AIM: To investigate the factors influencing non-response to intravitreal injection of anti-vascular endothelial growth factor(VEGF)therapy in fundus vascular diseases in a real-world setting.METHODS: A retrospective analysis was conducted on 160 patients(160 eyes)with fundus vascular diseases, including 64 eyes(40.0%)of wet age-related macular degeneration(wARMD), 17 eyes(10.6%)of polypoidal choroidal vasculopathy(PCV), 45 eyes(28.1%)of diabetic macular edema(DME), 26 eyes(16.3%)of retinal vein occlusion-macular edema(RVO-ME), and 8 eyes(5.0%)of choroidal neovascularization(PM-CNV). All patients received 3+PRN anti-VEGF therapy. Factors influencing anti-VEGF treatment on the fundus vascular diseases were analyzed.RESULTS: There were statistical significant difference in age, preoperative best corrected visual acuity(BCVA), hyper reflective dots(HRD), PCV, subretinal hyperreflective material(SHRM), and PM-CNV(all P<0.05). Logistics regression analysis noted that poor preoperative BCVA, age, intraretinal HRD, SHRM, PCV and PM-CNV were influencing factors of non-response to intravitreal injection of anti-VEGF in the treatment of fundus vascular diseases.CONCLUSION: Non-response to anti-VEGF therapy in patients with fundus vascular diseases is associated with various factors, including age, baseline visual acuity, and disease pathology. Individualized treatment strategies should be explored to optimize outcomes for non-responding patients.