Erlotinib-related Corneal Melting
2013; Elsevier BV; Volume: 120; Issue: 5 Linguagem: Inglês
10.1016/j.ophtha.2012.12.025
ISSN1549-4713
AutoresVanissa W. S. Chow, Vishal Jhanji, Stanley C.C.,
Tópico(s)Multiple Myeloma Research and Treatments
ResumoWe read with interest the article entitled, "Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases" by Saint-Jean et al.1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar The severity of ocular toxicities of epidermal growth factor (EGF) receptor inhibitors is now being more widely recognized, with reports of permanent visual impairment from corneal scarring after persistent epithelial defect2Foerster C.G. Cursiefen C. Kruse F.E. Persisting corneal erosion under Cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody).Cornea. 2008; 27: 612-614Crossref PubMed Scopus (49) Google Scholar to severe corneal melting and even perforation.1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Whereas Johnson et al3Johnson K.S. Levin F. Chu D.S. Persistent corneal epithelial defect associated with erlotinib treatment.Cornea. 2009; 28: 706-707Crossref PubMed Scopus (51) Google Scholar and Saint-Jean et al1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar report reversibility of corneal epithelial erosions with lubricants and cessation of the EGF receptor inhibitors, we encountered a more severe case that did not respond to such treatment and was ultimately managed with autologous serum eye drops.A 49-year-old diabetic woman with metastatic lung cancer presented with bilateral sterile corneal melting after using oral EGF receptor inhibitor erlotinib 150 mg/d for 1 month. Before that she was on gefitinib 250 mg/d, another oral EGF receptor inhibitor, for 2 years. She had started to experience dry eye symptoms for the past year requiring the use of lubricants every 4 hours. At the time of presentation, slit-lamp examination showed axial ulceration in the right eye and paraxial ulceration in the left eye (Fig 1, available at http://aaojournal.org). Bilateral corneal thinning was noted, more severe in the left than the right eye. There was no frank corneal infiltrate. Anterior chamber was quiet in both eyes. Corneal scrapings were negative for bacteria, fungi, and Acanthamoeba. Schirmer's test I was 4 mm in the right eye and 3 mm in the left eye. A diagnosis of erlotinib-associated sterile corneal melting was made and the patient was advised to withhold erlotinib. Carboxymethylcelluose every hour and lanolin ointment 4 times a day were commenced in both eyes. Both lower lid puncta were cauterized thermally and both upper lid puncta were occluded with collagen punctal plugs. Even so, the eyes were still too dry to retain soft bandage contact lenses. The patient was advised to return frequently for close monitoring.No response in the ocular condition was noted despite 10 days of intensive lubrication and withholding of erlotinib. In view of the impending corneal perforation, 2-hourly autologous serum eye drops were commenced empirically in both eyes. Autologous serum eye drops were prepared by centrifuging patient's clotted blood at 1800 rpm for 5 minutes and diluting the serum to 20% with sterile saline.A rapid response was observed with autologous serum eye drops. Corneal melting was halted and complete epithelialization was achieved within 3 days of treatment with autologous serum eye drops. Slit-lamp examination showed mild residual corneal thinning and scarring bilaterally (Fig 2, available at http://aaojournal.org). The best-corrected visual acuity improved from 5/60 in the right and 0.3 in the left eye to 0.4 in the right and 0.7 in the left eye, respectively.Saint-Jean et al1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar doubted the efficacy of autologous serum or topical EGF in counteracting the effects of low-molecular-weight EGF inhibitors (such as erlotinib) that act on tyrosine kinase intracellularly. However, as evident from our case, autologous serum eye drops seem to be effective in these settings. Given its ease of preparation and efficacy, we recommend a trial of autologous serum eye drops in cases failing lubrication and cessation of EGF receptor inhibitor treatment. The efficacy of topical EGF remains yet to be determined in such cases still, and whether it may be used while patients continue with their EGF receptor inhibitor treatment will be an important finding in this era of targeted anticancer therapy. We read with interest the article entitled, "Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases" by Saint-Jean et al.1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar The severity of ocular toxicities of epidermal growth factor (EGF) receptor inhibitors is now being more widely recognized, with reports of permanent visual impairment from corneal scarring after persistent epithelial defect2Foerster C.G. Cursiefen C. Kruse F.E. Persisting corneal erosion under Cetuximab (Erbitux) treatment (epidermal growth factor receptor antibody).Cornea. 