Eyeworld

50 | EYEWORLD | FALL 2025 C ORNEA belantamab mafodotin, which is used to treat multiple myeloma; more than 70% of patients had corneal toxicity in clinical trial data. Real- world data suggests it could be even higher. In addition to being the number one ad- verse event, it can also be the dose-limiting ad- verse event, preventing the patient from getting the cancer drug as frequently due to its impact on the ocular surface. In the ASCRS webinar, faculty members highlighted their concerns about the number of ADCs, with Dr. Farooq commenting that with drugs currently in development, this could be a huge wave of patients. "In ophthalmology and optometry, we all have to be prepared and plan ahead for the number of patients who will be on these drugs," he said. These are patients who often will require regular eye exams with a cadence that might be determined by regulatory policy, depending on toxicity. Dr. Farooq discussed some of the diagnos- tics and how to define the nature of the disease. Sometimes the patient may not have a lot of symptoms other than blurred vision. A slit lamp exam with vital dye stain is important, and eye- lid eversion can be helpful to get at the extent of ocular surface involvement. He also suggested using refraction and topography, when avail- able, to help understand the impact on vision. Other things like confocal microscopy of the cor- neal epithelium or corneal nerves may be used. Commenting further to EyeWorld, Dr. Farooq said, "I think one of the more common signs is what I have called pseudomicrocysts. These are cystic-appearing lesions in the epi- thelium of the cornea." These pseudomicrocysts generally start in the periphery of the cornea, and with time and subsequent doses, they mi- grate toward the center. Having seen these patients for several years, we know the lesions tend to go away if the patient is on a dose hold, dose reduction, or the drug is stopped, he said. However, these pseu- domicrocysts are impacting vision. Patients can have changes in vision, including from refractive shift. Patients can also experience glare, light sensitivity, or irritation, and some of that may be related to the lesions and what they're doing in terms of light scatter or from other mechanisms. We also have anecdotally seen worsening or onset of dry eye, indicated by punctate staining of the corneal epithelium with fluorescein, Dr. Farooq said. Some patients have increased stain- ing of the cornea. In some cases, there can be a whorl-like pattern of staining with fluorescein. This is separate from the pseudomicrocysts or the general pattern of punctate corneal stain- ing. This whorl pattern seems to start from the corneal periphery. This could indicate a form of limbal stem cell dysfunction. These findings tend to improve with dose modifications and supportive treatments. Dr. Pasricha also noted patients presenting with corneal pseudomicrocysts. Initially patients are asymptomatic. Soon after they develop these, they develop symptoms and start to get breakdown of the epithelium. Additionally, he said it's been found that the pseudomicrocysts cause a refractive change in the cornea. "When they start off in the periph- ery, they're steepening the periphery, so it's causing a hyperopic shift. As they move to the center, they're steepening the center, so it's a myopic shift," he said. "For patients, it's frustrat- ing because it's like having a moving target." Fortunately, these changes so far are reversible. If you stop the ADC, things will get better over time, he said. "What's interesting is if it was truly just affecting the epithelium and going away, one would expect within a week or two that it would be better because the corneal epithelium turns over about every week. But we've found it takes anywhere from 2–6 months for it to fully reverse, and I've even had some patients where it takes a year to get fully back to normal. These ADCs are thought to accumu- late in the basal epithelium and stay there like a reservoir." These issues are something that companies working on ADCs are aware of, Dr. Pasricha said, and ophthalmologists and oncologists are becoming more aware as well. The problem, he said, is that the pre-clinical models to look at these toxicities are not great. Even when doing animal studies, they don't always find the same corneal problems. Companies are spending a lot of time and money to develop these drugs, doing cell culture safety, and animal safety mod- els, and they find a reasonable safety profile pre-clinically, but then they sometimes learn about issues in the Phase 1 trial. That's a huge limitation. The holy grail would be to design ADCs that don't have this toxicity, Dr. Pasricha said, adding that there are 11 FDA-approved ADCs, continued from page 49

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