Acanthamoeba spp. gets all the glory, yet are you aware that Vermamoeba vermiformis (previously Hartmannella vermiformis), Vannella, and Vahlkampfia species have all been associated with amoebic keratitis (AK)? As more is learned about the organisms and how to differentiate species, an understanding of treatment protocols and emerging drugs is gained.

Diagnosing Amoebic Keratitis

AK infection signs and symptoms include tearing, photophobia, corneal and intraocular inflammation, corneal staining and ulceration, blurred vision, foreign body sensation, edema, stromal infiltration, ring ulcers, cataract, glaucoma, and, eventually, corneal perforation and vision loss if left untreated (Szentmáry et al, 2018). Many of these signs and symptoms also occur concomitantly with bacterial, fungal, and viral coinfections, often leading to delayed diagnosis or misdiagnosis. AK is often only considered after failure of first-line therapies for herpes simplex virus or bacterial or fungal keratitis.

Diagnostic techniques for AK vary; most rely on corneal scrapes with cultures and confocal microscopy (Maycock and Jayaswal, 2016). However, rpolymerase chain reaction (PCR) and 18S rRNA sequencing techniques can provide genus-specific diagnoses. Although Acanthamoeba T4 genotype (A. castellani and A. polyphaga) is the most prevalent, other Acanthamoeba genotypes are more aggressive and lead to worse outcomes, so genotype identification is imperative (Diehl et al, 2021).

There are 22 known genotype-defined species of Acanthamoeba (Corsaro et al, 2017). However, the literature reports other amoeba, including the above-mentioned species, to be coinfected 21% of the time (Moran et al, 2022). Like Acanthamoeba keratitis, non-Acanthamoeba AK cases predominantly occur in young lens wearers and are equally distributed worldwide (Moran et al, 2022). It is unknown currently how these diverse amoebae affect clinical outcomes or whether they require different treatment plans.

Treatment Options

Current first-line treatments include a combination of antimicrobial agents such as biguanides and diamidine (Elsheikha et al, 2020). However, these are toxic to human cells and result in side effects such as toxic keratopathy. So, there are continued efforts to improve efficacy and bioavailability into the cornea.

The fruit of the tropical Mangosteen tree (Garcinia mangostana) has a xanthone group that has been studied for its antibacterial, antifungal, antioxidant, anti-cancer, anti-inflammatory, and antiparasitic activities (Sangkanu et al, 2021). A recently published study evaluated isolate compounds from the G. mangostana flower and tested its anti-Acanthamoeba and anti-adhesion activity against Acanthamoeba triangularis (Sangkanu et al, 2021). Tests were performed on a polystyrene microtiter plate and soft contact lenses using a scanning electron microscope. The study demonstrated a synergistic effect of chlorhexidine, combined with the G. mangostana extract, against A. triangularis cysts.

Similarly, nanoparticle (NP)-based anti-acanthamoebic drug delivery has shown increased efficacy of chlorhexidine with increased drug bioavailability, sustained release, and intracellular permeability (Sharma et al, 2020). These particles have at least one dimension of 1 to 100 nanometers and are a growing area of drug delivery research. Metallic nanoparticles, such as silver, gold, copper, titanium, and zinc, have demonstrated antimicrobial activity (Sánchez-López et al, 2020).

Nanoparticles may work via generation of reactive oxygen species, increasing drug transport across cell membranes or endocytosis (Abdal et al, 2017). Nanoparticle-based anti-acanthamoebic drug delivery seems to enhance bioavailability of the drug, with sustained release and intracellular permeability, as well as reducing toxic side effects (Sánchez-López et al, 2020).

While AK is rare, it can be visually devastating. As we gain an understanding of the biodiverse nature of these infections, we are also gaining insight into effective treatment plans. CLS

References

1. Szentmáry N, Daas L, Shi L, et al. Acanthamoeba keratitis - Clinical signs, differential diagnosis and treatment. J Curr Ophthalmol. 2018 Oct 19;31:16-23.
2. Maycock NJ, Jayaswal R. Update on Acanthamoeba Keratitis: Diagnosis, Treatment, and Outcomes. Cornea. 2016 May;35:713-720.
3. Diehl MLN, Paes J, Rott MB. Genotype distribution of Acanthamoeba in keratitis: a systematic review. Parasitol Res. 2021 Sep;120:3051-3063.
4. Corsaro D, Köhsler M, Filippo MM, et al. Update on Acanthamoeba jacobsi genotype T15, including full-length 18S rDNA molecular phylogeny. Parasitol Res. 2017 Apr;116:1273-1284.
5. Moran, S, Mooney, R, Henriquez, FL. Diagnostic Considerations for Non-Acanthamoeba Amoebic Keratitis and Clinical Outcomes. Pathogens. 2022 Feb;11:219.
6. Elsheikha HM, Siddiqui R, Khan NA. Drug Discovery against Acanthamoeba Infections: Present Knowledge and Unmet Needs. Pathogens. 2020 May;9:405.
7. Sangkanu S, Mitsuwan W, Mahabusarakam W, et al. Anti-Acanthamoeba synergistic effect of chlorhexidine and Garcinia mangostana extract or α-mangostin against Acanthamoeba triangularis trophozoite and cyst forms. Sci Rep. 2021 Apr;11:8053.
8. Sharma G, Kalra SK, Tejan N, Ghoshal U. Nanoparticles based therapeutic efficacy against Acanthamoeba: Updates and future prospect. Exp Parasitol. 2020 Nov;218:108008.
9. Sánchez-López E, Gomes D, Esteruelas G, et al. Metal-Based Nanoparticles as Antimicrobial Agents: An Overview. Nanomaterials (Basel). 2020 Feb 9;10:292.
10. Abdal Dayem A, Hossain MK, Lee SB, et al. The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles. Int J Mol Sci. 2017 Jan 10;18:120.