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Clinical Features of Corneal Adverse Events Associated With Trastuzumab Botidotin: Payload-Driven Epitheliopathy and

Yongyi Zhang1, Gege Tang1, Jingjie Zhang1

  • 1From the Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

American Journal of Ophthalmology
|May 23, 2026
PubMed
Abstract

Insights

Trastuzumab botidotin, a HER2-targeted antibody-drug conjugate, caused ocular adverse events including corneal epitheliopathy and blurred vision in all patients studied. Early detection and collaboration are key for managing these side effects.

Area of Science:

  • Ophthalmology
  • Oncology
  • Pharmacology

Background:

  • HER2-targeted antibody-drug conjugates (ADCs) are effective cancer therapies.
  • Ocular adverse events (AEs), such as corneal epitheliopathy and blurred vision, are known side effects of ADCs.
  • Trastuzumab botidotin is a HER2-targeted ADC used for HER2-mutated or HER2-positive tumors.

Purpose of the Study:

  • To characterize the clinical features of corneal AEs associated with trastuzumab botidotin.
  • To evaluate the impact of trastuzumab botidotin on ocular surface parameters and corneal cellular structures.

Main Methods:

  • Retrospective case series of eight adult patients treated with trastuzumab botidotin.
  • Ophthalmic assessments included visual acuity, Ocular Surface Disease Index (OSDI), Schirmer's test, tear break-up time (TBUT), tear meniscus height (TMH), and corneal fluorescein staining (CFS).
  • In vivo confocal microscopy (IVCM) was used to examine corneal cellular structures and nerve damage.

Main Results:

  • All patients experienced corneal AEs, with visual impairment onset around 37 days and peak severity around 83 days.
  • Trastuzumab botidotin induced dry eye, significantly reducing tear production, TBUT, and TMH.
  • Corneal epitheliopathy manifested as pseudomicrocysts and vortex keratopathy, confirmed by IVCM showing cellular disorganization and neurotoxic damage to subbasal nerves.

Conclusions:

  • Trastuzumab botidotin is associated with significant visual impairment, corneal epitheliopathy, and nerve damage.
  • Prompt identification of these corneal AEs is crucial for managing patients on ADC therapy.
  • Collaboration between ophthalmologists and oncologists can improve patient outcomes and quality of life.

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