Emerging Research in ADC Ocular Toxicity: Targeting the Underlying Pathophysiology

The experts conclude their discussion on ocular toxicity by exploring emerging research aimed at addressing the underlying mechanisms of ADC-associated corneal changes.

A discussion of current treatment limitations highlights that existing therapies, including preservative-free artificial tears and topical steroids, provide symptomatic relief but do not address the underlying pathophysiology. Dr. Pasricha explains that while these treatments may reduce dryness and improve patient comfort, corneal pseudomicrocysts remain visible on examination despite symptomatic improvement.

Key considerations include understanding the mechanism by which ADCs enter corneal epithelial cells. Dr. Pasricha describes ongoing laboratory research investigating macropinocytosis—a nonspecific cellular "drinking" process through which corneal epithelial cells take up substances from the extracellular space. This pathway may explain how ADCs accumulate in corneal tissue independent of antibody-target binding. The research aims to develop an eye drop capable of blocking this process, potentially preventing corneal pseudomicrocyst formation rather than merely treating symptoms.

This segment underscores that although current management strategies, such as patient education, early detection, and multidisciplinary collaboration, effectively mitigate risk for agents such as datopotamab deruxtecan and telisotuzumab vedotin, a mechanistic solution remains an unmet need. Dr. Rugo notes that trials using ADCs with more predictable ocular toxicity profiles may help evaluate preventive interventions. The panel emphasizes that for currently available agents, risks remain relatively low when clinicians know what to look for, educate patients appropriately, and implement the collaborative approaches discussed throughout the session.