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OXYGEN CONSUMPTION AND 22
MEASUREMENT
R.M. Hill
(a)
r7 ~L
.c:»;
Air IlL1
~ Emptying time
(b)
Impermeable PMMA r7 ~L
contact lens
IE
~ ~ Emptying time
(c)
Semi-permeable
r~~
~
contact lens
.r:»; ri1
~ Emptying time
(d)
Goggle r: ~~
1;/00 21
~
~ ~ Emptying time
Figure 22.1 Corneal responses to four oxygen conditions. (a) Just following a prolonged period in air;
note the slow emptying rate of the measuring probe's oxygen reservoir. (b) Just following a prolonged
period under an impermeable PMMA contact lens; note the very rapid reservoir emptying rate. (c) Just
following a prolonged period under a semi-permeable contact lens. (d) Just following prolonged
exposure to an oxygen percentage (contained by a goggle over the eye), which produces immediately
afterwards, a reservoir emptying rate equal ('equivalent') to that caused by the semi-permeable contact
lens.
instance has an immediate past history of able lens wear is somewhere between those
oxygen impermeability (e.g. thick PMMA two extreme conditions in Frames (a) and (b).
contact lens wear). The reservoir exhaustion A means of calibrating the oxygen passing
rate here is very rapid, indicating that the performance of that semi-permeable lens is
cornea during that period of wear had fallen shown in Frame (d), wherein a series of
to, and had been maintained at, some very known oxygen percentages are maintained
much lower oxygen level. The steepness of in a goggle over the cornea, until that par
the graphical slope (in mmHg/s units) is ticular percentage is identified which pro
directly related to the relative severity of that duces the identical reservoir exhaustion rate
hypoxic condition. In Frame (c), the reservoir (graphical slope) as did the semi-permeable
exhaustion rate following semi-gas perme- contact lens being tested. Once that slope
The equivalent oxygen percentage (EOP) 489
match is made, the test lens can then be said 'steady state' conditions, i.e, without a lid
to have caused the cornea to behave as if it lens pump acting, and following the estab
had been living in an atmosphere equivalent lishment of a steady flow of oxygen into the
to that percentage of oxygen which mim cornea based on the tension gradient across
icked it in the goggle experiments - hence it, the associated tear and tissue resistances,
the equivalent oxygen percentage (EOP) des and the on-going oxygen demands of the
ignation. Standard calibration curves based cornea. The 'static' EOP, then, should be
on statistically constructed goggle experi reflective of (or related to) the transmissivity
ments have been generated, originally for properties of a test lens only. As the lid-lens
rabbit, and now for the human cornea as well pump is unique for each lens-eye examina
(Benjamin, 1982; Roscoe & Wilson, 1984). tion, the 'static' EOP offers the unique
The 'air' experiment in Frame (a) is of advantage of 'factoring out' the pump vari
course a kind of 'natural' (i.e. open eye, best able.
oxygen condition) control, against which the Should it be desirable, however, to know
performances of test lenses can be directly for a given eye the summed effects of pump
compared. However only certain flexible and transmissivity, a 'dynamic' EOP can be
'pure' silicon rubber lenses have approached measured, i.e. following a sufficient
that level of oxygen passage (Hill, 1977). sequence of blinks for the regular oscillations
Another control, in diametric contrasi: to of oxygen within the tear pool to remain
the 'air' condition, is the tight impermeable about a stable average. Efron and Carney
(e.g. a thick PMMA) lens condition. Under (1981) have demonstrated for example, using
static circumstances, such a lens fitted 'paral the dynamic EOP, the very small oxygen
lel' to the eye surface can produce a state of contribution made by the lid-lens pump in
near maximum hypoxia within 120 s. A hydrophilic lens systems. Their measure
nitrogen filled goggle can be used to create ments directly confirm the fluorescein obser
this extreme condition as well, but may differ vations described by PoIse (1979), who found
slightly in the final steady state level of very little tear exchange per blink under
oxygen achieved, as the two methods vary in hydrophilic lenses as well. Although Efron
several fundamental ways. For example, a and Carney did not include rigid lenses
100% nitrogen atmosphere may actually directly in their study, the dynamic EOP for
drain oxygen from the eye, acting like an these lens types based on the earlier ion
infinite sink for that gas; carbon dioxide may tracking measurements of Cuklanz and Hill
be vented in an unusually efficient way for (1969) might be predicted to be substantially
the same reason. A gas impermeable (contact higher, most particularly, however, because
lens) shell, on the other hand, would not the success of earlier impermeable (i.e.
