Download The influence of elevated intraocular pressure on vascular

The Influence of Elevated Intraocular Pressure on
Vascular Pressures in the Cat Retina
Rajpaul Attariwala, Claudine P. Giebs, and Matthew R. Glucksberg
Purpose. Elevated intraocular pressure is known to reduce retinal blood flow, although the
effect of intraocular pressure on retinal vascular pressures is unknown. Direct measurements
of intravascular pressures were taken in the cat retina at various intraocular pressures.
Methods. Micropipettes of 2- to S-fim tip diameter were used in conjunction with a servonull
pressure-measuring system to determine retinal intravascular pressures in supine anesthetized
cats. Pressures in large (80 to 120 /*m diameter) vessels near the optic disc were measured over
a wide range of intraocular pressures.
Results. Measurements show that retinal artery pressure depends on both intraocular pressure
and mean systemic blood pressure, and that retinal vein pressure is determined by, but generally is different from, intraocular pressure, with no significant correlation to mean systemic
blood pressure. Empirical equations are presented that predict statistically significant retinal
artery, vein, and microvascular perfusion pressures.
Conclusions. Intraocular pressure is an important determinant of the microvascular perfusion
pressure in the retina of the cat, particularly at low mean systemic blood pressure. It is also
apparent that retinal vein pressure is always greater than intraocular pressure, which implies
the existence of a high-resistance extraretinal segment of the retinal vein. The results suggest
mechanisms for the loss of visual function in glaucoma and other retinal circulatory disorders.
Invest Ophthalmol Vis Sci. 1994;35:1019-1025.
Hilevated intraocular pressure (IOP) impairs visual
function1"3 in the eye, perhaps by reducing blood flow
in the retinal circulation.45 The decreased blood flow
has been attributed to a decreased microcirculatory
perfusion pressure.6 The effects of elevated IOP on
retinal vascular pressure, however, have not been directly measured.
The micropuncture servonull technique has long
been an effective method for determining fluid pressures within small-diameter blood vessels in in vivo7"11
preparations. In the eye, the servonull technique has
been used to measure pressures in extraocular and
choroidal vessels.1213 Our laboratory has reported servonull pressure measurements in the vasculature of
From the Biomedical Engineering Department, Northwestern University, Evanston,
Illinois.
Supported by a grant from the Ralph M. Parsons Foundation and by National
Institutes of Health grant EY09714. RA was partially supported by an award from
Fight for Sight Research Division of the National Society to Prevent Blindness.
Submitted for publication July 16, 1993; revised September 2, 1993; accepted
October 29, 1993.
Proprietary interest category: N.
Reprint requests: Matthew R. Glucksberg, Ph.D., Biomedical Engineering
Department, Northwestern University, Evanston IL 60201-3107.
the cat retina14 that showed lower perfusion pressures
through the retinal vascular bed than previously believed. We now present the direct measurements of
intravascular pressures in the retina of the cat eye subjected to elevated IOP.
MATERIALS AND METHODS
Eight mixed-breed, conditioned cats were used for this
study, and we adhered to the ARVO Resolution for
the Use of Animals in Ophthalmic and Vision Research. We anesthetized (30 mg/kg ketamine hydrochloride mixed with 0.5 mg/kg acepromazine, intramuscularly) cats weighing 3 to 4.5 kg and cannulated
the left saphenous vein with a catheter containing 5%
sodium thiamylal, which was given as needed during
surgery. We cannulated the right saphenous vein to
administer a loading dose (300 mg/hr) followed by a
maintenance dose (50 mg/kg/hr) of urethane for
long-term anesthesia. We cannulated the right femoral
artery with Teflon tubing, then used this line to sample
blood gas, pH (128 blood gas monitor; Corning,
Corning, NY), and to measure systemic arterial pressure with a physiologic pressure transducer (P23XL;
Investigative Ophthalmology & Visual Science, March 1994, Vol. 35, No. 3
Copyright © Association for Research in Vision and Ophthalmology
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017
1019
1020
Investigative Ophthalmology & Visual Science, March 1994, Vol. 35, No. 3
Spectramed, Oxnard, CA). We maintained the animal's body temperature using a rectal probe connected to a continuous temperature monitor (73A;
YSI, Yellow Springs, OH) that controlled the operation of a heated water blanket.
