{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:10:01Z","timestamp":1790633401638,"version":"4.1.0"},"reference-count":143,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T00:00:00Z","timestamp":1705104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and\/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto\/neuro-toxicity and inflammatory reactions. Ocular surface side effects are recognized to significantly impact patient\u2019s quality of life and quality of vision. Blepharoconjunctivitis is known to be a common side effect caused by oxaliplatin, cyclophosphamide, cytarabine, and docetaxel, while anastrozole, methotrexate, and 5-fluorouracil can all determine dry eye disease. However, the potential processes involved in the development of these alterations are yet not fully understood, especially for novel drugs currently available for cancer treatment. This review aims at analyzing the potential ocular surface and adnexal side effects of novel anticancer medications, trying to provide a better understanding of the underlying pharmacological processes and useful insights on the choice of proper management.<\/jats:p>","DOI":"10.3390\/cancers16020344","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:54:38Z","timestamp":1705294478000},"page":"344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Ocular Surface Side Effects of Novel Anticancer Drugs"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7867-3342","authenticated-orcid":false,"given":"Livio","family":"Vitiello","sequence":"first","affiliation":[{"name":"Eye Unit, \u201cLuigi Curto\u201d Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0956-4925","authenticated-orcid":false,"given":"Filippo","family":"Lixi","sequence":"additional","affiliation":[{"name":"Eye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, CA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-6366","authenticated-orcid":false,"given":"Giulia","family":"Coco","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, RM, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-0289","authenticated-orcid":false,"given":"Giuseppe","family":"Giannaccare","sequence":"additional","affiliation":[{"name":"Eye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, CA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,13]]},"reference":[{"key":"ref_1","unstructured":"National Cancer Institute (2018). Cancer Statistics."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285851","DOI":"10.1155\/2012\/285851","article-title":"The Role of Medications in Causing Dry Eye","volume":"2012","author":"Fraunfelder","year":"2012","journal-title":"J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.jtos.2017.05.004","article-title":"TFOS DEWS II iatrogenic report","volume":"15","author":"Gomes","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_4","unstructured":"Bristol-Myers Squibb Company (2020). Yervoy (Ipilimumab) Injection [Prescribing Information], Bristol-Myers Squibb Company."},{"key":"ref_5","unstructured":"Keytruda, M.C.I. (2020). (Pembrolizumab) for Injection [Prescribing Information], Merck & Co., Inc."},{"key":"ref_6","unstructured":"Bristol-Myers Squibb Company (2020). Opdivo (Nivolumab) Injection [Prescribing Information], Bristol-Myers Squibb Company."},{"key":"ref_7","unstructured":"Genentech Inc (2019). Tecentriq (Atezolizumab) Injection [Prescribing Information], Genentech, Inc."},{"key":"ref_8","unstructured":"EMD Serono Inc (2019). Bavencio (Avelumab) Injection, for Intravenous Use [Prescribing Information], Pfizer, Inc."},{"key":"ref_9","unstructured":"AstraZeneca Pharmaceuticals LP (2020). Imfinzi (Durvalumab) Injection, for Intravenous Use [Prescribing Information], AstraZeneca Pharmaceuticals LP."},{"key":"ref_10","unstructured":"Regeneron (2020). Libtayo (Cemiplimab) Injection [Prescribing Information], Regeneron."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1097\/IAE.0000000000002181","article-title":"Checkpoint Inhibitor Immune Therapy: Systemic Indications and Ophthalmic Side Effects","volume":"38","author":"Dalvin","year":"2018","journal-title":"Retina"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1136\/bjophthalmol-2020-316970","article-title":"Ophthalmic adverse effects of immune checkpoint inhibitors: The Mayo Clinic experience","volume":"105","author":"Fortes","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s40265-021-01507-z","article-title":"Ocular Toxicity of Targeted Anticancer Agents","volume":"81","author":"Fortes","year":"2021","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/acr.23177","article-title":"Rheumatic and Musculoskeletal Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors: A Systematic Review of the Literature","volume":"69","author":"Cappelli","year":"2017","journal-title":"Arthritis