draw oxygen from the eye by such an aque PMMA) lens systems relied entirely on tear
ous to atmosphere gradient, and would tend pump exchange for corneal oxygen.
as well to block carbon dioxide escape by While determination of oxygen passage
containing it in the post-lens tear pool. For through a given lens and at a particular site
contact lens testing, then, the impermeable (e.g. the centre) would be the most funda
plastic control rather than the 'infinite' nitro mental yield of the static procedures above,
gen sink would seem to be the more appro an EOP evaluation over a range of material
priate model to use for lens testing. thicknesses can be very useful to the manu
It should be noted that the fundamental facturer and practitioner alike - to the
steps for determining an EOP value, as former, for determining the thinnest warp
described above, related to how the cornea free dimension for a test material while
responds to a test lens under 'static' or achieving the highest oxygen throughout.
490 Oxygen consumption and measurement
For the practitioner, knowing the oxygen ence value) taken from that physical testing
limitations of materials helps in the choice of procedure was the Dk, or oxygen permeabil
the most effective trade-offs between that ity value, of the material from which a test
property and others of special importance in lens was to be made (obtained by multiply
the ultimate choice of lenses. An 'EOP curve' ing the Dk/L of a lens or flat which was
is such a summary of 'static' condition oxy actually measured by L, the thickness of the
gen performances across the lens thickness tested specimen in centimetres). Two prob
spectrum, and can be used to determine
lems chronically resulted however from
. oxygen availability at local sites under a lens
using the Dk value alone as a performance
or, knowing its average thickness, the aver
index: (1) deriving the Dk is dependent on
age EOP performance for the entire lens. knowing the exact thickness at the site(s) of
EOP values generated in this laboratory measurement of a test lens (or better, a
have three inherent characteristics: (1) they uniform thickness flat). Maintaining a con
are relative to an altitude of 235 metres above stant thickness in hydrophilic cases and
sea level, thus approximating the tension then measuring it accurately remains a
environments of a large proportion of the challenge; and (2) as lenses or flats (of the
contact lens wearing population; (2) being same material) are made progressively
done on a living eye, EOP values relate only thinner (particularly in the range of com
to eye temperature conditions; and (3) in the mon myopia prescriptions), the calculated
case of hydrophilic lenses, the water level of Dk, may not be constant throughout (i.e.
the tested lens is set to approximately 90% of the ratings for thinner samples tend to be
the label value in order to reside within the relatively poorer than their performances
hydration range characteristic of most ambi should actually merit (Fatt & Chaston,
ent wearing conditions. 1982).
Use of a directly measured Dk/L, i.e. lens
22.7 OTHER OXYGEN ESTIMATES
or flat transmissivity, combined with the
application of a carefully calibrated system
The Dk/L estimate of lens performance dif for determining thickness (or better average
fers from the in vivo method above in that it thickness for the whole lens), should provide
does not involve an eye in its measurement a more reliable measure of oxygen passage
process. It is, rather, a physical or 'bench' than a Dk (i.e. material permeability) for a
measurement of oxygen passage, and as such particular polymer being studied.
