From the Departments of Neuroradiology (J.W., L.R., C.O., G.S.),
Neurology (J.W., H.P.M., R.W.B., M.S.), and Ophthalmology (U.K., F.K.),
Inselspital, University of Bern, Bern, Switzerland.
Correspondence to G. Schroth, MD, University of Bern, Department of Neuroradiology, Inselspital, 3010 Bern, Switzerland. E-mail gerhard.schroth{at}insel.ch
Methods—Intra-arterial fibrinolysis
was performed within 6 hours after symptom onset in 17 patients with
thromboembolic CRAO. Symptoms were painless, acute and severe decrease
of vision. Urokinase (100 000 to 900 000 IU) was given through a
microcatheter into the ophthalmic artery over 10 to 90 minutes. For
comparison, the history and visual outcome of 15 control patients who
did not receive fibrinolytics were evaluated. In both groups some of
the patients underwent paracentesis and/or received carboanhydrase
inhibitors.
Results—Patients who underwent fibrinolysis fared
better than control patients (P=0.01). Three patients
(17.6%) recovered completely after fibrinolysis and
regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional
patients (11.8%) showed a marked improvement to a visual acuity of
20/30. In 6 patients (35.3%) vision improved slightly. They were able
to count fingers, detect hand movements, or perceive light. In 6
patients (35.3%), fibrinolytic treatment was without effect. Among
control patients, 1 patient (6.7%) showed partial, 4 patients (26.7%)
minimal, and 10 (66.7%) no improvement of vision.
Conclusions—A complete or marked improvement of visual acuity was
achieved in one third of intra-arterial
fibrinolysis patients but in none of the control
patients. Intra-arterial fibrinolysis seems
to have the potential to "lighten" the spontaneously poor outcome
of CRAO.
The retina is part of the brain; therefore, many principles of
fibrinolysis in brain vessels can be applied to CRAO as
well. The time window for successful treatment in stroke is short,
usually within 3 to 6 hours.8 9 In the
monkey, the retina tolerates complete ischemia for about 100
minutes.10 In human CRAO there may be some
residual blood flow.11 12 Therefore, the human
retina might sustain ischemia for longer periods and
recanalization with fibrinolytics within hours
might result in a better clinical outcome. For these reasons, we tried
to restore the retinal circulation by local intra-arterial
fibrinolysis in a series of patients with acute
CRAO.
Fibrinolysis Group
The delay from decrease of vision to fibrinolytic therapy was on
average 4.2 hours (range, 1 to 6 hours). Fibrinolytic therapy was
performed by the neuroradiologist. Before treatment, complete
angiography of both carotids and the vertebrobasilar system was
performed in every patient to exclude vessel occlusions and
stenoses and to assess collateral blood supply. The ophthalmic
artery, its branches, and the chorioretinal blush were assessed before
and after fibrinolysis as seen on angiography and by
funduscopy. Urokinase served as the fibrinolytic agent. We applied
100 000 to 900 000 IU (mean, 594 000 IU) over 10 to 90 minutes. We
injected the drug manually and stepwise (approximately 100 000 IU per
10 minutes) through a microcatheter (Tracker 18). Its tip was placed in
the proximal segment of the ophthalmic artery. Immediately after
fibrinolysis, full-dose heparinization with
unfractionated heparin was started, and the patient admitted to the
neurological ward.
Control Group
Statistical Analysis
Visual outcome in fibrinolysis patients was
significantly better than in control patients (P=0.01). With
fibrinolysis, 3 patients (17.6%) recovered completely
and regained a visual acuity of
Among control patients the initial visual deficit remained the same or
got worse in the majority of patients (66.7%). Four control patients
showed slight improvement of their vision (26.7%), and 1 had a visual
acuity of 20/60 at follow-up (Figure
Conventional therapy was better than no treatment among control
patients (P=0.005), but anterior chamber paracentesis,
carboanhydrase inhibitors, or a combination of the 2 did
not have any additional effect on visual outcome in the
fibrinolysis group (P=0.428). There was no
evidence for other statistically relevant influences on visual
improvement. In neither group was there a significant correlation
between age and visual outcome (fibrinolysis,
P=0.172; control, P=0.095). The delay between
symptom onset and treatment within the limits of 6 hours did not affect
the resulting vision (P=0.692 versus P=0.396,
fibrinolysis versus controls). Initial visual acuity
had no predictive value for the visual outcome either
(P=0.564 versus P=0.618,
fibrinolysis versus controls). In the
fibrinolysis group there was no correlation between the
severity of the chorioretinal blush before (P=0.58) or after
(P=0.347) fibrinolysis, between
severity of blush and dose (P=0.807), or between severity of
blush and application time of urokinase (P=0.293) and visual
improvement.