Care Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1158\/1078-0432.CCR-14-2468","article-title":"Safety, Correlative Markers, and Clinical Results of Adjuvant Nivolumab in Combination with Vaccine in Resected High-Risk Metastatic Melanoma","volume":"21","author":"Gibney","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1056\/NEJMoa1305133","article-title":"Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma","volume":"369","author":"Hamid","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1158\/2326-6066.CIR-14-0053","article-title":"Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma","volume":"2","author":"Hodi","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1158\/2326-6066.CIR-15-0193","article-title":"Phase I\/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab","volume":"4","author":"Weber","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Boucher, R., Haigh, O., Barreau, E., Champiat, S., Lambotte, O., Adam, C., Labetoulle, M., and Rousseau, A. (2023). Ocular surface toxicities associated with modern anticancer therapies. Surv. Ophthalmol., Epub ahead of print.","DOI":"10.1016\/j.survophthal.2023.10.002"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zimmer, L., Vaubel, J., Mohr, P., Hauschild, A., Utikal, J., Simon, J., Garbe, C., Herbst, R., Enk, A., and K\u00e4mpgen, E. (2015). Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Na\u00efve Patients with Metastatic Uveal Melanoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118564"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.21767\/2471-8041.100044","article-title":"Bilateral Uveitis and Keratitis Following Nivolumab Treatment for Metastatic Melanoma","volume":"3","author":"Baughman","year":"2017","journal-title":"Med. Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.ophtha.2019.01.031","article-title":"Ophthalmic Immune-Related Adverse Events of Immunotherapy: A Single-Site Case Series","volume":"126","author":"Kim","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/cxo.12973","article-title":"Corneal melting in a case undergoing treatment with pembrolizumab","volume":"103","author":"Weng","year":"2020","journal-title":"Clin. Exp. Optom."},{"key":"ref_26","first-page":"109","article-title":"Prevalence and Clinical Patterns of Ocular Complications Associated With Anti-PD-1\/PD-L1 Anticancer Immunotherapy","volume":"202","author":"Bitton","year":"2019","journal-title":"Arch. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1001\/archopht.124.5.735","article-title":"Report of a Conjunctival Myxoma Case and Review of the Literature","volume":"124","author":"Demirci","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e0005","DOI":"10.1097\/coa.0000000000000005","article-title":"Corneal Melt Associated With Cancer Immunotherapy","volume":"2","author":"Hsu","year":"2023","journal-title":"Cornea Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.lungcan.2016.10.008","article-title":"Corneal graft rejection in a patient treated with nivolumab for primary lung cancer","volume":"102","author":"Gohier","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/ICO.0000000000002460","article-title":"Nivolumab-Induced Ulcerative Keratitis\u2014A Case Report","volume":"40","author":"Losonczy","year":"2021","journal-title":"Cornea"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/ICO.0000000000000724","article-title":"Cyclosporine for Dry Eye Associated With Nivolumab: A case progressing to corneal perforation","volume":"35","author":"Nguyen","year":"2016","journal-title":"Cornea"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1056\/NEJMicm1910925","article-title":"Autoimmune Keratitis after Atezolizumab Treatment","volume":"383","author":"Oh","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_33","first-page":"140","article-title":"Ipilimumab-induced Ocular and Orbital Inflammation\u2014A Case Series and Review of the Literature","volume":"24","author":"Papavasileiou","year":"2016","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ajoc.2019.01.013","article-title":"Corneal ulceration associated with Nivolumab use","volume":"14","author":"Parker","year":"2019","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1097\/ICO.0000000000002372","article-title":"Bilateral Corneal Graft Rejection Associated With Pembrolizumab Treatment","volume":"39","author":"Vanhonsebrouck","year":"2020","journal-title":"Cornea"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e356","DOI":"10.1200\/JCO.2011.41.4359","article-title":"Anti\u2013Cytotoxic T-Cell Lymphocyte Antigen-4\u2013Induced Regression of Spinal Cord Metastases in Association with Renal Failure, Atypical Pneumonia, Vision Loss, and Hearing Loss","volume":"30","author":"Voskens","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1137637","DOI":"10.3389\/ftox.2023.1137637","article-title":"Ocular surface complications following biological therapy for cancer","volume":"5","author":"Ma","year":"2023","journal-title":"Front. