Treatment of Acanthamoeba keratitis

Keratitis by Acanthamoeba is a rare eye infection, but with potentially very serious consequences, occurring mainly in contact lens wearers. Additional risk factors are the presence of corneal surface damage and exposure to contaminated water.¹

Acanthamoeba is a free-living, ubiquitous protozoan that can be present in air, soil, dust, drinking water and even seawater. It occurs in two forms: a quiescent, i.e. silent, cyst and an infectious form, called a trophozoite.¹

When it infects the cornea, Acanthamoeba binds, firstly, to the corneal epithelial cells through a protein, called a binding protein, mannose. This binding causes the protozoa to secrete specific molecules (metalloproteases, serine and cysteine proteinases,) which have toxic effects on corneal epithelial cells and sui keratocytes. Secretion of these molecules allows corneal penetration of the trophozoite. Acanthamoeba. If the infection is not properly diagnosed and treated, it can also migrate along the corneal nerves and damage them.¹

Unfortunately, the keratitis from Acanthamoeba is difficult to diagnose and may be incorrectly treated, as the symptoms it induces are very similar to those of herpetic, bacterial or fungal keratitis.¹

Management of keratitis by Acanthamoeba

At present, there is no authorised drug in any country for the treatment of keratitis by Acanthamoeba. Effective treatment should allow the eradication from the organism of both the encysted form, which is resistant to biocides, and the trophozoites, which are much more sensitive to treatment.²

The most widely used therapy to date is based on diamidine and biguanide, often used in combination.

Other non-specific drugs are also used, such as antibiotics (to reduce the presence of trophozoites and prevent bacterial superinfection), steroids (which, however, support encystment and may cause an increase in the number of trophozoites) and antifungals.¹

However, current recommendations from the Centres for Disease Control and Prevention (CDC) in the US and the Royal College of Ophthalmologists in the UK recommend treatment with polyhexanide (0.02%) or chlorhexidine 0.02% eye drops, either as monotherapy or with the addition of a diamidine.²

The approval of polyhexanide therapy would finally make a specific treatment for keratitis by Acanthamoeba.²

The polyhexanide treatment is, in fact, in the study phase: for the time being, its efficacy and safety profile has been evaluated at concentrations of 0.04%, 0.06% and 0.08%.²

In particular, the efficacy of polyhexanide has been demonstrated both as monotherapy and in the combinations polyhexanide + diamidine, polyhexanide + chlorhexidine + diamidine.²

A recent study has shown that polyhexanide monotherapy, including the 0.08% concentration (the highest of those tested) is not only effective but, being easier to use and less expensive than diamidine combination therapy, could be used as a first-line treatment for Acanthamoeba.³

These results are supported by evidence that polyhexanide monotherapy, administered as initial therapy after diagnosis, was associated with both better cure rates over 12 months and better visual outcomes compared with patients treated with other drugs.²

Surgical treatment

Surgical epithelial abrasion of the cornea has both a diagnostic and therapeutic function, as it allows microorganisms to be removed and topical drugs to penetrate better. If topical treatment does not improve symptoms, corneal cryotherapy, amniotic membrane transplantation or penetrating keratoplasty can be performed.¹

Corneal cryotherapy is an adjuvant treatment to topical therapy. Amniotic membrane transplantation, on the other hand, is practised in the case of epithelial defects.¹

Finally, photodynamic therapy may be an alternative treatment option in therapy-resistant infectious keratitis.¹

In the case of expansion of keratitis by Acanthamoeba in the direction of the sclero-corneal junction, it is necessary to intervene with a keratoplasty. In perforated corneal ulcers, an excimer laser keratoplasty is performed to remove the infected corneal zone.¹

Bibliography

1) Nora Szentmary et al, Acanthamoeba keratitis and Clinical signs, differential diagnosis and treatment, J Curr Ophthalmol. 2018 Oct 19;31(1):16-23. doi: 10.1016/j.joco.2018.09.008. eCollection 2019 Mar.

2) Pope V, Rama P, Radford C, Minassian DC, Dart JKG. Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases. Br J Ophthalmol. 2020 Apr;104(4):575-581.

3) Papa V, van der Meulen I, Rottey S, Sallet G, Overweel J, Asero N, Minassian DC, Dart JKG. Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers. Br J Ophthalmol. 2020 Nov 25:bjophthalmol-2020-317848. doi: 10.1136/bjophthalmol-2020-317848. Epub ahead of print. PMID: 33239413.

Dr. Carmelo Chines
Direttore responsabile