We performed a tracheotomy and inserted a
breathing tube into the trachea, and all incisions were
closed with surgical wound clips. The spontaneously
breathing cat was placed in the supine position on a
flat bed, and we immobilized the head in a stereotaxictype head holder. After a lateral canthotomy, which
involved removing some of the orbital bone, we stabilized the eye with a stainless steel eye ring fixed to the
conjunctiva. We dilated the pupil with topical mydriatics (atropine and cyclopentolate hydrochloride; Alcon, Fort Worth, TX) and instilled flurbiprofen sodium 0.03% (Ocufen; Allergan, Irvine, CA) drops to
maintain mydriasis at high IOP and to minimize the
physiological effects of the surgical trauma. A 22gauge needle connected to a height-adjustable saline
reservoir was placed in the anterior chamber for IOP
regulation, and the IOP was continuously monitored
via a second 21-gauge needle placed in the anterior
chamber and connected to a pressure transducer.
To prepare for vascular micropuncture, we positioned the tip of a 17-gauge, thin-walled needle with
trocar at the center of rotation of our goniometric
micromanipulator and aligned it with the superior retinal vessels. After a topical application of proparacaine
hydrochloride (Alcaine; Alcon), we positioned the needle near the equator of the eye and pushed the needle
through the sclera.
We filled a sharp, 2- to 3-/zm tip diameter glass
micropipette, which we manufactured in our own laboratory,15 with dyed (Fast Green; Sigma Chemical Co.,
St. Louis, MO) 2 M saline. We used concentrated saline to achieve a low electrical impedance through the
tip of the micropipette in accordance with the principles of the servonull device (Model 5A; IPM, La Mesa,
CA), and included the dye in the mixture to improve
the micropipette visibility in the vitreous. We then removed the trocar from the needle and fed the pressure-measuring mieropipette though the needle lumen and into the vitreal chamber before securing the
micropipette to the micromanipulator. The micropipette was connected electrically and hydraulically to
the servonull apparatus. The details of our micropuncture set-up and procedures have been previously
described.15
We placed a plastic planoconcave lens on the cornea and viewed the tip of the micropipette and the
retina through the dilated pupil with an operating microscope (Zeiss OPMI1; Carl Zeiss, Thornwood, NY).
Using the positioning knobs on our goniometric micromanipulator, we maneuvered the micropipette tip
above a retinal vessel at a location within 1.5 disc diam-
eters of the edge of the optic disc. Just before micropuncturing the vessel, we checked that the servonull
system was operating properly by increasing the gain
until the pressure tracing showed that the fluid at the
micropipette tip was oscillating. The eye is particularly
well suited to the servonull system because a calibration check is built into the measurement: before each
measurement we recorded the cardiac-induced pulse
of the IOP that is transmitted throughout the aqueous
and vitreous (Fig. 1). As a further check of the system,
we momentarily increased the IOP by elevating the
controlling reservoir and observing the simultaneous
pressure increase measured by the anterior chamber
needle and the servonull micropipette apparatus. We
then set the reference pressure for the servonull equal
to the IOP before directly measuring intravascular
pressure. The details of our calibration procedures
and testing criteria have been described previously in
detail.14
With the micropipette tip above a retinal artery or
vein, we punctured the vessel with a smooth forward
movement of the microdrive (Narishige, Greenvale,
NY) mounted on the micromanipulator. We determined that the micropipette was within the lumen of
the vessel by visual inspection and by observing a distinct pressure tracing on the chart recorder (RS3400;
Gould, Cleveland, OH). This tracing was characterized
by smooth, pulsatile oscillations at the same frequency
as the systemic blood pressure (Fig. 1). Conversely,
pressure measurements produced by the micropipette
160
140
'bfl
•ffi
jj 120
0)
!g
Micjropipette
of vein
40
W
W
^
20
0 Li
45
Seconds
FIGURE l. Portion of a sample tracing showing BP, IOP, venous transmural pressure (P,v), and retinal venous pressure
(P^). The time axis starts shortly after micropuncture, and
the measured pressure can be seen to return to reference
pressure after removal of the micropipette from the vein at
44 seconds. The IOP and venous pulse amplitudes measured
by the servonull are nearly identical. BP is measured in the
femoral artery, and therefore the phase offset is of little
consequence.
