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NR 4-6/2007
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Assessment of blood
flow velocity in eyeball arteries in multiple sclerosis patients
with past retrobulbar optic neuritis in color Doppler
ultrasonography
Dopplerowska ocena przepływu
krwi w tętnicach gałki ocznej u chorych z zapaleniem
pozagałkowym nerwu wzrokowego w przebiegu stwardnienia
rozsianego
Monika Modrzejewska1, Danuta
Karczewicz1, Grażyna Wilk2
1 Department of Ophthalmology, Pomeranian Medical
University, Szczecin
Head of the Department: prof. Danuta Karczewicz, MD, PhD
2 Department of Radiology Pomeranian Medical
University
Head of the Department: prof. Grażyna Wilk, MD, PhD |
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| Summary: |
Purpose: The aim of the
study was to evaluate blood flow velocity in eyeball
arteries in affected and unaffected eyes in patients
with past retrobulbar optic neuritis in the course of
multiple sclerosis (MS).
Material and methods: Evaluation of blood flow velocity
in 16 eyes of 16 patients with unilateral retrobulbar
optic neuritis was performed in ophthalmic artery (OA),
central retinal artery (CRA) and short posterior ciliary
artery (SPCA). In the arteries the following parameters
have been assessed: peak systolic velocity (PSV),
end-diastolic velocity (EDV), mean flow velocity (MV),
indicators of peripheral vascular resistance such as
Gosling Index (PI) and Pourcelot Index (RI). The
obtained values have been compared to values of blood
flow in the same arteries of the control group. Using
Shapiro-Wilk test, mode of distribution of each
parameter was analyzed. The statistic analysis has been
done between group of affected eyeballs (group 1) and
control group and between group of unaffected eyeballs (group
2) in multiple sclerosis patients and control group (13
individual, 26 eyes), regarding the age. The assessment
was performed with the assistance of t-Student test, and
in case of lack of normal distribution, by U
Mann-Whitney test. Statistically significant difference
was established when p value was below 0.05 (p≤0.05).
Results: Among the analyzed parameters of blood flow
velocity, statistically significant disturbances in the
examined eyeball arteries were found. The most
significant disturbances of blood flow were found in CRA
and SPCA. The affected parameters were: diminished MV
velocity in OA; PSV, MV, RI in CRA and PSV, EDV, MV and
RI indices in SPCA. The similar blood flow velocity
disturbances were also found in unaffected eyeball
arteries.
Conclusions: In MS patients with past optic neuritis
disturbances of ocular circulation can be observed. The
statistically significant diminishing blood flow
velocity parameters and vascular resistance indices in
eyeball arteries may indicate alterations of blood flow.
Lowering of systolic and mean velocities and resistance
indices of blood flow are most expressed in CRA and SPCA.
Reduction in blood flow parameters in the examined
arteries occur both, in the eyes previously affected by
past optic neuritis and in contra lateral, unaffected
eyes. |
| Słowa kluczowe: |
zapalenie pozagałkowe
nerwu wzrokowego, przepływ krwi w gałce ocznej,
ultrasonografia dopplerowska w kolorze, stwardnienie
rozsiane. |
| Key words: |
retrobulbar neuritis,
ocular blood flow, colour Doppler ultrasound, multiple
sclerosis. |
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Introduction
One of the factors in pathogenesis of retrobulbar optic
neuritis in multiple sclerosis (MS) patients is the vascular
factor. Endothelin 1 (ET-1) is produced by endothelial cells and
is the main physiological factor in vascular constriction. ET-1
occurs in different organs and tissues, among others in neuronal
cells, glial tissue in central nervous system (CNS) and in
ocular tissues (1,2). ET – 1 is found in blood of patients
suffering from autoimmune diseases, as well as diseases of
vascular origin, such as: hypertension, migraine, rheumatoid
arthritis, temporal arteritis and multiple sclerosis
(3,4,5,6,7,8). Considering vasoconstricting properties of ET – 1
it seems probable that this substance may play a major role in
nerve fiber damaging in MS patients having disturbances of
eyeball circulation and retrobulbar optic neuritis (5,6,9). The
goal of the study was to establish parameters of blood flow
velocity in bulbar and retrobulbar circulation in MS patients
with past retrobulbar optic neuritis.
Material and Method
The examined group consisted of 16 patients with past
unilateral optic retrobulbar neuritis, suffering from MS, who
were hospitalized in the Department of Ophthalmology, Pomeranian
Medical University in Szczecin, in years 2000-2005. The average
age of the patients was 39,5 (16 to 47). In 80% of cases
retrobulbar optic neuritis occurred for the first time, in 20%
of cases occurred for the second time. Among studied patients
80% were women and 20% were men. The levels of individual blood
flow velocity parameters were analyzed.
Ultrasound examinations as a routine were performed by
Ultrasound Laboratory of Radiology Department of Pomeranian
Medical University after obtaining consent from patients. Based
on data from case histories it was established that time elapsed
from the first symptoms until admission to the ultrasound
examination ranged from 6 months to 2 years. The examinations of
endothelin – 1 level were not performed on the studied group of
patients since this was not the aim of this research.