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/ICO.0000000000002490","article-title":"Bilateral Corneal Perforation in a Patient Under Anti-PD1 Therapy","volume":"40","author":"Ramaekers","year":"2021","journal-title":"Cornea"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e940688","DOI":"10.12659\/AJCR.940688","article-title":"Corneal Perforation in a Patient Treated with Atezolizumab-Bevacizumab Combination Therapy for Unresectable Hepatocellular Carcinoma","volume":"24","author":"Alkharashi","year":"2023","journal-title":"Am. J. Case Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ayati, A., Moghimi, S., Salarinejad, S., Safavi, M., Pouramiri, B., and Foroumadi, A. (2020). A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy. Bioorg. Chem., 99.","DOI":"10.1016\/j.bioorg.2020.103811"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2147\/OTT.S54606","article-title":"Ocular side effects of biological agents in oncology: What should the clinician be aware of?","volume":"7","author":"Hager","year":"2013","journal-title":"OncoTargets Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/eye.2017.222","article-title":"Neuro-ophthalmic side effects of molecularly targeted cancer drugs","volume":"32","author":"Bhatti","year":"2017","journal-title":"Eye"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1200\/JCO.2003.10.038","article-title":"Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non\u2013Small-Cell Lung Cancer (The IDEAL 1 Trial) [corrected]","volume":"21","author":"Fukuoka","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_44","first-page":"195","article-title":"Clinical Benefit in NSCLC: Advanced-Stage Patients Require Symptom-Improving Palliation. Experiences from the \u2018Iressa\u2019 Expanded Access Program","volume":"28","author":"Schuette","year":"2005","journal-title":"Onkologie"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/sj.eye.6701630","article-title":"Ocular findings in patients with solid tumours treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (\u2018Iressa\u2019, ZD1839) in Phase I and II clinical trials","volume":"19","author":"Tullo","year":"2005","journal-title":"Eye"},{"key":"ref_46","first-page":"379132","article-title":"Perforating Corneal Ulceration in a Patient with Lung Metastatic Adenocarcinoma Treated with Gefitinib: A Case Report","volume":"2012","author":"Ibrahim","year":"2012","journal-title":"Case Rep. Ophthalmol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1055","DOI":"10.1111\/aos.14454","article-title":"A case report of pseudo-exfoliation syndrome with prolonged corneal epithelial regeneration because of erlotinib-induced unilateral corneal ulcer and anterior uveitis","volume":"98","author":"Tamura","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100630","DOI":"10.1016\/j.ajoc.2020.100630","article-title":"Rapidly progressive streptococcus dysgalactiae corneal ulceration associated with erlotinib use in stage IV lung cancer","volume":"18","author":"Sobol","year":"2020","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e7000","DOI":"10.1097\/MD.0000000000007000","article-title":"Plasma rich in growth factors for the treatment of rapidly progressing refractory corneal melting due to erlotinib in nonsmall cell lung cancer","volume":"96","author":"Guarnieri","year":"2017","journal-title":"Medicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1016\/j.ophtha.2012.03.002","article-title":"Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases","volume":"119","author":"Morral","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"468","DOI":"10.18240\/ijo.2023.03.19","article-title":"Peripheral corneal ulcer secondary to acquired eyelash trichomegaly following treatment with erlotinib in Asia: A case report","volume":"16","author":"Tam","year":"2023","journal-title":"Int. J. Ophthalmol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/JTO.0b013e3181c20063","article-title":"A Phase II Trial of Erlotinib Monotherapy in Pretreated Patients with Advanced Non-small Cell Lung Cancer Who Do Not Possess Active EGFR Mutations: Okayama Lung Cancer Study Group Trial 0705","volume":"5","author":"Yoshioka","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajoc.2016.06.003","article-title":"Erlotinib-associated severe bilateral recalcitrant keratouveitis after corneal EDTA chelation","volume":"4","author":"Zhou","year":"2016","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1016\/j.jcjo.2016.11.018","article-title":"Corneal edema with a systemic epidermal growth factor receptor inhibitor","volume":"52","author":"Moloney","year":"2017","journal-title":"Can. J. