive recovery during long-term wear.
The reason for greater epithelial thinning with lower-Dk/t lenses compared to higher-Dk/t lenses seems to be that oxygen deprivation creates an imbalance between the production of new cells at the basal epithelium and the loss of old cells from the corneal surface. A slower rate of cell shedding signals a lower demand for new cells from the limbus. This reduced demand ultimately results in fewer cells moving toward the surface, and the central epithelium eventually thins. The Göteborg Study10 showed that low-Dk/t extended wear disturbed epithelial metabolism, lowering the eye's oxygen uptake and thinning the epithelium. Jalbert and colleagues37 have recently shown this effect is minimized with silicone hydrogels. They found 7% epithelial thinning with high-Dk silicone hydrogels, compared to 23% for low-Dk hydrogel lenses.
The implications of oxygen deprivation at the corneal periphery become critical when we consider how the limbus helps the cornea maintain overall health. The limbus is the sole source of epithelial stem cells, which provide an unlimited supply of new epithelial cells and ensure rapid recovery from superficial injury. Any loss or injury to stem cell production can result in serious sequelae, including recurrent erosion, chronic keratitis and vascularization.38
What Dk/t Is Needed?
The true test of the utility of Dk/t is how well it aligns with clinical data. If all silicone hydrogel lenses were to deliver essentially the same levels of oxygen to the cornea, there would be no differences in how these lenses perform when measured against clinical indicators of hypoxia. Brennan's model39 of diminishing returns predicts that lenses with oxygen transmissibilities greater than 15 and 50 units will provide no benefit during daily or extended wear, respectively. But differences in limbal redness and corneal swelling do not support this prediction.
Papas has established a clear relationship between limbal hyperemia and oxygen deprivation beneath the lens periphery, indicating that a minimum Dk/t of 125 units is required to eliminate limbal redness with daily wear.40 If there's no advantage to wearing lenses with oxygen transmissibilities greater than 15 units for daily wear, then one would expect no differences in the level of limbal redness observed during daily wear with almost all the conventional hydrogel lenses and silicone hydrogel lenses. However, this is not the case. Maldonado-Codina's41 comparison of limbal redness with soft-lens daily wear detected significant differences between lenses with central oxygen transmissibilities of 26 and 86 units.
Corneal swelling is one of the most recognizable signs of corneal oxygen deprivation used by practitioners and researchers to assess lens performance. At 4% to 6% swelling, fine structural changes in the form of striae appear at the posterior stroma; at 8% swelling, endothelial folds become observable. Moreover, stromal swelling is not uniform across the cornea but mirrors the variation in oxygen availability in the post-lens tear film. When patients wear "donut" hydrogel lenses with a large central hole, the cornea swells under the portion of the cornea covered by the lens and not in the central area42 (Figure 5). Corneal edema correlates well with Dk/t in open and closed eyes.
Figure 5. Mean corneal swelling (%) across the cornea after 6 hours of wear of a donut lens (n = 10), with respect to the average lens thickness profile covering the cornea during wear.
The differences in Dk/t between different silicone hydrogel lenses are reflected in a study by Mueller and colleagues,43 which compared overnight swelling with 140-Dk and 99-Dk silicone hydrogel lens types. Researchers found using 140-Dk silicone hydrogel lenses that there was no significant difference in overnight central and peripheral swelling for –1.00D and –6.00D lenses and no differences in overnight edema with these lenses from no lens wear among patients. However, patients wearing the 99-Dk silicone hydrogel lens showed significantly greater corneal swelling in the center and periphery compared to no lens wear. Moreover, in another study with 99-Dk lenses, 11% of 30 adapted soft contact lens-wearers experienced greater than 7.7% edema after overnight wear.44
Average lens Dk/t across the optical zone and lens peripheral Dk/t are two practical benchmarks that enable practitioners to assess oxygen supply. The former is the basis for the Holden-Mertz criteria28 for preventing lens-induced hypoxia during open- and closed-eye wear, and the latter is the Papas criterion for avoiding limbal hypoxia (and possible hypoxic stem cell effects).40
The Holden-Mertz criteria of
24, 35 and 87 units for avoiding end-of-first-day edema, end-of-seventh-day edema,
and 4% overnight edema respectively were based on average lens thickness.45
Using the Holden-Mertz equations to calculate the Dk/t average to avoid 3.2% overnight
edema (the level of non-lens overnight edema found by La Hood and colleagues46
with more subjects than originally used by Mertz45), we arrive at 125
Dk/t to avoid overnight edema. Harvitt and Bonanno's mathematical model of oxygen
diffusion across the cornea in the closed eye supports the
efficacy of 125 units as a criterion for overnight wear.47
Coincidentally, the Papas model of the impact of peripheral lens Dk/t also points to 125 units for avoiding open-eye limbal hyperemia.40 The Papas model sets the most stringent standard for daily wear of modern contact lenses. Clearly, any suggestions that oxygen transmissibilities above 15, 25 or even 80 units do not matter are based on very limited, restrictive modeling of contact lens requirements.1
Oxygen Transmissibility to Ensure Health
Practitioners should use the highest levels of Dk/t possible, if for no other reason than to avoid chronic limbal inflammation and to ensure healthy maintenance and turnover of epithelial and limbal cells during contact lens wear.
Several long-term clinical trials have compared the performance of high-Dk silicone hydrogel lenses to both no lens wear48 and hydrogel lens wear.49 The results firmly establish that eyes wearing silicone hydrogel lenses are clinically indistinguishable from eyes without lenses, and they exhibit excellent clinical physiology.
Sufficient oxygen flow through a lens is critical for all patients, but it is particularly important for those who require high lens powers or lenses that are thicker in the periphery. Some 35% of wearers are higher myopes, astigmats or hyperopes who require lenses up to 0.35 mm thick in the center or periphery. Over 23% of the population is presbyopic and requires thicker lenses, at least in the alternating lens form. Dk is a reliable and practical method to predict a lens's oxygen performance, providing lens topography and thickness and the various conditions that wearers experience with both open and closed eyes are considered.
We predict that practitioners will continue the trend toward using more lenses of the highest possible oxygen permeability. All other performance characteristics being equal, why would practitioners do anything else? Already, in the United States, the proportion of silicone hydrogel lenses prescribed for daily wear has increased approximately 8-fold over the last 2 years.50 Our theoretical discussions of oxygen levels and calculated flux should not distract us from the clinical imperatives.
Dr. Holden is Scientia Professor at the University of New South Wales; CEO, the Institute for Eye Research (IER); and deputy CEO, Vision Cooperative Research Centre (CRC), Sydney, Australia.
Dr. Stretton is a project scientist at the IER and Vision CRC.
Dr. Lazon de la Jara is project director, clinical research, at the IER.
Dr. Ehrmann is project director, technology at the IER and Vision CRC.
Dr. LaHood is a senior project scientist at the IER.
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