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The relationship between pressure and volume
changes in living and dead rabbit eyes
John E. Eisenlohr and Maurice E. Langham
A study has been made of the relationship between the volume of fluid infused into the living
and dead eyes of individual rabbits and the intraocular pressure. To minimize loss of fluid from
the eye during the experimental procedure the infusion was made either at 197 pi minr1 or
by a very rapid injection procedure. In individual rabbits the pressure/infusion volume relationship was found to differ significantly between the living ami dead eye. In the dead eye
the coefficient of ocular rigidity was found to be approximately constant for pressures of 30 to
60 mm. Hg and to decrease below and above these pressures. In the living eye the coefficient
of ocular rigidity was found to be at a maximum at a pressure of 25 to 30 mm. Hg and to
decrease at pressures below and above this value provided the blood pressure tvas not exceeded. When the intraocular pressure exceeded the blood pressure the coefficient increased
and approximated closely the -value found in the dead eye at similar pressures. The marked
influence of the blood supply to the eye on the pressure/infusion volume of the living eye has
been demonstrated in experiments in which either the general blood pressure was varied or
the local blood supply to the eye ivas decreased. The physiologic and practical significance of
the results are discussed. It is emphasized that the volume of fluid injected into the living eye
is not equal to the volume change of the eye. Thus, it is quite unjustifiable to utilize this type
of relationship in tonographic measurements of the intraocular dynamics.
T,
tonometer. Friedenwald concluded that
the volume change of the eye was directly
proportional to the common logarithm of
the ratio of the final and initial pressures
and that the proportionality constant, which
he termed the coefficient of ocular rigidity,
had a mean value of 0.0215 for human eyes.
The validity of this relationship was confirmed by Grant and Trotter7 in manometric studies on enucleated human and
rabbit eyes before and after death. On the
other hand, Perkins and Gloster13- " and
Macri and co-workers10 in similar studies
on rabbit and cat eyes, respectively, could
not confirm the relationship. None of these
investigators reported detailed comparative
studies on living and dead eyes of individual animals, but Grant and Trotter7
observed no difference in the coefficient of
ocular rigidity in two rabbits before and
immediately after death, while Perkins and
. he measurements of intraocular pressure
and dynamics by the conventional techniques of indentation tonometry and tonography are dependent on a knowledge of
the exact relationship between pressure
and volume changes of the living eye. However, at the present time the pressure
volume relationship in general use is based
on Friedenwald's5 analysis of the experimental observations of earlier investigators
on dead animal and human eyes and his
own studies0 on the volume of corneal indentation produced by a standard Schiotz
From the Wilmer Institute, The Johns Hopkins
University Medical School, Baltimore, Md.
This work was supported in part by Special Fellowship BT-627, National Institute of Neurological Diseases and Blindness, United States
Public Health Service, and by United States
Public Health Service Grant B-2591.
63
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Investigative Ophthalmology
February 1962
64 Eisenlohr and Langham
Gloster13 stated that the pattern of results
was similar in living and dead eyes but
that values at any given pressure tended to
be lower in life. Finally, Macri and coworkers10 concluded that the reaction of
living and dead eyes was essentially identical.
It is the principal purpose of this investigation to evaluate the pressure response of
the living and dead eyes of individual rabbits to injections of a known volume of
fluid and to ascertain to what extent this
response is influenced by the blood supply
to the eye. In this connection the assumption made in previous studies that
the volume of fluid injected and the volume
change of the eye are equal has been
examined experimentally. At the same time
it was hoped to resolve the apparent discrepancies in the literature concerning the
validity of the constancy of the coefficient
of ocular rigidity by a re-examination of
the method used in the earlier studies. This
method comprised a measurement of pressure changes resulting from a very rapid
injection of a known volume of fluid into
the eye. In this study the results with this
technique have been compared with those
derived from observations of the pressure
changes induced by a continuous infusion
of physiologic saline into the eye. Our results indicate that living and dead eyes react differently to infused volumes of fluid
and that the results on the living eye vary
significantly with the level of the systemic
blood pressure. The results agree closely
with those found in a similar manometric
study on the human eye before and after
enucleation.'1
Methods
Adult rabbits of the New Zealand white strain
which weighed between 2.0 and 3.0 kilograms
were used throughout the experiments. Animals
were anesthetized with urethane (1.0 to 1.75 Gm.
per kilogram). Vascular and intraocular pressures
were recorded by means of Sanborn transducers,
Model No. 267B, in conjunction with Sanborn
1100 AS carrier preamplifiers and a multichannel
150 M rectilinear recorder.
Rapid injections of fluid into the eye were made
RECORDER
MICROMETER
SYRINGE
CONTINUOUS
I NFUSION
APPARATUS
Fig. 1. Diagram of the infusion and recording apparatus. By means of the saline reservoir the
intraocular pressure could be established at any
predetermined level. Then by excluding the reservoir from the system by closing the tap in the
plastic block, saline could be injected into the eye
from either the micrometer syringe or the continuous infusion machine. The pressure response
was then recorded by the transducer through the
same carmula used for infusion.