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017
1021
IOP and Retinal Vascular Pressure
resting on, or perhaps partially within, the wall of the
vessel or surrounding connective tissue would typically produce flat traces with distinct spikes due to
either cardiac or respiratory movements. As a further
check to be certain that the micropipette was within
the lumen of the vessel, we occasionally injected dye
through the micropipette tip; if the dye was not visible
or appeared as a plume proceeding downstream
within the vessel, the micropipette tip was judged to be
inside the vessel, whereas if the dye appeared as a stagnant cloud in the vitreous, the micropipette tip was
judged to lie outside the lumen of the vessel. Dye injection was particularly useful for venous measurements at extremely elevated IOP (> 60 mm Hg), where
a small difference between venous pressure and IOP
was observed. In virtually every case where we injected
dye after a recording, the characteristically stable intravascular pressure tracing was sufficient for confirming
that the micropipette tip was located within the vessel
lumen.
Systemic blood pressure, IOP, and servonull pressure were monitored continuously on a chart recorder, and digitized for further analysis by a PCbased data acquisition system (Keithley Dataq [Cleveland, OH] system in a Zenith [Franklin Park, IL] AT
class computer). We normally left the micropipette
within the vessel lumen for over a minute, which was
sufficient time to change IOP; however, we were unable to change IOP with the micropipette tip in the
vessel lumen because of the globe deformation and
vessel movement that accompanies a change in IOP.
To measure intravascular pressures at different values
of IOP without damage to the vessel or micropipette
tip, we withdrew the micropipette from the immediate
vicinity of the vessel while we changed IOP. Each measurement therefore represents a separate micropuncture.
The servonull pressure recordings, with the pressure offset equal to IOP, measured transmural pressures directly. Therefore we analyzed all the data as
average arterial (Pta) or venous (Ptv) transmural pressure, whereas IOP was averaged and mean systemic
blood pressure (BP) was calculated from the femoral
diastolic plus one-third pulse pressure. Minitab (State
College, PA) software was used for statistical regression analysis, giving Student's t test for coefficients
and the /^-statistic for the relationships reported between transmural pressure, IOP, and BP.
RESULTS
Retinal Vein Pressure
We made 54 measurements of Ptv at IOPs set between
14 and 80 mm Hg. A portion of a sample tracing from
a 120-/im retinal vein measurement is shown in Figure
1. The transmission of the cardiac pulse pressure to
the IOP and retinal vein pressure is apparent. The
venous pressures were typically characterized by pulse
pressures ranging from 1 to 3 mm Hg, with an average
pulse (systolic-diastolic) of 2 mm Hg.
The Ptv measurements at specific IOP values are
plotted in Figure 2. These values were consistently
greater than IOP until vascular collapse prevented any
further micropuncture. The best-fit equation predicted by linear regression for 14 < IOP < 80 mm Hg
is given by:
Ptv = 9.12-0.0964 IOP
(1)
The coefficients and the relation are significant (t test
P < 0.001; F-stat P < 0.001), with an RMS error of
2.17 mm Hg. We used multiple linear and nonlinear
regression to determine the influence of BP to be not
significant (P ^ 0.88). We could not determine the
influence of Pta on Ptv because we lacked a sufficient
number of paired data.
Retinal Artery Pressure
We made 49 measurements of Pta in 100-Atm diameter
arteries with IOP ranging from 18 to 75 mm Hg. Pta
measurements typically had pulse pressures between 7
and 20 mm Hg, but clean pulse pressures sometimes
were difficult to obtain because the motion of the arteries often caused the micropipette tip to strike the
inside of the vessel wall, causing spikes in the tracings.
A portion of a sample arterial trace is given in Figure 3.
The dependence of Pta on both BP and IOP made
the data analysis more complex than the analysis for
Ptv. BP varied widely between cats, and ranged from 77
to 167 mm Hg. For each measurement, IOP was set at
specified pressures between 18 and 75 mm Hg. Figure 4
15
em
S
10
0
10
20
30
40
50
60
70
80
IOP (mmHg)
FIGURE 2. Measured P,v data (n = 54) and the best-fit regression line from equation (1) with an RMS error of 2.17 mm Hg.
This line relates Ptv to IOP, and at low IOPs is well represented by equation (3).
