Acanthamoeba is the protozoan responsible for a severe form of keratitis, which is very common in contact lens wearers, but can also occur following ocular trauma. The clinical manifestations of this keratitis are often difficult to recognise, resulting in a delay in correct diagnosis and initiation of appropriate treatment. Unfortunately, it is a severely debilitating eye infection that causes acute pain, reduced visual acuity, and in the worst cases, after a long and painful clinical course, can even lead to enucleation of the eye.
The main goals of therapy against Acanthamoeba infection are:
- eradicate Acanthamoeba cysts and eliminate trophozoite infestation from corneal tissue;
- managing painful inflammatory responses in the patient.
These goals can be pursued either through surgical treatments or topical drug therapies. The latter type of therapy can be very lengthy and complex, lasting up to 6-12 months. Furthermore, it must be considered that some patients do not respond to topical therapy.
Keratoplasty in the treatment of Acanthamoeba keratitis
Corneal transplantation in the treatment of Acanthamoeba keratitis is a solution when the cornea is severely and irreparably compromised. Several techniques can be used, which can be applied in the early or late stages of the disease.
Early surgical procedures may be useful in reducing the risk of corneal perforation and endothelial damage, but they increase the rate of recurrence of infection, compared to delayed surgery performed after Acanthamoeba eradication through drug treatment. Normally, corneal transplantation in the treatment of Acanthamoeba keratitis, known as therapeutic keratoplasty, is limited to severe and progressive infections that do not respond to medical treatment, since performing a graft in a host with an ongoing infection and inflammation would greatly increase the risk of rejection and failure of the procedure.
However, in cases where the diagnosis has been delayed, the infection may lead to deep stromal keratitis. In such conditions, prolonged medical treatment leads to corneal toxicity, with poor penetration of the topical drug. In these patients, early surgical treatment by anterior lamellar keratoplasty (DALK) or optically penetrating keratoplasty (OPK) may be an alternative intervention. Nevertheless, penetrating optic keratoplasty in terms of visual rehabilitation, if performed in an eye in which the infection has already been cleared, appears to offer better results.
The surgical approach is also mandatory in cases of drug-resistant keratitis. In this case, a therapeutic penetrating keratoplasty (TPK) is preferable, which is performed when there is an infection that does not respond to clinical therapy or in the last stage of the disease, usually when the arrangement of Acanthamoeba cysts is deeper than 250 mm. Therapeutic penetrating keratoplasty (TPK) also appears to be the best choice in very advanced stages of the disease.
Alternatively, in cases of stromal disease, without endothelium involvement, therapeutic deep anterior lamellar keratoplasty (TDALK) has been proposed. TDALK allows the damaged corneal stroma to be replaced with healthy donor stroma, sparing the Descemet's membrane and endothelium of the recipient, thus reducing the risk of allograft reaction compared to full corneal transplantation.
Keratoplasty and keratitis: what to consider when choosing treatment
According to studies, eyes with Acanthamoeba keratitis treated surgically show fewer aberrations than eyes treated only pharmacologically, which is reflected in a better quality of vision and life.
However, the choice to proceed with corneal transplantation in Acanthamoeba keratitis should take into account:
- of the risks of corneal surgery in highly vascularised settings after previous inflammation;
- the limited improvement in vision (in terms of higher-order aberrations, HOA, and better corrected visual acuity, BCVA) compared to topical treatment alone.
Basically, after resolution of Acanthamoeba keratitis following topical treatment, OPK appears to be the best surgical choice. However, if keratitis cannot be eradicated by drug therapy, TDALK may be the choice in the early stages of the disease, while TPK in more advanced stages.
It is important to emphasise that there are currently no authorised drugs for the treatment of Acanthamoeba keratitis in any country. The most widely used 'off-label' therapy to date is based on a combination of diamidine and biguanide, or other non-specific drugs such as antibiotics, steroids and antifungals are used.
However, current recommendations from the Centres for Disease Control and Prevention (CDC) in the United States and the Royal College of Ophthalmologists in the United Kingdom recommend treatment with polyhexanide (0.02%) or chlorhexidine (0.02%) eye drops, either as monotherapy or with the addition of a diamidine.
As for the near future, it is expected that the first specific and effective drug for the pharmacological treatment of Acanthamoeba keratitis will be available.
After more than 15 years of research, the pharmaceutical company SIFI has, in fact, submitted an application to the EMA (European Medical Agency) for marketing authorisation of a polyhexanide-based drug 0.08%which is a candidate to become the first drug authorised for the treatment in monotherapy of this serious eye disease. It is expected to be on the European market by the end of 2023.