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Introduction: Central retinal artery occlusion (CRAO) rapidly leads to irreversible retinal damage with spontaneous visual recovery in only 10-20%. IV tPA may improve visual outcomes in CRAO, but protocols are heterogeneous. Deviation from acute ischemic stroke guidelines (AISG) for IV tPA is associated with symptomatic intracranial hemorrhage (sICH). Our study characterizes outcomes for CRAO patients treated with IV tPA per AISG to better define the risk and benefit.Methods: We executed a systematic literature review (SLR) of IV tPA for CRAO in Cochrane, Embase, and Medline. Subsequently, we performed a retrospective chart review at two local academic hospitals. All CRAO patients identified locally or via SLR who were treated with IV tPA per AISG were included in our study. Primary outcomes included improvement in visual acuity (VA), defined as ≥0.3 logMAR, and safety, specifically sICH.Results: Our SLR yielded 136 articles of which 19 were eligible. 137 total CRAO patients were identified, 32 (23%) of whom received IV tPA per AISG. 13 additional CRAO patients treated per AISG were identified locally (Table 1A). Of these 45 cases, VA was reported in 39, with improvement in 64%, no change in 28%, and worsening in 8%. The risk of sICH was 2.2% (n=1) (Table 1B). The case of sICH occurred locally, with hemorrhage adjacent to 2 chronic appearing infarcts. Post-sICH it was impossible to determine radiographically whether a component of his infarct may have been subacute. Interestingly, in our local cases, clinically silent diffusion restriction was evident on MRI in 6 patients (46%).Conclusion: Our study suggests that IV tPA administered per AISG may improve visual outcomes in comparison to the natural history of CRAO, however, the rate of sICH was not inconsequential. Additionally, our case series includes the first reported sICH in a CRAO patient administered IV tPA per AISG. Randomized studies are warranted to assess the efficacy and safety of IV tPA administered per AISG in CRAO.