Acta Ophthalmologica 2011

The association of ocular blood

flow with haemorheological
parameters in primary open-
angle and exfoliative glaucoma
Mehmet Ali Sekeroglu,1 Murat Irkec,1 Mehmet Cem Mocan,1
Esin Ileri,2 Neslihan Dikmenoglu,2 Nurten Seringec,2
Devrim Karaosmanoglu3 and Mehmet Orhan1
1
Department of Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey
2
Department of Physiology, Hacettepe University School of Medicine, Ankara, Turkey
3
Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey

ABSTRACT. Introduction
Purpose: To evaluate the ocular blood flow velocities and haemorheological
parameters in patients with primary open-angle glaucoma (POAG), exfoliative Glaucoma is a progressive multifacto-
glaucoma (XFG) and exfoliation syndrome (XFS) and to compare their results rial optic neuropathy, characterized
with those of healthy controls. by optic nerve head excavation and
Methods: Twenty-five patients with POAG (group 1), 25 patients with XFG retinal ganglion cell loss with corre-
sponding visual field damages (Van
(group 2), 25 patients with XFS (group 3) and 25 healthy controls (group 4)
Buskirk & Cioffi 1992). Although
were included in the study. Ocular blood flow velocities of ophthalmic artery
intraocular pressure (IOP) is an
(OA), central retinal artery (CRA) and short posterior ciliary arteries important risk factor for the develop-
(SPCAs) were measured using colour Doppler imaging (CDI). Haemorheologi- ment of glaucoma (AGIS Investiga-
cal parameters (erythrocyte elongation and aggregation index, aggregation tors 2000), the exact mechanism(s)
amplitude, aggregation half-life, plasma viscosity, haematocrit) were measured leading to glaucomatous damage have
in venous blood samples of all patients. not been clarified. In addition to
Results: The peak systolic velocity (PSV) and end-diastolic velocity (EDV) val- increased IOP, an increasing body of
ues were lower and resistive indices (RI) were higher for the OA, CRA and evidence suggests that ocular blood
SPCA of glaucomatous (groups 1 and 2) patients compared with those of con- flow (OBF) abnormalities may be
trols (group 4) (PSV: OA, 40.4 ± 11.3 versus 52.6 ± 12.8 cm ⁄ second, involved in the pathogenesis of glau-
p < 0.001; CRA, 12.9 ± 2.9 versus 15.3 ± 4.2 cm ⁄ second, p = 0.02; SPCA, coma (Grieshaber & Flammer 2005;
21.7 ± 6.6 versus 26.6 ± 8.3 cm ⁄ second, p = 0.013) (EDV: OA, 10.3 ± 4.3 Harris et al. 2005; Grieshaber et al.
versus 14.2 ± 5.1 cm ⁄ second, p < 0.001; CRA, 3.7 ± 1.1 versus 2007; Januleviciene et al. 2008).
4.5 ± 1.3 cm ⁄ second, p = 0.025; SPCA, 5.2 ± 1.8 versus 7.7 ± 3.2 cm ⁄ sec- Reduction in OBF, which is thought
ond, p = 0.001) (RI: OA, 0.75 ± 0.05 versus 0.66 ± 0.07, p < 0.001; CRA, to be secondary to vascular dysregula-
tion, is hypothesized to lead to both
0.73 ± 0.08 versus 0.68 ± 0.10, p = 0.223; SPCA, 0.70 ± 0.10 versus
low perfusion pressure and insufficient
0.63 ± 0.11, p = 0.004). There were no statistically significant differences
autoregulation (Flammer et al. 2002)
between the haemorheological parameters of glaucomatous and non-glaucoma-
of the optic nerve head circulation.
tous patients. The reduction in ocular blood flow velocities in groups 1, 2 and 3 Colour Doppler imaging (CDI) is one
were not associated with changes in haemorheological parameters. of several methods to evaluate the
Conclusion: Our results suggest that impairment of the retrobulbar blood flow in OBF in which the blood flow veloci-
POAG and XFG is not associated with alterations in haemorheological parameters. ties of the retrobulbar vessels [oph-
Key words: erythrocyte deformability – exfoliation glaucoma – haemorheology – ocular blood thalmic artery (OA), central retinal
flow – plasma viscosity artery (CRA) and short posterior cili-
ary arteries (SPCAs)] are determined
Acta Ophthalmol. 2011: 89: 429–434 (Harris et al. 2008). CDI has been
ª 2009 The Authors shown to be a valid method with
Journal compilation ª 2009 Acta Ophthalmol reproducible OBF measurements
doi: 10.1111/j.1755-3768.2009.01713.x

