Thrombolysis for central retinal artery occlusion
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1 The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1, UK
2 Department of Ophthalmology, University Hospital Zurich, Frauenklinikstrasse 24, Zurich, Switzerland
Correspondence to:
Gordon T Plant
Department of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; gordon@plant.globalnet.co.uk
Results of a controlled trial are needed before recommending this treatment
Keywords: thrombolysis; central retinal artery occlusion
Central retinal artery occlusion is an uncommon cause of unilateral visual loss and a rare cause of blindness. In this issue (see pp 196–9), Arnold et al1 describe a retrospective analysis of intra-arterial thrombolysis (IAT) of central retinal artery occlusion within six hours of symptom onset in 37 patients. The visual outcome was compared with 19 control patients. Before treatment, cranial computed tomography was carried out (to exclude intracranial haemorrhage), along with four vessel angiography. The cases are divided into those with local thrombotic causes (73%), cardioembolism (24%), and carotid stenosis (3%). The classification was based on the TOAST criteria,2 which were developed for the evaluation of cerebral strokes where there is no possibility of observing the embolus. One third of patients seen within six hours could not be treated because no neuroradiologist was available. Periprocedural adverse events occurred in two patients who experienced transient ischaemic attacks and in one patient who suffered brain infarction. No haemorrhagic complications were seen. The outcome measure was visual acuity.
Thrombolysis in central retinal artery occlusion is not new3 but it is Deiter Schmidt and Martin Schumacher in Freiburg, Germany, who have championed the technique,4 treating over 60 cases5 and compelling us to examine our practice. IAT to treat ischaemic stroke is a goal of stroke units; however, the time interval between event and intervention is critical. Sudden visual loss tends to present to eye casualty departments. In cases of acute blindness a competent ophthalmic examination is essential but will increase the "time to treat", especially where the eye hospital is a stand-alone unit.
Who is doing it? In the United Kingdom a few anecdotal cases are described at meetings but only over coffee. In the USA the procedure is being done, but no systematic information is available (Miller N and Aldrich E, personal communication). In contrast IAT for central retinal artery occlusion is commonplace in Germany, Switzerland, and Austria. In Zurich, for example, 88 consecutive patients with central retinal artery occlusion have been treated between 1995 and 2002: IAT was undertaken in 23 patients while 65 were managed conservatively (unpublished data). A trend for a better visual acuity outcome was observed in the thrombolysis group, which became statistically significant for younger patients who had slightly better initial visual acuities. A small subgroup of patients profited significantly from IAT, all of whom were treated within six hours. Unknown factors other than the time to thrombolysis contribute to the outcome.
It is not our opinion that the results presented by Arnold et al should encourage centres to begin using this treatment in advance of a randomised study. Such a study is under way in Europe (no UK centre is involved but the acronym is English: EAGLE, European assessment group for lysis in the eye).
Our reasons for this view are as follows. First, central retinal artery occlusion is usually a monocular disorder and therefore (apart from the risk of pre-existing or subsequent pathology in the fellow eye) the likelihood of significant disability is less than with cerebral arterial occlusions.
Second, the logistic problems associated with setting up a protocol for IAT in central retinal artery occlusion are substantial. In our experience patients often do not notice monocular visual loss for some time or may "wait for it to clear" before seeking medical advice. Furthermore the additional review by an ophthalmologist mentioned above adds time compared with the journey of a patient with a hemisphere stroke. Furthermore, many patients wake with loss of vision, so how can we know when the event occurred?
Third, there is no information in this study on the extent of visual field loss as an outcome measure. This is significant for disability and may not correlate well with visual acuity because acuity may be preserved where a cilioretinal artery is present and with residual retinal branch artery based defects.
Fourth, there was a low level of statistical significance in the study under review.
Finally, Arnold et al defined a subclass of patients with central retinal artery occlusion who would have a greater chance of benefiting from IAT. In the light of a trend in their own data, existing animal studies, and recommendations for thrombolysis in cerebral ischaemic stroke, they suggest that treatment within three hours might be the goal.
The following analysis should be carried out in a large city:
The incidence of unilateral central retinal artery occlusion needs to be established.
A logistic study should be undertaken of the likelihood of such patients presenting to an interventional neuroradiological unit within three hours having undergone an ophthalmological examination, a medical/neurological examination, brain neuroimaging to exclude haemorrhage (but is this necessary in central retinal artery occlusion as opposed to hemisphere strokes?), sufficient blood tests with laboratory results available to exclude vasculitis and blood dyscrasias, and four-vessel interventional angiography to ensure adequate access to the ophthalmic artery.
