Thrombolysis Beneficial for ‘Eye Stroke’?

ABU DHABI, UAE — Thrombolysis to treat central retinal artery occlusion, also known as “eye stroke,” appeared to improve visual acuity compared with oral aspirin but this did not reach statical significance, results from a randomized control trial showed.

“While patients receiving thrombolysis were able to read more lines of the vision test chart, and safety appeared acceptable, the aspirin control group did better than expected and our study was clearly underpowered,” study author Benoit Guillon, MD, Nantes University Hospital, Nantes, France, concluded.

“Our results are encouraging as we observed 17% more patients reaching a visual recovery, defined as the primary endpoint in the alteplase arm,” he told Medscape Medical News.

Noting that two more randomized trials are ongoing, with results expected soon, Guillon recommends that “until these results become available, clinicians should make individual decisions on thrombolysis for each patient based on their risk benefit ratio.”

Guillon presented the results of the THEIA trial on October 26 at the 16th World Stroke Congress (WSC) 2024.

Sudden Vision Loss in One Eye

Central retinal artery occlusion is a rare event that results in sudden, painless, and severe vision loss in one eye.

“As the damage to the retina often becomes irreversible after around 4 hours, we need to manage these patients fast, but to date, no treatment has been validated,” said Guillon.

Approximately one third of patients have a simultaneous asymptomatic hemispheric ischemia and are at an increased risk for further ischemic events, particularly ischemic stroke, so these patients should be managed in a stroke unit by stroke neurologists, he added.

Studies testing thrombolysis have yielded conflicting results. Some observational studies have been positive, but two randomized trials were negative and showed a risk for intracranial bleeding associated with thrombolysis.

However, in the randomized trials, the mean time from symptom onset to treatment was more than 12 hours, and a meta-analysis suggested there may be benefits if patients were treated within 4.5 hours, Guillon noted.

In 2021, the American Heart Association published a scientific statement on central retinal artery occlusion, emphasizing that this condition is a medical emergency, that treatment with thrombolysis may be effective, but that high-quality randomized trials are needed.

Three new randomized trials have since been initiated to test the early administration of thrombolysis. The THEIA trial is the first to report results.

The trial was conducted in 16 centers in France. Patients with sudden, severe, and sustained visual loss were referred to an ophthalmology department to confirm the diagnosis and then referred to a stroke unit for clinical examination, neurologic examination, brain imaging, and laboratory tests.

If patients met inclusion criteria, they were randomized to receive either IV alteplase (at the standard dose) plus oral placebo or IV placebo plus oral aspirin 300 mg.

The primary outcome was an improvement of visual acuity at 1 month as measured using the Logarithmic Measure of Angle of Resolution (LogMAR) scale, in which 0 equates to perfect vision and 2.9 as the worst score indicative of no light perception.

A total of 70 patients were enrolled in the trial. They had a mean baseline LogMAR score of 2.4, with the vast majority unable to read any letter on the LogMAR vision testing chart. The mean time from symptom onset to thrombolysis administration was 232 minutes.

Results showed that both the thrombolysis group and the aspirin group experienced significantly improved visual acuity at 1 month. Vision improved by −0.44 LogMAR in the aspirin group and by −0.62 LogMAR in the thrombolysis group.

In terms of the primary outcome, which was improvement of at least 0.3 LogMAR (three lines on the vision testing chart), this was achieved by 48.1% of the aspirin group and 65.5% of the thrombolysis group with an odds ratio of 1.10 (95% CI, 0.07-18.39), which was not statistically significant.

The key safety endpoint — intracranial hemorrhage (ICH) occurred in one patient in the alteplase group (ICH was asymptomatic) vs zero in the aspirin group.

Guillon pointed out that two further randomized trials would be completing soon (TenCRAOS and REVISION), and a pooled analysis of the three trials is planned.

Reducing Time to Treatment

During the discussion, Amit Kandel, MD, University at Buffalo, Buffalo, New York, noted that central retinal artery occlusion is a neglected and disabling type of stroke.

He reported that his center has been treating these patients with thrombolysis for the past 2 years at the stroke unit, and they have found that having the diagnosis made by an ophthalmologist causes too many delays. So they have acquired an optical coherence tomography (OCT) scanner and have been treating patients with tenecteplase after documenting the retinal artery occlusion on the OCT.

“If we want to get the benefit, we have to treat early. If the occlusion is caused by a calcified plug, then thrombolysis would not work, so we have to find the cases where it’s more of a thrombus,” said Kandel.

Guillon responded that if thrombolysis can be established as effective in this condition, then the next step would be to work out the best diagnostic tools to use and systems of care which may be different in different hospitals.

The issue of whether brain imaging was necessary before thrombolysis in these patients was also discussed. Guillon noted that because around one third of patients can have simultaneous intracranial ischemia, brain imaging is advisable.

However, another commentator suggested that if the intracranial ischemia was asymptomatic, then it would not be a contraindication for thrombolysis, and time could be saved by skipping the CT scan. Guillon said this was a good question which could be investigated in future if thrombolysis was proven to be effective in the condition.

The THEIA trial was funded by French Ministry of Health, Boehringer Ingelheim, and Nantes University. Guillon reported no disclosures.