429
Acta Ophthalmologica 2011
(Luksch et al. 2008). OBF measure-
ments using CDI have revealed
increased blood flow resistance and
decreased blood flow velocities in the
retrobulbar vessels of patients with pri-
mary open-angle glaucoma (POAG),
exfoliation glaucoma (XFG) and nor-
mal tension glaucoma (NTG) (Kaiser
et al. 1997; Martinez & Sanchez
2008a, 2008b).
Altered erythrocyte deformability
and aggregability may be a possible
pathogenic mechanism contributing to
impaired OBF in glaucoma (Vetrugno
et al. 2000). The purpose of the pres-
ent study was to evaluate the possible
association of OBF velocities with
haemorheological parameters in
patients with POAG, XFG and XFS
and to compare these parameters with
those of healthy controls.
Materials and Methods
This study was designed as a prospec-
tive, observational study undertaken
at a single university-based hospital
between June 2007 and June 2008.
The tenets of the Declaration of Hel-
sinki were followed throughout the
study. Informed consent was obtained
from all patients and the study was
carried out with approval from the
Institutional Review Board. One hun-
dred eyes of 100 patients [25 POAG
(group 1), 25 XFG (group 2), 25
XFS (group 3) and 25 healthy con-
trols (group 4)] were recruited consec-
utively for this study.
All patients underwent complete
ophthalmological examination includ-
ing best-corrected Snellen visual acu-
ity testing, slit-lamp examination,
Goldmann applanation tonometry,
ultrasound corneal pachymetry,
gonioscopic evaluation, dilated fundus
examination using a 90-dioptre (D)
lens and visual field evaluation using
the 30-2 SITA-Standard algorithm
(Humphrey Visual Field Analyser;
Humphrey Instruments Inc., San
Leandro, California, USA). A detailed
medical history was also obtained.
Glaucoma patients (POAG and
XFG) who had been diagnosed and
were being followed up by the glau-
coma service of the Department of
Ophthalmology at Hacettepe Univer-
sity were recruited into the study.
The diagnosis of POAG had been
initially established based on the
presence of consistently elevated IOP
430
(> 21 mmHg) without treatment,
normal anterior-segment and gonio-
scopic findings, characteristic optic
disc changes and glaucomatous visual
field defects. The diagnosis of XFS
was made on slit-lamp examination
following mydriasis, as well as gonio-
scopic evaluation, and included the
presence of exfoliation material on the
pupillary margin and the anterior lens
capsule and trabecular hyperpigmen-
tation. The diagnosis of XFG was
made when anterior-segment findings
of XFS accompanied an IOP
> 21 mmHg without treatment, typi-
cal optic nerve head changes and
visual field defects. Twenty-five con-
secutive patients aged > 50 years with
no history of ocular disease (except
refractive errors or presbyopia), an
IOP £ 21 mmHg, a normal optic disc
appearance and no visual field defects
were included as controls. The IOPs
of all patients included in the study
were measured by the same observer
(M.A.S.) using Goldmann applana-
tion tonometry at three time-points in
an outpatient setting.
The criteria for exclusion included a
prior history of ocular disease, a his-
tory of ocular surgery or trauma,
myopia or hyperopia ‡ 4 D, astigma-
tism ‡ 1.5 D, central corneal thickness
< 500 or > 580 lm, a history of cen-
tral nervous system disease that might
have interfered with visual field test-
ing, a history of smoking and ⁄ or
alcohol, diabetes mellitus, cardiovas-
cular disease, dyslipidaemia, renal
failure, malignancy, autoimmune dis-
eases, haematological diseases, chronic
obstructive pulmonary disease, uncon-
trolled arterial hypertension and a
history of transient ischaemic attack
or stroke. Patients who had IOP
> 21 mmHg and were receiving topi-
cal antiglaucomatous treatment at the
time of enrolment were also excluded.
For each patient, only one eye that
fulfilled the inclusion criteria was
included in the study. When both eyes
of a patient were eligible for inclusion,
one eye was randomly included using
a randomization table.
After at least 8 hr of fasting, fresh
whole blood samples of all patients
were collected from the antecubital
vein at the same time interval
(between 14.00 and 15.00 hr).
Haemorheological analysis was car-
ried out by the same observer (N.D.),
who was masked to the patients’ eye
disease status. For haemorheological
analysis, whole blood samples antico-
agulated with ethylen-diamin-tetra-
acetic acid (EDTA) were evaluated
within 1 hr of extraction using a laser-
assisted optical rotational cell analyser
(LORCA; Mechatronics, Amsterdam,
Netherlands) to determine the red
blood cell (RBC) elongation and
aggregation indices, as described else-
where (Vetrugno et al. 2004). Erythro-
cytes were suspended in a phosphate-
buffered saline (PBS) solution with
5.5% polyvinylpyrrolidone (PVP).
The standard viscosity used in the
PVP-PBS solution was 29.7 miniPas-
cals (mPa.s) to recapitulate in vivo
conditions. LORCA is optimized to
operate at 37 on a suspension that
underpasses increasing rotational
forces ranging from 0.3 to 30 Pa. The
laser beam was diffracted by erythro-
cytes while the beam traversed the cup
containing diluted blood in suspen-
sion. The laser-generated diffraction
patterns of erythrocytes, which are
indicative of the ability of an erythro-
cyte to deform in a shear field, were
monitored. The diffraction pattern
was projected on a screen monitored
by photoelectric sensors, linked to a
computer-integrated frame grabber.
The best fitting ellipse representative
of deformed RBCs was determined.
The long and short axes of this ellipse,
labelled as A and B, respectively, were
then used to calculate the elongation
index (EI), which is the most com-
monly used RBC deformability inde:
[EI = (A ) B) ⁄ (A + B)]. EIs calcu-
lated in shear stresses of 3 and 30 Pa
were used in statistical analysis.
The measuring principle of erythro-
cyte aggregability with LORCA is
based on laser back-scattering. The
instrument analyses the change in the
intensity of back-scattered light when
shear rates imposed on RBC suspen-
sions are arrested abruptly. This mea-
surement was performed on a 2-ml
whole blood sample in EDTA. By
using syllectogram analysis for the
analysis of erythrocyte aggregability,
the following parameters were deter-
mined: aggregation amplitude (Amp)
of erythrocytes, which shows the total
amount of aggregation; aggregation
half-life (t½) of erythrocytes, which is
the time for back-scattered light to
decrease from maximum to half of its
amplitude; disaggregation shear rate
(cIscmax) of erythrocytes; and

