Trastuzumab‑botidotin linked to corneal events

The American Journal of Ophthalmology published a report this week describing corneal adverse events associated with trastuzumab-botidotin, an antibody-drug conjugate used in HER2-positive cancer research and treatment settings. Ophthopedia flagged the paper on May 24, 2026, summarizing the ocular findings as payload-driven epitheliopathy and neuropathy. The report adds trastuzumab-botidotin to a growing list of antibody-drug conjugates linked to ocular surface toxicity. The authors said the drug was associated with visual impairment, corneal epitheliopathy and corneal nerve damage. ### Why are corneal findings showing up with this drug? The American Academy of Ophthalmology said in its 2025 clinical statement that ocular adverse events from antibody-drug conjugates most commonly involve the ocular surface and often appear within weeks of treatment initiation. The statement said baseline slit-lamp examination and reassessment at every or every other infusion cycle are typically recommended, depending on the agent. (ajo.com) The AAO statement said these toxicities can be “on-target” when the antigen is present in ocular tissue or “off-target” when toxicity reflects other uptake mechanisms. Reviews of antibody-drug conjugate ocular toxicity have said corneal epithelial cells may take up these agents through nonspecific endocytosis, helping explain why epithelial injury can occur even when the intended cancer target is outside the eye. (aao.org) ### What does “payload-driven epitheliopathy” mean in practice? The AJO paper, as summarized in search results, described corneal epitheliopathy as part of the trastuzumab-botidotin toxicity pattern. In antibody-drug conjugate practice, epitheliopathy usually refers to damage centered in the corneal epithelium rather than a primary infectious process. That distinction matters because the exam can resemble dry-eye flaring, postoperative surface disease or medication toxicity from other causes. (aao.org) Cancer Treatment Reviews said practical management of antibody-drug conjugate ocular events depends on recognizing the drug-specific pattern early and coordinating with oncology teams on dose interruption, reduction or supportive care. The AAO statement separately said treatment decisions remain the responsibility of the treating physicians and should be guided by severity grading and repeat ophthalmic assessment. (ajo.com) ### Why is corneal nerve damage a separate concern? The AJO report said corneal nerve damage accompanied epithelial toxicity in trastuzumab-botidotin-associated cases. That raises the possibility that symptoms may not map neatly to the amount of visible staining or surface breakdown, because neuropathic involvement can alter corneal sensation and symptom reporting. That inference is supported by the paper’s framing of both epitheliopathy and nerve damage as part of the same adverse-event profile. (cancertreatmentreviews.com) A prior mechanistic literature base has already linked systemic cancer therapies, including trastuzumab-containing regimens, to corneal nerve changes. One published report described a burst of corneal dendritic cells during trastuzumab and paclitaxel treatment, alongside discussion of chemotherapy-associated peripheral neuropathy and ocular complications. ### How should clinicians distinguish this from infection or routine postoperative disease? (ajo.com) The AAO clinical statement said ophthalmologists are now an essential part of the cancer treatment team because ocular adverse events can alter cancer therapy delivery and patient quality of life. In practice, that means a new epithelial defect, punctate keratopathy, reduced vision or unexplained ocular discomfort in a patient receiving an antibody-drug conjugate should trigger medication review and communication with oncology, not only a search for infection or routine dry eye. (pmc.ncbi.nlm.nih.gov) The AJO report’s conclusion, as indexed online, was that close collaboration between ophthalmologists and oncologists is crucial for early detection of corneal adverse events related to trastuzumab-botidotin. The AAO statement said follow-up is generally needed at baseline, during infusion cycles, at the end of treatment and whenever new ocular symptoms occur. ### What comes next for this story? The May 2026 publication gives clinicians a named reference point for trastuzumab-botidotin-associated corneal toxicity, and the next step is likely to be incorporation into broader antibody-drug conjugate monitoring protocols. (aao.org) The full paper is now available through the American Journal of Ophthalmology, while existing AAO guidance provides the current framework for baseline examination, interval follow-up and severity-based management during treatment. (ajo.com)