using an Agla micrometer syringe. This was fitted
with a mechanical stop so that predetermined
volumes of physiologic saline (5 to 7 /tl) could be
injected with one quick twist of the micrometer
screw; the time taken for this volume of fluid to
be expelled from the syringe was 100 to 300
msec. The accuracy of the micrometer screw in
delivering the calculated volume was within 0.5
per cent. The plunger of the syringe and all taps
were lubricated with Dow-Corning silicone stopcock grease. Continuous injections of physiologic
saline were made with the apparatus described
recently by Langham.9
A diagram of the apparatus used to make the
rapid and continuous infusion studies is shown
in Fig. 1. Infusions into and pressure recordings
from the eye were made through the same needle.
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Volume 1
Number 1
Pressure and volume relationship
This was accomplished by the use of a four-way
block which permitted interconnection of the injection apparatus, a saline pressure reservoir, the
pressure transducer, and the anterior chamber
either simultaneously or separately. A 23 gauge
needle was inserted into the eye and connected
to the four-way block by a short length (approximately 3 inches) of No. 50 polyethylene tubing.
Prior to an experiment, the entire apparatus was
cleaned, filled with deoxygenated physiologic
saline, and examined carefully for trapped air
bubbles and leaks. The recording system was
balanced hydrostatically and the sensitivity set at
1 mm. per millimeter mercury for the continuous
technique and 2 mm. per millimeter of mercury
for the rapid technique. Since a small volume of
fluid was required to raise the pressure of the
transducer and the infusion system itself, this
amount had to be subtracted from the total volume
delivered by the syringe to obtain the net volume
of saline entering the eye. Fig. 2 illustrates the
method of measuring the system's volume capacity which was found to be linear with respect to
pressure and to average 0.014 1*1 mm. Hg- 1
(range 0.003 to 0.027 id. mm. Hg- 1 ) for the rapid
technique and 0.012 /il mm. Hg- 1 (range 0.003
to 0.037 jul mm. Hg- 1 ) for the continuous technique. In addition, a small correction for the
amount of fluid escaping through the outflow
channels of the eye had to be applied in the case
of the continuous method. The value for this
estimate of aqueous outflow at varying pressures
was taken from the mean steady-state perfusion
data of Langham.s
Experimental procedure. The anesthetized
animal was placed on an operating table equipped
VOLUME
65
with a warming plate so that the body temperature could be maintained constant. The femoral
artery was cannulated for the blood pressure
record and in certain experiments a similar
cannulation was made of the median ear artery.
In general, it was found unnecessary to use a
head holder and cannulation of the eye was made
with the animal lying on its side.
In the rapid injection experiments at least
three infusions of 5 to 7 pi were performed at
each pressure level. Determinations were made
at the lowest pressure level first and then the
pressure in the eye was increased in steps of 10
mm. Hg over the pressure range of 15 to 55 mm.
Hg. Similar experiments were then made at
descending steps of 10 mm. Hg starting at 50 mm.
Hg. In this way die entire pressure range from
15 to 55 mm. Hg was covered in 5 mm. Hg
intervals. No systematic difference was found
between the first and third reading at any given
pressure and the average pressure change was
used in the subsequent calculations. In certain
additional experiments similar studies were made
for pressure exceeding 55 mm. Hg.
The continuous infusion technique was carried
out in the following manner: The volume capacity
was measured by connection of the apparatus
directly to the pressure transducer. Then all four
taps on the Lucite block were opened and the
pressure in the eye brought to 15 mm. Hg. The
tap to the reservoir was then turned oft, and the
record taken. This was repeated three or more
times and the average readings vised in the subsequent calculations.
Changes in the general blood pressure were induced by allowing blood from a femoral artery
CAPACITY
CONTINUOUS
TIME (SEO
Fig. 2. Method for the determination of the volume capacity of the system, excluding
the eye. On the left, 0.8 id. of fluid was injected rapidly into the closed system and the
pressure rose by approximately 40 mm. Hg. On the right is shown a record of the
pressure responses of the closed system when an infusion of 197 id min.-1 was made.
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tigatioe Ophthalmology
February 1962
66 Eisenlohr and Lansham
to flow into a pressure reservoir set at the desired
pressure level with respect to the heart.
