piperidines and Corneal-Diseases

We sought to describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis.. Retrospective chart review.. Among 6871 patients and 17 EGFR or FGFR inhibitors, 1161 patients (16.9%) referred for ophthalmologic examination. In total, 1145 patients had disease-related or unrelated ocular complications. Among 16 patients with treatment-related ocular complications, three patients had treatment-related radiation retinopathy and one patient showed treatment-related corneal ulcer. Finally the authors identified that, in 12 patients, three EGFR inhibitors and two FGFR inhibitors caused corneal epithelial lesions. Vandetanib, Osimertinib, and ABT-414 caused vortex keratopathy in nine patients, while ASP-5878 and FPA-144 caused epithelial changes resembling corneal dysmaturation in three patients. The mean interval until symptoms appeared was 246 days with vandetanib, 196 days with osimertinib, 30 days with ABT-414, 55 days with ASP-5878, and 70 days with FPA-144. The mean of the lowest logarithm of minimal angle of resolution visual acuity results of the right and left eyes after chemotherapy were 0.338 and 0.413. The incidence rates of epithelial changes were 15.79% with vandetanib, 0.5% with osimertinib, 100% with ABT-414, 50.0% with ASP-5878, and 18.2% with FPA-144. After excluding deceased patients and those who were lost to follow-up or still undergoing treatment, we confirmed the reversibility of corneal lesions after the discontinuation of each agent. Seven patients showed full recovery of their vision and corneal epithelium, while three achieved a partial level of recovery. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy.. EGFR and FGFR inhibitors are chemotherapy agents that could make corneal epithelial changes. Contrary to the low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed a high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with these agents that decreased visual acuity could develop due to corneal epithelial changes and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops.. This study was approved by the institutional review board (IRB) of Samsung Medical Center (IRB no. 2019-04-027) and was conducted according to the principles expressed in the Declaration of Helsinki.

Topics: Acrylamides; Adult; Aniline Compounds; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Corneal Diseases; Drug-Related Side Effects and Adverse Reactions; Epithelium, Corneal; ErbB Receptors; Female; Humans; Immunoconjugates; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Quinazolines; Receptors, Fibroblast Growth Factor; Retrospective Studies; Therapies, Investigational; Vision Disorders; Visual Acuity

To report 2 cases of cornea verticillata (CV) after vandetanib treatment for medullary thyroid carcinoma (MTC).. In this retrospective interventional, case-report study, 2 patients who under vandetanib treatment for MTC were referred to our ophthalmology department because of vision complaints. Both subjects underwent a complete ophthalmologic examination, including confocal microscopy (CM) using the Heidelberg Retina Tomograph and Rostock Cornea Module.. A 70-year-old man and a 43-year-old woman, both with a history of MTC under treatment with vandetanib for 5 months and 30 months, respectively, presented with blurred vision. In both patients, a mild CV pattern was observed although deposits were more evident in the male patient. CM images showed hyperreflective deposits in the corneal epithelium and subepithelial nerve plexus. Bright microdots were also seen throughout the stroma, along with a few hyperreflective keratocytes in the anterior stroma.. In both patients, vandetanib seemed to be the cause of CV. The CM images supported the idea of drug-lipid complex deposits in vandetanib-induced CV.

Topics: Adult; Aged; Antineoplastic Agents; Corneal Diseases; Female; Humans; Male; Microscopy, Confocal; Piperidines; Protein Kinase Inhibitors; Quinazolines; Retrospective Studies

We report a case of vortex keratopathy in a patient treated with vandetanib for non-small cell lung cancer (NSCLC). A 44-year-old female who underwent two cycles of chemotherapy for NSCLC complained of visual blurring in both eyes after the initiation of vandetanib, an anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor. On ophthalmic examination, visual acuities were 20 / 20 OU and, with the exception of diffuse vortex keratopathy in both eyes, other findings were unremarkable. Vandetanib is believed to have caused vortex keratopathy in this patient. Anti-EGFR properties affecting normal corneal epithelial cell migration and wound healing or drug associated metabolite deposition, which is the case in numerous drug-associated vortex keratopathies, may be possible underlying mechanisms in the formation of this corneal complication.

Topics: Adult; Carcinoma, Non-Small-Cell Lung; Cornea; Corneal Diseases; Diagnosis, Differential; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Lung Neoplasms; Microscopy, Acoustic; Piperidines; Quinazolines; Visual Acuity

To describe a patient with a history of epithelial basement membrane dystrophy who developed symptomatic corneal verticillata after vandetanib therapy for anaplastic astrocytoma.. Retrospective interventional case report.. A 48-year-old female patient with a history of anaplastic astrocytoma status post resection, external beam radiation, and chemotherapy presented with glare symptoms, decreased contrast sensitivity, and increased lacrimation after approximately 12 months of therapy with the anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor, vandetanib. Ophthalmic examination revealed diffuse corneal verticillata and fine subepithelial opacities. Schirmer 1 testing was normal bilaterally. Therapy with carboxymethylcellulose, 5% sodium chloride ointment, and a decrease in the dose of vandetanib led to an improvement in the patient's ophthalmic symptoms despite persistence of the corneal findings. The patient remained under surveillance for tumor recurrence.. Vandetanib (ZD6474), a protein tyrosine kinase inhibitor with dual anti-EGFR and anti-vascular endothelial growth factor receptor 2 action, may have contributed to the formation of corneal verticillata in our patient. Inhibition of EGFR, which is involved with corneal epithelial cell migration and wound healing, may play a role in the pathogenesis underlying corneal vortex keratopathy and ocular surface conditions with significant epithelial turnover.

Topics: Astrocytoma; Brain Neoplasms; Cellulase; Corneal Diseases; Corneal Opacity; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; ErbB Receptors; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ointments; Piperidines; Quinazolines; Retrospective Studies; Sodium Chloride; Vascular Endothelial Growth Factor Receptor-2