aggregation index (AI) of erythro-
cytes. A detailed description of syllec-
togram analysis has been described in
a previous article (Hardeman et al.
2001). The plasma viscosity was
measured in plasma (0.5 ml) at 37 at
different shear rates by using cone-
plaque viscometry.
The OBF evaluation was performed
by CDI in all patients. The technique
has been described in detail elsewhere
(Tranquart et al. 2003). CDI (Siemens
Quantum 2000; Siemens Medical Sys-
tem, Issaquah, Washington, USA;
7.5 MHz linear phase transducer) was
performed by a single radiologist
(D.K.) who had prior experience in
OBF measurements and who was
masked to the patients’ disease status.
All measurements were obtained in
supine position when both eyes were
closed. CDI measurements of the
SPCA were taken temporal to the
optic nerve behind the posterior pole
of the globe. Nasally located SPCAs
were not measured.
CDI was performed at the same
time interval (between 15.00 and
16.00 hr). For each patient, the peak
systolic velocity (PSV), the end dia-
stolic velocity (EDV) and the resistiv-
ity index (RI) of the OA, CRA and
SPCAs were recorded.
Statistical analyses were performed
using spss version 15.0 (SPSS Inc.,
Chicago, Illinois, USA) software.
One-way analysis of variance (anova)
was used to compare quantitative data
between multiple groups when a nor-
mal distribution was found and Krus-
kal–Wallis one-way anova on ranks
was used if data were not normally
distributed. The Kruskal–Wallis
Z-value test was used for all pairwise
multiple comparisons. Student’s
unpaired t-test or the Mann–Whitney
U-test was used to compare quantita-
tive data and v2 analysis was used for
qualitative data. Post-hoc calculation
of statistical power was performed
using NCSS-PASS software (NCSS,
Table 1. Comparison of clinical characteristics of the patients included in the study.
Age (years) (mean ± SD)
Male ⁄ female
Systemic hypertension
Venous occlusion
Glaucomatous VF loss (early ⁄ moderate ⁄ advanced)
POAG, primary open-angle glaucoma; XFG, exfoliation glaucoma; XFS, exfoliation syndrome; SD, standard deviation; VF, visual field.
Kaysville, Utah, USA). Correlations
were tested using Spearman’s rho cor-
relation coefficient. For all evalua-
tions, p < 0.05 was considered
significant.
Results
Of the 520 patients who had either
POAG or XFG and were followed by
the glaucoma service, 50 glaucoma-
tous patients (25 with POAG and 25
with XFG) who were deemed eligible
according to the inclusion and exclu-
sion criteria were included in the
study. Twenty-five patients with XFS
as well as 25 normal controls were
recruited consecutively as they were
seen in the outpatient clinic. There
were no statistically significant differ-
ences with regard to the mean age
(p = 0.057), sex ratio (p = 0.391),
the presence of systemic diseases
(p = 0.324) and systemic medication
use (p = 0.476) between the study
