Corneal Toxicity From Antibody–Drug Conjugates in Fuchs Corneal Dystrophy
Alisha Dhallan, Jimmy Nguyen, Praneetha ThulasiPurpose:
The aim of this study is to describe the clinical course of antibody–drug conjugate (ADC)–associated keratopathy in patients with Fuchs endothelial dystrophy and examine how underlying endothelial dysfunction may affect recovery.
Methods:
We present 2 cases of ADC-induced ocular toxicity in patients with preexisting Fuchs dystrophy. The clinical history, treatment course, slit-lamp findings, and recovery timeline were reviewed to assess corneal response following ADC therapy.
Results:
Case 1 involves a 79-year-old man with relapsed-remitting multiple myeloma treated with belantamab mafodotin. He developed microcystic epithelial changes (MECs) and marked corneal edema after initial infusions. Despite treatment hold, visual recovery required several months. On reinitiation at a lower dose, symptoms recurred, prompting withdrawal from the trial. Case 2 involved a 60-year-old man with metastatic prostate cancer treated with ARX517 study drug. He developed asymmetric keratopathy, with greater severity in the eye with untreated Fuchs dystrophy compared with the eye with endothelial keratoplasty. Recurrent microcystic epithelial changes and prolonged corneal edema persisted despite dose adjustments and extended treatment holds.
Conclusions:
Current screening protocols for antibody–drug conjugates recommend exclusion of patients with significant epithelial disease but lack guidance for patients with stable endothelial disease. Although ADC-associated keratopathy is typically attributed to epithelial toxicity, these cases suggest that underlying endothelial dysfunction may prolong and exacerbate corneal findings and need to be taken into account when evaluating patients on ADCs.