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Emerging treatments in fungal keratitis
Aafreen Bari1, Tushar Agarwal1, Rajesh Sinha1
1Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Abstract:
Fungal keratitis is a major cause of corneal blindness, particularly in tropical and low-resource settings, and remains challenging to manage due to delayed diagnosis, limited drug penetration, emerging resistance, and host-mediated tissue damage. Conventional antifungal therapies, including natamycin and voriconazole, are often inadequate in deep, severe, or refractory infections, underscoring the need for alternative strategies. This narrative review summarizes and critically appraises emerging treatments in fungal keratitis, with a focus on recent pharmacological advances, innovative drug delivery systems, adjunctive therapies, and immunomodulatory approaches. Newer-generation azoles, echinocandins, and repurposed agents are discussed alongside advanced formulations such as liposomal amphotericin B, solubilized natamycin, nanoparticle-based delivery, and intrastromal drug administration. Adjunctive modalities, including photo-activated corneal cross-linking, photodynamic therapy, therapeutic contact lenses, and low-temperature plasma, are reviewed for their antimicrobial and corneal-stabilizing effects. The role of immunomodulators in mitigating excessive inflammation while preserving antifungal defense is also highlighted. In addition, evolving strategies for managing infections caused by emerging and fungus-like pathogens, including Pythium sp., are addressed. While many of these therapies show promising experimental and early clinical outcomes, robust randomized controlled trials and standardized treatment protocols remain limited. This review emphasizes the need for translational research, ocular-specific antifungal development, and integrated therapeutic approaches to improve visual outcomes and reduce the burden of fungal keratitis.
Insights
Fungal keratitis causes corneal blindness, with current treatments often failing. Emerging therapies, including new drugs and delivery methods, offer hope for better visual outcomes.
Area of Science:
- Ophthalmology
- Mycology
- Infectious Diseases
Background:
- Fungal keratitis is a leading cause of corneal blindness, especially in tropical regions.
- Management is difficult due to late diagnosis, poor drug penetration, resistance, and tissue damage.
- Standard antifungals like natamycin and voriconazole are insufficient for severe cases.
Purpose of the Study:
- To review and assess emerging treatments for fungal keratitis.
- Focus on pharmacological advances, novel drug delivery, adjunctive therapies, and immunomodulation.
- Address challenges in managing infections caused by fungi and fungus-like organisms.
Main Methods:
- Narrative review of recent literature on fungal keratitis treatments.
- Appraisal of newer azoles, echinocandins, repurposed drugs, and advanced formulations (liposomal amphotericin B, nanoparticles).
- Evaluation of adjunctive therapies (corneal cross-linking, photodynamic therapy, plasma) and immunomodulators.
Main Results:
- Newer antifungals, advanced drug delivery systems, and adjunctive therapies show promise in experimental and early clinical studies.
- Immunomodulators may help control inflammation while maintaining antifungal defense.
- Strategies for emerging pathogens like Pythium are also being explored.
Conclusions:
- Emerging treatments offer potential improvements for fungal keratitis management.
- Limited randomized controlled trials and standardized protocols necessitate further research.
- Translational research and ocular-specific antifungal development are crucial for better visual outcomes.
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