Treatment of Acanthamoeba keratitis

Keratitis by Acanthamoeba (CA) 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

Aetiology

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

Risk factors

Acanthamoeba can enter the eye either as a result of direct contact with contaminated tap water, but also through wet hands, or due to the use of an ineffective multipurpose solution to disinfect against the parasite.

Data indicate that AK cases are on the rise and there have been some outbreaks in thethe last few years, often related to a low disinfectant power of the products used for the care of the contact lenses.

The vast majority of cases (approximately 85%) of Acanthamoeba keratitis occurs in contact lens wearersdue to incorrect use of the lenses, such as: inadequate cleaning and storage, night and prolonged use and other incorrect practices.

Infection, however, can also occur after corneal trauma, especially in rural settings.

Prevalence

This is a form of keratitis with a fairly low prevalence (7 cases per 1,000,000 in Europe), but it can have devastating effects on patients, as it can cause intense pain and, if not effectively treated, significant deterioration of vision, up to blindness, and perforation of the cornea.

Characteristics of the infection

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 keratocytes. The 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

Symptoms and clinical signs

In the case of CA, the most common symptoms are similar to those of other eye infections: severe pain, redness and irritation in the eye, visual disturbances, hypersensitivity to light and excessive tearing. These symptoms may persist for several weeks.

I clinical signs of CA are varied and range from epithelial changes (e.g. epithelial microerosions and microcysts) to the presence of different types of infiltrates (e.g. multifocal stromal infiltrates and peripheral perineurial infiltrate).

Corneal infection with Acanthamoeba can also lead to the onset of complications, some common (broad-based anterior synechiae, secondary glaucoma, iris atrophy, persistent mature endothelial defect cataract), while others are rarer (anterior sterile uveitis, scleritis, chorioretinitis and retinal vasculitis).

Precisely because many of the signs and symptoms that sufferers present with this infection may appear similar to those due to other types of keratitis, CA may be misdiagnosed and treated like other types of keratitis (herpetic, bacterial or fungal). This delay in diagnosis, as well as the use of inappropriate treatment, has a negative impact on the patient's clinical course.

Diagnosis

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

In case of clinical signs of AC, the ophthalmologist will perform some or all of the following examinations:

• molecular analysis of corneal scrapingsIt has a very high sensitivity and can give a result within 60 minutes. However, this test can have the disadvantage that even the presence of genetic material from the non-living micro-organism can give a positive result
• confocal microscopy in vivo: has a higher sensitivity than 90% when performed by experts; however, with this method only cysts of Acanthamoeba are well recognisable
• cultivation in vitro: has variable sensitivity and has the disadvantage of giving results after 3 weeks
• histopathological analysis: has a discrete sensitivity and corneal scrapings or excision or excised tissue from keratoplasty can be analysed.

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 biocide-resistant encysted form and the trophozoites, which are much more sensitive to treatment.2

Medical therapy

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 prospects of polyhexanide therapy

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 monotherapy with polyhexanide, 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, excimer laser keratoplasty is performed to remove the infected corneal zone.1

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.