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017
1022
Investigative Ophthalmology & Visual Science, March 1994, Vol. 35, No. 3
140
^
120
B
6
100
w
BP: 75-95 (mmHg)
80
10
80
0)
w
w
96-105
80
B0 r
10
80
IOP (mmHg)
60
40
106-115
80
140-150
80
20
0
Seconds
10
FIGURE 3. Portion of a recording for a retinal artery, showing IOP, Pta, and retinal arterial pressure (Pra). The micropipette was removed from the artery at 46 seconds, where the
measured pressure returned to the reference pressure. Systemic blood pressure for this measurement was 195/120
mm Hg.
p _
(2)
The coefficients and the nonlinear relation are significant (t test P < 0.001; F-stat P < 0.001) with an r2 of
0.771. Equation (2) fits the data well for 20 < IOP <
80 mm Hg and 80 < BP < 170 mm Hg. This relationship is also shown in Figure 4, where it was generated
at the midpoint of each graph's BP range. Figure 5
shows the family of curves generated by equation (2),
plotted relative to atmospheric pressure as retinal arterial pressure (Pra, where Pra = Pta + IOP) versus IOP.
Retinal Microvascular Perfusion Pressure
We generated perfusion pressure curves based on
equations (1) and (2); therefore, the perfusion pressure curves are valid under the same conditions. The
perfusion pressure plotted against IOP, with BP isobars, is shown in Figure 6, and Figure 7 shows the
perfusion pressure versus BP with IOP isobars.
DISCUSSION
The servonull micropuncture technique is an effective
method for measuring pressures within retinal vessels.
10
151-160
80
161-167
80
80
10
80
10
80
FIGURE 4. The complete set of Pta measurements versus IOP,
where each graph represents an arbitrary subdivision of the
data into mean systemic blood pressure categories for clarity
of presentation. Data analysis was performed on the pooled
data using multiple nonlinear regression analysis, resulting
in equation (2) with an r2 of 0.771. In each graph, the solid
line represents the Pta values given by equation (2) generated
at the midpoint of the respective mean systemic blood pressure category.
120
100
K
80
g
60
Pra
shows the complete set of Pta measurements divided
into arbitrarily assigned BP ranges for clarity. Thus,
multiple regression was required to obtain a relation
between Pta and both IOP and BP. We propose a statistically derived empirical equation for this relation
based on both x (IOP, BP) and y (Pta) coordinate transformations, which results in the inverse logarithmic
equation:
80
40
20
0L
10
20
30 40 50 60
IOP ( m m H g )
70 80
FIGURE 5. Pra versus IOP curves generated from the inverse
logarithmic regression equation ([2]). Isobars correspond to
BP and are valid for 80 < BP < 170. The dashed line represents an identity line with slope of 1. The dependence of Pra
on IOP, particularly for low BP, is evident.
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017
IOP and Retinal Vascular Pressure
1023
60
Si
£ 50
40
30
20
10
10
20
30 40 50 60
IOP (mmHg)
70
80
FIGURE 6. Perfusion pressures versus IOP with BP isobars.
Curves were generated from equations (1) and (2). The perfusion pressure demonstrates the effect of autoregulation at
low IOPs, whereas above 40 mm Hg, the linear drop suggests a pressure-passive response.
The sharp, 2- to 3-fim tip diameter allowed repeated
measurements without vascular hemorrhage or noticeable vasoconstriction.
The results of this study are consistent with the
results of our previous work14 in cats with IOPs set at
10 and 20 mm Hg. Both studies obtained values for Ptv
that were significantly above IOP, and values for Pra
that were well below ophthalmodynamometric measurements,16 which are the only estimates of ophthalmic artery pressure available. In this series of experiments, we measured Pta and Ptv with IOP between 14
and 80 mm Hg and generated regression equations to
fit this data.
We point out that the pressures we have recorded
in cat retinal veins contradict some current thought,17
and preclude the possibility of the retinal veins being
partially collapsed, leading to a "vascular waterfall"18
within the globe near the edge of the optic disc.
The regression equation for the Ptv data (equation
[1]) has an RMS error of 2.17 mm Hg; therefore, adding and subtracting this value to equation (1) statistically envelopes at least two thirds of the data distributed around the regression line. This property allows
us to approximate equation (1), with a reasonable degree of accuracy (Ptv error < 0.3 mm Hg for IOP < 40
mm Hg), by the following simpler equation:
P =9
r
tv
•?
