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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Ocular safety evaluation of toplic and systemic antifungal medications: A multi-source pharmacovigilance and genomic
Dangdang Wang1, Yang Peng1, Qi Zhang1
1Department 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.
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.
Insights
Systemic antifungal drugs pose greater ocular risks than topical ones, potentially causing severe vision issues. This study highlights PI3K-Akt signaling and CES1 as key players in antifungal-related eye toxicity.
Area of Science:
- Ophthalmology
- Pharmacovigilance
- Genomics
Background:
- Antifungal agents are used for fungal infections but have known ocular side effects.
- The ocular safety profiles of antifungals are not fully understood.
Purpose of the Study:
- To investigate ocular adverse events (AEs) associated with antifungal drugs.
- To explore the molecular mechanisms underlying these ocular toxicities.
Main Methods:
- Utilized FDA Adverse Event Reporting System (FAERS) data (2004-2024).
- Performed disproportionality analysis, retrospective clinical data validation, and systems pharmacology analyses.
- Employed network analysis and summary-data-based Mendelian randomization (SMR) with keratitis genome-wide association studies (GWAS).
Main Results:
- Identified 71,529 antifungal-related AE reports.
- Systemic antifungals were linked to severe vision-threatening events (e.g., toxic optic neuropathy), while topical agents were associated with surface-level symptoms.
- Discovered hub genes (STAT3, AKT1, SRC) in PI3K-Akt and apoptotic pathways, and identified CES1 as a gene associated with keratitis risk.
Conclusions:
- Systemic antifungals present a wider and more severe range of ocular AEs compared to topical agents.
- PI3K-Akt signaling and CES1 may mediate antifungal-induced ocular toxicity.
- Findings provide insights for risk assessment and mechanistic understanding, requiring further validation.
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