2008; 27: 612-614Crossref PubMed Scopus (49) Google Scholar to severe corneal melting and even perforation.1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Whereas Johnson et al3Johnson K.S. Levin F. Chu D.S. Persistent corneal epithelial defect associated with erlotinib treatment.Cornea. 2009; 28: 706-707Crossref PubMed Scopus (51) Google Scholar and Saint-Jean et al1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar report reversibility of corneal epithelial erosions with lubricants and cessation of the EGF receptor inhibitors, we encountered a more severe case that did not respond to such treatment and was ultimately managed with autologous serum eye drops. A 49-year-old diabetic woman with metastatic lung cancer presented with bilateral sterile corneal melting after using oral EGF receptor inhibitor erlotinib 150 mg/d for 1 month. Before that she was on gefitinib 250 mg/d, another oral EGF receptor inhibitor, for 2 years. She had started to experience dry eye symptoms for the past year requiring the use of lubricants every 4 hours. At the time of presentation, slit-lamp examination showed axial ulceration in the right eye and paraxial ulceration in the left eye (Fig 1, available at http://aaojournal.org). Bilateral corneal thinning was noted, more severe in the left than the right eye. There was no frank corneal infiltrate. Anterior chamber was quiet in both eyes. Corneal scrapings were negative for bacteria, fungi, and Acanthamoeba. Schirmer's test I was 4 mm in the right eye and 3 mm in the left eye. A diagnosis of erlotinib-associated sterile corneal melting was made and the patient was advised to withhold erlotinib. Carboxymethylcelluose every hour and lanolin ointment 4 times a day were commenced in both eyes. Both lower lid puncta were cauterized thermally and both upper lid puncta were occluded with collagen punctal plugs. Even so, the eyes were still too dry to retain soft bandage contact lenses. The patient was advised to return frequently for close monitoring. No response in the ocular condition was noted despite 10 days of intensive lubrication and withholding of erlotinib. In view of the impending corneal perforation, 2-hourly autologous serum eye drops were commenced empirically in both eyes. Autologous serum eye drops were prepared by centrifuging patient's clotted blood at 1800 rpm for 5 minutes and diluting the serum to 20% with sterile saline. A rapid response was observed with autologous serum eye drops. Corneal melting was halted and complete epithelialization was achieved within 3 days of treatment with autologous serum eye drops. Slit-lamp examination showed mild residual corneal thinning and scarring bilaterally (Fig 2, available at http://aaojournal.org). The best-corrected visual acuity improved from 5/60 in the right and 0.3 in the left eye to 0.4 in the right and 0.7 in the left eye, respectively. Saint-Jean et al1Saint-Jean A. de la Maza M.S. Morral M. et al.Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.Ophthalmology. 2012; 119: 1798-1802Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar doubted the efficacy of autologous serum or topical EGF in counteracting the effects of low-molecular-weight EGF inhibitors (such as erlotinib) that act on tyrosine kinase intracellularly. However, as evident from our case, autologous serum eye drops seem to be effective in these settings. Given its ease of preparation and efficacy, we recommend a trial of autologous serum eye drops in cases failing lubrication and cessation of EGF receptor inhibitor treatment. The efficacy of topical EGF remains yet to be determined in such cases still, and whether it may be used while patients continue with their EGF receptor inhibitor treatment will be an important finding in this era of targeted anticancer therapy. Supplementary dataFigure 2Slit-lamp photographs showing both corneas 3 days after commencing autologous serum eye drops. Corneal epithelialization and scarring was noted bilaterally. OD = right eye; OS = left eye.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 CasesOphthalmologyVol. 119Issue 9PreviewTo describe the ocular effects associated with the administration of the systemic epidermal growth factor receptor (EGFR) inhibitors panitumumab and erlotinib. Full-Text PDF Author replyOphthalmologyVol. 120Issue 5PreviewWe would like to thank Chow et al1 for sharing their interesting case report. Epidermal growth factor (EGF) receptor plays an important role in corneal remodeling. As they mentioned, ophthalmic complications secondary to the use of EGF receptor inhibitors (EGFRi) are now being more widely recognized. As a matter of fact, we are developing a prospective, compared, and observational study to evaluate the risk of experiencing ophthalmologic side effects with EGFRi treatment. Full-Text PDF
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