TenCRAOS
(2026)Objective
To assess the efficacy and safety of intravenous tenecteplase administered within 4.5 hours after symptom onset in patients with acute central retinal artery occlusion
Study Summary
• Safety concerns emerged with more serious adverse events in the tenecteplase group, including one fatal intracranial hemorrhage
• Findings do not support routine use of thrombolytic therapy for central retinal artery occlusion
Intervention
IV tenecteplase 0.25 mg/kg + oral placebo vs IV placebo + oral aspirin 300 mg
Inclusion Criteria
Adults ≥18 years with acute central retinal artery occlusion, BCVA ≥1.0 logMAR in affected eye, treatment within 4.5 hours of symptom onset
Study Design
Arms: Tenecteplase (IV 0.25 mg/kg + oral placebo) vs Aspirin (IV placebo + oral aspirin 300 mg)
Patients per Arm: Tenecteplase: 40, Aspirin: 38
Outcome
• Secondary: BCVA ≤0.5 logMAR at 30 days: 20% vs 18%
• Safety: 1 fatal intracranial hemorrhage in tenecteplase group; more serious adverse events with tenecteplase (10 vs 4 events)
Bottom Line
Intravenous tenecteplase at 0.25 mg/kg administered within 4.5 hours of symptom onset did not result in significantly greater vision recovery than oral aspirin 300 mg in patients with central retinal artery occlusion, and was associated with increased serious adverse events including one fatal intracranial hemorrhage. Routine thrombolytic therapy for central retinal artery occlusion is not supported.
Major Points
- Phase 3, double-blind, double-dummy RCT comparing IV tenecteplase 0.25 mg/kg to oral aspirin 300 mg in acute central retinal artery occlusion within 4.5 hours of symptom onset
- Primary endpoint (BCVA ≤0.7 logMAR at 30 days) was achieved by 20% in tenecteplase group vs 24% in aspirin group (risk difference -3.7 percentage points; 95% CI -22.0 to 14.7; P=0.69)
- No substantial differences in secondary visual endpoints including BCVA ≤0.5 logMAR (20% vs 18%) and mean BCVA improvement
- Subgroup analysis of patients treated within 3 hours (69% of population) showed no benefit: 23% vs 22% achieved primary endpoint
- One fatal intracranial hemorrhage occurred in the tenecteplase group due to hemorrhagic transformation of unrecognized cerebral ischemia
- More adverse events (30 vs 19) and serious adverse events (10 vs 4) in tenecteplase group
- Results consistent with prior THEIA trial of IV alteplase and EAGLE trial of intraarterial thrombolysis
- Central retinal artery occlusion appears resistant to reperfusion strategies effective in cerebral ischemia despite similar pathophysiology
Study Design
- Study Type
- Phase 3, double-blind, double-dummy, parallel-group, randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind with double-dummy design; patients, investigators, and outcome assessors were blinded to treatment allocation
- Sample Size
- 78
- Follow-up
- 30 days (±5 days)
- Centers
- 16
- Countries
- Norway, Denmark, Finland, Belgium, Lithuania, Sweden
Primary Outcome
Definition: BCVA of 0.7 logMAR or lower in the affected eye at 30 days after treatment (equivalent to decimal BCVA ≥0.2 or fraction BCVA ≥20/100), reflecting an improvement of at least 0.3 logMAR (15 letters on ETDRS chart)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 9/38 (24%) | 8/40 (20%) | - (-22.0 to 14.7 percentage points) | 0.69 |
Limitations & Criticisms
- Small sample size (78 patients) with statistical power to detect only a 30 percentage-point difference; trial was underpowered to detect smaller but potentially clinically meaningful differences
- Trial was powered based on 2015 meta-analytic data suggesting large treatment effect, but later observational data showed no superiority of thrombolysis
- Mean change in BCVA required conversion of no light perception and light perception to logMAR values, which is inherently inaccurate
- Time of symptom onset relied solely on patient report
- 95% confidence interval for primary endpoint includes up to 14.7 percentage points in favor of tenecteplase, so modest benefit cannot be ruled out
- Single fatal event should be interpreted in broader context of bleeding risk in stroke and prior thrombolysis trials
- Baseline imbalances in carotid artery disease (higher in aspirin group) and diabetes mellitus (higher in tenecteplase group)
- Unable to rule out arteritic central retinal artery occlusion with laboratory/imaging within 4.5-hour window; relied on clinical assessment
Citation
N Engl J Med 2026;394:442-50