Results
Preliminary experiments were carried out
to confirm the validity of recording pressure from the anterior chamber through
the same needle used for infusion. For
this purpose a No. 23 gauge cannula was
passed into the anterior chamber and arranged for infusion and pressure recording
as outlined in Fig. 1. In addition, a second
cannula attached to a separate transducer
was inserted into the anterior chamber for
an independent measurement of pressure.
During rapid injections of saline the pressure changes recorded by the two cannulas
were identical. However, during an infusion
of 197 /xl min."1 the pressure recorded directly from the anterior chamber was 2 mm.
CONTINUOUS
RAPID
Fig. 3. Equilibration of pressure throughout the
eye. The pressures in the anterior chamber and
the vitreous humor were recorded simultaneously
during the rapid and continuous infusion of fluid
into the anterior chamber. The infusion of 197 lA
min.-1 into the anterior chamber caused the pressure in the anterior chamber to appear to be 2
mm. Hg above that in the vitreous. This constant
pressure difference was due to the resistance to
flow in the infusion system. After the rapid injection of saline into the anterior chamber, the
pressures recorded in the two spaces were identical. In this case, however, it will be noticed that
the pressure overshoot within the first short interval of time was greater in the anterior chamber.
The paper speed was equivalent to one large
square per second.
Hg lower than that recorded from the infusion cannula. This pressure gradient was
found to be a function of the rate of infusion and independent of the intraocular
pressure. This discrepancy could be eliminated by employing a larger cannula, but
this in turn increased the volume capacity
of the system. Furthermore, in order to
minimize disturbance to the eye it was desirable to use the smallest needle practicable. Since the 2 mm. Hg pressure gradient was found to be constant for all pressures studied up to 100 mm. Hg, the 23
gauge needle was used in all the infusion
studies. The resistance to flow offered by
the cannula and its polyethylene connection
was responsible also for a pressure overshoot observed during rapid saline injections. This overshoot had a measured
duration of approximately 0.25 second.
Therefore, in agreement with the methods
of previous investigators, the earliest
portion of each rapid infusion record was
ignored and the slope of the decay curve
1 second after injection was extrapolated
back to zero time.
Typical results from both the rapid and
continuous infusion methods in which
pressures in the anterior chamber and in
the vitreous humor were recorded simultaneously are shown in Fig. 3. The pressure
changes resulting from the rapid and continuous injection of saline were identical
in the two compartments. Similar results
were observed in dead eyes.
A typical record of the continuous infusion of 197 jA min."1 of normal saline
into the anterior chamber of the rabbit
eye before and after death is seen in Fig.
4. The slope of the infusion curve in the
dead eye, which is a reflection of the eye's
ocular rigidity, was consistently found to
be higher than that of the living eye in
each of the animals studied. Altogether 12
living eyes of 10 rabbits were examined by
the continuous technique and of these 8
eyes were also studied in situ after death
from an overdose of urethane. Mean values
for the coefficient of ocular rigidity (where
AV equaled the volume of saline infused)
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Volume 1
Number 1
Pressure and volume relationship
L I VING
20 -
__
67
DEAD
4
15
20
0
5
10
:
TIME C S E O
Fig. 4. A typical pressure response of the rabbit eye to the infusion of
197 MI min.-1 into the anterior chamber before and after death from an
overdose of urethane.
were calculated from the continuous tracings in steps of 10 mm. Hg and the results
are summarized in Fig. 5 and Table I. It
will be seen that the mean coefficients for
both the living and the dead eye increased
until the intraocular pressure reached 25
to 30 mm. Hg after which there was a
progressive decrease in rigidity with a
further increase in pressure. The values
for the dead eye were higher than those
for the living eye, the difference being
significant at the 5 per cent level at 28 mm.
Hg (0.02 < P < 0.05) and highly significant for pressure levels above this (P <
0.001). A plot of the logarithm of the intraocular pressure against the volume of
saline infused into the 12 living eyes gave
a curve of sigmoid shape with a point of
inflexion at a pressure of 25 to 30 mm. Hg
(Fig. 6).
The effect on the intraocular pressure of
a rapid injection of saline into the eye was
studied on 16 eyes of 12 anesthetized rabbits, and one eye of each rabbit was also
Table I. The coefficients of ocular rigidity
of the living and dead rabbit eye calculated
over successive intervals of 10 mm. Hg
from the continuous infusion records. The
figures shown are mean values (±S.E.)