In this retrospective study we performed fibrinolysis
in 17 patients with CRAO within 6 hours after decrease of vision.
Treatment was performed locally in the ophthalmic artery with the help
of a microcatheter. The outcome was compared with that in 15 control
patients who did not receive fibrinolytics. Patients with
fibrinolysis had a better outcome than patients treated
conservatively (P=0.01). Three patients regained a complete
vision and 2 a vision of 20/30 after fibrinolysis.
There were more patients who regained complete or partial vision after
fibrinolysis than without, and there were fewer
patients in the fibrinolysis group who did not show any
improvement at all. Without fibrinolysis, the best
results achieved were a visual acuity of 20/200 and 20/60 in 1 patient
each, but none regained a normal vision.
Thus, our data corroborate previous retrospective observations that
fibrinolysis improves visual outcome when performed
early after symptom onset. However, as demonstrated by the 2 patients
with transient ischemic attacks during the procedure,
fibrinolysis for CRAO is not without danger. To avoid
complications, patients with CRAO should be selected carefully for
fibrinolysis. Patients with vasculitis or hematological
disorders such as leukemia carry a higher risk of bleeding and should
probably be excluded from fibrinolysis. In addition,
stenoses of the carotid arteries can be both an obstacle and a
risk for local intra-arterial fibrinolysis.
For this reason, we first performed an ordinary angiography to assess
the aortic arch and the extracranial and intracranial cerebral arteries
bilaterally. If there was a high-grade carotid stenosis, lysis
was not attempted. The angiographer did not pass the stenosis
with the catheter because of the potential risk of
arterio-arterial embolism and stroke. In patients without
stenosis, if technically feasible, the tip of the microcatheter
was placed in the proximal segment of the ophthalmic artery to perform
a selective angiography. On average, 594 000 IU urokinase was
applied.
The time window for fibrinolysis within 6 hours after
visual decrease is somewhat arbitrary. This time window was chosen by
analogy with stroke. In stroke, systemic fibrinolysis
within 3 hours turned out to be beneficial (NINDS rt-PA
study).8 It can be beneficial up to 6 hours when
patients are selected according to strict criteria (ECASS
).9 The main risk is cerebral hemorrhage.
In the study of Schumacher and coworkers,5
fibrinolysis of CRAO was performed within 36 hours.
Patients treated before 6 hours showed better results than patients
treated later. In our study, patients with complete recovery underwent
fibrinolysis no later than 4 hours after visual
decrease. This may be chance, because statistical analysis did
not show any significant correlation between outcome and delay of
treatment up to 6 hours. Intracranial or retinal bleeding did not occur
in this series.
Frequently, in ophthalmic artery angiography, a contrast enhancement of
the posterior eye bulb is seen, a so-called chorioretinal blush. If
present, it did not correlate with a better visual outcome in our
patients. The chorioretinal blush results from contrast filling of the
choroidal arterioles, which are supplied by the posterior ciliary
arteries and branches of the circle of Haller-Zinn. Anastomoses to the
CRA or branches do not exist. This may explain why the presence or
absence of a chorioretinal blush does not influence the outcome of
fibrinolysis.
Patients with a tight internal carotid artery stenosis or
occlusion pose a problem for ophthalmic artery
catheterization and local fibrinolysis.
Systemic application of fibrinolytic agents might be more beneficial
for these patients, because the fibrinolytics could reach the CRA over
numerous collaterals from the external carotid artery to the ophthalmic
artery. In addition, the risk of cerebral hemorrhage may be
lower than in stroke and closer to the risk of patients with myocardial
infarction. However, no study has yet demonstrated whether a systemic
intravenous fibrinolysis in CRAO is
effective and safe. Alternatively, the fibrinolytics could be applied
locally into the external carotid artery because most tight internal
carotid artery stenoses cause a flow reversal in the ophthalmic
artery and the eye becomes mostly supplied by the external carotid
artery. For these reasons and because of the easier practicability of
intravenous fibrinolysis, future
therapeutic trials in CRAO should study both local and systemic
fibrinolysis in patients with and without carotid
stenosis.