groups. Clinical and demographic
characteristics of the patients are dem-
onstrated in Table 1. Of the 50 glau-
comatous patients (groups 1 and 2
combined), 80% were on prostaglan-
din analogues, 48% were on beta-
blockers, 38% were on carbonic anhy-
drase inhibitors and 10% were using
alpha-2 agonist drops (either alone or
as a part of a combination therapy) at
the time of enrolment.
Among the OBF parameters, the
mean PSV and EDV values were
lower and the mean resistive indices
were higher for the OA, CRA and
SPCA of glaucomatous patients
(groups 1 and 2) compared with those
of controls (group 4) (Table 2). The
PSV and EDV values were lower and
RIs were higher for the OA, CRA
and SPCA of glaucomatous (groups 1
and 2) patients compared with those
of controls (group 4) (PSV: OA,
40.4 ± 11.3 versus 52.6 ± 12.8
cm ⁄ second, p < 0.001; CRA, 12.9 ±
2.9 versus 15.3 ± 4.2 cm ⁄ second,
POAG XFG XFS
(n = 25) (n = 25) (n = 25)
64.4 ± 8.5 68.9 ± 9.1 70.8 ± 7.0
10 ⁄ 15 16 ⁄ 9 13 ⁄ 12
6 12
0 0
15 ⁄ 3 ⁄ 7 12 ⁄ 6 ⁄ 7
Acta Ophthalmologica 2011
p = 0.02; SPCA, 21.7 ± 6.6 versus
26.6 ± 8.3 cm ⁄ second, p = 0.013)
(EDV: OA, 10.3 ± 4.3 versus 14.2 ±
5.1 cm ⁄ second, p < 0.001; CRA,
3.7 ± 1.1 versus 4.5 ± 1.3 cm ⁄ sec-
ond, p = 0.025; SPCA, 5.2 ± 1.8 ver-
sus 7.7 ± 3.2 cm ⁄ second, p = 0.001)
(RI: OA, 0.75 ± 0.05 versus 0.66 ±
0.07, p < 0.001; CRA, 0.73 ± 0.08
versus 0.68 ± 0.10, p = 0.223; SPCA,
0.70 ± 0.10 versus 0.63 ± 0.11,
p = 0.004). This relationship was sta-
tistically significant for almost all of
the haemodynamic parameters mea-
sured with the exception of the CRA-
RI parameter (Table 2). PSV and
EDV values were also lower and resis-
tive indices were higher for the OA,
CRA and SPCA of patients with XFS
(group 3) compared with those of the
controls (group 4). The retrobulbar
haemodynamic parameters of the
glaucomatous patients (groups 1 and
2) were not correlated with mean devi-
ation (MD) values. The only excep-
tion was for the CRA-PSV parameter,
which showed a weak correlation with
the MD values (p = 0.015, rho =
)0.34, Spearman’s correlation test).
There were no statistically sig-
nificant intergroup differences in hae-
morheological parameters (Table 3).
In addition, the haemorheological
parameters of the glaucomatous
patients (groups 1 and 2) were not
correlated to a significant extent with
MD values. None of the CDI parame-
ters correlated with any of the haemo-
rheological parameters to a significant
extent (Spearman’s rank correlation
test).
The mean MD value of patients
with POAG ()8.46 ± 7.75 dB) was
not significantly different from that of
patients with XFG ()8.91 ± 8.47 dB)
(p = 0.513, Student’s t-test).
Discussion
In glaucomatous optic neuropathy, a
potential factor that may be involved
Control
(n = 25) Test p-value
67.3 ± 9.2 anova 0.057
12 ⁄ 13 v2 0.391
8 10 v2 0.476
0 0 v2 1.000
– – v2 0.508
431
Acta Ophthalmologica 2011

