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Original Investigation |

Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion A Patient-Level Meta-analysis

Matthew Schrag, MD1; Teddy Youn, MD1; Joseph Schindler, MD1; Howard Kirshner, MD2; David Greer, MD1
[+] Author Affiliations
1Department of Neurology, Yale University, New Haven, Connecticut
2Department of Neurology, Vanderbilt University, Nashville, Tennessee
JAMA Neurol. 2015;72(10):1148-1154. doi:10.1001/jamaneurol.2015.1578.
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Importance  Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that can result in blindness. At present, no proven therapy for CRAO exists. Treatment with fibrinolytic agents has shown promise but remains of unproven benefit.

Objectives  To assess the efficacy of systemic fibrinolytic therapy for patients with CRAO and to define a time window of efficacy.

Data Sources  We systematically queried PubMed, Web of Science, and Scopus using the following index terms: “retinal artery occlusion” OR “retinal ischemia” AND “thrombolysis” OR “fibrinolysis” OR “tissue plasminogen activator” OR “streptokinase” OR “urokinase.” Search was not limited by year of publication or language and was conducted in August 2014. In addition, we evaluated the references from relevant review articles.

Study Selection  We assembled observational studies reporting on visual acuity outcomes after CRAO. Inclusion criteria were complete reporting of visual outcomes after CRAO (with or without fibrinolytic therapy) and a series of more than 5 patients for fibrinolysis treatment or more than 20 cases when untreated or treated with conservative modalities.

Data Extraction and Synthesis  Patient-level data were sought for studies reporting outcomes of treatment with fibrinolysis. Summary statistics were obtained for conservative treatment and natural history studies. The studies were weighted by the inverse of variance and merged in a random-effects model.

Main Outcomes and Measures  Rate of visual recovery (defined as improvement of visual acuity from 20/200 or worse at presentation to 20/100 or better) was calculated for patients treated with fibrinolytic and conservative therapies and those who received no treatment.

Results  We obtained summary statistics from 7 studies that included 396 patients who received no treatment after CRAO and from 8 studies that included 419 patients treated with ocular massage, anterior chamber paracentesis, and/or hemodilution (conservative treatment). Patient-level data were obtained for 147 patients treated with systemic fibrinolysis. We found that fibrinolysis was beneficial at 4.5 hours or earlier after symptom onset compared with the natural history group (17 of 34 [50.0%] vs 70 of 396 [17.7%]; odds ratio, 4.7 [95% CI, 2.3-9.6]; P < .001). Absolute risk reduction was 32.3%, with a number needed to treat of 4.0 (95% CI, 2.6-6.6). We also found that conservative treatment significantly worsened visual acuity outcomes and recovery rates after CRAO compared with the natural history group (31 of 419 [7.4%; 95% CI, 3.7%-11.1%] vs 70 of 396 [17.7%; 95% CI, 13.9%-21.4%]; P < .001; number needed to harm, 10.0 [95% CI, 6.8-17.4]).

Conclusions and Relevance  Our analysis suggests that a clinical trial of early systemic fibrinolytic therapy for CRAO is warranted and that conservative treatments are futile and may be harmful.

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Figure 1.
Forest Plot for Estimated Rate of Spontaneous Visual Recovery

A, After central retinal artery occlusion, patients in the natural history cohorts (those with no or minimal treatment) had a spontaneous recovery rate of 17.7% (95% CI, 13.9%-21.4%). B, Patients in the intravenous fibrinolysis cohort had a recovery rate of 31.8% (95% CI, 24.3%-39.3%). C, Patients in the conservative treatment cohorts received ocular massage, anterior chamber paracentesis, and/or hemodilution, with a significantly lower recovery rate of 7.4% (95% CI, 3.7%-11.1%). We found heterogeneity only in the conservative treatment group owing to the impact of a single outlier study (exclusion of this study would reduce measurements of heterogeneity to nonsignificant levels). Different sizes of data markers represent the weight given to the study in the random-effects model; diamonds, the recovery rate in the combined meta-analysis with the 95% CI.

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Figure 2.
Effect of Fibrinolysis by Time to Administration

Fibrinolytic treatment within 4.5 hours resulted in a significantly higher rate of visual recovery (95% CI) compared with the natural history cohort (17 of 34 patients [50.0%; 95% CI, 32.4%-67.6%] vs 70 of 396 patients [17.7%; 95% CI, 13.9%-21.4%]; P < .001). We found no statistical benefit to treatment beyond 4.5 hours after onset. Error bars indicate 95% CI.

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