| アブストラクト | BACKGROUND: Antifungal agents, used topically and systemically to treat fungal infections, have been associated with ocular adverse events (AEs), yet their ocular safety profiles remain under-characterized. METHODS: This study utilized data from the FDA Adverse Event Reporting System (FAERS, 2004-2024), a single-center retrospective study validation, and systems pharmacology analyses to investigate ocular AEs linked to antifungal drugs. Disproportionality analysis identified AE signals, while retrospective clinical data validated key findings. Drug-gene interaction networks, pathway enrichment (GO/KEGG), and summary-data-based Mendelian randomization (SMR) using keratitis GWAS were employed to explore molecular mechanisms. RESULTS: A total of 71,529 antifungal-related AE reports were identified. Topical agents were mainly linked to surface-level ocular symptoms (e.g., eyelid and periorbital oedema), whereas systemic agents showed stronger associations with vision-threatening events such as macular opacity, color vision disturbances, and toxic optic neuropathy (e.g., ROR >50). Collected clinical data partially supported these trends. Network analysis revealed hub genes (e.g., STAT3, AKT1, SRC) involved in PI3K-Akt and apoptotic signaling pathways. SMR analysis identified CES1 as a gene significantly associated with keratitis risk, suggesting a metabolic role in antifungal-induced toxicity. CONCLUSION: Systemic antifungals are associated with a broader and more severe spectrum of ocular AEs than topical agents. Integration of pharmacovigilance, clinical data, and genomic analysis highlights PI3K-Akt signaling and CES1 as potential mediators of antifungal-related ocular toxicity. These findings offer new insights for risk assessment and mechanistic understanding, warranting further experimental validation. |
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| ジャーナル名 | European journal of pharmacology |
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| Pubmed追加日 | 2025/8/29 |
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| 投稿者 | Wang, Dangdang; Peng, Yang; Zhang, Qi; Pu, Yanyu; Gao, Xi; Zeng, Lihong; Lan, Yufan; Lei, Junqin; Zhu, Huiyu; Huo, Yujia; Du, Shaowen; Wu, Ping; Li, Hong |
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| 組織名 | Department of Ophthalmology, Chongqing Key Laboratory for the Prevention and;Treatment of Major Blinding Eye Diseases, Chongqing Eye Institute, Chongqing;Branch of National Clinical Research Center for Ocular Diseases, The First;Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic;of China.;Department of Ophthalmology, The University-Town Hospital of the Chongqing;Medical University, Chongqing, People's Republic of China.;Chongqing University of Technology, Chongqing, People's Republic of China.;Department of Ophthalmology, Chongqing Aier Eye Hospital, Chongqing, People's;Republic of China.;of China. Electronic address: lihong@hospital.cqmu.edu.cn. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/40876614/ |
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