from 12 living and 8 dead eyes in situ
Table II. The coefficients of ocular rigidity
of the living and dead rabbit eye measured
at varying intraocular pressures by the
rapid technique. The figures shown are
mean values (±S.E.) from 16 living and
12 dead eyes in situ
Intraocular
pressure
(mm. Hg)
18-28
23-33
28-38
33-43
38-48
43-53
48-58
53-63
63-73
Intraocular
pressure
Living
.0216
.0242
.0246
.0234
.0217
.0194
.0174
.0154
.0134
±
±
±
±
±
±
±
±
±
.0026
.0014
.0014
.0014
.0013
.0013
.0014
.0014
.0019
Dead
.0253
.0289
.0295
.0307
.0293
.0280
.0270
.0243
.0241
±
±
±
±
±
i
±
±
±
.0047
.0026
.0016
.0020
.0014
.0016
.0014
.0008
.0013
(mm. Hg)
Living
15
20
25
30
35
40
45
50
55
.0164 dt .0029
.0237 dt .0013
b .0014
.0281 d
.0260 d: .0010
.0256 dt .0013
.0241 dt .0016
.0209 dt .0016
.0199 dt .0019
.0156 :t .0013
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Dead
.0227 :t
.0291 dt
.0351 dt
.0360 d:
.0374 dt
.0356 dt
.0357 d
t
.0353 dt
.0344 d
t
.0031
.0022
.0016
.0014
.0013
.0012
.0009
.0012
.0012
Investigative Ophthalmology
February 1962
68 Eisenlohr and Langham
030
• • *
020-
*
0
0
•
o
20
30
40 50
60 70
10 P (MMHG)
80
Fig. 5. The variation in the coefficient of ocular
rigidity with pressure. The values were calculated
from the results of the continuous infusion technique and were based upon 12 living ( • ) and 8
dead (O) rabbit eyes. The results are expressed
as the arithmetic mean ± the standard error of the
mean (A.M. ± S.E.).
examined in situ after death by the same
technique (Fig. 7). The results of these
experiments are summarized in Fig. 8 and
Table II. The mean coefficients of ocular
rigidity derived from these results are
similar to those of the continuous infusion
method. Thus, the coefficient of ocular
rigidity in the living eye increased until
the initial intraocular pressure reached 25
mm. Hg after which it fell progressively.
In dead eyes, the coefficient of ocular
rigidity was virtually constant above a
pressure of 25 mm. Hg. Statistically, the
difference between the living and dead
eye was significant at the 5 per cent level
(0.02 < P < 0.05) at 20 mm. Hg, and
highly significant for all pressure levels
above this (P < 0.001).
In the rapid-injection studies the volume
of saline injected was maintained constant
while observations were made first with increasing and then decreasing initial pressure steps of 10 mm. Hg. The values obtained for ocular rigidity during the
descending phase tended to be slightly
higher than those noted at ascending pressure steps, particularly in the dead eye.
However, repeated continuous infusions of
saline over the same pressure range failed
to reveal a tendency for each successive
infusion curve to become steeper than the
preceding one.
The influence of blood pressure on the
pressure response of the living eye to infusions of fluid was studied by reduction of
the general blood pressure and by local restriction of the blood supply to the eye.
Six rabbits were anestlietized and prepared
for study in the usual manner, and, in addition, a femoral artery was attached to a
blood reservoir by means of a polyethylene
cannula. By opening the cannula and adjusting the level of the blood reservoir
with respect to the heart, stable vascular
hypotension could be readily produced.
Under these conditions a marked dependence of ocular rigidity on blood pressure
70605040CL
O
O
O
30-
20-
10
20
30
Fig. 6. The relationship between the logarithm of
the intraocular pressure (plotted as ordinate) and
the net volume of saline infused into the anterior
chamber by the continuous technique. The solid
and dotted lines represent, respectively, the A.M.
± S.E. of 12 living eyes. It will be noted that the
curve has a point of inflection at approximately
25 mm. Hg. By definition the slope of this line
at any pressure is equivalent to the coefficient of
ocular rigidity and it will be seen that this increased in value up to the point of inflection and
then decreased over the remaining range of pressures studied.
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Pressure and volume relationship
69
DEAD
LIVING
o
I
2
2
Fig. 7. A typical record of the intraocular pressure following three rapid injections
of 5 ill each into the anterior chamber of the living and dead eye of an individual
rabbit. The rjaper speed was equivalent to one large square per second. Note that
the pressure response to equal volumes of saline injected was greater in the dead than
in the living eye. The record of the femoral arterial pressure has been electronically
damped to record the mean blood pressure.
