{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:01:49Z","timestamp":1780038109810,"version":"3.53.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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>Serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely used in the treatment of neuropsychiatric disorders and chronic pain; however, their comprehensive ocular safety profile has not been systematically evaluated. This study aimed to investigate and compare the safety signals of ocular adverse events (AEs) associated with five major SNRIs (venlafaxine, duloxetine, desvenlafaxine, milnacipran, and levomilnacipran).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective pharmacovigilance analysis. Ocular AEs associated with the SNRIs were extracted from the FAERS database (Q1 2004-Q4 2024). Disproportionality analyses were conducted using four algorithms, proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), to identify statistically significant signals. Time-to-onset analysis and sex subgroup analyses were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 5,860 SNRI-related ocular AEs were included. At the System Organ Class level, no significant positive signals of ocular AEs were observed. At the Preferred Term (PT) level, distinct risk profiles emerged for different SNRIs. Mydriasis was one of the strongest and most common signals for duloxetine, desvenlafaxine, and venlafaxine. Venlafaxine was also strongly associated with anisocoria and accommodation disorder. Vision blurred and visual impairment were the most frequently reported Preferred Term across all drugs. TTO analysis revealed that AEs occurred later for levomilnacipran (median 161 days) and venlafaxine (median 147 days), but earlier for desvenlafaxine (31 days) and milnacipran (11.5 days). Sex subgroup analyses revealed significant differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on real-world data, this study identified drug-specific and sex-specific differences in the ocular safety signals of SNRIs. Mydriasis represents a common strong risk signal across multiple SNRIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1837592","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:03:34Z","timestamp":1780034614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of ocular adverse events associated with SNRIs"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhengtai","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiJuan","family":"Que","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1093\/ijnp\/pyab086","article-title":"Differential potency of venlafaxine, paroxetine, and atomoxetine to inhibit serotonin and norepinephrine reuptake in patients with major depressive disorder","volume":"25","author":"Aldosary","year":"2022","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S454","DOI":"10.4103\/ijo.Ijo_2804_24","article-title":"Comparing the effect of sympathomimetic\/anticholinergic psychotropic drugs with that of non-sympathomimetic\/anticholinergic psychotropic drugs on IOP and angle parameters among patients on long-term therapy","volume":"73","author":"Behera","year":"2025","journal-title":"Indian J. Ophthalmol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1737113","DOI":"10.3389\/fphar.2026.1737113","article-title":"The post-marketing safety of venlafaxine: a real-world two-decade pharmacovigilance study using the FAERS database","volume":"17","author":"Chokkakula","year":"2026","journal-title":"Front. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2147\/opto.S355091","article-title":"A review of ocular complications associated with medications used for anxiety, depression, and stress","volume":"14","author":"Constable","year":"2022","journal-title":"Clin. Optom. (Auckl)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1345\/aph.18465","article-title":"Gender differences in depression and antidepressant pharmacokinetics and adverse events","volume":"34","author":"Frackiewicz","year":"2000","journal-title":"Ann. Pharmacother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1007\/s00701-023-05569-8","article-title":"Brimonidine eye drops reveal diminished sympathetic pupillary tone in comatose patients with brain injury","volume":"165","author":"Jakobsen","year":"2023","journal-title":"Acta Neurochir. (Wien)"},{"key":"B7","first-page":"2855","article-title":"Excavation of adverse event signals of serotonin-norepinephrine reuptake inhibitor based on FAERS","volume":"38","author":"Jiang","year":"2023","journal-title":"Drugs and Clin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"9520512","DOI":"10.1155\/2022\/9520512","article-title":"Distribution of pupil size and associated factors: results from the population-based gutenberg health study","volume":"2022","author":"Kiel","year":"2022","journal-title":"J. Ophthalmol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1017\/s1092852924002360","article-title":"Association of antidepressants with cataracts and glaucoma: a disproportionality analysis using the reports to the United States food and drug administration adverse event reporting system (FAERS) pharmacovigilance database","volume":"29","author":"Le","year":"2024","journal-title":"CNS Spectr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s40360-024-00790-2","article-title":"Safety assessment of tafamidis: a real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events","volume":"25","author":"Li","year":"2024","journal-title":"BMC Pharmacol. Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"119484","DOI":"10.1016\/j.jad.2025.119484","article-title":"Gastrointestinal adverse events associated with SNRIs: a FAERS-Based pharmacovigilance study","volume":"387","author":"Lin","year":"2025","journal-title":"J. Affect Disord."},{"key":"B12","first-page":"4470","article-title":"Sex differences in neural mechanisms of anxiety and depressive disorders","volume":"69","author":"Liqiang","year":"2024","journal-title":"Sci. Bull."},{"key":"B13","doi-asserted-by":"publisher","first-page":"23cr03595","DOI":"10.4088\/PCC.23cr03595","article-title":"Visual hallucinations after duloxetine use","volume":"26","author":"Martins","year":"2024","journal-title":"Prim. Care Companion CNS Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.21873\/invivo.14007","article-title":"Time-to-Onset analysis of rhabdomyolysis associated with selective serotonin and serotonin-noradrenaline reuptake inhibitors using the Japanese pharmacovigilance database","volume":"39","author":"Ohyama","year":"2025","journal-title":"Vivo"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.1007\/s00277-025-06480-1","article-title":"A pharmacovigilance study of adverse events associated with polycythemia vera treatments using the FDA adverse event reporting system (FAERS) database","volume":"104","author":"Reeves","year":"2025","journal-title":"Ann. Hematol."},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.5204\/thesis.eprints.114124","volume-title":"The Influence of the Autonomic Nervous System on the Human Choroid","author":"Sander","year":"2017"},{"key":"B17","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2165\/00003495-200767010-00006","article-title":"Ocular adverse effects associated with systemic medications: recognition and management","volume":"67","author":"Santaella","year":"2007","journal-title":"Drugs"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1016\/j.ophtha.2018.05.018","article-title":"Posterior vitreous detachment","volume":"125","author":"Sebag","year":"2018","journal-title":"Ophthalmology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"14604582211033014","DOI":"10.1177\/14604582211033014","article-title":"Real-world data-based adverse drug reactions detection from the Korea adverse event reporting system databases with electronic health records-based detection algorithm","volume":"27","author":"Shin","year":"2021","journal-title":"Health Inf. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"474","DOI":"10.2174\/1573412915666190204144202","article-title":"A systematic review on analytical methods to determine chiral and achiral forms of venlafaxine and its metabolite O-desmethylvenlafaxine","volume":"16","author":"Sunil","year":"2020","journal-title":"Curr. Pharm. Anal."},{"key":"B21","doi-asserted-by":"publisher","first-page":"15167","DOI":"10.1038\/s41598-024-66155-1","article-title":"Risk of stress cardiomyopathy associated with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors: a real-world pharmacovigilance analysis","volume":"14","author":"Tan","year":"2024","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e70176","DOI":"10.1111\/cns.70176","article-title":"Reproductive toxicity induced by serotonin-norepinephrine reuptake inhibitors: a pharmacovigilance analysis from 2004 to 2023 based on the FAERS database","volume":"30","author":"Xi","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s00228-025-03931-6","article-title":"Itraconazole-associated adverse events in fungal infections: a study of a large real-world sample based on the FAERS database (2019-2024)","volume":"82","author":"Xia","year":"2025","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B24","first-page":"2855","article-title":"Signal mining of adverse events of 5-hydroxytryptamine and norepinephrine reuptake inhibitors based on FAERS","volume":"38","author":"Xiao","year":"2023","journal-title":"Mod. Drugs Clin."},{"key":"B25","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1055\/a-2575-1530","article-title":"A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for gender of voriconazole drugs","volume":"75","author":"Xu","year":"2025","journal-title":"Drug Res. (Stuttg)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1559972","DOI":"10.3389\/fmed.2025.1559972","article-title":"Mining and analysis of adverse event signals of isotretinoin based on the real-world data of FAERS database","volume":"12","author":"Yang","year":"2025","journal-title":"Front. Med. (Lausanne)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"4783","DOI":"10.1038\/s41598-025-89272-x","article-title":"Real-world pharmacovigilance study of drug-induced autoimmune hepatitis from the FAERS database","volume":"15","author":"Zhu","year":"2025","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1837592\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:03:36Z","timestamp":1780034616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1837592\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":27,"alternative-id":["10.3389\/fphar.2026.1837592"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1837592","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1837592"}}