What is the role of intra-arterial fibrinolysis in the treatment of central retinal artery occlusion (CRAO)?

Updated: Jun 11, 2019
  • Author: Robert H Graham, MD; Chief Editor: Andrew G Lee, MD  more...
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CRAO is one of the few ophthalmology emergencies in which management depends on time of onset. Intraarterial thrombolysis has been used anywhere from 1 hour to up to 24 hours, although this procedure is very controversial. [37]

Thrombolytic agents that have been studied for CRAO treatment include intra-arterial tissue plasminogen activator (tPA) and urokinase.

According to Wang et al, digital subtraction angiography (DSA)–guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. [38] More recently, branch retrograde thrombolytic intervention of the ophthalmic artery (urokinase and papaverine) was shown to be effective for CRAO. [38] Mercier et al reported that fibrinolysis was more effective than conservative management in 16 patients with CRAO. [39] In 11 patients, Nedelmann et al found clinically relevant visual improvement with thrombolysis in patients with CRAO only in the absence of a “spot sign,” an ultrasonographic sign they hypothesize may indicate calcified intra-arterial emboli due to atherosclerotic plaques. [40]

Conversely, Pielen et al found no clear benefit from intra-arterial fibrinolysis, even in otherwise ideal candidates (ie, young age, without history of coronary heart disease, and early treatment). [41] Ahn et al showed that approximately 40% of patients undergoing intra-arterial thrombolysis showed a no-reflow phenomenon, and those with the no-reflow phenomenon suffered a worse visual outcome, with more retinal atrophy and disruption of photoreceptors. [42] However, in a separate study, Ahn et al concluded that intra-arterial thrombolysis may help patients with incomplete CRAO. [43]

McLeod and Beatty reported that, once CRAO exceeds 2 hours, emergency fibrinolytic therapy is inappropriate. [44]

Systemic complications of fibrinolytic therapy include transient ischemic attack (TIA), stroke, intra-cerebral hemorrhage, and hematoma.

In a meta-analysis, Schrag et al suggested that early systemic intravenous fibrinolytic therapy might be helpful in CRAO and called for a clinical trial. [45]

The European Assessment Group for Lysis in the Eye (EAGLE) [46] trial was a multicenter, randomized, controlled trial involving 82 patients with acute CRAO (<20 hours). EAGLE compared the effect of intra-arterial tPA to “conservative” treatments (eg, IOP lowering medications, IV heparin, hemodilution, ocular massage, daily ASA therapy). In this trial, 42 patients (51.2%) received localized intra-arterial tPA in either the ophthalmic artery or external carotid artery collaterals feeding into the ophthalmic artery. There was no statistically significant improvement in visual acuity after intra-arterial tPA administration compared to conservative treatment. Interestingly, 60% of patients in the conservative treatment group and 57% of patients in the thrombolysis group experienced 3 or more lines of improvement in visual acuity. However, 37.1% of the thrombolysis group (versus only 4.3% of the conservative treatment group) experienced adverse reactions (eg, epistaxis, oral hemorrhage, dizziness, headaches, intracranial hemorrhages, hemiparesis, postprocedural hemorrhage). The study was terminated at the first interim analysis because of the increased incidence of adverse events in the tPA treatment group.

A second placebo-controlled randomized trial studying the effect of intravenous (IV) tPA on visual outcome in 8 patients with CRAO also did not show a significant improvement. One patient in the IV tPA cohort developed intracranial hemorrhage.

A meta-analysis of studies comparing standard therapy with intra-arterial thrombolysis included 5 retrospective studies and one randomized controlled trial (ie, EAGLE study). Pooled data from these studies favored use of intra-arterial thrombolysis over standard therapy, with 50.4% of those treated with intra-arterial thrombolysis demonstrating improved visual acuity versus 31.8% of those treated with standard therapy (P <  0.005). This was despite the fact that the EAGLE study did not show any statistical significance in improvement of best-corrected visual acuity (BCVA) among the two groups. However, the included studies showed dramatic variations in the efficacy of both intra-arterial thrombolysis (23.5%-80% in visual acuity improvement) and conservative therapies. The EAGLE study design has been questioned owing to its broad inclusion criteria, as it included patients with incomplete, subtotal, and complete occlusion. The treatment outcomes vary significantly depending on the type of presentation. Clinically significant visual outcomes can be expected in patients with incomplete or subtotal occlusion, as opposed to those with complete occlusion.

More randomized controlled studies, including limiting the study group to incomplete or subtotal CRAO, as opposed to including those with complete occlusion, which by itself has a poor prognostic outcome, would be a better design to analyze and compare the efficacy of standard therapy with intra-arterial thrombolysis. [47]

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