serves as a predictor of what a lens may Also, as the performance of an ophthalmic
provide on the eye (i.e. its 'static' or non-lid plastic must ultimately be judged under 'in
lens pump contribution). Reference to Fatt the eye' conditions, the convention of mea
(1978) is recommended for a detailed suring all Dk/L values at eye temperature
description of the Dk/L method. should be encouraged. Such a convention
Being a physical test which can be done would (1) eliminate different Dk/L values
under carefully controlled and replicated being cited for the same specimen due to
conditions, the Dk/L estimate does have the different testing temperatures; and (2) make
potential for good accuracy and repeatability. comparisons with EOP findings (which are
As with all such critical testing procedures, only made at eye temperature) legitimate
however, best absolute (and comparative, i.e. then in all cases.
between lenses) results can be expected only Can reasonable agreement be found
when samples are measured within the same among predictors of oxygen performance? As
laboratory. the EOP and Dk/L procedures can both be
Initially the most popular index (or refer done without the presence of the lid-lens
Some exceptional subjects and circumstances 491
tear pump, a comparison of their results overnight' swelling response with lens trans
should be possible. The more fundamental missivity, being - 0.96 and - 0.92, respec
question then becomes: How well does each tively.
predict the other? The EOP and DklL procedures might be
Several sets of independent observations classed as 'leading indicators' (i.e. by hav
and assessments have been made upon ing early feasibility and by being immedi
which equations containing these two pre ate in outcome) of long-term wear results to
dictors have been based. Three of the more be expected from an experimental material.
recent analyses are: Corneal enzyme analyses, e.g SOH and
1. Fatt and Chaston's (1982) model fitted to LOH/MOH determinations under labora
the data of Novicky and Hill (1981). Their tory conditions may prove to be useful
equation for relating those two numbers is: advance (pre-human trial) estimates of
material performance as well (Rengstorff &
EOP = 2.06 X 108 (Dk/L) -0.07 Hill, 1974; Fullard & Carney, 1984).
Pachometry, for the purpose of monitoring
The correlation coefficient of the two based
corneal swelling, lends itself very well to the
on the original data was found to be +0.94.
tracking of those changes over extended
2. Holden and Mertz's (1984) model fitted
periods in the daily or extended wear. Par
to EOP data from Hill's laboratory for vari
ticularly where weeks or months may be
ous lens types during the period of 1975 to
involved, pachometry can be considered a
1980 for which Dk/L values could be
highly useful, non-invasive 'intermediate
obtained. Their equation for relating these
indicator' of hypoxic responses (Holden et
two measures is:
al.,1983).
EOP (%) = 6.915 X In (Dk/L X 109 ) -9.778 One example of a promising 'following
indicator' may be endothelial polymegath
The correlation coefficient of the two from ism. Although this long-term result of lens
that database was found to be +0.995. wear may have multiple bases (e.g. pH,
3. Roscoe's (1984) model derived from his enzyme or waste disturbances), its relatively
own EOP and Dk/L data base on the same greater prominence in association with
lenses yielding the equation: impermeable (e.g. PMMA) materials, versus
its lesser development or near absence in
EOP (%) = '7.2 X 10~ Dk/L - 0.50 association with progressively more perme
able materials, suggest oxygen deprivation to
The correlation coefficient for those two
be a primary aetiological factor (Schoessler,
measures fOT the open eye was found to be
1983).
+0.96.
