Critical Oxygen Levels to Avoid Corneol Edema for Daily and Extended Wear Contact Lenses

Transcription

1 Critical Oxygen Levels to Avoid Corneol Edema for Daily and Extended Wear Contact Lenses Drien A. Holden and George W. Merrz The relationship between cornea! edema and hydrogel lens oxygen transmissibility was examined for both daily and extended contact lens wear by measuring the cornea! swelling response induced by a variety of contact lenses over a 36-hr wearing period. The relationships derived enable average edema levels that occur with daily and extended wear in a population of normal young adults to be predicted to within ±1.0%. The critical lens oxygen transmissibilities required to avoid edema, for the group as a whole, for daily and extended contact lens wear were obtained from the derived curves. It was found under daily wear conditions that lenses having an oxygen transmissibility of at least 24.1 ± 2.7 X 10~ 9 (cm X ml C>2)/(sec X ml X mmhg), an Equivalent Oxygen Percentage (EOP) of 9.9%, did not induce corneal edema. This level of oxygen transmissibility can be achieved (1) in standard, low water content, poly-hema lenses by using an average lens thickness of 33 n«\ or less, or (2) in a higher water content material, such as, by using an average thickness of 166 nm or less. The critical hydrogel lens oxygen transmissibility needed to limit overnight corneal edema to 4% (the level experienced without a contact lens in place) was found to be 87.0 ± 3.3 X 10~ 9 (cm X ml O 2 )/(sec X ml X mmhg) an EOP of 17.9%. This ideal level of oxygen transmissibility cannot, at present, be provided with hydrogel materials. We suggest a compromise criterion for acceptability of hydrogel lenses for extended wear: zero residual swelling, ie, the level of oxygen transmissibility required to allow the cornea to return to normal thickness soon after eye opening following sleep with lenses. To meet this criterion, the oxygen transmissibility needs to be 34.3 ± 5.2 X 10~ 9 (cm X ml O 2 )/(sec X ml X mmhg) an EOP of.1%. The authors suggest this as the minimum desirable oxygen transmissibility for extended wear as it limits the overnight swelling to approximately 8%, allowing the cornea to recover normal thickness soon after eye opening. Invest Ophthalmol Vis Sci 25: , 1984 When a hydrogel contact lens is worn, the maintenance of normal corneal function depends primarily on sufficient oxygen diffusing through the lens material. 1 " 3 The oxygen transmissibility of such a lens (Dk/L) is directly proportional to the oxygen permeability (Dk) of the material polymer (a function of water content in hydrogel materials 4 ) and inversely proportional to the thickness of the lens (L). While the minimum oxygen level necessary to avoid corneal swelling has been investigated, 5 " 8 the critical lens oxygen transmissibilities to support both daily and extended wear have not yet been established. Recently, Holden, Mertz, and McNally 9 reported From the Cornea and Contact Lens Research Unit, School of Optometry, University of New South Wales, Kensington, Sydney, N.S.W., Australia. Supported by Optometric Vision Research Foundation of Australia grant #6969 and National Health and Medical Research Council grant no Submitted for publication: August 9, Reprint requests: Brien A. Holden, PhD, Associate Professor Cornea and Contact Lens Research Unit, School of Optometry, University of New South Wales, P.O. Box 1, Kensington, Sydney, N.S.W., Australia on corneal thickness changes in ten subjects during 7 days continuous wear of three types of hydrogel contact lenses of different back vertex powers. The two main findings from this study were (1) that current extended wear lenses cause 10-15% overnight corneal edema and 2-6% swelling during the day and (2) that when the lenses were left in place, the cornea showed an ability to consistently deswell approximately 8% once the eyes were opened following sleep. Although the long-term effects of the levels of edema occurring with current extended wear lenses are