Table 2. Comparison of retrobulbar haemodynamic parameters as evaluated with colour Doppler imaging in patients with primary open-angle
glaucoma (POAG), exfoliation glaucoma (XFG), exfoliation syndrome (XFS) and control patients (Kruskal–Wallis one-way anova).

POAG (1) XFG (2) XFS (3) Controls (4)

(n = 25) (n = 25) (n = 25) (n = 25) p-value Post-hoc test

OA-PSV (cm ⁄ second) 41.5 ± 11.2 39.2 ± 11.3 45.4 ± 9.2 52.6 ± 12.8 <0.001* 1–4, 2–3, 2–4
OA-EDV (cm ⁄ second) 11.8 ± 4.6 8.7 ± 3.9 10.4 ± 3.7 14.2 ± 5.1 <0.001* 1–2, 2–4, 3–4
OA-RI 0.73 ± 0.06 0.76 ± 0.05 0.72 ± 0.05 0.66 ± 0.07 <0.001* 1–2, 1–4, 2–3, 2–4
CRA-PSV (cm ⁄ second) 12.9 ± 3.2 12.9 ± 2.6 14.6 ± 3.1 15.3 ± 4.2 0.020* 1–3, 1–4, 2–3, 2–4
CRA-EDV (cm ⁄ second) 3.7 ± 1.0 3.6 ± 1.1 3.8 ± 0.8 4.5 ± 1.3 0.025* 1–4, 2–4
CRA-RI 0.72 ± 0.09 0.73 ± 0.06 0.71 ± 0.05 0.68 ± 0.10 0.223 –
SPCAs-PSV (cm ⁄ second) 21.2 ± 6.4 22.2 ± 6.8 26.0 ± 5.7 26.6 ± 8.3 0.013* 1–3, 1–4, 2–3, 2–4
SPCAs-EDV (cm ⁄ second) 5.3 ± 1.8 5.1 ± 1.7 5.9 ± 1.3 7.7 ± 3.2 0.001* 1–4, 2–3, 2–4
SPCAs-RI 0.70 ± 0.10 0.70 ± 0.09 0.62 ± 0.08 0.63 ± 0.11 0.004* 1–3, 1–4, 2–3, 2–4

* Statistical significance.

Presence of a statistically significant difference between each two subgroups for a given haemodynamic parameter.
OA-PSV, ophthalmic artery peak systolic velocity; OA-EDV, ophthalmic artery end diastolic velocity; OA-RI, ophthalmic artery resistive index;
CRA-PSV, central retinal artery peak systolic velocity; CRA-EDV, central retinal artery end diastolic velocity; CRA-RI, central retinal artery
resistive index; SPCAs-PSV, short posterior ciliary arteries peak systolic velocity; SPCAs-EDV, short posterior ciliary arteries end diastolic veloc-
ity; SPCAs-RI, _ short posterior ciliary arteries resistive index.

