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Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
Published on: February 15, 2019
The Search for Antifungal Prophylaxis After Artificial Corneal Surgery-An In Vitro Study
Sarah Kim1,2, Paulo J M Bispo2,3, Eden E L Tanner4
1The Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear, Boston, MA.
Purpose:
To evaluate the antifungal properties of topical antibiotics (already being used successfully to prevent bacterial endophthalmitis) and some promising antiseptics for antifungal prophylaxis in the setting of artificial corneal implantation.
Methods:
Several commonly used antibiotics for antimicrobial prophylaxis after artificial corneal implantation, in addition to antiseptics [benzalkonium chloride (BAK), povidone-iodine (PI), and some ionic liquids (ILs)], were tested in vitro against Candida albicans, Fusarium solani, and Aspergillus fumigatus. The time-kill activity was determined. Toxicity was assayed in vitro on human corneal epithelial cultures using trypan blue. Adhesion and tissue invasion experiments were also carried out on porcine corneas and commonly used contact lenses, with or without gamma irradiation, and by analysis with fluorescence microscopy.
Results:
Polymyxin B (PMB)/trimethoprim/BAK (Polytrim), PMB alone, gatifloxacin with BAK (Zymaxid), and same-concentration BAK alone exhibited antifungal activity in vitro. Moxifloxacin (MOX) or gatifloxacin without BAK-as well as trimethoprim, vancomycin, and chloramphenicol-had no effect. 1% PI and ILs had the highest efficacy/toxicity ratios (>1), and Polytrim was species dependent. Subfungicidal concentrations of Polytrim reduced adhesion of C. albicans to Kontur contact lenses. Gamma-irradiated corneas showed enhanced resistance to fungal invasion.
Conclusions:
Of antibiotic preparations already in use for bacterial prophylaxis after KPro surgery, Polytrim is a commonly used antibiotic with antifungal effects mediated by both PMB and BAK and may be sufficient for prophylaxis. PI as a 1% solution seems to be promising as a long-term antifungal agent. Choline-undecanoate IL is effective and virtually nontoxic and warrants further development.
Insights
Topical antibiotics like Polytrim and antiseptics such as povidone-iodine show antifungal potential for artificial cornea prophylaxis. Choline-undecanoate ionic liquid is effective and safe, warranting further study.
Area of Science:
- Ophthalmology
- Microbiology
- Materials Science
Background:
- Artificial corneal implantation (KPro) requires prophylaxis against bacterial and fungal infections.
- Evaluating existing topical antibiotics and novel antiseptics for antifungal efficacy is crucial.
Purpose of the Study:
- To assess the in vitro antifungal properties of topical antibiotics and antiseptics for prophylaxis in artificial cornea settings.
- To determine the efficacy, toxicity, and tissue interaction of these agents against common fungal pathogens.
Main Methods:
- In vitro testing of antibiotics (e.g., Polytrim, Zymaxid) and antiseptics (benzalkonium chloride, povidone-iodine, ionic liquids) against Candida albicans, Fusarium solani, and Aspergillus fumigatus.
- Time-kill assays, cytotoxicity testing on corneal epithelial cells, and adhesion/invasion studies on porcine corneas and contact lenses were performed.
Main Results:
- Polymyxin B/trimethoprim/benzalkonium chloride (Polytrim), polymyxin B alone, and gatifloxacin with benzalkonium chloride demonstrated antifungal activity.
- 1% povidone-iodine and certain ionic liquids exhibited favorable efficacy/toxicity ratios.
- Polytrim reduced fungal adhesion, and gamma-irradiated corneas showed increased resistance to fungal invasion.
Conclusions:
- Polytrim possesses antifungal properties and may be sufficient for prophylaxis after KPro surgery.
- 1% povidone-iodine shows promise as a long-term antifungal agent.
- Choline-undecanoate ionic liquid is a highly effective and non-toxic candidate for further development.

