EAGLE Trial: Intra-Arterial tPA for Central Retinal Artery Occlusion
In patients with central retinal artery occlusion presenting within 20 hours, does local intra-arterial fibrinolysis via ophthalmic artery microcatheter improve visual acuity compared with conservative standard treatment?
Schumacher et al. (Ophthalmology 2010) · 84 patients
Population
Included
- Central retinal artery occlusion with onset within 20 hours of symptom onset
- BCVA of hand motion or worse in the affected eye
- Age 18 years or older
- Appropriate for catheter angiography
Eligible patients
- Patient age between 18 and 75 years
- Acute nonarteritic central retinal artery occlusion with symptoms for less than 20 hours
- Best-corrected visual acuity worse than 0.5 logMAR (Snellen equivalent of 20/63)
- Angiographically confirmed, persistent arterial occlusion
Excluded
- Onset more than 20 hours prior to treatment
- Contraindication to fibrinolytic therapy
- Prior significant ocular disease in the affected eye
- Evidence of carotid or aortic dissection
Ocular diseases (Table 1)
- Branch retinal artery occlusion
- Cilioretinal arteries supplying the macula
- Combined arterial-venous occlusion
- Proliferative retinal diseases
- Elevated intraocular pressure
General diseases (Table 1)
- Systemic arterial hypertension (systolic pressure above 200 mmHg) despite medical therapy
- Acute systemic inflammation (erythrocyte sedimentation rate above 30 mm in the first hour, or C-reactive protein above 1.0 mg/dL)
- Antithrombin-III deficiency, thrombocytopenia below 100,000/mL, or pathologic clotting time
- Acute pancreatitis with elevated pancreatic enzymes
- Heart attack within the last 6 weeks
- Intracerebral bleeding or surgery within the last 4 weeks
- Therapy with marcumar or warfarin
- Allergic reaction to contrast agent
- Hemorrhagic diathesis
- Aneurysms
- Inflammatory vascular diseases (for example giant cell arteritis, Wegener granulomatosis)
- Endocarditis
- Gastric ulcer
- Patient participation in other studies during the prior 4 weeks
- Patient unwillingness to participate
Source: Schumacher M et al., Ophthalmology 2010· Retrieved 2026-06-09
Secondary outcome: ≥15-letter improvement (dichotomized)
Primary endpoint note: The trial primary endpoint was continuous change in logMAR BCVA at 1 month, which was not significant (P=0.69). This chart displays the secondary dichotomized endpoint (proportion with clinically meaningful visual improvement of 15 or more ETDRS letters) for visual clarity.
Negligible absolute difference
≥15-Letter Visual Improvement at 1 Month
Study Arms
- Agent
- Intra-arterial recombinant tissue plasminogen activator (rtPA, Actilyse)
- Dose
- Up to a maximum of 50 mg rtPA, delivered in steps with visual acuity and funduscopy checks after 15, 30, 45, and 50 mg
- Route
- Superselective microcatheter injection into the ophthalmic artery (or external carotid artery via collaterals if internal carotid occluded or high-grade stenosis), under heparin anticoagulation (5000 IU)
- Frequency
- Single intra-arterial procedure
- Duration
- One-time fibrinolysis; followed by 5 days of low-dose heparin and at least 4 weeks of aspirin (shared with control)
- Co-interventions
- Both groups received weight-adapted low-dose heparin twice daily for 5 days starting the first postinterventional day, plus acetylsalicylic acid 100 mg daily for at least 4 weeks
Adverse reactions occurred in 37.1% of LIF patients versus 4.3% of conservative-treatment patients, including 2 intracranial hemorrhages; the trial was stopped early by the data monitoring committee for apparent similar efficacy and higher adverse reactions
- Agent
- Multimodal conservative therapy
- Dose
- Isovolemic hemodilution (500 mL blood withdrawn, 500 mL 10% hydroxyethyl starch infused, for hematocrit above 40%); ocular massage; topical beta-blocker (for example timolol 0.5%); intravenous acetazolamide 500 mg
- Route
- Combination of intravenous, topical, and mechanical measures
- Frequency
- Per protocol at presentation
- Duration
- Acute treatment; followed by 5 days of low-dose heparin and at least 4 weeks of aspirin (shared with intervention)
- Co-interventions
- Both groups received weight-adapted low-dose heparin twice daily for 5 days starting the first postinterventional day, plus acetylsalicylic acid 100 mg daily for at least 4 weeks
No patient underwent anterior chamber paracentesis. Visual improvement was similar between arms (60.0% of CST vs 57.1% of LIF achieving clinically significant gain); the superiority trial detected no difference (P=0.69)
Safety
Adverse events (LIF vs conservative)
37.1%
4.3%
Adverse events including 2 procedure-related intracranial hemorrhages in the LIF arm; 0 hemorrhages in the conservative arm. The 8.6x higher adverse event rate with no efficacy signal was the basis for early DSMB termination. /* claimId: eagle-safety-ae | source: Schumacher Ophthalmology 2010 Table 3 */
Trial Design
Type
- Prospective randomized multicenter trial
- Open-label (non-blinded)
- 1:1 allocation (LIF vs. CST)
Timeline
Enrolled 2002-2007
N
84
Enrollment
84 of 200 planned patients (42 LIF / 42 CST). Stopped early by DSMB for futility and safety. Enrolled 2002 to 2007.
Bedside Pearl
EAGLE definitively showed that IA tPA for CRAO causes significant harm (37% adverse events including intracranial hemorrhage) with no visual benefit. The procedure is not indicated for CRAO. The current clinical debate is about IV tPA in the very early window (within 4.5 hours), which was not tested in EAGLE. If a CRAO patient presents within hours, the stroke team conversation is about IV tPA eligibility, not IA fibrinolysis.
See also