Table 3. Comparison of haemorheological parameters of patients with primary open-angle glaucoma (POAG), exfoliation glaucoma (XFG), exfo-
liation syndrome (XFS) and control patients (Kruskal–Wallis one-way anova).

POAG (n = 25) XFG (n = 25) XFS (n = 25) Controls (n = 25) p-value

Hct (%) 41.9 ± 3.9 42.0 ± 4.5 41.5 ± 3.4 40.1 ± 4.9 0.356
EI-3 0.314 ± 0.029 0.314 ± 0.020 0.313 ± 0.022 0.323 ± 0.026 0.374
EI-30 0.602 ± 0.013 0.605 ± 0.016 0.605 ± 0.009 0.608 ± 0.009 0.587
PV (mPa.s) 1.39 ± 0.12 1.39 ± 0.10 1.40 ± 0.10 1.37 ± 0.10 0.712
Amp (au) 21.88 ± 3.18 23.25 ± 2.92 22.32 ± 2.58 22.39 ± 2.79 0.381
AI 65.52 ± 5.01 64.11 ± 7.21 63.76 ± 8.72 64.12 ± 7.71 0.835
t½ (second) 2.07 ± 0.56 2.26 ± 0.87 2.29 ± 1.04 2.22 ± 0.83 0.893
cIscmax (per second) 227.4 ± 64.6 276.3 ± 134.9 281.9 ± 137.1 295.3 ± 168.1 0.287

Hct, haematocrit; EI-3, elongation index at a shear stress of 3 Pa; EI-30, elongation index at a shear stress of 30 Pa; PV, plasma viscosity;
Amp, aggregation amplitude; AI, aggregation index; t½, aggregation half life; cIscmax, disaggregation shear rate.

in impaired OBF is the abnormal
deformability and aggregability prop-
erties of erythrocytes. Although
haemorheological factors have been
evaluated in glaucomatous patients
(Klaver et al. 1985; Trope et al. 1987;
Garcia-Salinas et al. 1988; Hamard
et al. 1994; Vetrugno et al. 2004), to
the best of our knowledge the effect
of haemorheological parameters on
OBF properties has not been investi-
gated extensively. The current study
aimed to evaluate whether there was
any association between OBF proper-
ties and the haemorheological parame-
ters of patients who had XFG and
POAG.
Our findings demonstrate that PSV
and EDV are decreased and RI is
increased in the OA, CRA and SPCAs
of patients with POAG and XFG
compared with those of XFS patients
and healthy controls. In accordance
with the results of this study, altera-
tions of OBF have been implicated in
the pathogenesis of glaucoma in previ-
ous reports (Hayreh 1994; Flammer
et al. 2002; Grieshaber & Flammer
2005; Harris et al. 2005; Grieshaber
et al. 2007). Several studies have pro-
vided evidence for haemodynamic
changes in the OA, CRA and SPCA,
and have suggested that these obser-
vations may be important indicators
in the development of various glau-
coma types including POAG and
NTG (Rojanapongpun et al. 1993;
Butt et al. 1997; Kaiser et al. 1997;
Findl et al. 2000; Yüksel et al. 2001a,
2001b). Previous studies have also
reported that independent of the
extent of damage or IOP level, the
visual field progression correlates sig-
nificantly with retrobulbar haemody-
namic variables (Galassi et al. 2003;
Satilmis et al. 2003; Martinez & San-
chez 2005; Plange et al. 2006). Ultra-
structural studies have demonstrated
the accumulation of fibrillogranular
material not only in the anterior seg-
ment but throughout the basement
membranes of systemic vessels
(Schlötzer-Schrehardt & Naumann
2006), making exfoliation syndrome a
systemic disorder affecting large artery
functions (Visontai et al. 2006). In this
aspect, evaluation of retrobulbar ves-
sel flow characteristics in exfoliative
patients may provide further insight
to the understanding of glaucoma
pathogenesis associated with abnor-
mal OBF.
Although several factors such as
age, blood pressure, blood viscosity
and smoking status could influence
the retrobulbar CDI measurements
(Williamson et al. 1995), the study
groups in the present study appeared
to be similar with respect to age, sex,
smoking status and systemic diseases.
It must be pointed out that although
the difference between the mean age
was not found to be statistically sig-
nificant (p = 0.057) for the sample
sizes (n = 25) determined for each
group, this difference may indeed have
been significant if a larger sample had
been included in the study. However,
because the cut-off point for statistical
significance was set at 0.05 for the
integrity of statistical evaluations, it
was accepted that the groups were
similar with respect to mean age (a
statistical power of 0.62). Because

