Severe ocular surface toxicity associated with a tissue factor-targeted antibody-drug conjugate: a case series

To characterize the spectrum of severe ocular surface toxicity associated with a tissue factor-targeted antibody-drug conjugate carrying an monomethyl auristatin E (​MMAE)​ payload (TF-ADC-MMAE), using multimodal ophthalmic imaging in a retrospective case series. Five consecutive male patients with metastatic pancreatic adenocarcinoma who developed Grade ≥ 3 ocular surface toxicity (CTCAE v5.0) were identified among 116 patients who received TF-ADC-MMAE in the Phase III clinical trial (incidence, 4.3%; 5/116). A comprehensive ocular surface evaluation included best-corrected visual acuity, slit-lamp biomicroscopy with Oxford grading, infrared meibography (Keratograph 5 M), and in vivo confocal microscopy (IVCM). Metagenomic next-generation sequencing (mNGS) and conventional cultures excluded microbial infection in corneal ulceration cases. Five distinct phenotypes were identified: persistent epithelial defects, superficial corneal ulceration, deep stromal ulceration, cicatricial entropion, and symblepharon. Grade 3 meibomian gland dropout and profound tear film instability (TBUT < 1 s) were recorded in three patients. IVCM revealed a spectrum of sub-basal nerve plexus damage ranging from attenuation to marked loss of visible fibers, with activated stromal keratocytes and endothelial inflammation in severe cases. mNGS supported a sterile, non-infectious etiology in all ulcerative cases. Whereas corneal ulcers showed partial response to intensive topical corticosteroids and dose modification, cicatricial adnexal changes and meibomian gland loss were still present at final follow-up. TF-ADC-MMAE therapy may induce a severe, multifaceted ocular surface toxicity encompassing direct epithelial compromise, meibomian gland failure, and conjunctival cicatrization. Multimodal imaging and microbiological assessment may assist clinical evaluation. Structured ophthalmic monitoring protocols are warranted as this drug class advances toward broader clinical application. Not applicable.