IOP
10
lar collapse indicates that a resistance segment must be
present somewhere downstream. Bill19 has measured
extraocular venous pressures by cannulation of the
cat's anterior ciliary veins and found the pressure to be
equal to 7 mm Hg for IOPs between 12 and 26 mm Hg.
The anterior ciliary vein and the retinal veins drain
directly into a venous plexus in the retrolaminar region of the optic nerve.20'21 Hence, the resistance segment must maintain the large pressure drop from intraocular venous pressure relative to atmospheric
pressure (P^, where P^ = Ptv + IOP), which increases
with increasing IOP, to extraocular venous pressure.
Based on anatomy, the resistance segment responsible
for this pressure drop undoubtedly lies anterior to the
venous plexus. Although it is conceivable that the extraretinal resistance is controlled by active mechanisms, the rapidity of the change in vascular pressure
after a change in IOP (they are nearly simultaneous)
leads us to the reasonable conclusion that the mechanism is purely a passive mechanical effect.
Taylor et al,22 by serial sectioning of the human
lamina cribrosa, have shown the presence of a collagenous narrowing around the central retinal vein. They
hypothesize that this narrowing is responsible for
maintaining the intraocular venous pressure above
IOP. This mechanism for venous regulation is consistent with our measurements in the cat, because the
narrowing of the lamina cribrosa around the veins represents a possible anatomic site for passive control of
50
6 40
CD
30
20
1 10
CD
75
100
125
150
175
BP (mmHg)
(3)
In the cat, Ptv above IOP for all pressures below vascu-
FIGURE 7. Perfusion pressure versus BP with IOP isobars.
This figure compares well with noninvasive laser Doppler
velocimetry studies in humans.26
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017
1024
Investigative Ophthalmology 8c Visual Science, March 1994, Vol. 35, No. 3
extraretinal venous resistance, and may represent the
site of the so-called venous waterfall.
Our measurements of pressures in retinal arteries
demonstrate that the Pta depends on both IOP and BP,
and not just BP alone, as predicted by ophthalmodynamometric approximations. In ophthalmodynamometry, IOP is elevated until vascular collapse near the
disc is observed, but Bill18 has shown that elevating
IOP causes a subsequent elevation in ciliary artery
pressure. Therefore, this method cannot be used to
determine accurately arterial pressures at any IOP below vascular collapse because it overestimates the arterial pressures that influence the retinal circulation,
particularly at low BP, where a strong dependence on
IOP is observed.
Statistical analysis of the data led to a nonlinear
inverse logarithmic equation ([2]) which, although
complex, reasonably predicts Pta at all IOPs and BPs
measured. The general trend obtained from the multiple nonlinear regression shows a small plateau region
for low IOPs, followed by a nearly linear drop in Pta
with increasing IOP (refer to Figs. 5, 6). The Pra therefore increases with increasing IOP, consistent with
Bill's18 speculation that the pressure increase in the
ciliary artery would translate intraocularly to the retina at acutely elevated IOP.
The nonlinear response of Pra to BP at low IOPs is
not surprising, given that the arterial system is not a
passive conduit of blood.23 Within the retina, autoregulation24 and metabolic regulation25 have been well
documented. Traditionally, autoregulation is defined
as the maintenance of constant flow with changes in
perfusion pressure by vascular caliber changes in the
resistance vessels, and the retinal artery falls well
within the range of diameters for resistance vessels.
Our determination of perfusion pressures provides
complementary data to blood flow measurements in
the retina.45-26 Based on principles of fluid mechanics,
without changes in vascular caliber, flow and pressure
gradients are proportional. Figure 6 shows a near-linear drop in perfusion pressure at IOPs above 40 mm
Hg, whereas below 40 mm Hg, there is an even greater
drop in perfusion pressure, which results in a "semiplateau" region. This semiplateau region, determined
by regression analysis of our pressure data, is consistent with measurements of flow in normal human subjects by the blue field entopic phenomena technique4
and laser Doppler flowmetry studies.5 From these flow
studies, the region below 30 mm Hg is interpreted as
the range in which the retina's au toregulatory function is most effective. It is important to recognize that
the term "perfusion pressure" has been widely used to
refer to the difference between ophthalmic artery
pressure and IOP, whereas we have defined it to be the
difference between Pra and P™. Because our results
show that P^ is not equal to IOP, and that Pra is not
necessarily equal to the pressure in the ophthalmic
artery, our use of the term differs from the traditional
definition. The semiplateau region in Figure 6 is predominantly the result of the nonlinear response of Pra
to changes in IOP. The fact that Pra changes nonlinearly with IOP necessarily implies that the site of artery micropuncture lies within a region of the circulation that participates in blood flow regulation.