432

known systemic confounding factors
related to OBF interpretation have
been eliminated, it is the opinion of
the authors that the OBF measure-
ments obtained in this study accu-
rately reflect the blood flow
characteristics of the study groups.
The present study has demonstrated
that there were no significant differ-
ences between the retrobulbar haemo-
dynamic parameters of the XFG and
POAG patients except the OA-EDV,
which was found to be significantly
lower in XFG. Our results are in
agreement with the findings of a previ-
ous study in which no differences in
retrobulbar haemodynamic measure-
ments between patients with XFG and
POAG were detected (Yüksel et al.
2001a). On the other hand, Martinez
& Sanchez (2008a) have reported
reduced PSV and EDV and increased
RI in the retrobulbar vessels of POAG
patients compared with XFG patients;
conversely, Detorakis et al. (2007)
found reduced PSV and EDV and
increased RI in XFG patients com-
pared with those of POAG patients.
In our study, the mean MD values of
patients with POAG and XFG were
similar and thus the two groups had
comparable levels of glaucomatous
visual field losses. In this setting, the
results of our study suggest that XFG
is not particularly associated with
worse retrobulbar OBF parameters
compared with POAG or vice versa.
The retrobulbar haemodynamic
parameters of the glaucomatous
patients (groups 1 and 2) did not cor-
relate to a significant extent with MD
values in the current study. The only
exception was the CRA-PSV parame-
ter, which showed a weak correlation
with the MD values. This finding is
consistent with the results of Martinez
& Sanchez (2008b), who determined
that the PSV and EDV in the CRA of
patients with XFG were positively
correlated with MD.
In the present investigation, reduced
OBF velocities were demonstrated in
XFS patients compared with healthy
controls. Exfoliation material has been
detected in retrobulbar blood vessels
and may be responsible for altered
OBF and optic nerve head ischaemia,
as reported previously (Mitchell et al.
1997). Additionally, the present study
presents further evidence that reduc-
tion in OBF of the XFS patients is
less pronounced compared with those
of XFG patients. This finding is in
agreement with those obtained in pre-
vious studies (Yüksel et al. 2001b;
Detorakis et al. 2007). Gradual accu-
mulation of exfoliation material in the
ocular blood vessels, as in the anterior
segment, may be responsible for fur-
ther deterioration of OBF haemo-
dynamics and eventual progression to
glaucomatous optic nerve damage.
Increased vascular resistance is a
major mechanism by which blood
flow is reduced and is indicated by
high resistive index values as obtained
with CDI. The increase in vascular
resistance may be the result of organic
or functional vascular changes such as
vascular dysregulation (Emre et al.
2004; Resch et al. 2009). In addition
to morphological and functional
changes that may increase vascular
resistance, alterations in blood fluidity
may also compromise the microcircu-
lation of the optic nerve (Klaver et al.
1985; Trope et al. 1987; Garcia-Sali-
nas et al. 1988; Hamard et al. 1994).
Theoretically, by increasing blood vis-
cosity haemorheological characteristics
of erythrocytes such as altered eryth-
rocyte deformability and aggregability
can lead to reduced OBF (Vetrugno
et al. 2000).
In the present study, the haemorhe-
ological parameters were not found to
be different between the four groups.
Previous reports investigating the
potential contribution of haemorhe-
ological factors to the pathogenesis of
glaucoma have had inconsistent con-
clusions. Altered levels of haemorhe-
ological factors, in particular
increased blood and plasma viscosity
levels, have been detected in patients
with POAG and NTG (Klaver et al.
1985; Trope et al. 1987; Garcia-Sali-
nas et al. 1988; Hamard et al. 1994).
Vetrugno et al. (2004) found a signifi-
cant decrease in erythrocyte deform-
ability and increase in aggregability in
NTG patients. On the other hand,