In conclusion, this retrospective study demonstrates improved visual
outcome of local intra-arterial
fibrinolysis in CRAO compared with conventional
treatment if performed within 6 hours after symptom onset.
Fibrinolysis may have the potential to "lighten"
the otherwise gloomy outcome of CRAO. Our results, based on this
retrospective study, need confirmation by a larger prospective,
randomized trial.
Received March 2, 1998;
revision received May 28, 1998;
accepted July 3, 1998.
2.
Schmidt D, Schumacher M, Wakhloo AK. Microcatheter
urokinase infusion in central retinal artery occlusion. Am J
Ophthalmol. 1992;113:429–434.[Medline]
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Schumacher M, Schmidt D, Wakhloo AK. Intraarterielle
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Van Cauwenberge F. Fibrinolyse: indications en
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Schumacher M, Schmidt D, Wakhloo AK.
Intraarterial fibrinolytic therapy in central retinal
artery occlusion. Neuroradiology. 1993;35:600–605.[Medline]
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Türmer KH, Guhl A, Hettesheimer H, Kreissig I.
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Ophthalmologe. 1993;90:472–475.[Medline]
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The NINDS rt-PA Stroke Study Group. Tissue
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Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von
Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne M-H, Hennerici
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thrombolysis with recombinant tissue
plasminogen activator for acute hemispheric
stroke. The European Cooperative Acute Stroke Study Group
(ECASS). JAMA. 1995;274:1017–1025.
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David NJ, Norton EWD, Gass JD, Beauchamp J.
Fluorescein angiography in central retinal artery
occlusion. Arch Ophthalmol. 1967;77:619–629.
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© 1998 American Heart Association, Inc.
Original Contributions
Selective Intra-Arterial Fibrinolysis of Acute Central Retinal Artery Occlusion
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—Occlusion
of the central retinal artery (CRAO) causes a sudden decrease of
monocular vision. Because early restoration of blood flow may improve
outcome, we attempted to treat CRAO with selective intra-arterial
fibrinolysis.
Key Words: fibrinolysis • retinal artery occlusion • thrombolysis
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In acute central retinal artery occlusion (CRAO),
conventional therapies such as anterior chamber paracentesis, ocular
massage, pentoxifylline, or carboanhydrase inhibitors
hardly change the unfavorable spontaneous
course.1 Based on the increasing experience and
beneficial results of fibrinolytic therapy in cerebral,
coronary, and peripheral artery occlusions,
attempts have been made to use selective fibrinolysis
in treatment of CRAO also.2 3 4 5 In an animal
model,6 this technique proved its efficacy. With
the advent of advanced microcatheter technology and the growing
experience of investigators, the use of this technique in humans has
become feasible and safe.7
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Study Design
This is a retrospective nonrandomized study comparing 2 groups
of patients with CRAO. Inclusion criterion was acute decrease of vision
because of noninflammatory thromboembolic occlusion of the central
retinal artery (CRA). Patients with CRA branch occlusions, systemic or
local vasculitis, arteriovenous malformations, or blood dyscrasia were
excluded. All patients (patient group and control group) were seen at
the department of ophthalmology for diagnosis. Visual function was
assessed using a standardized chart and lighting. One group of patients
(n=17) was treated with intra-arterial
fibrinolysis, the other group (n=15) served as
controls. In addition, in both groups some patients underwent anterior
chamber paracentesis (35.3% and 6.7%,
fibrinolysis versus control), received carboanhydrase
inhibitors (5.9% and 13.3%, fibrinolysis
versus control), a combination (47.1% and 26.7%,
fibrinolysis versus control), or none (11.8% and
53.3%, fibrinolysis versus control) of those
conventional therapies. Initial symptoms of CRAO were acute, painless
monocular decrease of vision in all the patients.
Fibrinolysis was performed after conventional treatment
whenever possible. Patients who underwent fibrinolysis
were informed about the potential risks and benefits of
fibrinolysis, and they agreed to treatment.