Cats, compared to humans, are normally hypertensive, with widely varying BPs.27 This, along with the
vascular differences in the retrolaminar optic nerve
region, might lead to speculation that the response of
perfusion pressure to BP changes could be different in
cats and humans. We point out, however, that our results are consistent with noninvasive laser Doppler velocimetry studies in humans.26 This suggests that the
nature of the retinal vascular pressure response to BP
may be common to both cats and humans, and we may
therefore speculate on the importance of our results
in disease. Our measurements are particularly relevant
to the glaucomas, which are characterized by elevated
IOP or cardiovascular crises, and impaired retinal autoregulation with elevated IOP.28
Drance29 speculated that patients with glaucoma
probably have increased venous resistance, because he
and other researchers30 have found that flame-shaped
hemorrhages in the optic disc frequently precede the
development of retinal nerve fiber bundle damage.
Our measurements of high Ptv even at elevated IOP,
along with recent anatomic evidence of a venous constriction in the human lamina cribrosa,22 and the predisposition of patients with glaucoma to retinal vein
occlusion,31 support this hypothesis. Our data clearly
show that reduced BP, elevated IOP, or both, reduce
perfusion pressure more than expected from previous
assumptions, and suggest a direct link between the etiology of primary open-angle glaucoma and normaltension glaucoma.
Beyond glaucoma, we speculate that our results
may have profound implications for the understanding of the physiology of the retinal circulation in
health and disease. Although we currently are unable
to identify the mechanisms by which P^ is controlled,
it is possible that disease alters these mechanisms and
changes P^ as well as the autoregulatory performance
of the arterial side of the circulation. Our data indicate
that perfusion pressure is normally lower than common estimates, and, if further lowered by disease, the
resulting reduction in blood flow and consequently
lower hydrodynamic shear may promote the formation of retinal vascular occlusions. Retinal vein pressure, if normally greater than IOP, may become further elevated, and prove to be important in the
formation of microaneurysms and eventually the neo-
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017
1025
IOP and Retinal Vascular Pressure
vascularization seen in diabetic and hypertensive retinopathies, and may contribute to increased transvascular fluid flux and the formation of retinal edema.
14.
Key Words
micropuncture, intraocular pressure, retina, glaucoma, perfusion pressure
15.
Acknowledgments
16.
The authors thank R. Dunn, R. A Linsenmeier, and T. K.
Goldstick for useful discussions, and G. S. Attariwala for
supplies and clinical input.
17.
References
1. Drance SM. Studies in the susceptibility of the eye to
raised intraocular pressure. Arch Ophthalmol. 1962;
68:478-485.
2. Tsamparlakis JC. Effect of transient induced elevation
of the intraocular pressure on the visual field. Br J
Ophthalmol. 1964; 48:237-249.
3. Vanderburg D, Drance SM. Studies of the effects of
artificially raised intraocular pressure. AmJ Ophthalmol. 1966;62:1049-1063.
4. Riva CE, Sinclair SH, Grunwald JE. Autoregulation of
retinal circulation in response to decrease of perfusion pressure. Invest Ophthalmol Vis Sci. 1981; 21:3438.
5. Riva CE, Grunwald JE, Petrig BL. Autoregulation of
human retinal blood flow. Invest Ophthalmol Vis Sci.
1986;27:17O6-1712.
6. Ffytche TJ, Bulpitt CJ, Kohner EM, Archer D, Dollery
CT. Effect of changes in intraocular pressure on the
retinal microcirculation. Br J Ophthalmol. 1974; 58:
514-522.