plasma viscosity levels (Carter et al.
1990) and erythrocyte deformability
indices (Ates et al. 1998) were found
to be similar in glaucomatous patients
compared with those of healthy con-
trols. This difference may be the result
of different methods of analysing hae-
morheological parameters as well as
the selection bias of the study
patients. In the present study, care
was taken to avoid bias in the selec-
tion of patients to avoid the effect of
Acta Ophthalmologica 2011
age, sex, smoking status, systemic dis-
eases and medication on haemor-
heological parameters.
The present study is unique in that
several systemic confounding factors
of patients have been taken into con-
sideration in the design of the study
and an extensive array of haemorhe-
ological factors have been simulta-
neously evaluated in glaucomatous
patients. To the best of our knowledge
the present study is also the first to
evaluate the haemorheological param-
eters of patients with XFG and XFS.
One important limitation of this study
is the lack of a priori sample-size cal-
culation. In this study, post-hoc calcu-
lation of the statistical power rather
than a calculation of the sample size
was performed because of the paucity
of published data regarding the haemo-
rrheological parameters on glauco-
matous patients.
The use of CDI in determining
OBF characteristics has certain limita-
tions. CDI provides blood velocity
and not the actual blood flow of the
retrobulbar vessels. Because simulta-
neous blood vessel diameter measure-
ments are not obtained, CDI may be
used only indirectly for the interpreta-
tion of optic nerve head perfusion.
Furthermore, CDI does not evaluate
the blood velocities in the superficial
retinal nerve fibre layer. However,
studies using CDI consistently show
OBF changes such as decreased blood
velocities and increased resistivity
indices in patients with POAG, XFG
and NTG (Grieshaber & Flammer
2005; Harris et al. 2005; Grieshaber
et al. 2007). Recently, increased RI
was found to confer a higher risk for
the progression of glaucomatous
visual field loss in POAG (Galassi
et al. 2003; Martinez & Sanchez
2005). From a technical standpoint,
OBF measurements may be highly
variable when performed by different
observers, especially if the observers
are not experienced with CDI (Tran-
quart et al. 2003). In the current
study, the OBF velocities of all
patients were measured by a single
radiologist who had significant experi-
ence in CDI and OBF measurements
and who was masked to the patients’
disease status.
Glaucomatous patients enrolled in
the study were on various classes of
glaucoma drops. Although prior stud-
ies provided limited evidence that
433
Acta Ophthalmologica 2011
certain classes of topical antiglaucoma
medications were associated with
alterations in OBF in glaucomatous
patients (Costa et al. 2003; Koz et al.
2007; Sugiyama et al. 2008), these
findings have not been validated in
multicentre prospective clinical trials
and the methodology by which OBF
measurements were made are not con-
sistent within different studies.
The extent to which OBF changes
participate in the pathogenesis of
glaucoma is still an enigma. Although
OBF changes have been reported in
glaucoma, the causal relationship is
yet to be identified. The findings of
this study suggest that OBF velocities
are reduced in patients with POAG
and XFG. This reduction of OBF
appears to be independent of haemo-
rheological parameters.
Acknowledgements
The authors would like to recognize
and thank Dr Gábor Holló of Hun-
gary for his critical review of this
study. The authors would like to
acknowledge Umut Arslan from the
Department of Biostatistics for her
assistance in the statistical planning of
the study and interpretation of data.
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Accepted on July 7th, 2009.
Correspondence:
Professor Dr Murat Irkec
Hacettepe Üniversitesi
Göz Hastalıkları Anabilim Dalı
Sıhhiye, 06100
Ankara
Turkey
Tel: + 90 312 3051777
Fax: + 90 312 3094101
Email: mirkec@isnet.net.tr