Abstract:AIM: To analyze the etiologies, disease course, clinical characteristics, and surgical management patterns of non-traumatic corneal perforation in China. METHODS: This multicenter, retrospective study reviewed medical records from patients with non-traumatic corneal perforation treated at 16 tertiary hospitals in China from 2019 to 2021. Data collected included demographics, etiology, disease duration, perforation location, visual acuity on admission, and surgical procedures. RESULTS: A total of 796 eyes from 791 patients were included, comprising 271 women (34.2%) and 520 men (65.7%), with a mean age of 58.4±15.6y (range, 0.38–92y). Infectious keratitis was the leading cause (62.6%), followed by postoperative complications (12.8%) and autoimmune diseases (8.7%). Fungal infections were more prevalent in rural areas, while autoimmune-related perforations were more common in females. Autoimmune cases more frequently presented with a chronic disease course and better visual acuity at admission compared to infectious causes (P<0.001). Among infectious causes, viral keratitis exhibited the highest proportion of chronic cases (65.7%). Perforation location varied significantly by etiology, with infectious cases predominantly central and autoimmune cases more often peripheral or limbal (P<0.001). Overall, 88.3% of eyes presented with poor visual acuity on admission. Most eyes (90.0%) required surgical intervention. Penetrating keratoplasty was the most common procedure, especially for central perforations, while lamellar keratoplasty was preferred for peripheral and autoimmune-related cases. CONCLUSION: This nationwide, multicenter study provides a comprehensive epidemiologic characterization of non-traumatic corneal perforation. Infectious keratitis was identified as the predominant etiology. Distinct patterns in disease progression, perforation location, and surgical intervention were observed across etiologic subgroups. These findings underscore the relevance of etiology-stratified assessment and support the need for tailored clinical management strategies.