The additional cost to eye departments and stroke units of maintaining a 24 hour referral and treatment service for central retinal artery occlusion should be estimated, as should the geographical density required for such units, taking into account the results of the first two investigations above.
A meta-analysis of existing studies should be done, including those employing intravenous treatment and other thrombolytic agents.
The number of cases required should be determined, given the statistical significance in the existing retrospective studies, to permit not only a definitive overall result but also stratification of the cases according to time to thrombolysis, age, and other clinical features such as the type of embolus where visible.
Perimetry should be evaluated as an outcome measure.
Evaluation of visible emboli is required: can thrombolysis be effective in a patient with a calcific embolus sitting at the bifurcation of the central retinal artery as opposed to a local thrombosis?
An evaluation should be made of the presence or absence of a macular cilio-retinal artery, which will influence preservation of central acuity but not necessarily disability (patients with a macular cilio-retinal artery are often left with 6/9 acuity but a tiny central island of vision of little practical use).
As neuro-ophthalmologists our aim is to preserve vision wherever possible. There are times when the task of obtaining the evidence we need seems impossible. However, we should remember the words of Louis XVI’s finance minister, Charles Alexandre de Calonne: "Madame, si c’est possible, c’est fait; impossible? Cela se fera"—better known as the US Army paraphrase "The difficult we do immediately; the impossible takes a little longer." As Calonne discovered, it sometimes takes a little too long.
REFERENCES
Arnold M, K?rner U, Remonda L, et al. Comparison of intra-arterial thrombolysis with conventional treatment in patients with acute central retinal artery occlusion. J Neurol Neurosurg Psychiatry 2004;75:196–9.
Adams HP, Davis PH, Leira EC, et al. Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the trial of Org 10172 in acute stroke treatment (TOAST). Neurology 1999;53:126–31.
Ffytche TJ. A rationalization of treatment of central retinal artery occlusion. Trans Ophthalmol Soc UK 1974;94:468–79.
Schumacher M, Schmidt D, Wakhloo AK. Intraarterielle Fibrinolyse bei Zentralarterienverschluss. Radiologe 1991;31:240–3.
Schmidt DP, Schulte-M?nting J, Schumacher M. Prognosis of central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment. Am J Neuroradiol 2002;23:1301–7.(G T Plant1 and K Landau2)
2 Department of Ophthalmology, University Hospital Zurich, Frauenklinikstrasse 24, Zurich, Switzerland
Correspondence to:
Gordon T Plant
Department of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; gordon@plant.globalnet.co.uk
Results of a controlled trial are needed before recommending this treatment
Keywords: thrombolysis; central retinal artery occlusion
Central retinal artery occlusion is an uncommon cause of unilateral visual loss and a rare cause of blindness. In this issue (see pp 196–9), Arnold et al1 describe a retrospective analysis of intra-arterial thrombolysis (IAT) of central retinal artery occlusion within six hours of symptom onset in 37 patients. The visual outcome was compared with 19 control patients. Before treatment, cranial computed tomography was carried out (to exclude intracranial haemorrhage), along with four vessel angiography. The cases are divided into those with local thrombotic causes (73%), cardioembolism (24%), and carotid stenosis (3%). The classification was based on the TOAST criteria,2 which were developed for the evaluation of cerebral strokes where there is no possibility of observing the embolus. One third of patients seen within six hours could not be treated because no neuroradiologist was available. Periprocedural adverse events occurred in two patients who experienced transient ischaemic attacks and in one patient who suffered brain infarction. No haemorrhagic complications were seen. The outcome measure was visual acuity.
Thrombolysis in central retinal artery occlusion is not new3 but it is Deiter Schmidt and Martin Schumacher in Freiburg, Germany, who have championed the technique,4 treating over 60 cases5 and compelling us to examine our practice. IAT to treat ischaemic stroke is a goal of stroke units; however, the time interval between event and intervention is critical. Sudden visual loss tends to present to eye casualty departments. In cases of acute blindness a competent ophthalmic examination is essential but will increase the "time to treat", especially where the eye hospital is a stand-alone unit.
Who is doing it? In the United Kingdom a few anecdotal cases are described at meetings but only over coffee. In the USA the procedure is being done, but no systematic information is available (Miller N and Aldrich E, personal communication). In contrast IAT for central retinal artery occlusion is commonplace in Germany, Switzerland, and Austria. In Zurich, for example, 88 consecutive patients with central retinal artery occlusion have been treated between 1995 and 2002: IAT was undertaken in 23 patients while 65 were managed conservatively (unpublished data). A trend for a better visual acuity outcome was observed in the thrombolysis group, which became statistically significant for younger patients who had slightly better initial visual acuities. A small subgroup of patients profited significantly from IAT, all of whom were treated within six hours. Unknown factors other than the time to thrombolysis contribute to the outcome.
