What is the recommended dose and management approach for tenecteplase (generic name: tenecteplase) in a patient with acute central retinal artery occlusion (CRAO)?

Tenecteplase for Acute Central Retinal Artery Occlusion: Current Evidence Does Not Support Its Use

Based on the most recent and highest quality evidence, tenecteplase should NOT be used for acute central retinal artery occlusion (CRAO), as the 2026 TenCRAOS randomized controlled trial demonstrated no efficacy benefit over aspirin and was associated with serious safety concerns including fatal intracranial hemorrhage. 1

Critical Evidence from the TenCRAOS Trial

The definitive answer comes from the 2026 phase 3 randomized controlled trial published in the New England Journal of Medicine, which directly tested tenecteplase versus aspirin in acute CRAO 1:

• No efficacy benefit: Only 20% of patients receiving tenecteplase (0.25 mg/kg IV) achieved vision recovery at 30 days compared to 24% receiving aspirin 300 mg (risk difference -3.7%, 95% CI -22.0 to 14.7, P=0.69) 1
• Serious safety concerns: Greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage 1
• Treatment window: Patients were treated within 4.5 hours of symptom onset, the optimal therapeutic window 1

This trial definitively answers the question and supersedes all prior observational data and theoretical considerations.

Current Guideline Recommendations

The 2021 American Heart Association Scientific Statement on CRAO management, published before the TenCRAOS trial results, identified tenecteplase as a "novel thrombolytic agent" requiring future study 2. However, this recommendation is now outdated given the negative trial results 1.

The guidelines currently recommend 2:

• Intravenous alteplase (tPA) 0.9 mg/kg (10% bolus over 1 minute, remainder over 59 minutes) may be considered within 4.5 hours after thorough benefit/risk discussion 2
• Immediate triage to emergency department/stroke center without delay 2, 3, 4
• Treatment as a stroke equivalent requiring urgent evaluation 3, 4

Why Tenecteplase Failed Despite Theoretical Promise

The negative trial results are particularly significant because 1:

• The study design was optimal: double-blind, randomized, controlled trial with appropriate sample size (78 patients)
• Treatment was administered within the critical 4.5-hour window
• The dose used (0.25 mg/kg) was based on stroke literature
• Despite these ideal conditions, no benefit was observed and safety signals emerged

A small 2024 case series of 5 patients treated with tenecteplase showed no functional visual recovery in 4 CRAO patients, consistent with the larger trial 5.

Practical Management Algorithm for Acute CRAO

Within 4.5 hours of symptom onset 2, 3, 4:

1. Immediate actions:

   • Triage directly to emergency department/stroke center 2, 4
   • Do NOT delay for outpatient ophthalmology evaluation 4
   • Funduscopic examination to confirm diagnosis 2
   • Screen for giant cell arteritis (ESR, CRP) in patients >50 years 2, 4

2. Acute treatment considerations:

   • Alteplase (NOT tenecteplase) 0.9 mg/kg IV may be considered after thorough benefit/risk discussion 2
   • Start antiplatelet therapy (aspirin) without delay 4
   • If giant cell arteritis suspected, immediate high-dose IV corticosteroids 4

3. Diagnostic workup 2:

   • Brain CT without contrast to exclude hemorrhage 2
   • MRI with diffusion-weighted imaging (identifies concurrent brain infarction in 19-25% of patients) 3, 6
   • Carotid imaging (significant stenosis found in up to 70% of patients) 4, 6
   • Cardiac monitoring for atrial fibrillation 2
   • Echocardiography for cardioembolic source 2

Critical Pitfalls to Avoid

• Do NOT use tenecteplase based on the negative TenCRAOS trial showing no benefit and safety concerns 1
• Do NOT delay emergency referral to perform additional outpatient testing 4
• Do NOT use conservative treatments (anterior chamber paracentesis, ocular massage, hemodilution) as they may be harmful 2
• Do NOT miss giant cell arteritis in patients >50 years, as immediate steroids can prevent bilateral blindness 4, 6

Secondary Prevention

After acute management 2:

• Antiplatelet therapy: aspirin 81 mg daily or clopidogrel 75 mg daily 2
• For minor stroke equivalent (analogous to NIHSS ≤3): consider 21 days dual antiplatelet therapy (aspirin + ticagrelor or clopidogrel) 2
• Statin therapy for risk factor modification 2
• Carotid revascularization if high-grade symptomatic stenosis identified 2
• Anticoagulation if atrial fibrillation or cardioembolic source detected 2
• Monitor for neovascularization complications (occurs in up to 15% of cases) 6

Prognosis

Visual prognosis remains poor despite all interventions 2, 3:

• Only 17-20% of patients achieve functional visual acuity (≥20/100) in the affected eye 2, 3
• Highest stroke risk within first 7 days, remains elevated for 30 days 6
• Up to 24% have concurrent cerebrovascular infarction on MRI 6