For the closed eye, the relationship found
was: 22.8 SOME EXCEPTIONAL SUBJECfS AND
CIRCUMSTANCES
EOP (%) = 1.4 X 108 Dk/L - 0.27
Apart from normal variations of corneal
with a correlation coefficient of +0.99. demand and the superimposed effects of
Similarly, relationships between corneal environment e.g. blink rates (Carney & Hill,
swelling (pachometry) due to lens induced 1982), closed eye periods (Efron & Carney,
hypoxia and lens Dk/L have now been dem 1979), altitude (Hill, 1981), several other fac
onstrated by Holden and Mertz (1984) with tors may influence the oxygen demand of the
correlation coefficient values for 'Day 1 maxi cornea. Just four examples will be mentioned
mum' swelling responses, and the 'first here:
492 Oxygen consumption and measurement
22.8.1 DEMANDS OF THE OXYGEN range of PoIse and Mandell would, for most
DEPRIVED CORNEA patients today, be considered to indicate
measurable changes. And indeed, that
Responses of the cornea immediately follow lower range limit does correspond very
ing periods of reduced oxygen exposure have closely to the average change point in oxy
been studied recently (Benjamin, 1981; Ben gen uptake behaviour of those seven
jamin & Hill, 1985). Two kinds of questions human corneas described by Benjamin
were dealt with. First, how little reduction of (1982). Holden and Mertz, in 1984, recom
oxygen would the cornea 'notice'; and sec mended an EOP minimum for daily wear of
ond, were there any 'discontinuities' in the 9.9%.
responsiveness of the cornea as the concen
trations of oxygen were progressively 22.8.2 DEMANDS OF THE ANAESTHETIZED
reduced.
CORNEA
In answer to the first question, the effect
of reducing the oxygen percentage to even Since ophthalmic office visits may involve
three-quarters of its normal level, i.e. down topical anaesthetic procedures (i.e. for
to 16%, was readily apparent. Clear detect intra-ocular pressure measurements) as
ability from normal at that level suggests well as contact lens care, the possible
then that a point somewhere between 16% effects of ophthalmic analgesics on corneal
and a full atmosphere is where the 'hypoxic metabolism becomes an area of practical
threshold' must for most subjects reside. concern.
Holden et al.'s (1983) value of 17.9%, was The first in vivo measurements to explore
given as the ideal minimum contact lens the effects of specific agents on corneal
transmissivity to avoid abnormal corneal oxygen uptake were reported by Augs
swelling patterns due to extended wear burger and Hill (1972). Their results
lenses, may be an even closer indication of revealed a range of responses depending
that threshold (Holden & Mertz, 1984). on the particular agents and concentrations
The other observation from Benjamin's used. Most severe in its effects was cocaine.
relative deprivation studies was that when Using a concentration of 1.0% (a 4-drop
responses to progressive levels of oxygen application) was found to depress the nor
deprivation were analysed on a rate basis, mal oxygen flux level by as much as 20%.
i.e. by looking at the acceleration of the The effects of 0.5% (a 4-drop application)
cornea's oxygen demand, a level is reached, was very similar. Fewer drops of each of
at about the 1.5% EOP, where a very those same concentrations did result in less
marked increased in oxygen uptake takes flux depression however.
place. This level happens to correspond to Benoxinate, at a concentration of 0.4 % (a
the original lower limit set by PoIse and 4-drop application) caused only a very mild
Mandell (1970) as a minimum oxygen level flux depression (not statistically significant
for daily contact lens wear, and represents from no drug at all).
by today's standards a fairly discernible More recently Roscoe and Wilson (1983)
level of slit lamp evident change. The 5% examined further the effects of topical anaes
EOP level corresponds to the upper end of thesia on EOP values. The agent they inves
the Mandell and Farrell range, and is still tigated was proparacaine 0.25%. Their
accepted by many today as a daily wear conclusion was that the presence of this drug
minimum standard, with about 3% EOP did not produce a significantly different oxy
corresponding to the current lower limit gen uptake result from the anaesthetic-free
(Mandell & Farrell, 1980). The 1.5 to 2.5% state.
