title: Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion: A Patient-Level Meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  To assess the efficacy of systemic fibrinolytic therapy for patients with CRAO and to define a time window of efficacy.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schrag
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut.
authors.forename: Teddy
authors.initials: T
authors.lastname: Youn
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut.
authors.forename: Joseph
authors.initials: J
authors.lastname: Schindler
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, Tennessee.
authors.forename: Howard
authors.initials: H
authors.lastname: Kirshner
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut.
authors.forename: David
authors.initials: D
authors.lastname: Greer
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015356:Retinal Artery Occlusion / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D005343:Fibrinolytic Agents; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator