Dr. Casandra MacLeod discusses central retinal artery occlusions, recent trials, and those anticipated in the future.

Show citation:

Préterre C, Gaultier A, Obadia M, et al. Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4·5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial. Lancet Neurol. 2025;24(11):909-919. doi:10.1016/S1474-4422(25)00308-4

Poli S, Grohmann C, Wenzel DA, et al. Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial. Int J Stroke. 2024;19(7):823-829. doi:10.1177/17474930241248516

Ryan SJ, Jørstad ØK, Skjelland M, et al. A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. N Engl J Med. 2026;394(5):442-450. doi:10.1056/NEJMoa2508515

Show transcript:

Dr. Casandra MacLeod

Hello, this is Casandra MacLeod, a neurology resident at Cleveland Clinic with today's Neurology Minute. Today we will be discussing central retinal artery occlusions, or CRAOs, and the recent trials that have come out and even those further on the horizon. The 2026 American Heart Association and American Stroke Association guidelines for the early management of patients with acute ischemic stroke were recently published and in them highlight the uncertainty around the treatment of acute CRAOs with intravenous thrombolysis, even when the patient presents within four and a half hours and is otherwise eligible. These guidelines come after two recent trials, which we will further discuss.

The thrombolysis in patients with acute central retinal artery occlusion, or the THEIA trial, was published in the November issue of Lancet Neurology. This multicenter trial out of France randomized 70 patients with acute CRAOs presented within four and a half hours of time from last known well to either receive IV alteplase and oral placebo or IV placebo and oral aspirin.

While safety measures showed no symptomatic hemorrhage event, although they did have one asymptomatic intracerebral hemorrhage occur, the primary outcomes, which included visual acuity improvement at one month, showed some evidence for a trend of improved acuity in the IV thrombolytic group at 66% compared to 48 in the aspirin group, it did not reach significant. And now more recently, the Tenecteplase in central retinal artery occlusion study, or TenCRAOs, was published in the January 2026 issue of The New England Journal of Medicine. TenCRAOs was a six European country multicenter trial that randomized 78 patients with CRAOs all presenting within four and a half hours of time from last known well to either receive IV Tenecteplase or aspirin, both with placebo-matching as in THEIA.

The primary outcomes of TenCRAOs also included visual acuity at one month, but unfortunately this trial also did not show [inaudible 00:02:07]. They showed 20% in the IV TNK group compared to 24% in aspirin. And additionally, there was one fatal intracerebral hemorrhage in the TNK group that should be considered.

Overall, the AHA and ASA guidelines state the usefulness of treatment with intravenous thrombolysis is uncertain. And this is based largely on these studies as neither trial showed improved visual recovery. Although both of these trials are underpowered, leading many to believe that the jury is still out on the use of IV thrombolytics in CRAOs. But importantly, stay on the lookout for one last trial. The early reperfusion therapy with intravenous alteplase for recovery of vision and acute central retinal artery occlusion, or the Revision trial, is actively recruiting. Revision is similar in design as THEIA, but with a goal of up to 422 total patients for a goal of a well-powered study to guide decision making.