.040 1
.030 •
•
tSU >
o
o
•
°20 •
.010 -
20
30
I0P(MM
40
50
60
HG)
Fig. 8. The effect of pressure on the coefficient of
ocular rigidity calculated from experiments on 16
living ( • ) and 12 dead (O) eyes, studied by the
rapid injection technique. The results are expressed as the A.M. ± S.E.
was observed. Fig. 9 illustrates the effect
on intraocular pressure of the continuous
infusion of 197 /A min."1 into the eye of the
same animal before and during vascular
hypotension. It will be observed that, as
the intraocular pressure approached the
mean systemic blood pressure, the rate of
increase in the intraocular pressure diminished significantly. Then, as the intraocular
pressure exceeded the blood pressure, as
evidenced by a cessation of the ocular
pulse, there was a marked increase in the
slope of the infusion curve. In all animals
studied, this characteristic plateau in
the continuous infusion records was found
to be correlated with the level of
systemic blood pressure. In the hypotensive
animal, the plateau and the subsequent
rapid pressure increase were noted at a
correspondingly lower pressure than in the
normotensive animal. Comparative tracings
from one animal immediately after cannulation, during hypotension, and after death
from an overdose of urethane are seen in
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70
Inoestigativ Ophthalmology
February 1962
Eisenlohr and Langham
Fig. 10. The infusion curve from the hypotensive animal became indistinguishable
from that obtained after death once the
ophthalmic blood pressure had been exceeded. The effect of hypotension on the
ocular rigidity measurements of 3 individual eyes studied by both infusion tech-
niques is seen in Fig. 11 and is characteristic of all 6 animals in which the effect
of hypotension was evaluated.
A localized reduction in the vascular
pressure of the eye was also accomplished
by clamping one or both carotid arteries. A
typical result is shown in Fig. 12.
NORMOTENSIVE
HYPOTENSIVE
Fig. 9. The influence of vascular hypotension on the pressure response to a continuous
infusion of 197 /d. min.-1 into the anterior chamber of the eye of an anesthetized
rabbit. The first curve shows the results on the normal animal and it will be seen
that, as the intraocular pressure approached the blood pressure, the slope of the
pressure record decreased considerably, but then increased again as the blood pressure
was exceeded. The second curve shows the same experiment when the animal was
made hypotensive and exhibits the characteristic plateau at a correspondingly lower
level of intraocular pressure. The blood pressure was electronically damped for part
of the tracing.
NORMOTENSIVE
HYPOTENSIV E
M^liUbiUdiliUilil
DEAD
iMiUfaUil^yi
I. UI
7
40
20
20
Fig. 10. Comparative tracings of the pressure in the anterior chamber during an
infusion of 197 lA min."1 into an animal made hypotensive and then killed. The
characteristic marked difference in response of the hypotensive eye is seen, and, in
addition, it will be noted that when the intraocular pressure exceeded the arterial
pressure, the record in the living eye became very similar to that in the dead eye.
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Volume 1
Number 1
Pressure and volume relationship 71
2
3
RAPID
or
Q_
20
30
40
SO
60
O
O
20
30
40
50
60
20
30
40
30
20
30
40
SO
SO
CONTINUOUS
20
30
40
SO
60
20
I OP
30
40
JO
60
(MMHG)
Fig. 11. The effect of vascular hypotension on the coefficient of ocular rigidity of 3 individual
eyes studied by both the rapid and continuous injection techniques. The values for the rigidity
of the living ( • - • ) and dead (O-O) animals are compared with those obtained from the
same animal during hypotension (
). The figures to the right of the records of the living
and hypotensive rabbits indicate the mean femoral arterial blood pressure during the experiment. It will be seen that the ocular rigidity was dependent upon the systemic blood pressure
and that only when the intraocular pressure approached or exceeded the blood pressure did
the living and dead eyes react similarly to infusions of saline.
A reduction in the median ear arterial
pressure which is known to agree closely
with that of the ophthalmic arterial pressure1 was associated with a downward displacement of the pressure/infusion curve.
Discussion
The results of this study give strong support to the conclusion of recent investigators that the coefficient of ocular rigidity
in both living and dead eyes varies with
pressure, but they differ in certain qualitative and quantitative aspects which merit
discussion. Furthermore, the results fail to
support the contention of recent investigators that there is no significant difference
in the pressure/infusion volume relationship before and after death. On the contrary, two of the most important observations in this study have been the difference
in response of living and dead eyes and
the marked influence of the vascular pressures on the pressure/infusion volume relationship of the living eye.
The results derived from the rapid injection technique on the living and dead
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•.stigatiue Ophtliahnology
February 1962
72 Eisenlohr and Langham
TIME §E0
Fig. 12. The effect of localized ocular hypotension on the pressure response,
to a continuous infusion of 33 /id min.-' of saline. The top record shows the
pressure in the median ear artery which closely approximates that of the
ophthalmic arterial pressure. The three records show the response in the
normal animal (A) and following ipsilateral (B) and bilateral ligation (C)
of the common carotid arteries. It will be noted that there was a downward shift in the plateau of the pressure record of the eye corresponding
to each successive fall in the median ear arterial pressure. This response
was completely reversible on release of the arterial ligatures.
eyes of rabbits agree in some, but not in all,
respects with those of Perkins and Gloster.33
These investigators concluded that the coefficient of ocular rigidity increased with
pressure in both living and dead eyes and
that, in 5 out of 10 animals studied, the
values were similar before and after death.
