Comprehensive review of ocular toxicity risks across all currently approved antibody-drug conjugates

Ocular toxicity from anti-cancer drugs is frequently overlooked, largely because it is non-life-threatening, whereas clinical priorities often center on adverse events that pose immediate risks to survival. Antibody-drug conjugates (ADCs) have emerged as an important therapeutic modality in oncology, offering potent cytotoxicity against tumor cells through the targeted delivery of payloads. However, this potency also introduces a spectrum of toxicities, among which ocular toxicity has gained increasing attention. ADC-induced ocular toxicity can impair visual function and significantly compromise both quality of life and treatment adherence. This review compiles data on ocular toxicity reported during clinical development and postmarketing surveillance of all currently approved ADCs. This review analyzes the potential mechanisms underlying ADC-associated ocular toxicity and provides a detailed summary of the reported ocular adverse events and their incidence across approved ADCs. It also highlights the significance of effective toxicity management for early detection, monitoring, and treatment of ocular toxicity. Finally, this review explores potential strategies to mitigate ADC-associated ocular toxicity from a drug development perspective. A more comprehensive understanding of ocular toxicity, combined with innovative approaches to target selection, linker design, payload optimization, as well as the biological processes underlying in vivo interactions between ADCs and tissues, may enable the reduction of ocular toxicity and improvement of clinical outcomes in future ADC therapy.