not yet known, the development of contact lenses that do not produce corneal swelling is intuitively desirable. We, therefore, set out to determine (1) the relationship between the amount of contact lens-induced edema and lens oxygen transmissibility, so that the mean level of edema could be predicted for any lens of known oxygen transmissibility, and (2) the critical lens oxygen transmissibility necessary to avoid corneal edema for both daily and extended contact lens wear. These aims were achieved by measuring the corneal edema response over a 36-hr period including a normal wake/ sleep cycle with a variety of lenses having a wide range of oxygen transmissibilities. 1161

2 1162 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Ocrober 1984 Vol. 25 Table 1. Ocular parameters summary Age (years) Sph. refr. error (D) Cyl. refr. error (D) Horiz. K-reading (D) Corneal toricity (D) Mean Standard deviation Range 18 to to to to against rule to 1.25 with rule Materials and Methods Subjects Ten subjects (7 men, 3 women) from whom informed consent had been obtained, participated in the study. Ocular parameters for the group fell within normal limits and are summarized in Table 1. All subjects were unadapted to contact lens wear and free of ocular disease. Lenses Lens oxygen transmissibility: The specifications of the lenses used in this and the previous study 9 are provided in Table 2. Central and peripheral lens thickness measurements were made for all lenses to an accuracy of ±1 /*m with a device described elsewhere. 10 These data were used to calculate average lens thickness for the central 6 mm of each lens type in a manner similar to that proposed by Fatt." Using published polymer oxygen permeability data, 13 and manufacturers specifications (for Hydrocurve II, Weicon 38 and Weicon 60), lens oxygen transmissibilities were calculated for each lens. The data for the oxygen permeability (Dk), measured center thickness (L c ) and calculated average thickness (L avg ), with corresponding oxygen transmissibilities (Dk/L c and Dk/L avg respectively), are included in Table 2. Equivalent oxygen percentage: The level of corneal oxygenation for each lens was also calculated in terms of the "Equivalent Oxygen Percentage" (EOP) an expression used by Hill 14 " 18 to describe the oxygen level at the anterior corneal surface expressed as a percentage concentration of oxygen in the atmosphere. For example, a contact lens that transmits all the oxygen available in the atmosphere would have an EOP of 20.9%. Table 2. Lens data Manufacturer Lens name Water content Diameter Nominal center thickness Oxygen permeability (Dkft (Xl0 u ) Nominal back vertex power Measured center thickness (LJ mean SD Calculated avg. lens thickness Oxygen transmissibililyf Central Dk/L c (X1O V ) Average Dk/L avv (X10 9 ) B & L, Inc. (Rochester, NY) Soflens % 14.5 mm 35 M m 8.0 X D D 32 ± 4/im 39 ± 4 Mm Jo ± J M m 36 M m 60 Mm 78 Mm Cooper Labs, Inc. (Palo Alto, CA) Permalens 71% 75% 13.5 mm 13.8 mm Approx. 200 Mm (var. with power) 130 Mm D D 215 ± 11 Mm 153 ± 22 Mm 103 ± 7 Mm 221 M m 186 Mm I/O M m Soft Lenses Inc. (San Diego, CA) Hydrocurve II 45% 13.5 mm 60 fitn D 63 ± 10 Mm 41 ± Mm 74 Mm 114 Mm Hydron Australia, (Sydney, Australia) Hydron Thin Parallel* Hydron Mini Hydron Thick Parallel* 38.6% 38.6% 38.6% 14.0 mm 13.0 mm 13.9 mm 20 Mm 0 Mm 300 Mm 8.0 Piano D 22 ± 5 Mm 99 db 31 Mm 310 ± 18 Mm L\ M m 111 Mm 310 Mm Dow Corning Corp. (Midland, MI) Silsoft Silicone Elastomer 0%.5 mm 110 Mm D 9 ± 21 Mm 137 Mm Titmus Eurocon (Aschafenburg, Germany) Weicon 38 Weicon % 59.0% 13.0 mm 13.0 mm 35 M m Mm (var. with power) D D 38 ± 5 M m 88 ± Mm 5 1 M m 98 M m * Special order non marketed lenses. t Values quoted at room temperature. Units: (cm 2 X ml Oj)/(sec X ml X mmhg). $ Oxygen transmissibility. Units: (cm X ml O 2 )/(sec X ml X mmhg). Oxygen permeability of silicone is reported to increase with lens thickness 13 ' the Dk reported here is representative of the average thickness of the lenses in the study (137 jim). I ±1 SD.

