Take-home message: Natamycin appears to be the best treatment for fungal keratitis, whereas voriconazole is less effective and associated with more adverse effects.
By Vanessa Caceres; Reviewed by Prashant Garg, MD
Looking for the best treatment for fungal keratitis?
Available data show that natamycin appears to be the best antifungal agent against molds and yeast, said Prashant Garg, MD, LV Prasad Eye Institute, Hyderabad, India.
However, Dr. Garg is also quick to point out that the rigor of research on fungal keratitis has been suboptimal and that ophthalmologists need more high-quality studies exploring more molecules.
Dr. Garg and colleagues reviewed the literature for both animal and human clinical trials, as well as lab-based studies.
A variety of antifungal agents are used for fungal keratitis—including polyenes, imadazoles, econazoles, and triazoles—as well as antiseptic agents, including chlorhexidine, povidone iodine, and silver sulfadiazine.
In addition, there has been interest in newer azoles and echinocandins because of their unique mechanism of action, Dr. Garg said.
The various treatments have been used for topical monotherapy, in combination with systemic antifungal therapy, and in subconjunctival or intracorneal therapy.
The research on the best therapy for fungal keratitis does not match the diversity of treatment options available.
“We were surprised to find that most reports were in the form of case reports sharing individual experience,” Dr. Garg said.
There was paucity of comparative trials, and in the ones that do exist, only a few agents were tested.
The best evidence found so far has been a Cochrane meta-analysis that included 12 trials, 981 subjects, and eight different antifungal agents, Dr. Garg said.1
The authors had a primary outcome of a clinical cure in 2 months and secondary features such as time to clinical cure, best spectacle-corrected visual acuity, rate of adverse reactions, and quality of life.
“The authors concluded that there was a wide variety of quality in these studies and that most [of the studies] were underpowered and provided no good evidence for most pathogens,” Dr. Garg said.
The authors wrote that natamycin seemed to be more effective than voriconazole.
A study published by Dr. Garg and co-authors last year found similar trends favoring natamycin for filamentous fungal keratitis when compared with voriconazole 1%.2
“In multivariate analysis, the effect of drug was marginal while the effect of age and epithelial defect was significant,” the authors wrote in their abstract. “In the group treated with natamycin, the final visual acuity was significantly better in patients with Fusarium
keratitis but not with Aspergillus
Voriconazole is also associated with more adverse effects, Dr. Garg said.
Dr. Garg also noted that there have been lab studies to look at the in vitro susceptibility of filamentous fungi and candida. Lab data seem to favor natamycin as well, but amphotericin B also appeared promising in studies.
However, when reviewing lab studies, clinicians should remember that those results do not necessarily translate into treatment outcomes.
1. FlorCruz NV, Evans JR. Medical interventions for fungal keratitis. Cochrane Database Syst Rev.
2. Sharma S, Das S, Virdi A, et al. Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial. Br J Opthalmol
Prashant Garg, MD
E: [email protected]
This article was adapted from Dr. Garg’s presentation at Cornea Subspecialty Day during the 2015 meeting of the American Academy of Ophthalmology. He did not indicate any proprietary interest in the subject matter.