Severe Corneal Ulceration With Neurotrophic Perforation After Afatinib Use

To present a case with Afatinib (EGFR-TKIs) exprerienced severe corneal ulceration with neurotrophic Perforation and treated with AMT(amniotic membrane) transplatation and penertrating keratoplasty. 

Although prior literature has addressed ophthalmic side effects linked to afatinib, no case report has documented corneal ulceration of such severity and rapid onset.

A 58-year-old female was referred to our ophthalmology clinic due to tearing and the sudden onset of blurred vision experience in the days following three months of antineoplastic agent use. The patient had received a diagnosis of lung adenocarcinoma and had been under our regular care for the preceding three months. Genetic analysis identified an L858R mutation in exon 21 of the epidermal growth factor receptor, prompting the initiation of afatinib therapy. 

Following the ophthalmologic examination in our clinic, severe bilateral corneal ulcerations were identified during ophthalmologic examination, with unaided visual acuity measuring 1.7 (logMAR) in the right eye and counting fingers discernible at a distance of ten centimeters in the left eye. Comprehensive assessments for autoimmune diseases, bacterial, and viral infections yielded negative results. Consequently, the patient's eye condition was considered an adverse event of afatinib. In response, we reduced the dosage of afatinib and contemplated its replacement with erlotinib, the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). 

After two months of therapy, the patient demonstrated variable improvement in eye function. Visual acuity was measured at 1.15 (logMAR) in the right eye and 1.05 (logMAR) in the left eye. Owing to the poor healing of corneal epithelium, amniotic membrane was applied after 3 months following up. Despite ongoing corneal healing facilitated by the use of autoserum 20% eye drops, TSCL, and amniotic membrane. Spontaneous corneal perforation with microleakage due to persistent corneal thining was found during following-up.  Penertrating keratoplasty was done smoothly but poor epithelium healing happened again after Afatinib reloading. The vision was deemed to be permanently impaired with a limited likelihood of further recovery.

Since its introduction in 2003, EGFR-TKIs have been crucial therapeutic agents for various cancers. With the advancement of EGFR-TKIs, different generations of drugs have yielded improved therapeutic outcomes, albeit accompanied by the occurrence of side effects. In comparison to other common infectious corneal ulcerations, patients using EGFR-TKIs may experience compromised migration of corneal epithelial cells, resulting in hindered corneal epithelium healing. This case were evidently disproportionate to the extent of corneal damage, prompting consideration of the potential for neurotrophic ulcer and corneal perforation.