Early thrombolysis may be beneficial in CRAO

Atlanta-The use of intravenous thrombolysis for treating patients with central retinal artery occlusion (CRAO) may be beneficial within a narrow clinical scenario, according to Valerie Biousse, MD, who pointed out the importance of very early intervention in patients with acute vision loss.

She focused on the case of a 71-year-old woman who previously had good vision bilaterally, and who reported a sudden onset of visual loss in the right eye shortly after awakening. The patient had a history of hypertension and hypercholesterolemia for which she was being treated. The right eye had a relative afferent pupillary defect and retinal edema with a cherry red spot suggesting an acute CRAO.

The real question in this case from Dr. Biousse’s perspective was whether or not to recommend thrombolysis for this patient. She is the Cyrus H. Stoner Professor of Ophthalmology, Professor of Ophthalmology and Neurology, Emory University School of Medicine, Atlanta.

Before answering that question, however, she advised ophthalmologists to ascertain the location of the patient and the elapsed time since the loss of vision, with emphasis on determining if the visual loss occurred more or less than 6 hours previously.

With the patient in a nearby emergency department fewer than 2 miles away and vision loss having occurred less than 6 hours previously, this may be the best possible scenario in which to consider thrombolysis, Dr. Biousse said.

However, there are other considerations, such as the status of the fellow eye, and whether giant cell arteritis has been ruled out. The types of vision tasks that the patient engages in daily is a further consideration, for example, does the patient have a high activity level that includes working and driving or is less dependent on excellent vision bilaterally.

“Although there are many things we still don’t know about CRAO, I know that the visual prognosis of this patient is poor in the affected eye, the vision is counting fingers, and even though the time from visual loss is less than 6 hours, a cherry red spot is already present and the arteries are attenuated. No matter the treatment the visual prognosis is likely not very good,” Dr. Biousse commented.

In the patient under discussion, she was concerned about the vascular prognosis because ipsilateral carotid stenosis is the most important cause of CRAO, putting the patient at high risk of cerebral infarction.

“The risk is the highest within the next few hours and days. With the vascular risk factors in the setting of acute ischemia, she also has a high risk of myocardial infarction and other vascular complications,” she said. Dr. Biousse’s course of action in this case is hospital admission for a work-up by a stroke team to begin secondary prevention of stroke and myocardial infarction.

The main issue, according to Dr. Biousse, is to determine if thrombolysis would be helpful to improve vision.

She pointed out the importance of the results of the EAGLE Trial carried out over 5 years at five European centers. Eighty-four patients were randomly assigned to either conservation treatment at the discretion of the treating physicians or intra-arterial recombinant tissue plasminogen activator (r-tPA) (Alteplase, Genentech Inc.) thrombolysis up to 50 mg daily and 5 days of heparin administration, considered an aggressive treatment. The patients, however, were treated late, within 24 hours of visual loss.

The results showed no difference in visual outcomes between the treatment groups, likely because of the late timing of the intervention. In addition, there was a high rate of development of adverse effects, 37.5% in the thrombolysis group. The investigators concluded that thrombolysis should not be administered intra-arterially.

Dr. Biousse concurred with that conclusion despite the results from the Hopkins Study that concluded 2 years before the EAGLE Trial. The Hopkins Study investigators determined that lower doses of r-tPA (up to 15 mg) can be administered safely and efficiently if the patient is treated early, which they defined as shorter than 15 hours after the onset of vision loss. The Hopkins Study showed the visual outcomes of r-tPA treated patients were better than the natural course of CRAO with no major complications.

“However, I still would not recommend intra-arterial thrombolysis because intravenous thrombolysis performs as well and it is easier to administer,” Dr. Biousse said and supported her statement with the results of study by Hattenback et al., in which 28 nonrandomly assigned patients received 50 mg of r-tPA and 5 days of heparin and aspirin. The patients were treated within 12 hours of vision loss and some in less than 6.5 hours after onset. The conclusions of this study were the same as those of the Hopkins Study. The patients treated within 6.5 hours of vision loss had better visual recovery compared with those treated later.

For Dr. Biousse, she would like to see patients with acute CRAO included in a trial in which they are randomly assigned to intravenous r-tPA, according to the class stroke protocol, which is an off-label use of r-tPA. No heparin is administered. These patients would be compared with those treated with placebo. She again underscored the importance of very early treatment, within 6 hours of vision loss, which should be the cut-off for intravenous r-tPA treatment.

Because there is no ongoing clinical trial of thrombolysis in North America, Dr. Biousse would consider treating with intravenous thrombolysis, as for the treatment of acute cerebral infarction, in otherwise healthy patients who had a vision loss within 6 hours before presentation to minimize the adverse events. She would also consider this treatment in patients with CRAO up to 12 hours after vision loss in a patient with monocular vision. She also strongly emphasized that she would only carry out this treatment in a highly specialized center with a stroke team that administers thrombolysis routinely, to minimize the side effects.

Dr. Biousse has no financial interest in this subject matter.

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