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/15569527.2015.1072546","article-title":"Erlotinib-related keratopathy in a patient underwent laser in situ keratomileusis","volume":"35","author":"Kau","year":"2016","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000358082","article-title":"Spontaneous Healing of Corneal Perforation after Temporary Discontinuation of Erlotinib Treatment","volume":"5","author":"Morishige","year":"2014","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"NP31","DOI":"10.1177\/1120672120958300","article-title":"When EGFR inhibitor meets autoimmune disease: Severe corneal complications in a patient with Sj\u00f6gren syndrome after erlotinib treatment","volume":"32","author":"Li","year":"2022","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_58","unstructured":"Boehringer Ingelheim Pharmaceuticals, Inc (2021). Gilotrif (Afatinib) [Package Insert]."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/ICO.0000000000001808","article-title":"Bilateral Ulcerative Keratitis Associated With Afatinib Treatment for Non\u2013Small-cell Lung Carcinoma","volume":"38","author":"McKelvie","year":"2019","journal-title":"Cornea"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1093\/annonc\/mdu216","article-title":"A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck","volume":"25","author":"Seiwert","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_61","unstructured":"AstraZeneca Pharmaceuticals LP (2021). Tagrisso (Osimertinib) [Package Insert]."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Shin, E., Lim, D.H., Han, J., Nam, D.-H., Park, K., Ahn, M.-J., Kang, W.K., Lee, J., Ahn, J.S., and Lee, S.-H. (2020). Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-019-1285-9"},{"key":"ref_63","first-page":"1807","article-title":"Vortex Keratopathy Presumed Secondary to AZD9291","volume":"10","author":"Chia","year":"2015","journal-title":"J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/S1470-2045(17)30608-3","article-title":"Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): A randomised, open-label, phase 3 trial","volume":"18","author":"Wu","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_65","unstructured":"Eli Lilly and Company (2015). Portrazza (Necitumumab) [Package Insert]."},{"key":"ref_66","first-page":"1167","article-title":"Spectrum of ocular toxicities from epidermal growth factor receptor inhibitors and their intermediate-term follow-up: A five-year review","volume":"21","author":"Borkar","year":"2013","journal-title":"Support. Care Cancer Off. J. Multinatl. Assoc. Support. Care Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e678","DOI":"10.1200\/JCO.2011.35.0694","article-title":"Human Epidermal Growth Factor Eyedrops for Cetuximab-Related Filamentary Keratitis","volume":"29","author":"Kawakami","year":"2011","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/CAD.0000000000001006","article-title":"Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: A single-center retrospective study","volume":"32","author":"Kurosaki","year":"2021","journal-title":"Anti-Cancer Drugs"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1097\/ICO.0b013e318166f483","article-title":"Persisting Corneal Erosion Under Cetuximab (Erbitux) Treatment (Epidermal Growth Factor Receptor Antibody)","volume":"27","author":"Foerster","year":"2008","journal-title":"Cornea"},{"key":"ref_70","unstructured":"Amgen, I. (2009). Vectibix (Panitumumab) [Package Insert]."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Dai, S., Zhou, Z., Chen, Z., Xu, G., and Chen, Y. (2019). Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells, 8.","DOI":"10.3390\/cells8060614"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s40265-019-01142-9","article-title":"Erdafitinib: First Global Approval","volume":"79","author":"Markham","year":"2019","journal-title":"Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1158\/1078-0432.CCR-18-3334","article-title":"Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors","volume":"25","author":"Bahleda","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jfo.2020.03.018","article-title":"Reversible corneal stromal thinning, acute-onset white cataract and angle-closure glaucoma due to erdafitinib, a fibroblast growth factor receptor inhibitor: Report of three cases","volume":"44","author":"Bauters","year":"2021","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/bs.pmbts.2015.05.002","article-title":"Corneal Epithelial Wound Healing","volume":"134","author":"Liu","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41523-020-0153-3","article-title":"Clinical development of immunotherapies for HER2(+) breast cancer: A review of HER2-directed monoclonal antibodies and beyond","volume":"6","author":"Costa","year":"2020","journal-title":"NPJ Breast Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1200\/JCO.2009.23.8451","article-title":"Neoadjuvant Treatment with Trastuzumab in HER2-Positive Breast Cancer: Results From the GeparQuattro Study","volume":"28","author":"Untch","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_78","first-page":"108","article-title":"Infectious crystalline keratopathy in an immunosuppressed patient","volume":"27","author":"Sridhar","year":"2001","journal-title":"CLAO J. Off. Publ. Contact Lens Assoc. Ophthalmol. Inc."