Tenecteplase Fails to Improve Vision in Acute Retinal Artery Occlusion: NEJM
Central retinal artery occlusion (CRAO) is an ophthalmic emergency that usually leads to sudden and permanent blindness, and there has been no proven effective treatment available until now. A phase 3 randomized controlled trial has recently demonstrated that intravenous tenecteplase, given within 4.5 hours of onset of symptoms, did not lead to an improvement in visual recovery outcomes compared with oral aspirin and was also associated with severe safety issues. This suggests that thrombolysis with tenecteplase is not a beneficial treatment for acute CRAO. The study was published in The New England Journal of Medicine by Stephan J. and colleagues.
Owing to the similarities in pathophysiology between CRAO and acute ischemic stroke, thrombolytic therapy has been investigated as a possible treatment strategy. Tenecteplase, a fibrin-specific thrombolytic agent, has been proven effective in selected patients with stroke, but there is a paucity of data in CRAO patients. The purpose of this study was to assess the effect of intravenous tenecteplase on visual recovery compared with aspirin in patients with acute, nonarteritic CRAO within 4.5 hours of onset.
This was a phase 3, double-blind, double-dummy, randomized, controlled trial performed at 16 sites in six countries. Adults with acute, nonarteritic CRAO, presenting within 4.5 hours of the onset of symptoms, were randomly assigned in a 1:1 ratio to receive either intravenous tenecteplase 0.25 mg/kg body weight, together with oral placebo, or intravenous placebo, together with oral aspirin 300 mg. The primary outcome was recovery of vision at 30 days, defined as best corrected visual acuity (BCVA) of ≤0.7 logMAR (or ≥20/100) in the affected eye.
Key findings
A total of 78 patients underwent randomization, with 40 patients receiving tenecteplase and 38 patients receiving aspirin.
All patients had acute vision loss from CRAO and fulfilled rigorous inclusion criteria, including early treatment and absence of arteritic causes.
At 30 days, vision recovery was achieved in 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group.
Risk difference was -3.7 percentage points (95% CI, -22.0 to 14.7; P = 0.69), showing no statistically significant benefit of tenecteplase.
Secondary visual endpoints, such as the proportion of patients achieving BCVA of ≤0.5 logMAR (20/63 or better), mean change in BCVA, and perimetry results, also failed to show any significant difference between the two groups.
More patients in the tenecteplase group experienced adverse events than in the aspirin group.
There was one fatal intracranial hemorrhage event in the tenecteplase group.
Intravenous tenecteplase administered within 4.5 hours of acute central retinal artery occlusion did not show greater visual recovery than aspirin and was also associated with severe safety issues. These findings support the ineffectiveness of acute treatment for CRAO and emphasize the need for safe and evidence-based therapeutic agents.
Reference:
Ryan, S. J., Jørstad, Ø. K., Skjelland, M., Pesonen, M., Simonsen, C. Z., Bek, T., Blauenfeldt, R. A., Ijäs, P., Laitinen, A., Khanevski, A., Krohn, J., Rødahl, E., Lemmens, R., Demeestere, J., Cassiman, C., Nakstad, I., Evensen, K., Sandell, T., Hamann, S., Truelsen, T. C., … TenCRAOS Investigators (2026). A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. The New England journal of medicine, 394(5), 442–450. https://doi.org/10.1056/NEJMoa2508515
