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Central retinal artery occlusion

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Q) What is the evidence of giving intravenous (IV) and intra-arterial (IA) thrombolysis for patients with central retinal artery occlusion (CRAO)?

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A) IV-Thrombolysis

Currently, we do not have a randomized controlled trial (RCT) of IV-thrombolysis administration in CRAO. A patient-level meta-analysis of retrospective and non-randomized studies showed that IV fibrinolysis was beneficial if it was given ≤ 4.5 hours.
When comparing IV thrombolysis versus the natural history group, the odd ratios of improvement of visual acuity from 20/200 or worse at presentation to 20/100 or better was 4.7 [95% CI, 2.3-9.6];p<0.001 with necessary treatment of 4. The medicines that were used in the studies were streptokinase, urokinase and alteplase. Of 147 patients who received IV-thrombolysis, 5 developed major hemorrhage (3.4%) which all received streptokinase. No hemorrhage occurred after administration urokinase and alteplase.

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IA-Thrombolysis

The EAGLE study was the only RCT that was done to answer whether IA-thrombolysis is beneficial for CRAO patients. They enrolled 84 patients who had CRAO ≤ 20 hours. This study failed to show the benefit of IA-alteplase in CRAO patients in 1 month. However, the mean time between onset to IAT was 12.78 hours. They found an improved outcome of the patients when there was a shorter time from symptom onset to presentation. Some patients still had improvement of their vision even after 20 and 23 hours of conservative treatment (CST) and IAT.

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Out of 44 patients who received IAT, two developed asymptomatic intracerebral hemorrhage. Patients in IAT group had minor adverse effects (34.3%) compared to 2.1% in conservative treatment group.

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A systemic review and meta-analysis of 5 retrospective and one RCT of 236 patients received IAT and 255 patients received CST showed estimated odds ratio of 2.52, 95% CI (1.69-3.77, P < 0.0001) favoring IAT. The onset to IAT varied ranging from 4.2 to 22.7 hours. The definition of visual improvement and the time of vision assessment were varied.

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In summary, we do not have enough evidence to support IA-thrombolysis for CRAO yet. We urgently need more RCT studies that enroll patients in the shorter onset to treatment time. The important points to keep in mind that vision outcome depends on the type of CRAO. Patients might have complete or incomplete CRAO (CRAO with sparing cilioretinal artery) and therefore their prognosis will be different. Furthermore, some CRAO visual function do recover without treatment. Dr. Havreh mentioned in his review paper the following “my experimental study showed that CRAO lasting for 4 h results in irreversible ischemic retinal damage”.

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Reference:

  1. Schrag M, Youn T, Schindler J, Kirshner H, Greer D. Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion: A Patient-Level Meta-analysis. JAMA Neurol. 2015;72(10):1148-1154.

  2. Hayreh SS. Central retinal artery occlusion. Indian J Ophthalmol. 2018;66(12):1684-1694.

  3. Schumacher M, Schmidt D, Jurklies B, et al. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology. 2010;117(7):1367-75.

  4. Page PS, Khattar NK, White AC, et al. Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A Systematic Review and Meta-Analysis. Front Neurol. 2018;9:76.

  5. Chronopoulos A, Schutz JS. Central retinal artery occlusion-A new, provisional treatment approach. Surv Ophthalmol. 2019;64(4):443-451.

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