The studied group consisted of patients with affected eyes (n =
16) – group 1 and patients with unaffected eyes (n = 16) – group
2. An eye examination including the determination of visual
acuity on Snellen chart was as follows: 0.9-1.0, mean value 0.95
(sd 0.12). Ophthalmoscopic eye fundus examination was normal.
The systolic and diastolic blood pressure measured during blood
flow velocity investigation did not exceed values of 120 mmHg
and 75 mmHg respectively. Estimation of intrabulbar pressure did
not exceed 17.3 mmHg.
Control group included 13 healthy individuals, n = 26 eyes, in
whom cardiac and vascular diseases and ophthalmic ailments did
not occur and who were matched for age and sex with the studied
group. The control group consisted of non-smoking individuals in
whom application of general and ocular medications was excluded.
Visual acuity in this group equaled 1.0 on the Snellen chart.
With assistance of Shapiro-Wilk test, normality of distribution
of given attributes was analyzed. The average of analyzed
parameters between affected eye group and control group,
unaffected eye group and control group, according to age, by
means of t-Student test, and in case of lack of normal
distribution by means of U Mann-Whitney test, were compared. The
level of significance is given in each of presented tables, and
the difference was considered statistically significant at p
value p ≤ 0.05. It has been indicated in the tables which test
was used depending on normality of distribution of a given
attribute.
Blood flow velocity in ophthalmic (OA), central retinal (CRA)
and short posterior ciliary arteries (SPCA) was measured with
assistance of Acuson 128 X P10 apparatus, with color option and
sector probe 7.5 MHz as a routine examination of hospitalized
patients. Ultrasound probe was applied on closed eyes, using
ultrasound gel, without exertion of pressure. During the exams
patients were recumbent, motionless, looking straight ahead so
that the best signal from the examined arteries could be
achieved. During the examination, angle correction was applied
to the pulsed Doppler recordings to minimize errors in the
examined velocities. Ophthalmic artery was localized medially to
optic nerve, 15-18 mm from posterior pole of an eyeball, after
its crossing with optic nerve. Central retinal artery was
localized in the head of optic nerve, 2-3 mm before its entry
into the eyeball. Signals from short posterior ciliary arteries
were found in lateral and medial sections of an eyeball. Because
numerous branches of short posterior ciliary arteries were
available for assessment, only temporal branch was chosen for
analysis. In Doppler ultrasound the following parameters were
assessed: peak systolic velocity (PSV, m/s), peak end-diastolic
velocity (EDV, m/s), mean flow velocity (MV, m/s), Gosling Index
(PI), Pourcelot Index (RI). PSV was described as the highest
value of blood flow during cardiac systole; EDV was the lowest
value of blood flow at the end of cardiac diastole; RI as the
quotient of difference between peak systolic and peak diastolic
velocity over peak systolic velocity; PI as quotient of
difference between peak systolic and peak diastolic velocity
over mean flow velocity. Shifts of blood flow patterns in the
examined arteries were compared between affected patients and
control group.
Results
In group 1 the analysis of changes in vascular blood flow
was as follows: in ophthalmic artery – PSV, EDV and MV were
lower than in control group. The difference was statistically
significant at p = 0.04 for MV parameter. Values of PI and RI
indexes showed higher, but statistically insignificant numbers
when compared to control group.
In central retinal artery values of PSV and MV velocities were
diminished in relation to age norm of the control group.
Statistically significant differences were found for PSV (p =
0.001) and MV (p = 0.008). Values of PI and RI were below normal,
showing statistical significance for RI (p = 0.012). In short
temporal posterior ciliary artery diminished PSV, EDV and MV
velocities were found. Of those, statistically significant were
values for systolic (p = 0.0001) and mean velocity (p = 0.0001).
Values for RI and PI were lowered in this artery, but
insignificantly.
Shorts used in tables: peak systolic velocity (PSV), peak
end-diastolic velocity (EDV), mean velocity (MV), pulsation
index (PI), vascular resistance (RI), n-number of cases,
sd-standard deviation, p value ≤ 0.05.
Subsequent measurements took place in order to assess parameters
of blood flow in contra lateral, theoretically unaffected eye,
in which no disease was diagnosed. In ophthalmic, central
retinal and in short posterior temporal ciliary artery
statistical analysis of parameters of blood flow in unaffected
eyes of group 2, patients showed decreased MV in OA; PSV, MV in
CRA and PSV, EDV and MV velocities in SPCA. Decrease these
parameters were statistically significant. Most impressive
changes were observed in SPCA, where all velocities parameters
of blood flow were significantly below normal, compared to
control group. For PSV p = 0.000, for EDV p = 0.0117, for MV p =
0.0000. Indices PI and RI did not show major changes in all the
examined arteries.
