Topical Voriconazole as Supplemental Treatment for Acanthamoeba Keratitis

Abstract

Purpose: Voriconazole was shown to inhibit ergosterol synthesis in various acanthamoeba species. The purpose of this study was to evaluate the clinical outcome of treatment with supplemental topical voriconazole in patients with acanthamoeba keratitis (AK). Methods: All patients who had been treated for AK with voriconazole 1% drops in conjunction with topical first-line antiacanthamoeba therapy composed of polyhexamethylene biguanide (PHMB) 0.02% and propamidine isethionate 0.1% (Brolene) between November 2014 and August 2017 at the Department of Ophthalmology, University Medical Center Mainz, were included. The main outcomes were treatment failure and recurrence rate. Secondary outcomes were visual acuity, need for keratoplasty, and presence of adverse reactions. Results: Twenty-eight eyes of 28 patients with AK, whose treatment had included topical voriconazole, were identified (12 men, 16 women, mean age: 41.7 ± 16.3 years), and 26 of them could be tracked for at least 3 months after cessation of therapy. Resolution of infection under therapy was seen in all eyes, and only one of 26 (3.85%) had a relapse after the therapy had been stopped. Best-corrected visual acuity improved during therapy. Keratoplasty because of central corneal scarring was scheduled in 5 of 26 patients (19.2%) after the pharmacological therapy had been stopped. Five of 26 patients (19.2%) reported on stinging or burning sensation after application of voriconazole 1% drops. Conclusions: Topical voriconazole 1% combined with first-line therapy composed of polyhexamethylene biguanide 0.02% and propamidine isethionate 0.1% appears to be an effective option with minor side effects for the treatment of AK.

An Update on the Initial Treatment of Acanthamoeba Keratitis

“…However, an assay study from 2019 reported that voriconazole was not cysticidal and that it antagonized the activity of both chlorhexidine and propamidine 34. Nonetheless, a 2020 retrospective case series reported resolution of AK in all 26 eyes treated with a combination of topical voriconazole 1%, PHMB 0.02%, and propamidine isethionate 0.1% followed for at least 3 months after cessation of therapy 35…”

Applications of medicinal chemistry for drug discovery against Acanthamoeba infections

“…AK treatment also involves hourly topical application of combined drugs such as polyhexamethylene biguanide or chlorhexidine digluconate with propamidine isethionate or hexamidine. In addition, chloramphenicol or neomycin is commonly used to prevent bacterial infection 35–38 . Despite of aforementioned, these therapeutic approaches result in post‐therapy problems of drug resistance, side effects, and toxicity.…”

“…In addition, chloramphenicol or neomycin is commonly used to prevent bacterial infection. [35][36][37][38] Despite of aforementioned, these therapeutic approaches result in post-therapy problems of drug resistance, side effects, and toxicity. Additionally, the combinational treatment strategy is mostly effective in early stages of infection, but it becomes ineffective after prolonged exposure.…”

“…Additionally, the combinational treatment strategy is mostly effective in early stages of infection, but it becomes ineffective after prolonged exposure. 4,32,35 Another important aspect is that the marketed contact lens disinfectants usually have an efficient bactericidal potential, but often do not demonstrate the same efficacy against Acanthamoeba trophozoites and cysts. [39][40][41][42] Among the commercially available multipurpose contact lens cleaning solution (MPS), only Opti-Free and ReNu solution show amoebicidal effect to eradicate amoebae.…”

Current Trends in Treating Acanthamoeba Keratitis: A Brief Narrative Review

“…Some studies have shown that more than 80% of cases of Acanthamoeba keratitis occur in contact lens wearers. 3 Acanthamoeba exists in two forms, quiescent cyst and active trophozoite form. Under unfavorable conditions, trophozoites are encysted.…”