3 No. 10 CRITICAL OXYGEN TRANSMISSIDILITY OF CONTACT LENSES / Hoiden ond Merrz 1160 It is assumed with this technique that a lens that produces a corneal oxygen uptake rate identical to that of a gas of known oxygen concentration (balance nitrogen), must be delivering the same level of oxygen to the cornea. Although this may not be strictly true, because the goggle situation does not incorporate the other environmental changes induced by contact lenses such as raised temperature and decreased tear tonicity, l9>2 the Hill method provides an extremely useful relative index. Figure 1 shows EOP as a function of Dk/L for some of the lenses studied by Hill. 15 " 18 The regression analysis of this data shows that there is strong correlation between EOP and lens oxygen transmissibility, the empirical relationship derived from the data in Figure 1 is: EOP (%) = X In (Dk/L X 10 9 ) ; r = 0.995, S es, = 0.74%. Procedures Five of the subjects who had previously participated in the Hoiden, Mertz, and McNally study 9 wore a silicone lens (Dow Corning Silsoft silicone elastomer) on one eye and an extremely thin, low water content hydrogel lens (Hydron special order, 20-^m thick, parallel front and back surface) on the opposite eye for 35 hr. After a month of no lens wear, the same five subjects wore Titmus Eurocon Weicon 38 lenses on one eye and Titmus Eurocon Weicon 60 lenses on the opposite eye for 36 hr. After an additional month of no lens wear, the same five subjects wore a CooperVision lens on one eye for 36 hr and no lens on the opposite eye. Corneal swelling response to the lenses was determined by measuring corneal thickness with an electronic digital pachometer as previously described. 919 ' 21 Baseline pachometry measurements were taken before and immediately after lens insertion on the morning of the first day of wear. Subsequent measurements with lenses in place were taken after 1, 2, 4, 6, 8, and hr of lens wear. Measurements were taken at the moment of eye opening following 8 hr of overnight eye closure (sleep) and at 1,5, and hr after eye opening. Corneal swelling was calculated as the percentage difference in corneal thickness compared with the measurements taken immediately after lens insertion. The corneal swelling responses of the other five subjects were recorded after 2,4, and 6 hr wear of medium (0.11 mm) and thick (0.31 mm) Hydron lenses. It was considered inadvisable to allow these subjects to sleep with these lenses considering the magnitude of their day 1 swelling responses. These data are included in this paper, however, to give a greater range with which g DK/Lx10 (cmxml OjJ/secxml x mm Hg) Fig. 1. Equivalent oxygen percentage (EOP) at the anterior corneal surface during contact lens wear versus lens oxygen transmissibility for various lens types studied by Hill during the period to derive the relationship between the level of oxygen transmissibility and maximum corneal swelling with daily wear. Published Data Data from Hoiden, Mertz, and McNally 9 that were collected in an identical manner over the first 36 hr of lens wear to that reported for the lenses studied in this paper (Tables 2, 3), are included in the analysis (Table 4) to provide information from a wider range of lenses. Results The mean corneal swelling results for 36 hr wear of Dow Corning Silsoft silicone elastomer and Hydron 20 /iin parallel surface lenses are shown in Figure 2. Similarly, the degree of swelling during 36 hr wear of Weicon 38 and Weicon 60 lenses is shown in Figure 3 and that for CooperVision lenses and the no lens condition in Figure 4. The mean swelling results during 6 hr wear of thicker Hydron lenses are shown in Figure 5. Table 3 summarizes the corneal swelling results obtained in both this and the Hoiden, Mertz, and McNally study 9 for the maximum swelling measured on day 1, the overnight swelling measured at eye opening, and the day 2 residual swelling measured hr after eye opening. These data were submitted to a regression analysis to derive empirical relationships for corneal swelling as a function of lndk/l c and lndk/l avg. The results of this analysis are summarized in Table 4. The highest correlations were achieved using the lens average oxygen transmissibility. Plots of day 1 maximum swelling, overnight swelling, and day 2 residual swelling as a function of Dk/L avg are shown in Figures 6-8, respectively.