Discussion
In MS patients with retrobulbar optic neuritis, disturbances
in bulbar arteries blood flow are observed in color Doppler
ultrasound. According to many investigators’ opinions it is well
known that endothelin – 1, as a vessel constricting agent, can
disturb axoplasm flow in optic nerve. Disturbance of circulation
in eye tissues can be a consequence of this substance’s action
(1,5,9,10). It seems that analyzing the changes of blood flow
parameters in choroid and retinal arteries can give an idea
about disturbances of haemodynamic in this region. Results of
our study confirm that in post optic neuritis eyes, systolic,
diastolic and mean velocities of blood flow are diminished in
all eyeball arteries. In all of the examined patients the
largest decrease of blood flow occurs in central retinal and
short posterior temporal arteries and these values are
statistically significant. The decreased values of the
parameters are probably due to vascular spasm. In MS patients
elevated levels of endothelin-1 are found (5,9). In vitro
studies ET-1 exerts constricting action on ophthalmic and short
posterior ciliary arteries, causing a powerful and prolonged
vascular spasm and diminished blood flow in choroidea (11). |
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ET-1 also causes powerful narrowing
in retinal vessels (4). It has been shown in experimental
studies that intravitreal and intravenous administration of ET-1
in animals and humans causes diminished blood flow in optic
nerve papilla (6). In works of Akarsu and all, similar results
to ours were obtained. The investigators found decreased blood
flow in central retinal artery in post retrobulbar optic
neuritis patients. Eyeball blood flow velocity studies were
performed several months after optic neuritis by means of color
Doppler ultrasound, as in our study (9). According to other
investigators, i.e. Karaali and all, velocity of blood flow can
increase in ophthalmic artery in initial period of acute
inflammation of an optic nerve. They have not found changes in
blood flow in other eyeball arteries (10). Still, according to
other investigators, vascular resistance in eyeball arteries of
MS patients does not change but increases slightly in central
retinal artery. It can be due to higher concentration of ET-1 in
MS patients’ blood, which has edema of a retrobulbar part of an
optic nerve in the course of neuritis (1,5,9,12,13). In our
study we have not found major changes in Pourcelot index (RI) or
Gosling index (PI) in post retrobulbar optic neuritis patients,
when compared to control group. It may be a result of a decrease
of inflammation features of an optic nerve, in the group of
patients receiving treatment. Application of corticosteroids and
calcium channel blockers generally, can partially reverse
disturbances of microcirculation in optic nerve disc (14,15). In
the group of the examined patients the treatment course with
steroids had been terminated, which undoubtedly influenced the
healing process of inflammation and could cause reversal of
disturbances in vascular resistance in central retinal artery,
in which blood flow was most commonly affected. There are not
many accessible reports in literature about abnormalities in
vascular resistance in eyeball arteries of MS patients with
retrobulbar optic neuritis. Some investigators observe slight
increase of vascular resistance index (RI) in central retinal
artery (8,9). In the studies of Karaali, mean elapsed time from
the first symptoms of optic neuritis until the admission of
Doppler ultrasound examination was 5.2 days, in Elvin’s studies
– 27 days (10,12). Increase of values in vascular resistance
index (RI) is described in optic neuritis patients with acute
clinical symptoms. According to investigators, the key issue is
the period of time between appearance of symptoms of retrobulbar
optic neuritis and blood flow velocity examination. It is
suggested that lack of abnormalities in vascular resistance is
due to quite a long period of time that has elapsed since
clinical manifestations of this disease. During Doppler
ultrasound examinations in the studied group, our patients went
through remission of symptoms of optic neuritis (remission
spanned between 6 months and 2 years).
Interesting phenomenon is an abnormally low blood flow in
eyeball arteries of unaffected eyes of MS patients. In both
study groups of patients statistically diminished systolic and
mean velocity of blood flow and decreased RI index were observed
in short posterior ciliary arteries and especially central
retinal artery in comparison to control group. This may indicate
that in past optic neuritis patients, circulation disturbances
occur both, locally and systemically, and it can be observed in
affected optic neuritis eye and in unaffected eye of the same
patient. Systemic action of ET – 1 probably is responsible for
the influence on retinal and choroidal arteries diameters
changes and local haemodynamic of eyeball. However, in order to
confirm the outcomes of this research further examinations among
larger number of patients are necessary.
It is thought that Doppler ultrasonography as a non invasive and
repeatable method continues to be a suitable examination of
imaging the dysfunction of blood flow in vascular system of an
eyeball.
Conclusions
1. The statistically significant diminishing of blood flow
velocity parameters and resistance indices in studied arteries
mainly in CRA and SPCA may indicate disturbances of retinal and
choroidal circulation in MS patients with past retrobulbar
neuritis.
2. In examined patients abnormalities in CRA and SPCA blood flow
in contra lateral, unaffected eye were also found in color
Doppler examination.
3. Colour Doppler ultrasound is an effective and helpful method
in the assessment of haemodynamic disturbances of eye
circulation in MS patients with past optic neuritis.
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Praca wpłynęła do Redakcji 07.087.2007 r. (866)
Zakwalifikowano do druku 25.02.2007 r.
Adres do korespondencji (Reprint requests to):
Monika Modrzejewska, MD, PhD
ul. Wierzbowa 21 BC/3
72-005 Szczecin
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