Perforating Corneal Ulceration in a Patient with Lung Metastatic Adenocarcinoma Treated with Gefitinib: A Case Report

Abstract

We present a case of a sixty-year-old female who presented with sudden onset of painless loss of vision in one eye due to a perforated corneal ulcer, following three months of treatment with gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for metastatic adenocarcinoma of the lung with confirmed EGFR gene mutation. The eye did not show any sign of infection or inflammation and had no associated lid problems to account for the development of corneal ulceration. The patient went on to have a corneal graft surgery but postoperatively developed corneal graft melt. This paper aims to raise awareness among ophthalmologists and oncologists of the probable association between gefitinib and corneal ulceration.

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

“…Alkylating agent/platinum Blurred vision, retinotoxicity (retinal ischaemia and neovascularization), optic neuropathy [33] Doxorubicin anthracyline drug conjunctivitis (m/c), periorbital edema, lacrimation, blepharospasm, keratitis, and decreased visual acuity [34] Everolimus mTOR inhibitor posterior reversible encephalopathy syndrome,bilateral optic neuropathy [35] Geftinib EGFR-inhibitor Dry eye, corneal ulcer [36,37] Gemcitabine antimetabolite agent uveal effusion and outer retinal disruption or Purtscher-like retinopathy with combination of docetaxel [25,38] Irinotecan topoisomerase I inhibitor None [39], none in combination regimen with 5-fluorouracil, oxaliplatin and bevacizumab [40] Oxaliplatin platinum dry eye, lacrimation, conjunctivitis, damage of the retinal pigment epithelium and the optic nerve, visual field defect [30,41] Paclitaxel Antimicrotubule agent epiphora, eye pain, conjunctivitis, blepharitis, blurred vision [24,42] Pemetrexed Antimetabolite /antifolate AION [1], eyelid edema [24,43] Ramucirumab monoclonal Ab of VEGFR-2 none [28] Sorafenib anti-VEGF agent blurred vision, periocular edema, retinal detachment, ptosis, optic neuropathy, macular edema [27,44] Temozolomide alkylating/methylating agent blurred vision with concurrent radiation therapy [45].…”

Preclinical antitumor activity of S‐222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2

“…The corneal abnormality is considered to have resulted from the intervention of EGFR signals in the cornea . This adverse effect was less commonly reported with EGFR inhibitiors, but rarely led to serious consequences like persistent corneal epithelial defect and perforating corneal ulceration . As these histopathological findings have clinical relevance, S‐222611 should have a better safety profile than irreversible inhibitors.…”

Ocular side effects of biological agents in oncology: what should the clinician be aware of?

“…There is one report of the development of refractory corneal erosion during cetuximab therapy, which healed following local application of EGF; cetuximab therapy did not need to be interrupted 24. The worst case scenario is the progression of corneal erosion to corneal perforation under EGFR inhibitors, which has been described for gefitinib, panitumumab, and erlotinib 25,23…”

“… 24 The worst case scenario is the progression of corneal erosion to corneal perforation under EGFR inhibitors, which has been described for gefitinib, panitumumab, and erlotinib. 25 , 23 …”