7. Wiederhielm CA, WoodburyJW, Kirk S, Rushmer RF.
Pulsatile pressures in the microcirculation of frog's
mesentery. AmJ Physiol. 1964; 207:173-176.
8. Brenner BM, Troy JC, Daugharty TM. The dynamics
of glomerular ultrafiltration in the rat. J Clin Invest.
197l;50:1776.
9. Wiederhielm CA, Weston BV. Microvascular, lymphatic, and tissue pressures in the unanesthetized
mammal. AmJ Physiol. 1973; 225:992-996.
10. Stromberg DD, Shapiro H. Preparation of cat cerebral cortical surface for microvascular pressure measurement. Microvasc Res. 1973; 5:410.
11. Bhattacharya S, Glucksberg MR, Bhattacharya J. Measurement of lung microvascular pressure in the intact
anesthetized rabbit by the micropuncture technique.
CircRes. 1989; 64:167-172.
12 Maepea O, Bill A. The pressures in the episcleral
veins, Schlemm's canal and the trabecular meshwork
in monkeys: effects of changes in intraocular pressure.
ExpEyeRes. 1989;49:645-663.
13. Maepea O. Pressures in the anterior ciliary arteries,
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
choroidal veins and choriocapillaris. Exp Eye Res.
1992;54:731-736.
Glucksberg MR, Dunn R. Direct measurement of retinal microvascular pressures in the live anesthetized
cat. Microvasc Res. 1993;45:158-165.
Glucksberg MR, Dunn R, Giebs CP. In vivo micropuncture of retinal vessels. Graefes Arch Clin Exp Ophthalmol. 1993;231:405-407.
Weigelin E, Lobstein A. Ophthalmodynamometry. New
York: Hafner; 1963:1-134.
Duke-Elder S. The ocular circulation: its normal pressure relationships and their physiological significance.
Br J Ophthalmol. 1926;10;513-572.
Bill A. Circulation in the eye. In: Renkin EM, Michel
CC, eds. The Handbook of Physiology: Cardiovascular
System IV. Bethesda, MD: American Physiological Society; 1984;4:1001-1029.
Bill A. The intrascleral venous pressure in the eye of
the cat. Exp Eye Res. 1964; 3:188-191.
Wong VG, Macri FJ. Vasculature of the cat eye. Arch
Ophthalmol. 1964; 72:351-358.
Motti EDF, Niemeyer G. Scanning electron microscopy on vascular casts of the cat eye. Klin Monatsbl
Augenheilkd. 1983; 182:518-521.
Taylor AW, Sehu W, Williamson TH, Lee WR. Morphometric assessment of the central retinal artery and
vein in the optic nerve head. CanJ Ophthalmol. 1993;
28:320-324.
Paulson OB, Strandgaard S, Edvinsson L. Cerebral
autoregulation. Cerebrovasc Brain Metab Rev. 1990; 2:
161-192.
Bill A. Blood circulation and fluid dynamics in the eye.
Physiol Rev. 1975;55:383-417.
Anderson DR. Anatomy and physiology of ocular
blood Row. In: Lambrou GN, Greve EL, eds. Ocular
Blood Flow in Glaucoma: Means, Methods and Measurements. Milano: Kugler & Ghedini; 1989:55-59.
Robinson F, Riva CE, Grunwald JE, Petrig BL, Sinclair SH. Retinal blood flow autoregulation in response to an acute increase in blood pressure. Invest
Ophthalmol Vis Sci. 1986; 27:722-726.
Thuransky K. Der Blutkreislaujder Netzhaut. Budapest:
Verlag der Ungarischen Akademie der Wissenschaften; 1957:66-67.
Grunwald JE, Riva CE, Stone RA, Keates EU, Petrig
BL. Retinal autoregulation in open-angle glaucoma.
Ophthalmology. 1984; 91:1690-1694.
Drance SM. Disc hemorrhages in the glaucomas. Surv
Ophthalmol. 1989; 33:331-337.
Geijssen HC. Local vascular risk factors. In: Studies on
Normal Pressure Glaucoma. Milano: Kugler Publications; 1991:83-107.
David R, Zangwill L, Badarna M, Yassur Y. Epidemiology of retinal vein occlusion and its association with
glaucoma and increased intraocular pressure. Ophthalmologica. 1988; 197:69-74.
Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933180/ on 05/14/2017