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Orlandi, A., Fasciani, R., Cassano, A., Agresta, A., Calegari, M.A., Caporossi, A., and Barone, C. (2015). Trastuzumab-induced corneal ulceration: Successful no-drug treatment of a \u201cblind\u201d side effect in a case report. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1969-3"},{"key":"ref_80","unstructured":"Genentech USA, Inc (2013). Perjeta (Pertuzumab) [Package Insert]."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Braicu, C., Buse, M., Busuioc, C., Drula, R., Gulei, D., Raduly, L., Rusu, A., Irimie, A., Atanasov, A.G., and Slaby, O. (2019). A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers, 11.","DOI":"10.3390\/cancers11101618"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1097\/IAE.0000000000002451","article-title":"Ocular adverse events associated with mek inhibitors","volume":"39","author":"Calvo","year":"2019","journal-title":"Retina"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.4103\/ijo.IJO_2025_18","article-title":"A novel side effect of mitogen-activated protein kinase inhibitor cobimetinib: Acute corneal decompensation","volume":"67","author":"Asfuroglu","year":"2019","journal-title":"Indian J. Ophthalmol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.1158\/1078-0432.CCR-12-0868","article-title":"Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the MEK Inhibitor RO4987655 (CH4987655) in Patients with Advanced Solid Tumors","volume":"18","author":"Leijen","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_85","first-page":"96","article-title":"The MAPK (ERK) Pathway: Investigational Combinations for the Treatment Of BRAF-Mutated Metastatic Melanoma","volume":"38","author":"McCain","year":"2013","journal-title":"P T"},{"key":"ref_86","unstructured":"Genentech USA, Inc (2016). Zelboraf (Vemurafenib) [Prescribing Information], Genentech USA, Inc."},{"key":"ref_87","unstructured":"Novartis Pharmaceuticals Corporation (2018). Tafinlar Dabrafenib[Prescribing Information], Novartis Pharmaceuticals Corporation."},{"key":"ref_88","unstructured":"Array BioPharma Inc (2020). Braftovi (Encorafenib) [Prescribing Information], Array BioPharma Inc."},{"key":"ref_89","first-page":"831","article-title":"Ocular Toxicity in BRAF Mutant Cutaneous Melanoma Patients Treated With Vemurafenib","volume":"158","author":"Choe","year":"2014","journal-title":"Arch. Ophthalmol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1177\/1120672120930688","article-title":"Ocular side effects of target therapy and immunotherapy in patients with cutaneous malignant melanoma","volume":"31","author":"Eikenberry","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1177\/11206721221132872","article-title":"Ophthalmic adverse effects of BRAF inhibitors","volume":"33","author":"Becerra","year":"2022","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA A Cancer J. Clin."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jtos.2017.04.001","article-title":"TFOS DEWS II Sex, gender, and hormones report","volume":"15","author":"Sullivan","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/S0275-5408(98)00084-2","article-title":"Ocdjhular adverse reactions to tamoxifen\u2014A review","volume":"19","author":"Dulley","year":"1999","journal-title":"Ophthalmic Physiol. Opt. J. Br. Coll. Ophthalmic Opt."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/eye.1999.217","article-title":"Ocular toxicity in low-dose tamoxifen: A prospective study","volume":"13","author":"Noureddin","year":"1999","journal-title":"Eye"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1002\/1097-0142(19920615)69:12<2961::AID-CNCR2820691215>3.0.CO;2-W","article-title":"Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients","volume":"69","author":"Pavlidis","year":"1992","journal-title":"Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/01.icl.0000201396.74294.85","article-title":"Clinical and In Vivo Confocal Microscopy Findings in Patients Receiving Tamoxifen Citrate","volume":"32","author":"Muftuoglu","year":"2006","journal-title":"Eye Contact Lens Sci. Clin. Pr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/ICO.0000000000001098","article-title":"Refractory Tamoxifen-Induced Keratopathy Despite Drug Withdrawal","volume":"36","author":"Andreanos","year":"2017","journal-title":"Cornea"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"101661","DOI":"10.1016\/j.ajoc.2022.101661","article-title":"Raloxifene induced keratopathy: A case report","volume":"27","author":"Park","year":"2022","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_100","unstructured":"Kyowa Kirin Inc (2017). Fareston (Toremifene) [Prescribing Information], Kyowa Kirin Inc."