4 1164 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / October 1984 Vol. 25 Table 3. Mean corneal swelling results Lens type Power (D) Dk/L* (xl0r s ) Day 1 maximum swelling First overnight swelling Day 2 residual swelling (36 hr) Soflens 04f % 2.4% 3.6% 10.3%.0% 14.9% 0.5% 2.4% 5.8% Permalensf % 1.6% 11.5% 9.8% 3.0% 3.0% Hydrocurve Ilf % 2.4%.1%.6% 5.1% 5.5% Weicon 38 Weicon % 1.6% 11.8% 11.3% 2.1% 2.6% % 9.5% 1.6% Hydron 20 ^m Hydron 0 pm Hydron 300 urn piano % 4.8% 8.5% 7.2% -0.8% Silsoft % 2.6% -0.5% No lenst 0.7% 4.1% 0.7% * Units: (cm X ml O 2 )/(sec X ml X mmhg). \ See reference 9. Discussion The first objective of this study was to examine the relationship between lens oxygen transmissibility and the amount of corneal edema occurring during both daily and extended wear, so that it would be possible to predict the amount of corneal edema induced by any hydrogel lens of known oxygen transmissibility. The second objective was to derive the critical oxygen levels that must be transmitted by a contact lens to avoid corneal edema under daily and extended wear conditions. These objectives are important both (1) in evaluating the efficacy of current contact lens designs and materials and (2) in developing guidelines for the development of contact lenses that provide less physiologic challenge to the eye. The main deficiencies of previous attempts to define the oxygen transmissibilities needed to avoid edema in daily and extended contact lens wear 22 " 26 are that either: (1) center thickness was used to define Dk/L and/or (2) the studies were not carried out during a normal wake/sleep cycle. Average versus central oxygen transmissibility: As Wilson 27 has pointed out, using center thickness (L) of the lens to define oxygen transmissibility falsely implies that all lenses of a given polymer with the same center thickness will provide the same amount of oxygen. Indeed, we have shown 9 that higher minus-powered, hydrogel lenses cause greater central corneal swelling than lower minus-powered lenses of the same polymer and central thickness (due to the greater lens peripheral thickness). It also is clear from the present study that oxygen transmissibility based on the average thickness of the lenses studied is a better predictor of corneal swelling for day 1 maximum swelling, overnight swelling, and day 2 residual swelling. As can be seen from Table 4, in all cases the standard error of the estimate (S est ) for predicting corneal swelling using lens average thickness is approximately one-half that of the standard error of the estimate using lens central thickness. Normal wake/sleep cycle: Several investigators have studied corneal swelling caused by various types of Table 4. Regression analysis corneal swelling vs lens oxygen transmissibility Central oxygen transmissibility Average oxygen transmissibility Swelling response Correlation coefficient Standard error of the estimate (S e J Correlation coefficient Standard error of the estimate (S e J Regression equations relating corneal swelling (CS) and average oxygen transmissibility (Dk/L av J Day 1 maximum First overnight Day 2 residual ±1.1% ±1.7% ±2.0% ±0.6% ±0.8% ±1.2% CS(%) = In (Dk/L avg X 10 9 ) CS(%) = In (Dk/L avg X 10 9 ) CS(%) = In (Dk/L avg X 10 9 )

