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OXYGEN CONSUMPTION AND 22
MEASUREMENT
R.M. Hill

22.1 EARLYCLUES Other investigators, both earlier and later,


such as Fick, Pannus, Muller-Gladbach, Fis­
A jungle fighter under compromising condi­ cher, Duane, de Roetth and Smelser contrib­
tions, a street trader with keratoconus and a uted basic pieces to the mosaic as well, firmly
high myope given to an optimistic indiffer­ linking adequate oxygen to normal corneal
ence ... all shared one thing in common: physiology, and hypoxia to a catalogue of
gross degrees of overwear syndrome (Dallos, dysfunctions (Hill & Cuklanz, 1967), ranging
1946). When described by Dallos in the from the most subtle fading of sensation as
194Os, such examples were still fairly com­ described by Millodot and O'Leary (1980), to
mon, even though the origins of such stress frank loss of the epithelium.
were already being explored. Indeed, clinical
experiments with lens apertures and tear
22.2 HOW MUCH?
exchange by Dallos himself were pointing
ever more convincingly towards hypoxia as a By the early 1960s, the first measurements of
principal cause. corneal oxygen uptake directly on the living
On even cursory review, of course, the human eye were achieved. These observa­
earliest literature too was rife with dues of an tions were made by Hill and Fatt (1963) using
oxygen starvation problem. Such phenom­ several reservoir and contact chamber com­
ena as the gradual development of a 'slight binations. Retrospectively, it was a mini­
bluish haze in daylight and colored halos mum clearance scleral lens design having no
around lights in the dark' were described as membrane, but using balanced saline as a
early as 1889 by A. Muller, a response later reservoir, which provided the most consis­
designated 'Sattler's veil'. after Professor tent (and generally median) data. Although
C.H. Sattler of Koeningsberg. cumbersome, and lacking substantially in
By 1934, Dallos and Sattler, through per­ comfort over the period the subject was
sonal communications, had even reached the required to wear it (the better portion of an
shared opinion that oedema was the physical hour), this saline medium technique did
cause and the epithelium the site of that carry with it the inherent advantage of
veiling effect. It was however, left to Finkel­ known gas constants. The parallel constants
stein (1952), through his elegant observa­ for a series of membrane reservoirs now
tions and mathematical analyses, to relate the commonly used have, however, not been so
two directly. universally agreed upon, often making their
Contact Lens Practice. Edited by Montague Ruben and Michel Guillon.