In the remaining 5 animals, the values after
death were approximately 20 per cent
above those in life. No details were given
of their experiments on dead eyes but
analysis of their results on living animals
showed that the mean coefficients were
0.007 ± 0.001, 0.015 ± 0.003, and 0.018 ±
0.002 for pressures of 11 to 18 mm. Hg, 22
to 29 mm. Hg, and 33 to 40 mm. Hg, respectively. In the present studies, however,
an increase in the coefficient of ocular
rigidity in both living and dead eyes was
found only for pressures up to 25 to 30
mm. Hg. Furthermore, the absolute values
for the coefficient of ocular rigidity reported
by Perkins and Gloster were less than those
of the present study at corresponding levels
of intraocular pressure. The reason for
these discrepancies could well lie in the
relatively insensitive rubber membrane
manometer used by these workers. It is,
however, of interest that in Fig. 2 of a
subsequent paper by Perkins and Gloster14
the ocular rigidity of an eye before and
after death is recorded over a pressure
range of 40 to 107 mm. Hg and indicates
a difference between the living and dead
eye. Furthermore, the coefficient of ocular
rigidity reached a minimum value at 73
mm. Hg in the living eye and then increased until it reached a similar value to
that of the dead eye. This finding is in excellent agreement with the results of this
study in which the ocular rigidity increased
when the intraocular pressure exceeded the
systemic blood pressure.
The coefficient of ocular rigidity in living
and dead eyes of cats was studied in a
similar manner by Macri and co-workers.10
They found the coefficient to vary with
pressure in the living eye and their results
agree closely with those found in the
present study on the eyes of living rabbits.
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Volume 1
Number 1
However, their results on dead eyes differed from the present findings in that they
could find no difference between living and
dead eyes. This led these investigators to
conclude that the coefficient of ocular
rigidity was a function of the ocular coats
and was not influenced by either nervous
activity or circulatory changes. Although
no difference was found between living
and dead eyes, no specific studies were
made to rule out the possibility of a vascular effect. Indeed the influence of vascular
pressures on ocular rigidity in the living
cat is strongly suggested in the results of a
subsequent paper.11
The marked difference observed in the
pressure/infusion volume relationship between the living and dead eyes must be
considered from two aspects: first, the
validity of the assumption made by previous investigators that the volume of fluid
infused into the eye was equal to the
volume change of the eye; and second, the
significance of this difference to tonometric
and tonographic studies. The equation of
volume infused to the volume change of
the eye was made by Friedenwald5 in his
contribution to the theory and practice of
tonometry and has never since been seriously questioned. His view, however, cannot be upheld by the findings in this study
of a significant difference in the pressure
response of eyes before and immediately
after death and of a similarity in response
of a living eye to that of the dead eye when
the intraocular pressure exceeds that of
the blood pressure. In the living eye it was
evident that the inequality between the
volume of fluid injected and the volume
change of the eye became very great when
the intraocular pressure approached that
of the blood pressure. Under these conditions, the rate of change of intraocular
pressure fell nearly to zero even when 197
fA min."1 of fluid was infused into the eye.
This means that intraocular fluid was leaving the eye at nearly the same rate.
Further, this could be effected for any
pressure level in the eye by a suitable
adjustment of the blood pressure indi-
Pressure and volume relationship 73
cating the vascular nature of this phenomenon.
In the case of the enucleated eye, it is
not possible to determine from these
studies whether the volume infused equaled
the volume change of the eye. Although
there cannot be any vascular displacement
under these conditions, there still remains
the possibility that an increased pressure
caused a collapse of the intraocular vessels.
Certainly a pressure of 30 mm. Hg should
be more than sufficient to compress all the
veins and smaller vessels of the eye and the
present results are consistent with this
hypothesis. The observation that the coefficient of ocular rigidity in the dead eye
was approximately constant over the pressure range of 30 to 60 mm. Hg is in agreement with Friedenwald's contention. Thus,
it may be that the relationship between
actual volume and pressure change of the
eye follows his original expression. Such a
relationship would be of theoretical interest rather than of practical importance
to the measurement of pressure and intraocular dynamics.
The significance of the inequality of
volume infused and volume change in
the living eye lies in its application to
tonometric and tonographic studies. The
measurement of intraocular pressure by
indentation tonometry is analogous to the
infusion of a certain volume of fluid into
the eye. The tonometer causes a volume
of indentation and an increased pressure
in the eye (P t ) and derivation of the pressure in the untouched eye (Po) must be
based on knowledge of the relationship between the volume of corneal indentation
and the pressure change of the living eye.