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/tbj.12633","article-title":"Ocular Surface Disease in Breast Cancer Patients Using Aromatase Inhibitors","volume":"22","author":"Chatziralli","year":"2016","journal-title":"Breast J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.breast.2015.08.008","article-title":"Dry eyes and AIs: If you don\u2019t ask you won\u2019t find out","volume":"24","author":"Inglis","year":"2015","journal-title":"Breast"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1442-9071.2012.02865.x","article-title":"Dry eye syndrome in aromatase inhibitor users","volume":"41","author":"Turaka","year":"2013","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3109\/15569521003775013","article-title":"Exemestane-induced corneal epithelial changes","volume":"29","author":"Papathanassiou","year":"2010","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_105","first-page":"2259","article-title":"Joint pain with aromatase inhibitors: Abnormal frequency of Sj\u00f6gren\u2019s syndrome","volume":"34","author":"Laroche","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_106","first-page":"653","article-title":"Sj\u00f6gren\u2019s syndrome and aromatase inhibitors treatment: Is there a link?","volume":"31","author":"Guidelli","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"40","DOI":"10.21873\/invivo.12674","article-title":"Ocular Side Effects of Aromatase Inhibitor Endocrine Therapy in Breast Cancer\u2014A Review","volume":"36","author":"Serban","year":"2022","journal-title":"Vivo"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13045-018-0624-2","article-title":"Past, present, and future of Bcr-Abl inhibitors: From chemical development to clinical efficacy","volume":"11","author":"Rossari","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/S0140-6736(01)06535-7","article-title":"Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: A phase I study","volume":"358","author":"Judson","year":"2001","journal-title":"Lancet"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1089\/108076803322279426","article-title":"Ocular Side-Effects Associated with Imatinib Mesylate (Gleevec)","volume":"19","author":"Fraunfelder","year":"2003","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"FSO871","DOI":"10.2144\/fsoa-2022-0081","article-title":"Ocular complications of antineoplastic therapies","volume":"9","author":"Bader","year":"2023","journal-title":"Futur. Sci. OA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1007\/s10637-011-9763-9","article-title":"Nilotinib in patients with metastatic melanoma harboring KIT gene aberration","volume":"30","author":"Cho","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e570","DOI":"10.1097\/MJT.0000000000000650","article-title":"Nilotinib-Induced Ocular Toxicity: A Case Report","volume":"25","author":"Moore","year":"2018","journal-title":"Am. J. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Bhatia, S., Moon, J., Margolin, K.A., Weber, J.S., Lao, C.D., Othus, M., Aparicio, A.M., Ribas, A., and Sondak, V.K. (2012). Phase II Trial of Sorafenib in Combination with Carboplatin and Paclitaxel in Patients with Metastatic Uveal Melanoma: SWOG S0512. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048787"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1089\/jop.2018.0019","article-title":"Oral Anti-Vascular Endothelial Growth Factor Drugs and Ocular Adverse Events","volume":"34","author":"Fraunfelder","year":"2018","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_116","unstructured":"Ministry of Health, Labour and Welfare (2018, September 04). Pharmaceutical Evaluation Division PSaEHB-MoH, Report on the Deliberation Results, Available online: https:\/\/www.pmda.go.jp\/files\/000228502.pdf."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/PPO.0000000000000412","article-title":"Bruton Tyrosine Kinase Inhibitors: Present and Future","volume":"25","author":"Burger","year":"2019","journal-title":"Cancer J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1400376","article-title":"Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia","volume":"371","author":"Byrd","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1007\/s00417-019-04337-8","article-title":"Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics","volume":"257","author":"Kunkler","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_120","first-page":"429","article-title":"ALK inhibitors in non-small cell lung cancer: Crizotinib and