A retrospective case series reported severe, multifaceted ocular surface toxicity in patients treated with a tissue factor–targeted antibody-drug conjugate carrying a monomethyl auristatin E payload (TF-ADC-MMAE). In five consecutive male patients with metastatic pancreatic cancer, imaging and clinical assessments showed phenotypes including persistent epithelial defects and deep stromal ulceration, with sterile ulcerations based on cultures and metagenomic next-generation sequencing. Grade 3 meibomian gland dropout and marked tear-film instability were documented in multiple cases. The reported incidence—4.3% in the studied Phase III cohort—raises attention for ophthalmic monitoring and earlier toxicity recognition in ADC safety programs.