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Incidence and Mitigation of Corneal Pseudomicrocysts Induced by Antibody–Drug Conjugates (ADCs)

  • Ethan S. Lindgren,
  • Rongshan Yan,
  • Onur Cil,
  • Alan S. Verkman,
  • Matilda F. Chan,
  • Gerami D. Seitzman,
  • Asim V. Farooq,
  • Laura A. Huppert,
  • Hope S. Rugo,
  • Paula R. Pohlmann,
  • Janice Lu,
  • Laura J. Esserman,
  • Neel D. Pasricha

摘要

Purpose of Review

This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody–drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs).

Recent Findings

ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity.

Summary

Three of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.