The 17 patients who received fibrinolytics were on average 60.8
years old (range, 29 to 83 years; median, 64 years). Vascular risk
factors are given in the Table
[tbc]. The diagnosis of CRAO was
made by an ophthalmologist. Diagnosis was based on an acute decrease of
vision and funduscopic findings such as ischemic macular edema,
a cherry red spot, or reduced or absent retinal blood flow. To save
time, fluorescein angiography was not used. Visual acuity
was assessed before, 1 to 14 days after, and again 8 weeks after
fibrinolysis by an ophthalmologist.
View this table:
[in a new window]
Table 1. Baseline Characteristics of Patient and Control
Groups
The control group was made up of 15 patients seen at the
Department of Ophthalmology (Table
). The patients had a
mean age of 64.4 years (range, 39 to 93 years; median, 64 years) and
were all seen within 6 hours after decrease of vision. Five were seen
before fibrinolysis treatment was available at our
institution, and 7 arrived at the hospital when there was no
neuroradiologist on call who was capable of performing the procedure.
In 3 control patients angiography showed a tight carotid
stenosis. Because we felt it would be risky to pass the
stenosis with the microcatheter, fibrinolysis
was not performed. The presenting symptoms and signs were the same
as in the fibrinolysis group. Visual acuity was
assessed before and 
4 weeks after treatment by an
ophthalmologist.
Numerical values of vision were assigned for finger counting
(20/1000), perception of hand movement (20/2000), and perception of
light (20/20000). The Wilcoxon rank sum test served to assess
differences between fibrinolysis and control patients.
For correlations, the Spearman rank correlation test was used.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Visual acuity before treatment ranged from light perception to
20/250. It did not differ between the fibrinolysis and
the control groups (P=0.44). No patient in either group was
completely blind, 37.5% (35.3% in the fibrinolysis
group and 40% in the control group) perceived light, 46.9% (52.9%
and 40%, fibrinolysis versus control) detected hand
movements, 12.5% (11.8% and 13.3%, fibrinolysis
versus control) were able to count fingers, and 1 patient in the
control group (6.7%) had a visual acuity of 20/250. 20/20. Two patients (11.8%) showed a
marked improvement, with a posttreatment visual acuity of 20/30. Six
patients (35.3%) had an outcome with slight improvement. They were
able to perceive light, detect hand movements, or count fingers. In 6
patients fibrinolytic treatment did not improve vision (35.3%) (see
the Figure). In 2 patients a transient ischemic
attack was observed during angiography and
fibrinolysis. Complications causing permanent
neurological deficits did not occur. There were no intracranial or
retinal hemorrhages.
View larger version (51K):
[in a new window]
Figure 1. Improvement of vision in the control (n=15) and
fibrinolysis (n=17) groups, ie, vision at outcome minus
vision before treatment. Complete recovery represents a
difference in visual acuity of 0.98 (98/100), marked improvement of
0.5 (20/40) to 0.8 (20/25), partial improvement of 0.2 (20/100) to 0.5
(20/40), slight improvement of >0 to 0.2 (20/100), and no improvement
of 
0. Approximately one third of the patients undergoing
fibrinolysis improved markedly or recovered completely,
one third showed slight improvement, and the other third had no
improvement at all. Among control patients, one third showed slight or
partial improvement and two thirds did not improve or became
worse.).
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In general, CRAO is said to have a gloomy outcome although, to the
best of our knowledge, the exact natural history of patients with CRAO
without any therapeutic intervention has not been reported. In a
series1 of 34 patients treated with anterior
chamber paracentesis and carboanhydrase inhibitors or both,
only 2 recovered completely. The majority of patients (66.7%) did not
improve at all. In another series13 of 33 treated
patients, visual outcome was even worse. Recent attempts to treat CRAO
with local intra-arterial fibrinolysis have
been promising. Schumacher and coworkers5 noted
an improved visual outcome after fibrinolysis compared
with historic controls.
Acknowledgments
Johannes Weber was supported by a grant from IBRO, Swiss
National Foundation, CH-Bern. We thank Pietro Ballinari, PhD,
University of Bern, for statistical advice.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Augsburger JJ, Magargal LE. Visual prognosis
following treatment of acute central retinal artery obstruction.
Br J Ophthalmol. 1980;64:913–917.
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