Central Retinal Artery Occlusion: Local Intra-arterial Fibrinolysis versus Conservative Treatment, a Multicenter Randomized Trial

doi:10.1016/j.ophtha.2010.03.061

Ophthalmology

Volume 117, Issue 7, July 2010, Pages 1367-1375.e1

Presented at: Euretina meeting, May 2008, Vienna, Austria; meeting of the German Retinological Society, June 2008, Wuerzburg, Germany; meeting of the German Society of Ophthalmology, September 2008, Berlin, Germany; and annual meeting of the European Society of Neuroradiology, October 2009, Athens.

https://doi.org/10.1016/j.ophtha.2010.03.061 Get rights and content

Purpose

The reported outcomes of central retinal artery occlusion (CRAO) with or without treatment vary considerably. Although local intra-arterial fibrinolysis (LIF) using recombinant tissue plasminogen activator (rtPA) is a promising treatment, outcomes have not been compared in randomized trials.

Design

Prospective randomized multicenter clinical trial (the European Assessment Group for Lysis in the Eye Study) to compare treatment outcome after conservative standard treatment (CST) and LIF for acute nonarteritic CRAO.

Participants

Between 2002 and 2007, 9 centers in Austria and Germany recruited 84 patients (40 received CST, 44 received LIF), and data for 82 patients were analyzed.

Methods

Patients (age 18–75 years) with CRAO, symptoms for 20 hours or less, and best-corrected visual acuity (BCVA) <0.5 logarithm of the minimum angle of resolution (logMAR) were randomized to the CST or LIF group.

Main Outcome Measures

The primary end point was BCVA after 1 month; the secondary end point was safety.

Results

The mean interval between first symptoms and therapy was 10.99±5.49 hours (CST) and 12.78±5.77 hours (LIF). The mean BCVA (logMAR) improved significantly in both groups (CST: −0.44 [standard deviation 0.55]; LIF: −0.45 [standard deviation 0.55]; both P < 0.0001) and did not differ between groups (P=0.69). Clinically significant visual improvement (≥0.3 logMAR) was noted in 60.0% (CST) and 57.1% (LIF) of patients. Two patients in the CST group (4.3%) and 13 patients in the LIF group (37.1%) had adverse reactions. Because of apparently similar efficacy and the higher rate of adverse reactions in the LIF group, the study was stopped after the first interim analysis at the recommendation of the data and safety monitoring committee.

Conclusions

In light of these 2 therapies' similar outcomes and the higher rate of adverse reactions associated with LIF, we cannot recommend LIF for the management of acute CRAO.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Study Design

The EAGLE study was designed as a randomized, controlled, prospective multicenter clinical superiority trial.²⁴ Local intra-arterial fibrinolysis and CST were compared with respect to the functional outcome, measured as best-corrected visual acuity (BCVA), and safety in patients with acute nonarteritic CRAO.

Inclusion criteria were patient age between 18 and 75 years, nonarteritic CRAO with symptoms for less than 20 hours, and BCVA worse than 0.5 logarithm of the minimum angle of resolution

Study Patients

Between September 2002 and November 2007, 9 centers in Austria and Germany recruited 84 patients for the EAGLE Study. The DMC recommended that recruitment cease after the first interim analysis based on the data of the first 70 patients. Because patient recruitment was not suspended during conduction of the interim analysis, 14 additional subjects were recruited before recruitment was finally stopped. The median number of patients per center was 12 (range, 1–39). Three centers recruited more

Discussion

The EAGLE study is the first randomized clinical trial to compare the therapeutic efficacy of LIF using rtPA with CST in patients with acute nonarteritic CRAO. Our results revealed a significant visual improvement of 0.443 logMAR in the CST group and 0.447 logMAR in the LIF group after 1 month. No difference was detected between treatment arms. The study was discontinued after the first interim analysis on the DMC's recommendation because of the LIF group's apparent similar efficacy and higher

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La plupart des patients qui ont subi une OACR ont d'abord consulté un spécialiste des soins oculaires (14 sur 27); d'autres se sont rendus au service des urgences (10 sur 27) ou ont consulté leur médecin de famille (2 sur 27). Trois patients (11,1 %) ont consulté dans les 4,5 heures suivant l'apparition des symptômes. Lors de l'examen initial, l'acuité visuelle de 81 % des patients était de 20/400 ou pire dans l’œil atteint. Aucun patient n'a fait l'objet d'une thrombolyse. La majorité des cas d'OACR était d'origine non artéritique (92,6 %). Tous les patients présentaient déjà au moins un facteur de risque vasculaire, et 48 % des patients ont fait l'objet d'une intensification du traitement médicamenteux. Une sténose de la carotide homolatérale a été diagnostiquée chez 5 patients (18,5 %); d'ailleurs, 3 patients ont dû subir une endartériectomie de la carotide. On a noté la présence d'une fibrillation auriculaire chez 2 patients. Enfin, il s'est produit une ischémie cérébrale symptomatique chez 2 patients dans les 6 semaines suivant l'OACR.
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: Manuscript no. 2009-1270.

: *European Assessment Group for Lysis in the Eye: A list of members of the EAGLE Collaborative Study Group (Appendix 1) is available at http://aaojournal.org.

: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: The German Research Foundation of Health (DFG), Bonn, Germany, provided financial support (SCHU1454/1-3). The study does not necessarily reflect the view of the Foundation. Boehringer Ingelheim Pharma KG also provided funding. The Clinical Trials Center, University Hospital Freiburg, received funding from the BMBF (Federal Ministry of Education and Research).

: The EAGLE Study Group appears online-only in Appendix 1 (available at http://aaojournal.org).

^⁎: Group members listed online in Appendix 1 (available at http://aaojournal.org).

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Original articleCentral Retinal Artery Occlusion: Local Intra-arterial Fibrinolysis versus Conservative Treatment, a Multicenter Randomized Trial

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Study Design

Study Patients

Discussion

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Lancet

Control Clin Trials

Ophthalmology

Comparison of intra-arterial thrombolysis with conventional treatment in patients with acute central retinal artery occlusion

J Neurol Neurosurg Psychiatry

Visual prognosis following treatment of acute central retinal artery obstruction

Br J Ophthalmol

Occlusion of the central retinal artery and retinal branch arterioles: a clinical, tonographic and fluorescein angiographic study of 175 patients

Acta Ophthalmol Suppl

Evaluation of minimally invasive therapies and rationale for a prospective randomized trial to evaluate selective intra-arterial lysis for clinically complete central retinal artery occlusion

Arch Ophthalmol

Retinal artery occlusions

Ophthalmol Clin North Am

The treatment of acute retinal arterial occlusion

Intra-arterial fibrinolytic therapy in central retinal artery occlusion

Neuroradiology

Local intra-arterial fibrinolysis in the carotid territory

AJNR Am J Neuroradiol

Local intra-arterial fibrinolysis in acute vertebrobasilar occlusion: technical developments and recent results

Neuroradiology

Local fibrinolytic treatment in occlusions of the central retinal artery [in French]

J Fr Ophtalmol

Superselective ophthalmic angiography for diagnostic and therapeutic use

AJNR Am J Neuroradiol

Original article
Central Retinal Artery Occlusion: Local Intra-arterial Fibrinolysis versus Conservative Treatment, a Multicenter Randomized Trial