Published in 1994 by Chapman & Hall, London. ISBN 041235120 X

486 Oxygen consumption and measurement


associated results difficult to interpret in ences in corneal oxygen demand 'may pro­
absolute units. vide part of the explanation of the generally
The average corneal uptake value pub­ observed differences in the manner in which
lished by Hill and Fatt for the human cornea, patients respond to contact lens wear.'
based on their saline reservoir observations,
was 4.8 microlitres per square centimetre of 22.4 OPEN VERSUS CLOSED EYE
corneal surface per hour. There was however
another less widely recognized, but perhaps Among the more difficult of the natural cor­
even more important observation given in neal factors to analyse is the closed eye
that report, i.e. that the uptake rates mea­ condition. The difficulty in part lies in what
sured where found to slow to as little as 1.5 constitutes a state of 'closure.' If, for example,
ul/crrri/h, when the reservoir oxygen tension the lids are held tightly closed by clips, then
fell to 50 mmHg. Such reduced oxygen condi­ oxygen levels of 5% or lower (on a scale
tions may exist (on average) chronically where 21 % = air) may occur, as reported by
under a contact lens with varying conse­ Roscoe and Hill (1980). Natural closure, i.e.
quences ranging from the clinically undetect­ with the lid musculature more relaxed and
able (at very low levels and for extended with a less perfect seal, may result in higher
periods) to the extreme responses reported values (e.g 7% by Benjamin (1982) or even
by those early investigators listed above. 11 % by Efron and Carney (1979).
Even under those more physiological con­
ditions, however, Benjamin (1982) found that
22.3 NORMAL DIFFERENCE
the new closed-eye oxygen level was estab­
While the earliest figure for human corneal lished in little more than 3 min, and that
oxygen uptake cited by Hill and Fatt (1963) 'fluttering' of the eyelids could raise that
was a mid-range value, i.e. 4.8 ~.l1/cm2/h from level measurably. For the average patient,
a span of 3.2 to 7.2 !J,l/cm2/h measured for however, such reduced levels over night
near ambient (open eye conditions). Larke et appear to be less than optimum, as 2 to 4%
al. (1981) more recently, on studying 68 male swelling of the cornea is common on awak­
Caucasians, found an even broader range ening (Mandell & Fatt, 1965; Fatt & Deutsch,
among individuals of that population: some 1981)
3 to 91JI/cm2/h.
This three-fold variation among subjects
22.5 THE BLINK
(Larke et al., 1981) was well above the instru­
mental variation (i.e. error threshold) of their The blink, in the context of corneal oxygen­
systems (8.1%). Also, when sequences of ation assumes a special significance of course
measurements were done on a given eye, no with the presence of a contact lens. But the
progressive shift occurred, indicating that efficiency of the lid-lens tear pump resulting
irritation or debilitation due to repeated can differ markedly between rigid and soft
probe contact was not the basis of such (hydrophilic) lens types. As shown by Polse
differences; neither was the time of day (1979), very little dependence for oxygen
(between 9.00 a.m. and 9.00 p.m.) found to should be placed on the pump in hydrophilic
make a significant difference for any particu­ lens cases, as a 1 % exchange of tears per
lar eye. blink is about the most to be expected. This
Differences in the number of epithelial cell is not to say, however, that such a pump is
layers among corneas may however be one entirely without value. It may in fact be very
basis for that population range. Larke et al., significant in the clearance of both molecular
(1981) also point out that such natural differ­ level and grosser particles (e.g. desquamated
The equivalent oxygen percentage (EOP) 487
cells) from under the lens. 22.6 THE EQUIVALENT OXYGEN
In contrast to the soft lens, when acting in PERCENTAGE (EOP)
conjunction with a rigid lens the blink can
form, with appropriate design, a highly Although leading estimates of how a lens
effective tear (oxygen) pump system. The might influence or impair oxygen availabil­
efficiencies of such systems were calculated ity at the corneal surface have long been
by Cuklanz and Hill (1969) by loading the possible (i.e. by advance physical testing,
bowl of a contact lens with a known concen­ such as Dk/L measurements), as have trailing
tration of sodium ions and then measuring assessments (e.g. pachometry of a resulting
their progressive escape into the outside tear oedematous state), a rapid response, mini­
pool on successive blinks. The four eye-lens mum stress observation involving a particu­
systems studies were all fitted parallel to the lar lens on a particular eye could be very
flattest meridian of the cornea, and using a useful as well.
first order model (i.e. one that did not com­ Further, such a test should be non­
pensate for small amounts of backflow), the invasive and its results should be directly
proportion of the post-lens tear pool replaced and quantitatively comparable to common
per blink was found to range from 10 to 17%. standards and reproducible conditions, such
This exchange rate is on the average some 13 as a no lens state (i.e. the open eye in air), an
times more efficient than for the soft lens impermeable lens state (e.g. a thick PMMA
systems described earlier, and is, of course, lens under non-blink conditions) or to the
the physiological key to those many thou­ response of a reference lens with an oxygen
sands of oxygen impermeable PMMA lenses transmissivity between those two extremes.
that were fitted with reasonable success over Also, such a test of corneal oxygen demand
several decades. should lend itself to assessing a closed eye
By the end of the 196Os, it was possible to history, as well as the steady open eye state, or
observe the blink-driven lens-tear pump any blink rate (i.e. lid-lens tear pump) combi­
directly. This was done by Hill and Schoe­ nation of frequency and gaze positions. The
ssler (1969) by building a sensor right into a influences of temperature, humidity, pH, tear
corneal contact lens in such a way that the osmolality and other environmental factors
oxygen level of the post-lens tear pool could affecting corneal metabolism and lens status
be continuously monitored. This experiment should be detectable and assessable through
revealed a 'saw-toothed' cycle, composed of a such a procedure.
slow 'down-drift' segment (as the cornea A technique called the equivalent oxygen
drew oxygen from the post-lens tear pools percentage (EOP) method was developed in
during the interval between blinks), fol­ the late 1960s to approach these require­
lowed by a rapid up stroke (as the blink ments and needs for contact lens and corneal
action brought freshly oxygenated tears into studies (Hill, 1977). The rationale for the
the pool again). For any particular blink method if> reflected in the four effects shown
frequency, an average oxygen level would schematically in Figure 22.1. In Frame (a), an
eventually be established. The faster the oxygen probe and reservoir are placed down
blink rate, the higher that average would be. onto the surface of a cornea that has been
In certain systems however, if the blink rate freely exposed to air. The emptying time of
became very slow, the post-lens tear pool oxygen from the probe reservoir in this case
could become entirely depleted of oxygen is relatively slow, as indicated by the gentle
over the latter portion of the inter-blink slope of the graphical trace.
interval (Cuklanz & Hill, 1969; Fatt & Hill, In Frame (b), the same procedure is
1970). repeated except that the cornea in this
488 Oxygen consumption and measurement

(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.
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