Heterogeneous Corneal Toxicity Among Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Focus on Osimertinib
Claude Kaufmann, Marco Dressler, Katja C. IselinPurpose:
To report a case of unilateral new-onset keratitis after years of cancer therapy with osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and to review the patterns of EGFR TKI–induced corneal toxicity.
Methods:
A 56-year-old female patient presented with unilateral visual deterioration, ocular pain, and redness. Examination revealed ciliary injection, corneal erosions, a perilimbal infiltrate, and stromal edema. The patient had been undergoing treatment with the EGFR TKI osimertinib (Tagrisso) for 3 and a half years because of non-small cell lung cancer. An infectious cause was excluded through repeated scrapings and biopsy.
Results:
Eight months of anti-inflammatory (topical steroids) and ocular surface-protective measures (autologous serum drops, bandage contact lenses, punctum plugs) yielded no improvement but rather resulted in partial stromal melting. In contrast, discontinuation of osimertinib led to a dramatic recovery within 1 week, after which the medication was continued at half the original dose. After 9 additional months, corneal defects recurred, but this time they were bilateral and took a full 2 and a half months to heal after osimertinib was stopped again. Similar variable clinical patterns have been reported in the literature for older first- and second-generation EGFR TKIs.
Conclusions:
This case highlights the heterogeneous patterns of corneal adverse effects associated with EGFR TKIs, including variability in onset, laterality, and healing time after discontinuation. Ophthalmologists should maintain awareness of drug-induced toxicity in patients receiving these agents and consider early treatment suspension in collaboration with oncologists, regardless of the clinical presentation pattern.