It is not our opinion that the results presented by Arnold et al should encourage centres to begin using this treatment in advance of a randomised study. Such a study is under way in Europe (no UK centre is involved but the acronym is English: EAGLE, European assessment group for lysis in the eye).
Our reasons for this view are as follows. First, central retinal artery occlusion is usually a monocular disorder and therefore (apart from the risk of pre-existing or subsequent pathology in the fellow eye) the likelihood of significant disability is less than with cerebral arterial occlusions.
Second, the logistic problems associated with setting up a protocol for IAT in central retinal artery occlusion are substantial. In our experience patients often do not notice monocular visual loss for some time or may "wait for it to clear" before seeking medical advice. Furthermore the additional review by an ophthalmologist mentioned above adds time compared with the journey of a patient with a hemisphere stroke. Furthermore, many patients wake with loss of vision, so how can we know when the event occurred?
Third, there is no information in this study on the extent of visual field loss as an outcome measure. This is significant for disability and may not correlate well with visual acuity because acuity may be preserved where a cilioretinal artery is present and with residual retinal branch artery based defects.
Fourth, there was a low level of statistical significance in the study under review.
Finally, Arnold et al defined a subclass of patients with central retinal artery occlusion who would have a greater chance of benefiting from IAT. In the light of a trend in their own data, existing animal studies, and recommendations for thrombolysis in cerebral ischaemic stroke, they suggest that treatment within three hours might be the goal.
The following analysis should be carried out in a large city:
The incidence of unilateral central retinal artery occlusion needs to be established.
A logistic study should be undertaken of the likelihood of such patients presenting to an interventional neuroradiological unit within three hours having undergone an ophthalmological examination, a medical/neurological examination, brain neuroimaging to exclude haemorrhage (but is this necessary in central retinal artery occlusion as opposed to hemisphere strokes?), sufficient blood tests with laboratory results available to exclude vasculitis and blood dyscrasias, and four-vessel interventional angiography to ensure adequate access to the ophthalmic artery.
The additional cost to eye departments and stroke units of maintaining a 24 hour referral and treatment service for central retinal artery occlusion should be estimated, as should the geographical density required for such units, taking into account the results of the first two investigations above.
A meta-analysis of existing studies should be done, including those employing intravenous treatment and other thrombolytic agents.
The number of cases required should be determined, given the statistical significance in the existing retrospective studies, to permit not only a definitive overall result but also stratification of the cases according to time to thrombolysis, age, and other clinical features such as the type of embolus where visible.
Perimetry should be evaluated as an outcome measure.
Evaluation of visible emboli is required: can thrombolysis be effective in a patient with a calcific embolus sitting at the bifurcation of the central retinal artery as opposed to a local thrombosis?
An evaluation should be made of the presence or absence of a macular cilio-retinal artery, which will influence preservation of central acuity but not necessarily disability (patients with a macular cilio-retinal artery are often left with 6/9 acuity but a tiny central island of vision of little practical use).
As neuro-ophthalmologists our aim is to preserve vision wherever possible. There are times when the task of obtaining the evidence we need seems impossible. However, we should remember the words of Louis XVI’s finance minister, Charles Alexandre de Calonne: "Madame, si c’est possible, c’est fait; impossible? Cela se fera"—better known as the US Army paraphrase "The difficult we do immediately; the impossible takes a little longer." As Calonne discovered, it sometimes takes a little too long.
REFERENCES
Arnold M, K?rner U, Remonda L, et al. Comparison of intra-arterial thrombolysis with conventional treatment in patients with acute central retinal artery occlusion. J Neurol Neurosurg Psychiatry 2004;75:196–9.
Adams HP, Davis PH, Leira EC, et al. Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the trial of Org 10172 in acute stroke treatment (TOAST). Neurology 1999;53:126–31.
Ffytche TJ. A rationalization of treatment of central retinal artery occlusion. Trans Ophthalmol Soc UK 1974;94:468–79.
Schumacher M, Schmidt D, Wakhloo AK. Intraarterielle Fibrinolyse bei Zentralarterienverschluss. Radiologe 1991;31:240–3.
Schmidt DP, Schulte-M?nting J, Schumacher M. Prognosis of central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment. Am J Neuroradiol 2002;23:1301–7.(G T Plant1 and K Landau2)