5 No. 10 CRITICAL OXYGEN TRANSMISSIDILITY OF CONTACT LENSES / Holden and Merrz o Z 8» «Silsoft Hydron Parallel a? 10 o 2 8» «Control (no lens) Seep LU I 2 O U Fig. 2. Corneal swelling versus time for five unadapted subjects wearing a D Dow Corning Silsoft silicone elastomer contact lens on one eye and a special 20-^m thick parallel surface Hydron lens on the opposite eye continuously for a period of 36 hr. contact lenses worn during short periods of eye closure that were preceded by periods of at least 24 hr during which no lenses were worn. 23 " 26 In both the Holden, Mertz, and McNally paper 9 and this study, a period of normal sleep was preceded by a full day's open eye wear as would be encountered in the normal extended wear situation. Predicting Corneal Edema from Lens Oxygen Transmissibility The results of the regression analysis on the data from this study, reported in Table 4 and depicted Figures 6-8, enable the mean level of edema that will occur in daily and extended wear in young adults to be predicted from lens average transmissibility to approximately ±1%. The Derivation of Critical Oxygen Transmissibility In the model we present here for determining the critical oxygen requirements for daily and extended I 2 O u Fig. 4. Corneal swelling versus time for five unadapted subjects wearing a D contact lens continuously for a period of 36 hr on one eye and no lens on the opposite eye. wear contact lenses, we assume that corneal swelling response ranges from some finite maximum level for lenses with zero oxygen transmissibility, to a base level beyond which an increase in oxygen transmissibility does not reduce the swelling response. It has been shown experimentally, for example, that overnight swelling ranges from approximately 25% for presurgical cataract patients wearing very thick aphakic hydrogel lenses (Dk/L avg = 3 X 10" 9 (cm X ml 0 2 )/[sec X ml X mmhg]) 28 to about 4% for corneas not wearing any lenses (infinite Dk/L avg ). 9i29>3 The regression curves shown on Figures 6-8 and detailed in Table 4 were used to derive the critical oxygen transmissions necessary to avoid contact lens-induced edema under both daily (day 1 maximum swelling) and extended wear conditions (overnight and day 2 residual swelling). Table 5 summarizes the critical lens Dk/L avg values necessary for no edema on day 1, overnight corneal swelling to be limited to 4% the level experienced when no lens is worn, and the day 2 residual corneal swelling to fall to zero soon after eye opening (zero residual gio o z 8» «Weicon 38 i Weicon o zn 6 t «0.1 1mm Thick Hydron mm Thick Hydron Lens wear discontinued! Fig. 3. Corneal swelling versus time for five unadapted subjects wearing a D Weicon 38 contact lens on one eye and D Weicon 60 contact lens on the opposite eye continuously for a period of 36 hr. 16 Fig. 5. Corneal swelling versus time for five unadapted subjects wearing D Hydron "Mini" contact lens on one eye and a special 3l0-/tm parallel surface Hydron contact lens on the other eye for a period of 6 hr.

6 1166 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Ocrober 1984 Vol. 25 DAY 1 MAXIMUM 10r DAY 2 RESIDUAL DK/L»vofor ZERO SWELLING:24.1 xio" E.O.P. for ZERO SWELLING: 9.9% r= DK/L AVQ for ZERO SWELLING: 34.3x10 E.O.P. for ZERO SWELLING:.1% DK/L»VG x'o (cmxml OgJ/sec x ml x mm Htj) Fig. 6. Day I maximum corneal swelling versus average lens oxygen transmissibility for 13 lenses (see Table 3). Critical Dk/L avg and EOP values for reducing day 1 swelling to zero are also shown. swelling). These critical Dk/L avg values were converted to Hill's EOP values using the empirical relationship described previously. Also recorded in Table 5 are the critical average lens thicknesses for poly-hema and materials that would be necessary to meet the three criteria. The Critical Oxygen Transmissibility Needed to Avoid Edema with Daily Wear Critical lens oxygen transmissibilities for open and closed eye wear, based on previous estimates of the oxygen levels needed to avoid edema, 5 have been suggested as 5 X 10~ 9 (cm X ml O 2 )/(sec X ml X mmhg) for open eye lens wear and 15 X 10~ 9 (cm X ml O 2 )/ (sec X ml X mmhg) for closed eye lens wear. 26 As can be seen from Tables 2 and 3, a number of lenses meeting these criteria caused significant corneal swelling both during day and overnight wear. Our results indicate that the oxygen level needed to avoid edema is somewhat higher than previously proposed, and are closer to the levels determined by Holden, Sweeney, and Sanderson. 