Overview 493
22.8.3 DEMANDS OF mE HEALING CORNEA imposed. A compromise would be to retain
the protective presence of a lens, but to
Hill and Keates (1969) noted that, even when assure that that is of the very highest Dk/L
the epithelium of the cornea was completely value possible.
removed, the flow of oxygen into the cornea
continued at about 20% of the pre-wound 22.8.4 DEMANDS OF rns APHAKIC EYE
level. This residual flux appears to be
CORNEA
accounted for principally by the substantial
gradient of oxygen tension between atmo Recently, the impression of many contact
sphere and aqueous, although stromal cell lens fitters is that the cornea of the aphakic
uptake may account for a very small fraction eye is less demanding of oxygen, was
of that flow as well. explored by Polse, Holden and Sweeney
The oxygen demand course of the denuded (1983). They compared the eyes of 12 unilat
cornea as epithelial replacement progresses eral aphakes, all of whom had undergone
was recently explored in greater detail by uncomplicated intracapsular cataract extrac
Mauger and Hill (1985). Two phases of the tion. Ten of the aphakic eyes had oxygen
healing sequence were found and replicated uptake rates below their paired phakic
for six corneas followed over a 10-day period, mates. Although the mean difference of
post-injury. The initial hypoflux period, last uptake rates between phakic and aphakic
ing about 48 hours, would be expected of eyes was not great, it was found to be signifi
course to be based on the absence and then cant at the P < 0.005 level.
gradual build-up of very modest cell num
bers within the wound zone. Reduced oxy
22.9 OVERVIEW
gen uptake during that time may also be due,
however, to an inhibition of cell division It appears then; that we have now experience
over that period, during which energy is in three discernible phases of the oxygen
now known to be derived from stored glyco demand problem: (1) the identification and
gen within those cells (Kuwabara et al., 1976). reconfirmation of hypoxic effects on the cor
The healing cornea then enters a second nea: (2) the quantification of those short
phase in which a substantially greater than term, intermediate and long-term deficits in
normal oxygen uptake rate develops - the terms of the demand behaviour and physical
hyperflux period, which peaked here in the changes in the cornea; and (3) the apprecia
Mauger and Hill (1985) study at about 4 days tion of demand differences among patients
following the wound and then declined to and with particular ambient conditions. All
the pre-wound baseline by about the tenth three, but most certainly the last, have pro
day. The cause(s) of that increased rate may vided substantial challenges to the contact
be the exceptional activities of those cells, lens fitter for nearly a century now.
which include migration, adhesion and cell As this survey indicates, however, enor
division. The latter has been reported to mous progress has been made over that
begin with a lifting of miotic inhibition period, and those gains have every indica
following the initial migration period (Arey tion of continuing. Among those frontiers
& Corode, 1943). It may be, then, that the even now being more fully explored: (1) site
presence of a bandage lens during that differences in oxygen demand across the
hyperflux period should be weighed very surface of the cornea, i.e. between the lower
carefully, i.e. with regard to the benefits of exposed cornea, and that region chronically
mechanical protection versus the possible covered by the upper lid (Benjamin & Hill,
delay of healing due to the relative hypoxia 1988a): (2) the rapidity of demand increase
494 Oxygen consumption and measurement
immediately following lid closure, and the Dallos, J. (1946) Sattler's veil. Br. J. Ophthalmcl.,
degree of relief associated with lid 'flutter' 300,607-14.
(Benjamin & Hill. 1986); and (3) the individu Efron, N. and Carney, L.G. (1979) Oxygen levels
beneath the closed eyelid. Invest. Ophthalmol.
ality of oxygen demand among normal, Vis. ee«, 18, 93-5.
healthy corneas, and the implications of Efron, N. and Carney, L.G. (1981) Models of oxy
those differences (Benjamin & Hill, 1988b). In gen performance for the static, dynamic and
many areas,· the more subtle, but in the closed-lid wearer of hydrogel contact lenses.
long-term most critical, thresholds and toler Aust. ]. Optom., 64, 223-33.
ances associated with corneal oxygen Fatt, I. (1978) Gas transmission properties of soft
demand may just now be coming into view. contact lenses. In Soft Contact Lenses: Clinical
and Applied Technology (ed. M. Ruben), John
Wiley & Sons, New York, p. 83.
Fatt, I. and Chasten, J. (1982a), Measurement of
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