Tenecteplase not associated with visual improvement in central retinal artery occlusion

1. In this randomized controlled trial of adults with central retinal artery occlusion, tenecteplase administration shortly after symptom onset did not significantly improve visual recovery.   

2. Those who received tenecteplase experienced a greater incidence of adverse outcomes such as intracranial bleeding as compared to those who received placebo. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that lacks effective intervention, often leading to significant loss of vision. Because it is considered a cerebrovascular event, some observational studies have suggested thrombolysis as an initial reperfusion therapy. Trials of the tissue plasminogen activator (tPA) alteplase have not yielded success, but there is limited evidence surrounding tenecteplase (TNK), a genetically modified tPA approved as treatment for myocardial infarction and acute ischemic stroke. This randomized controlled trial was conducted to determine the efficacy and safety of intravenous tenecteplase within four and a half hours of CRAO symptom onset. When comparing tenecteplase versus placebo, it was found that there was no substantial difference in proportion of patients achieving clinically meaningful visual improvement. Both treatment groups also experienced similar rates of adverse events overall, though the tenecteplase group had a higher frequency of serious events. Notably, there was one fatal adverse event in the tenecteplase group due to intracerebral hemorrhage. Strengths of this study included a representative study population and evaluation of earlier intervention compared to previous trials involving thrombolytics. Limitations included small sample size and dependence on patient-reported time of onset. Overall, these results showed that tenecteplase was not efficacious in treating CRAO among adults and had a concerning safety profile.

Click here to read the study in NEJM

Relevant Reading: 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

In-Depth [randomized controlled trial]: This phase 3, multicenter, double-blind randomized controlled trial was conducted to determine the efficacy and safety of tenecteplase in adults with acute CRAO. Eligible participants were required to have a CRAO diagnosis via ophthalmologist assessment, to receive the trial treatment within 4.5 hours of symptom onset, and to have a best corrected visual acuity (BCVA) of at least 1.0 logarithm of the Minimum Angle of Resolution (logMAR). Participants were block randomized in a 1:1 ratio to receive either IV tenecteplase and oral placebo, or IV placebo and 300 milligrams of oral aspirin. Ultimately, 78 patients (40 in tenecteplase group, 38 in aspirin group) were included in analyses. Diabetes mellitus was more prevalent in the tenecteplase group, and carotid artery disease was more prevalent in the placebo group. The primary endpoint of the study was a BCVA of 0.7 logMAR or lower in the affected eye 30 days after treatment, which represented a clinically meaningful improvement in visual acuity. There was no significant difference in the primary endpoint between groups (risk difference, −3.7 percentage points; 95% confidence interval [CI], −22.0 to 14.7; p =0.69) nor in any of the assessed secondary endpoints including mean change in visual acuity or patient-reported quality of life measures. These results remained consistent in a sub-analysis involving the two-thirds of participants who received treatment within 3 hours of symptom onset. In terms of safety, 30 adverse events among 19 participants were reported in the tenecteplase group, and 19 adverse events among 13 participants were reported in the aspirin group. Of these events, 10 were classified as severe in the tenecteplase group versus 4 in the aspirin group. One event in the tenecteplase group was fatal, involving multiple intracerebral hemorrhages thought to be related to the trial medication. In summary, this randomized-controlled trial indicated that tenecteplase was neither safe nor efficacious for improving visual outcomes in acute CRAO.

Image: PD

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