{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:07:42Z","timestamp":1792123662538,"version":"4.4.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) can cause rare but potentially vision-threatening optic nerve toxicity. This study aimed to characterize ICI-associated optic nerve toxicity using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>FAERS reports from the first quarter of 2004 to the second quarter of 2025 were screened for optic nerve toxicity associated with five ICIs: pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab. Baseline characteristics, temporal trends, disproportionality signals, time-to-onset patterns, and potential associated factors were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 53,522 pembrolizumab-related, 67,178 nivolumab-related, 23,394 atezolizumab-related, 13,246 durvalumab-related, and 18,488 ipilimumab-related reports were included. Optic nerve toxicity was reported mainly in middle-aged and older adults, with the United States contributing most reports. In recent years, the number of relevant reports showed an increasing trend. Disproportionality analysis detected significant signals for optic nerve toxicity and related optic nerve events. Time-to-onset analysis revealed that all five ICIs exhibited a \u201cwear-out failure\u201d pattern, suggesting that the reporting probability of optic nerve-related adverse events might increase gradually with prolonged exposure. Age was the most important feature, followed by sex. Among concomitant medications, gabapentin showed a relatively strong association; among comorbidities, erosive gastritis and hypophysitis were more commonly reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This FAERS-based pharmacovigilance study identified optic nerve toxicity as a clinically relevant adverse event associated with five ICIs. Age and sex were key associated factors. These findings support closer ophthalmic monitoring during ICI therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1845963","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:31:04Z","timestamp":1787549464000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacovigilance analysis of immune checkpoint inhibitor-associated optic nerve toxicity based on the FAERS database"],"prefix":"10.3389","volume":"17","author":[{"given":"Hejing","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanmin","family":"Huan","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hehong","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, Chongqing University Three Gorges Hospital","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caijiu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazhu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]},{"name":"Cancer Institute of Panyu District, The Affiliated Panyu Center Hospital, Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First People\u2019s Hospital of Foshan (Foshan Hospital Affiliated to Southern University of Science and Technology), School of Medicine, Southern University of Science and Technology","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1038\/s41433-025-03683-8","article-title":"Prevalence of pediatric and adult optic neuritis in the United States from 2016 to 2023","volume":"39","author":"Abbass","year":"2025","journal-title":"Eye (Lond)."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1097\/WNO.0000000000000909","article-title":"Photopsias in the setting of nivolumab therapy","volume":"41","author":"Ahluwalia","year":"2021","journal-title":"J. Neuroophthalmol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.3390\/medicina59111963","article-title":"Pituitary-related adverse events and onset patterns caused by immune checkpoint inhibitors: analysis using the Japanese adverse drug event report database","volume":"59","author":"Asano","year":"2023","journal-title":"Med. Kaunas."},{"key":"B4","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/09273948.2020.1773867","article-title":"Ocular adverse events induced by immune checkpoint inhibitors: a comprehensive pharmacovigilance analysis","volume":"30","author":"Bomze","year":"2022","journal-title":"Ocul. Immunol. Inflamm."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1753466619885530","DOI":"10.1177\/1753466619885530","article-title":"Durvalumab for stage III non-small-cell lung cancer patients: clinical evidence and real-world experience","volume":"13","author":"Botticella","year":"2019","journal-title":"Ther. Adv. Respir. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1802121","DOI":"10.3389\/fmed.2026.1802121","article-title":"Real world pharmacovigilance study of FDA adverse event reporting system events for spiriva respimat","volume":"13","author":"Chen","year":"2026","journal-title":"Front. Med. (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"104073","DOI":"10.1016\/j.esmoop.2024.104073","article-title":"Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial","volume":"9","author":"Choueiri","year":"2024","journal-title":"ESMO Open"},{"key":"B8","doi-asserted-by":"publisher","first-page":"116594","DOI":"10.1016\/j.ejca.2026.116594","article-title":"Optic neuropathies induced by immune checkpoint inhibitors: a case series and systematic review of the literature","volume":"237","author":"Cuzzubbo","year":"2026","journal-title":"Eur. J. Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e012355","DOI":"10.1136\/jitc-2025-012355","article-title":"Acetaminophen interactions with immune checkpoint inhibitors: guilt by association?","volume":"13","author":"de Lemos","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00415-020-10352-1","article-title":"The changing landscape of optic neuritis: a narrative review","volume":"269","author":"De Lott","year":"2022","journal-title":"J. Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e008591","DOI":"10.1136\/jitc-2023-008591","article-title":"Chronic immune-related adverse events arising from immune checkpoint inhibitors: an update","volume":"12","author":"Fletcher","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"100595","DOI":"10.1016\/j.esmoop.2022.100595","article-title":"Symptom burden, psychological distress, and symptom management status in hospitalized patients with advanced cancer: a multicenter study in China","volume":"7","author":"He","year":"2022","journal-title":"ESMO Open"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1111\/1759-7714.15304","article-title":"Real-world evidence of efficacy of pembrolizumab plus chemotherapy and nivolumab plus ipilimumab plus chemotherapy as initial treatment for advanced non-small cell lung cancer","volume":"15","author":"Kaneko","year":"2024","journal-title":"Thorac. Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1245\/s10434-012-2741-4","article-title":"Longitudinal changes in function, symptom burden, and quality of life in patients with early-stage lung cancer","volume":"20","author":"Koczywas","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.ophtha.2025.01.010","article-title":"Clinical predictors in acute optic neuritis: analysis based on clinical trial data","volume":"132","author":"K\u00fcchlin","year":"2025","journal-title":"Ophthalmology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1007\/s00415-018-8890-z","article-title":"Severe neurologic complications of immune checkpoint inhibitors: a single-center review","volume":"265","author":"Mancone","year":"2018","journal-title":"J. Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1136\/jnnp-2023-333133","article-title":"Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes","volume":"95","author":"Min","year":"2024","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e247542","DOI":"10.1001\/jamanetworkopen.2024.7542","article-title":"Durvalumab after chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer","volume":"7","author":"Mooradian","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"B20","doi-asserted-by":"publisher","first-page":"637","DOI":"10.11477\/mf.1436203998","article-title":"A Surgical Case of Aseptic Meningitis and Secondary Hypophysitis due to Rupture of a Rathke's Cleft Cyst","volume":"47","author":"Morinaga","year":"2019","journal-title":"No Shinkei Geka"},{"key":"B21","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.wneu.2019.06.024","article-title":"Inflammatory reaction secondary to immune checkpoint inhibitor therapy mimicking a post-operative brain abscess","volume":"129","author":"Patel","year":"2019","journal-title":"World Neurosurg."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1007\/s10072-023-07252-3","article-title":"Neuromyelitis optica associated with the use of atezolizumab in a patient with advanced lung adenocarcinoma","volume":"45","author":"Pedrero Prieto","year":"2024","journal-title":"Neurol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.4103\/ijo.IJO_3415_20","article-title":"Approach to optic neuritis: an update","volume":"69","author":"Phuljhele","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/08820538.2023.2168494","article-title":"Immune checkpoint inhibitors and optic neuropathy: a systematic review","volume":"38","author":"Pietris","year":"2023","journal-title":"Semin. Ophthalmol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s10384-022-00932-1","article-title":"Update on glial antibody-mediated optic neuritis","volume":"66","author":"Song","year":"2022","journal-title":"Jpn. J. Ophthalmol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1167670","DOI":"10.3389\/fphar.2023.1167670","article-title":"Management and prediction of immune-related adverse events for PD1\/PDL-1 immunotherapy in colorectal cancer","volume":"14","author":"Sun","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1111\/jch.14709","article-title":"Amlodipine in the current management of hypertension","volume":"25","author":"Wang","year":"2023","journal-title":"J. Clin. Hypertens. (Greenwich)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1080\/01676830.2020.1867192","article-title":"Ophthalmic complications of immune checkpoint inhibitors","volume":"41","author":"Wladis","year":"2022","journal-title":"Orbit"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.3748\/wjg.v30.i9.1108","article-title":"Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: a multicenter real-world study in China","volume":"30","author":"Yang","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"139","DOI":"10.2147\/EB.S277760","article-title":"Neuro-ophthalmic complications of immune checkpoint inhibitors: a systematic review","volume":"12","author":"Yu","year":"2020","journal-title":"Eye Brain"},{"key":"B31","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3390\/ph17040501","article-title":"Neurological adverse events related to immune checkpoint inhibitors: a practical review","volume":"17","author":"Zammit","year":"2024","journal-title":"Pharm. (Basel)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.ejca.2017.01.009","article-title":"Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma","volume":"75","author":"Zimmer","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1007\/s10072-024-07895-w","article-title":"Review of atypical optic neuritis","volume":"46","author":"\u017dori\u0107","year":"2025","journal-title":"Neurol. Sci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1845963\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:31:07Z","timestamp":1787549467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1845963\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":32,"alternative-id":["10.3389\/fphar.2026.1845963"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1845963","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"article-number":"1845963"}}