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Introduction: Central retinal artery occlusion (CRAO) causes monocular visual loss adversely impacting quality of life and functional outcome. Spontaneous visual recovery occurs in only 10-20% of patients. Thrombolysis with IV tPA been reported in small series. We aim to summarize existing data on efficacy and safety of IV tPA for CRAO.Methods: We performed a systematic literature review (SLR) of studies of IV tPA in CRAO using Cochrane, Embase and Medline databases. Data extracted from the studies included: demographics, dose, timing, and infusion rate of IV tPA, concomitant anticoagulation, symptomatic intracranial hemorrhage (sICH), and post-treatment visual acuity (VA). Improvement in VA was defined as improvement ≥ 0.3 log mar.Results: Our SLR yielded 19 articles, identifying 137 patients who received IV tPA for CRAO. 55 patients (40%) received IV tPA within 4.5 hours. 71 patients (52%) received the standard dose and infusion rate of IV tPA used in acute ischemic stroke (AIS). Concomitant use of IV heparin within 24 hours was reported in 53 patients (36%). Follow-up VA was available for 67 subjects: 61% improved, 33% were unchanged, and 6% worsened. sICH occurred in 4 cases (2.9%) with 1 death (0.7%). All cases of sICH were associated with at least one deviation from AIS IV tPA guidelines (dose [n=2], concomitant heparin infusion [n=3], timing [n=3]).Conclusion: Our SLR found substantial heterogeneity in study design regarding IV tPA utilization for CRAO. The majority of CRAO patients did not receive IV tPA per AIS protocol. The reported improvement in VA for CRAO patients receiving IV tPA was considerably higher than the known natural history, however, sICH rates were not inconsequential. sICH was associated with deviation from established AIS IV tPA guidelines. Further study through prospective registries and/or randomized trials are warranted.