8 CRITICAL OK/L»,o for ZERO SWELLING. 87*10 CRITICAL E.O.P. lor ZERO SWELLING: 17.9% OK/L.vo XIO (cmxml O2)/s 10,30 Fig. 7. Overnight corneal swelling versus average lens oxygen transmissibility for. lenses (see Table 3). Critical Dk/L avg and EOP values for reducing overnight swelling to the 4% "no lens" level also are shown DK/LAVG X10 (cmxml O2)/secxml x mm Hg) Fig. 8. Day 2 residual corneal swelling versus average lens oxygen transmissibility for 11 lens types (see Table 3). Critical Dk/L ovg and EOP values for reducing day 2 residual swelling to zero also are shown. The results of this study indicate that, on average, no corneal swelling will occur under daily wear conditions if lenses have a Dk/L avg of at least 24.1 ± 2.7 X 10~ 9 (cm X ml O 2 )/(sec X ml X mmhg) an EOP of 9.9%. This result is in close agreement with the Sarver et al 25 figure of 20 X 10" 9 (cm X ml O 2 )/(sec X ml X mmhg) for the minimum Dk/L value for zero edema with opened-eye lens wear. With standard, low water content lenses (poly-hema), this can be achieved by using an average lens thickness of 33 /urn or less. With a higher water content material, such as, an average thickness of 166 ixm or less is required. The Critical Oxygen Transmissibility Needed to Avoid Edema with Extended Wear In considering the critical oxygen requirements for extended wear lenses, the alternatives we have suggested are: (1) the lens oxygen transmissibility needed to limit overnight edema to 4% (the level occurring without a lens) and (2) the lens oxygen transmissibility needed to allow the daytime level of edema to fall to zero soon after eye opening (zero residual swelling). The Dk/L avg which limits overnight swelling to 4% is predicted to be 87.0 ± 3.3 X 10" 9 (cm X ml O 2 )/ (sec X ml X mmhg) an EOP of 17.9%. To satisfy this criterion with hydrogel lenses, the average lens thickness would have to be reduced well below manufacturing feasibility (See Table 5). The results of this study suggest that this ideal 4% overnight swelling criteria can only be met at present with silicone lenses. However, the persistent problem of the adherence of these lenses to the cornea 31 questions their suitability for extended wear at the present time. The zero residual swelling criterion for extended wear allows overnight swelling levels of greater than 4%, as long as the cornea can eliminate the edema

7 No. 10 CRITICAL OXYGEN TRANSMISSIDIUTY OF CONTACT LENSES / Holden ond Merrz 1167 Table 5. Critical oxygen levels and lens thicknesses for low and high water content lenses Critical oxygen levels Criteria Dk/L a EOPj Poly-Hema (Dk = 8X 10-' Critical average lens thickness (Dk = 40 X 10'")% Zero day one corneal swelling 4% or less overnight corneal swelling Zero day two residual swelling 24.1 ± 2.7 X 1(T ± 3.3 X 1(T ± 5.2 X 1(T 9 9.9% 17.9%.1% 33 urn 9 Mm 23 nm * Oxygen transmissibility units: (cm X ml O 2 )/(sec X ml X mmhg). t Equivalent Oxygen Percentage: % atmospheric oxygen. $ Oxygen permeability units: (cm 2 X ml O 2 )/(sec X ml X mmhg). soon after eye opening. From the relationship derived between lens Dk/L avg and residual swelling shown in Figure 8 and Table 4, the critical lens Dk/L avg to meet this zero residual swelling criterion is 34.3 ± 5.2 X 10~ 9 (cm X ml O 2 )/(sec X ml X mmhg) an EOP of.1%. The lens thickness necessary to achieve this appears feasible from a manufacturing point of view, at least in higher water content hydrogel materials. We would, therefore, suggest that this oxygen transmissibility should be considered the desirable minimum value for extended wear contact lenses. Key words: contact lens, oxygen transmissibility, corneal edema, daily wear, extended wear Acknowledgments The authors thank Drs. Nathan Efron and Daniel O'Leary and Bruce Cook for their helpful comments as well as Stuart Ingham for assistance with the manuscript preparation. References 1. Fatt I and St. Helen R: Oxygen tension under an oxygen-permeable contact lens. Am J Optom Arch Am Acad Optom 48:545, Fatt I and Lin D: Oxygen tension under a soft or hard, gaspermeable contact lens in the presence of tear pumping. Am J Optom Physiol Opt 53:104, Poise KA: Tear flow under hydrogel contact lenses. Invest Ophthalmol Vis Sci 18:409, Refojo MF and Leong F: Water-dissolved-oxygen permeability coefficients of hydrogel contact lenses and boundary layer effects. J Memb Sci 4:415, Poise KA and Mandell RB: Critical oxygen tension at the corneal surface. Arch Ophthalmol 84:505, Carney LG: Studies on the basis of ocular changes during contact lens wear. PhD thesis, University of Melbourne, Mandell RB and Farrell R: Corneal swelling at low atmospheric oxygen pressures. Invest Ophthalmol Vis Sci 19:697, Holden BA, Sweeney DF, and Sanderson G: The minimum pre-corneal oxygen tension to avoid corneal edema. Invest Ophthalmol Vis Sci, 25:476, Holden BA, Mertz GW, and McNally JJ: Corneal swelling response to contact lenses worn under extended wear conditions. Invest Ophthalmol Vis Sci 24:218, Chan T, Payor S, and Holden BA: Corneal thickness profiles in rabbits using an ultrasonic pachometer. Invest Ophthalmol Vis Sci 24:1408, Fatt I: The definition of thickness for a lens. Am J Optom Physiol Opt 56:324, Morris JA and Fatt I: A survey of gas-permeable contact lenses. The Optician 174(4509):27, Fitzgerald JK and Jones DP: Oxygen flux can be misleading. Int Contact Lens Clin 5:134, Hill RM and Jeppe WH: Hydrogels: is a pump still necessary? Int Contact Lens Clin 2(4):27, Hill RM: Hydrogel lens design: the thick and thin of it. In Proceedings of the Second National Research Symposium on Soft Contact Lenses, Princeton, Excerpta Medica, 1977, pp Benjamin WJ and Hill RM: Ultra-thins: an oxygen update. Contact Lens Forum 4(1):43, Hill RM: Oxygen permeable contact lenses: how convinced is the cornea? Int Contact Lens Clin 4(2):34, Roscoe WR and Hill RM: Corneal oxygen demands: a comparison of the open- and closed-eye environments. Am J Optom Physiol Opt 57:67, Holden BA, Poise KA, Fonn D, and Mertz GW: Effects of cataract surgery on corneal function. Invest Ophthalmol Vis Sci 22:343, Terry JE and Hill RM: Human tear osmotic pressure: Diurnal variations and the closed eye. Arch Ophthalmol 96:0, Holden BA and Payor S: Changes in thickness in the corneal layers. Am J Optom Physiol Opt 56:821, Mandell RB and Poise KA: Contact lenses worn during sleep and rest periods. J Am Optom Assoc 41:937, Harris MG, Sanders TL, and Zisman F: Napping while wearing hydrogel contact lenses. Int Contact Lens Clin 2(1 ):84, Sarver MD and Staroba JE: Corneal edema with contact lenses under closed-eye conditions. Am J Optom Physiol Opt 55:739, Sarver MD, Baggett DA, Harris MG, and Louie K: Corneal edema with hydrogel lenses and eye closure: effect of oxygen transmissibility. Am J Optom Physiol Opt 58:386, Poise KA and Decker M: Oxygen tension under a contact lens. Invest Ophthalmol Vis Sci 18:188, Wilson G: Hydrogel lens power and oxygen transmissibility. Am J Optom Physiol Opt 56:430, Korb DR, Richmond PP, and Herman JP: Physiological response of the cornea to hvdrogel lenses before and after cataract extraction. J Am Optom Assoc 51:267, Mandell RB and Fatt I: Thinning of the human cornea on awakening. Nature 208:292, Mertz GW: Overnight swelling of the living human cornea. J Am Optom Assoc 51:211, Refojo MF and Leong FL: Water pervaporation and adhesion of silicone rubber contact lenses. ARVO Abstracts. Invest Ophthalmol Vis Sci 20(Suppl):155, 1981.