| Summary: | Submacular hemorrhage (SMH) is the accumulation of blood in the macular area that can severely damage the macular structure and visual function. Recently, the intraocular administration of tissue plasminogen activator (TPA) with anti-vascular endothelial growth factor (anti-VEGF) drugs was reported to have a positive effect on SMH. This meta-analysis aimed to explore the efficacy and safety of the drug combination. We systematically searched the Web of Science, MEDLINE, EMBASE, and Cochrane Library databases and screened relevant full-length literature reports. The quality of the reports was assessed by two independent reviewers. The best-corrected visual acuity (BCVA) and foveal thickness (FT) were considered the main indicators of efficacy. RevMan 5.4 software was used for this meta-analysis. Twelve studies were analyzed, and the results showed that BCVA at 1 month (<i>p</i> < 0.001), 3 months (<i>p</i> < 0.001), 6 months (<i>p</i> < 0.001), and the last follow-up (<i>p</i> < 0.001) was improved relative to the preoperative value. The postoperative FT was lower than the preoperative FT (<i>p</i> < 0.001). No significant difference in efficacy was observed between subretinal and intravitreal TPA injections (<i>p</i> = 0.37). TPA with anti-VEGF drugs is safe for SMH treatment and can significantly improve BCVA and reduce FT.
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