Eyeworld

FALL 2025 | EYEWORLD | 49 C BEYOND THE ROUTINE by Ellen Stodola Editorial Co-Director About the physicians Winston Chamberlain, MD, PhD Affiliate Professor of Ophthalmology Casey Eye Institute Oregon Health & Science University Northwest Permanente Portland, Oregon Asim V. Farooq, MD Professor of Ophthalmology and Visual Science University of Chicago Medical Center Chicago, Illinois Neel Pasricha, MD Assistant Professor of Ophthalmology University of California, San Francisco Francis I. Proctor Foundation San Francisco, California W ith many new cancer therapies in development, one emerging area is antibody drug conju- gates. However, sometimes these therapies can pose a risk to the eye and cause ocular adverse events. Several experts spoke about the research in this space, what they've seen in terms of side effects, and considerations for patients taking these drugs and the eyecare providers monitoring them. The ASCRS Cornea Clinical Committee recently hosted a webinar on the topic as well, "Antibody Drug Conjugates – An Emerging Class of Cancer Therapeutics Which Pose Risks to Cor- neal and Anterior Segment Health." The webi- nar featured moderators Naveen Rao, MD, and Winston Chamberlain, MD, PhD, with speakers Kamran Riaz, MD, Stella Kim, MD, and Asim V. Farooq, MD. Speakers in the webinar noted the growing number of antibody drug conjugates (ADC) to discuss. Dr. Chamberlain explained during the webinar what an ADC is and how these thera- pies target cellular markers on tumors. Some of the major concerns with ADCs are that despite being thought of as a "magic bullet" because of their specificity, only a small percentage of the drug (a macromolecule) gets to its target. Receptors on tumor cells may exist on healthy tissue as well, and this can produce a nonspecific uptake of the drug; there are many mechanisms by which this occurs. "But the end result is that it can lead to death or sickness of healthy cells, and we call these adverse events," he said in the webinar. One thing that may not be clearly under- stood is that when we kill tumor cells, we create bystander effects, he said. When cells die, they burst open and release immunological and inflammatory mediators and the toxic molecules bound to ADCs that can cause death, destruc- tion, or sickness of neighboring cells. This can lead to bystander inflammation and destruction of healthy tissue that's not targeted by an ADC. ADCs have a different approach than tra- ditional chemotherapy, said Neel Pasricha, MD. "Think of traditional chemotherapy as a toxic drug that's given, and the cells that replicate the fastest, like the cancer cells, get damaged more than the healthy cells that aren't replicating as fast," he said. "But there are effects in healthy tissues because a lot of cells are replicating fast, like the skin and the hair." This also includes the surface and epithelium of the cornea. Dr. Pasricha said the first ADC approved in 2000 was a breakthrough. The rationale behind it was to take the chemo component, the toxic drug, and link it to an antibody, and the an- tibody would shuttle the chemotherapy to its target. "In theory, it sounds like a great idea, and it had great impact, but there's still a lot of off-target effects from these targeted chemo- therapies," he said. In the webinar, Dr. Chamberlain said there has been a burst in ADCs in the last decade. There are more than 200 ADCs being investigat- ed or currently in clinical trials. "As ophthalmol- ogists, we have to be aware of a large surge of drugs that are going to come forward that our patients may be on and be aware of potential effects on the ocular surface," Dr. Chamberlain said. ADCs have many targets, including breast cancer and ovarian cancer. Many of the ADC therapies are not supposed to cluster in eye tissue, but many still affect the eye. Dr. Pasricha said that around 50% of all ADCs have some degree of ocular toxicity. Around 10–20% of patients on these drugs will have mild ocular surface toxicity. For other drugs, the ocular surface toxicity is the number one adverse event. For example, he mentioned Emerging cancer therapies and potential ocular impact continued on page 50 Central corneal pseudomicrocysts in a whorl-like pattern due to an antibody drug conjugate currently being investigated for the treatment of advanced or metastatic solid tumors Source: Neel Pasricha, MD

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