In tonography the object is to determine
the rate of loss of aqueous humor per unit
pressure gradient from the eye, and at
least two assumptions are made which
cannot be justified on the basis of the
present studies, namely, that the coefficient
of ocular rigidity is constant, and that the
volume change calculated is due solely
to loss of aqueous humor from the eye.
Comparison of the results of the rapid
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Inoextigatioc Ophthalmology
February 1962
74 Eisenlohr and Lanzham
and continuous infusion studies showed
general agreement in the living and dead
eyes although the coefficients of ocular
rigidity derived from the continuous infusion studies were as much as 30 per
cent below those of the rapid technique.
The techniques differ principally in the rate
of pressure change induced in the eye. It
is known that the elastic properties of the
dead eye include a viscoelastic component
which would tend to cause a reduction in
the coefficient of ocular rigidity with slower
rates of infusion. The alternative explanation that the discrepancy could be due to
an error in the correction for outflow of
aqueous humor appears most unlikely as
it represented only a very small fraction
of the volume infused.
REFERENCES
1. Barany, E. H.: The influence of local arterial
blood pressure on aqueous humour and intraocular pressure. Experimental study of the
mechanisms maintaining intraocular pressure.
Intraocular pressure and local blood pressure
from seconds to hours after unilateral carotid
occlusion. A search for homeostatic reflexes in
the undisturbed eye, Acta ophth. 24: 337,
1946.
2. Becker, B., and Friedenwald, J. S.: Clinical
aqueous outflow, A. M. A. Arch. Ophth. 50:
557, 1953.
3. Bettman, J. W., Fellows, V., Chao, P., and
Pratt-Johnson, E. J.: The effect of tonography
and other pressures on the intraocular blood
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
volume, A. M. A. Arch. Ophth. 60: 231,
1958.
Eisenlohr, J. E., Langham, M. E., and
Maumenee, A. E.: Manometric studies of the
pressure volume relationship in living and
enucleated eyes of individual human subjects,
Brit. J. Ophth. (in press).
Friedenwald, J. S.: Contribution to the theory
and practice of tonometry, Am. J. Ophth. 20:
985, 1937.
Friedenwald, J. S.: Standardization of tonometers. Decennial report by the Committee
on Standardization of Tonometers, Am. Acad.
Ophth. 1954, pp. 93-152.
Grant, W. M., and Trotter, R. R.: Tonographic measurements in enucleated eyes,
A. M. A. Arch. Ophth. 53: 191, 1955.
Langham, M. E.: Influence of the intra-ocular
pressure on the formation of the aqueous
humour and the outflow resistance in the
living eye, Brit. J. Ophth. 43: 705, 1959.
Langham, M. E.: Steady state pressure flow
relationships in the living and dead eye of
the cat, Am. J. Ophth. 50: (Pt. 2) 280, 1960.
Macri, F. J., Wanko, T., Grimes, P. A., and
von Sallmann, L.: The elasticity of the eye,
A. M. A. Arch. Ophth. 58: 513, 1957.
Macri, F. J.: Outflow patterns of the cat eye,
Am. J. Ophth. 47: (Pt. 2) 547, 1959.
Monnik, A. J. W.: Ein neuer Tonometer und
sein Gebrauch, v. Graefe's Arch. Ophth. 16:
49, 1870.
Perkins, E. S., and Gloster, J.: Distensibility
of the eye, Brit. J. Ophth. 41: 93, 1957.
Perkins, E. S., and Gloster, J.: Further studies
on the distensibility of the eye, Brit. J.
Ophth. 41: 475, 1957.
Ytteborg, J.: The role of intraocular blood
volume in rigidity measurements on human
eyes, Acta ophth. 38: 410, 1960.
Discussion
Dr. Robert A. Moses, St. Louis, Mo. It is a
privilege to be allowed to comment on a work
which tackles the thorny problem of change in
intraocular blood volume with changing intraocular pressure and changing blood pressure.
There can be little doubt that intraocular blood
volume is not fixed. The authors have demonstrated this and have quoted supporting documentation. That there are authors who did not
find these phenomena is not surprising for the
quantities are small.
Since there is such a shift of volume, it is
clear that what has been called "ocular rigidity"
includes this alteration. It is astounding that the
masterful simplifications of Dr. Friedenwald have
been so useful in our work. I offered further
evidence of the influence of blood pressure and
blood volume changes at the Wilmer Resident's
Association meeting this Spring when I showed
that ocular rigidity not only changes but becomes anomalous with change in the patient's
position (Fig. 13) (my figures numbered in
sequence with the authors'). Their illustrations
of relatively slow infusion into the anterior
chamber are particularly provocative (Fig. 12).
