Spontaneous Healing of Corneal Perforation after Temporary Discontinuation of Erlotinib Treatment
A 65-year-old Japanese man was diagnosed in April 2010 with stage IV lung adenocarcinoma, manifesting multiple metastases in the lung, adrenal gland and brain. He received 31 Gy of basicranial radiation for the brain metastases. Given that he was found to harbor an epidermal growth factor receptor (EGFR) mutation, he was also treated with the EGFR-specific tyrosine kinase inhibitor (TKI) gefitinib (250 mg/day). As a result of the development of adverse effects including fatigue, dermatitis, and liver dysfunction, however, the dose of gefitinib was initially reduced by half and treatment with the drug was subsequently discontinued after a total of 2 months. Computed tomography and magnetic resonance imaging revealed that the size of the original lesion and the number of brain metastases had increased. Treatment with the combination of cisplatin (125 mg) and pemetrexed (0.75 mg) was initiated. After 8 weeks, this regimen was switched to vinorelbine (32 mg) and docetaxel (80 mg) because of the development of adverse effects. This latter treatment was also not tolerated well, and so administration of the EGFR-TKI erlotinib (150 mg/day) was initiated. The patient again experienced general adverse effects including dermal exanthema. At this time, he developed a foreign body sensation in both eyes and visited his local ophthalmologist, who referred him to the corneal service at Yamaguchi University Hospital for the treatment of corneal epithelial disorders with corneal thinning.\nSlitlamp microscopy revealed bilateral superficial punctate keratopathy and conjunctival epithelial disorders. Corneal ulceration on his right eye was also observed, but no signs of infection or inflammation were apparent. His visual acuity was 20/25 OD and 20/25 OS. Schirmer's test detected bilateral mild hypolacrimation (5 mm), and his corneal and conjunctival epithelial disorders were thus attributed to aqueous-deficient dry eye. We treated him by insertion of punctal plugs in both lower lacrimal puncta. Three weeks after plug insertion, his corneal and conjunctival epithelial disorders had apparently improved. However, 2 months after his first visit to our clinic, he was referred to us again for the treatment of bilateral corneal ulcers, which were confirmed by slitlamp microscopy (fig. ). Slight stromal edema, ulceration with an opaque epithelium, and a shallow anterior chamber were also observed in the right eye. The next day, the anterior chamber of the right eye was flat, and so we treated this eye with a bandage soft contact lens. The right anterior chamber remained flat, however, and the patient was diagnosed with noninfectious corneal perforation of unknown cause and was prepared for tectonic keratoplasty. The oral administration of erlotinib was interrupted in preparation for general anesthesia, and the patient was treated with gatifloxacin eyedrops only. Two days later, the anterior chamber of his right eye had spontaneously reformed and the epithelial defects of both eyes had healed (fig. ). The keratoplasty was therefore canceled and we monitored the patient carefully, but his corneal condition remained stable. Treatment with erlotinib at half the original dose was reinitiated and both eyes were maintained by the administration of artificial tears, with the punctal plugs remaining in place. Corneal ulceration or other corneal disorders did not recur.