beyond","volume":"12","author":"Awad","year":"2014","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1097\/IOP.0000000000001710","article-title":"Chronic Conjunctival Chemosis\u2014A New Ocular Side Effect of Crizotinib","volume":"37","author":"Das","year":"2020","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jtho.2016.09.131","article-title":"Phase I Results from a Study of Crizotinib in Combination with Erlotinib in Patients with Advanced Nonsquamous Non\u2013Small Cell Lung Cancer","volume":"12","author":"Ou","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1097\/IAE.0000000000000179","article-title":"Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration","volume":"34","author":"Singh","year":"2014","journal-title":"Retina"},{"key":"ref_124","unstructured":"AstraZeneca Pharmaceuticals LP (2011). Caprelsa (Vandetanib) [Package Insert]."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3341\/kjo.2011.25.5.355","article-title":"Vortex Keratopathy in a Patient Receiving Vandetanib for Non-Small Cell Lung Cancer","volume":"25","author":"Ahn","year":"2011","journal-title":"Korean J. Ophthalmol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1097\/ICO.0b013e3181922146","article-title":"Corneal Verticillata After Dual Anti-Epidermal Growth Factor Receptor and Anti-Vascular Endothelial Growth Factor Receptor 2 Therapy (Vandetanib) for Anaplastic Astrocytoma","volume":"28","author":"Yeh","year":"2009","journal-title":"Cornea"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Sklar, B.A., Gervasio, K.A., Leng, S., Ghosh, A., Chari, A., and Wu, A.Y. (2019). Management and outcomes of proteasome inhibitor associated chalazia and blepharitis: A case series. BMC Ophthalmol., 19.","DOI":"10.1186\/s12886-019-1118-x"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1001\/jamaophthalmol.2015.3963","article-title":"Association between Bortezomib Therapy and Eyelid Chalazia","volume":"134","author":"Fraunfelder","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/j.clml.2016.04.013","article-title":"Treatment With Doxycycline for Severe Bortezomib-Associated Blepharitis","volume":"16","author":"Veys","year":"2016","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1541-7786.MCR-19-0582","article-title":"Antibody\u2013Drug Conjugates: A Comprehensive Review","volume":"18","author":"Khongorzul","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_131","unstructured":"Daiichi Sankyo, Inc (2019). Enhertu (Trastuzumab Deruxtecan) [Package Insert]."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s40123-020-00280-8","article-title":"Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody\u2013Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study","volume":"9","author":"Farooq","year":"2020","journal-title":"Ophthalmol. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41408-020-00369-0","article-title":"Single-agent belantamab mafodotin for relapsed\/refractory multiple myeloma: Analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study","volume":"10","author":"Richardson","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Mencucci, R., Cennamo, M., Alonzo, L., Senni, C., Vagge, A., Desideri, L.F., Scorcia, V., and Giannaccare, G. (2022). Corneal Findings Associated to Belantamab-Mafodotin (Belamaf) Use in a Series of Patients Examined Longitudinally by Means of Advanced Corneal Imaging. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102884"},{"key":"ref_135","unstructured":"GlaxoSmithKline (2020). Blenrep (Belantamab Mafodotin-Blmf) [Package Insert]."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e261","DOI":"10.3324\/haematol.2019.235937","article-title":"Characterization of response and corneal events with extended follow-up after belantamab mafodotin (GSK2857916) monotherapy for patients with relapsed multiple myeloma: A case series from the first-time-in-human clinical trial","volume":"105","author":"Popat","year":"2020","journal-title":"Haematologica"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.1016\/j.clbc.2018.03.005","article-title":"Corneal Changes in Trastuzumab Emtansine Treatment","volume":"18","author":"Kreps","year":"2018","journal-title":"Clin. 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PADCEV (Enfortumab Vedotin-Ejfv) [Package Insert]."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"101155","DOI":"10.1016\/j.gore.2023.101155","article-title":"Strategies for prevention and management of ocular events occurring with mirvetuximab soravtansine","volume":"47","author":"Hendershot","year":"2023","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1158\/1078-0432.CCR-18-2474","article-title":"Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody\u2013Drug Conjugate Mirvetuximab Soravtansine","volume":"25","author":"Matulonis","year":"2019","journal-title":"Clin. 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