They interpret the plateaus as evidence of blood
leaving the eye as aqueous is entering it. This is
the interpretation Macri gave in experiments
performed in the reverse order. That is, Macri
distended the eye and studied the slope of the
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Volume 1
Number 1
Pressure and volume relationship 75
FRIEDENWALD 1955 NOMOGRAM FOR SCHIOTZ TON 0 M ETER
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VOLUME OF INDENTATION CUBIC MILLIMETERS
Fig. 13. Ocular rigidity measurements on supine subject with applanation and Schiotz
tonometers (5.5 and 10 Cm. plunger loads). The lower curve was obtained with the patient
horizontal, the upper solid curve with the table tilted head down 30 degrees, and the dotted
curve after 15 minutes in the head-down position.
pressure decay curve. The phenomenon of volume
shift may be studied in a highly simplified model
(Fig. 14). Here we have an "artery" which has
a constant pressure at its origin. It traverses the
"eye" and is exposed to "intraocular pressure" and
discharges into an "extraocular vein" of fixed
height. Since the "corneosclera" is glass it should
have a virtually infinitely great rigidity, but as we
inject volume and record pressure changes in this
"eye" we find a pattern (Fig. 15) not unlike that
found by the authors in a living rabbit. (Correction for volume loss to the manometer has been
made.) I want to call attention to the similarity
of the authors' normotension and hypotension
curves (Fig. 9) to those of the model. In both
cases, when the arterial blood pressure is lowered,
apparent ocular rigidity is lowered also. I would
like to ask the authors' interpretation of their Fig.
10 in which the total volume injected into the eye
of the hypotensive animal is considerably greater
at each pressure level than in the normotensive.
This would seem to imply that, when hypotensive,
the animal had more blood in its eye than when
normotensive. The model and several experiments
with it are to be reported elsewhere.
Quantitation of the role of blood volume in
what we record as ocular rigidity is difficult. This
may be seen if one superimposes some of the
authors' records, on the same eye. In Fig. 16, I
have attempted to match some of the records
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Investigative Ophthalmology
February 1962
76 Eisenlohr and Langham
Fig. 14. Model eye. A, glass jacket; B, thinwalled rubber tube; C, syringe for altering pressure in jacket; D, manometer for jacket pressure;
E, water supply of constant pressure head; F,
clamp for adjusting resistance of supply tube; G,
manometer for pressure of water near entrance
to thin-walled tube; H, flow exit.
from the authors' Fig. 4, and we see that the
records from the living eye lie between those of
the dead eye.
There is a bonus in the paper. Dr. McEwen
has been studying the rheology of the eye and he
should be very interested in the peaks of pressure shown in the recordings from the vitreous
when fluid is injected rapidly into the anterior
chamber (Fig. 3). Such pressure peaks have
been explained away by several authors on an
instrumental basis. Here we have the pressure
recording completely isolated from the injection
system. The pressure peak is real and its decay
must represent either a somewhat slow stretch
of the ocular coats, or the time required for
blood to be forced out of the eye, or both. I
would like to ask the authors if they have noted
the behavior of dead eyes similarly doubly cannulated?
e
y
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/
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E 40/JF*
Q_
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3
1
3
1
5
10
Time (Sec.)
Fig. 16. Superposition of curves of Eisenlohr and
Langham's Fig. 4; a, b, living eye; c, d, dead eye.
5
7
AV ( m l )
5
7
AV ( m l )
1
9
Fig. 15. "Pressure-volume" relationships of model
eye.
Dr. Eisenlohr (closing). Dr. Moses' experiments
with volume shift in a simplified model eye are
most intriguing and appear to be analogous to
our findings in normotensive and hypotensive rabbit eyes.
Regarding our interpretation of Fig. 10, we have
no reason to think that the ocular blood volume
is greater in the hypotensive than in the normotensive animal. The plateaus in the infusion records are indicative of that pressure range over
which the greatest blood loss occurs from the eye
during continuous saline infusions. Since the
plateau occurs at a lower level of intraocular pressure in the hypotensive animal, the conclusion to
be drawn is that the greatest blood loss from these
eyes occurs at a correspondingly lower level of
intraocular pressure.
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Volume 1
Number 1
The interpretation of the pressure peaks or
overshoot associated with the rapid injection of
saline is a complex problem. With independent
pressure recordings from both the vitreous and
the anterior chamber, the overshoot was not
abolished in either compartment when the animals were killed. Furthermore, an artificial system
consisting of a saline-filled piece of rubber tubing
Pressure and volume relationship 77
clamped at both ends could be shown to demonstrate the same type of overshoot when cannulated in the same manner with two separate
needles. Thus, it may be that a mechanical or
kinetic factor contributes to the overshoot and at
the same time masks the very rapid changes occurring as a result of blood volume changes or the
stretch of the ocular coats.
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