Introduction

Acanthamoeba keratitis

Acanthamoeba keratitis (AK) is a rare but serious corneal infection caused by the Acanthamoeba species. It is well known for being painful, difficult to diagnose, and challenging to treat. In severe cases, it can lead to significant vision loss or, in extreme situations, the need to remove the affected eye. Vision loss mainly results from corneal ulceration and subsequent scarring.

AK most often affects young people who wear soft contact lenses, as well as agricultural workers. However, it can also develop in non–contact lens wearers, who often present later in the disease course and therefore face a poorer prognosis. Risk factors include corneal trauma, poor hygiene, biofilm formation, improper contact lens cleaning, and exposure to contaminated water or objects. Rarely, AK has also been reported as a complication after LASIK or radial keratotomy. The infection usually begins in the surface layer of the cornea (the epithelium) and then spreads deeper into the stroma, typically affecting only one eye. If left untreated or managed improperly, it can progress to corneal melting or perforation (a hole in the cornea).¹

Medications used in treatment

Amoebicidal agents

In Acanthamoeba keratitis, starting treatment early is critical, as delays are closely linked to poorer outcomes. Propamidine isethionate 0.1% was one of the first drugs used and is often combined with neomycin. In the initial stages, it is usually given hourly and then gradually tapered over several months. Because propamidine can be toxic to the eye, prolonged intensive use must be avoided, so careful adjustment of dosing is essential.

Polyhexamethylene biguanide (PHMB) 0.02%, a cationic disinfectant, represents another important advance in therapy. It has strong activity against both cysts and trophozoites of Acanthamoeba across multiple strains and shows relatively low toxicity. PHMB is usually applied hourly or every two hours in the acute phase, often in combination with propamidine. Once signs begin to improve, dosing is reduced to four times daily. To prevent recurrence—especially from cysts that may persist deep in the corneal stroma, where drug penetration is limited—treatment is continued for at least three to four months after inflammation has resolved.

Chlorhexidine 0.02% has also been studied as an alternative to PHMB, with several reports showing similar cysticidal activity. Some studies suggest minor differences in potency between the two agents; however, because randomised clinical trials are lacking, no clear advantage of one over the other has been established.²

Steroids

The role of steroids in treating Acanthamoeba keratitis (AK) is controversial because they can have both helpful and harmful effects. On the one hand, corticosteroids reduce inflammation, ease pain, and improve patient comfort. On the other hand, their immunosuppressive action may allow the parasite to form cysts or multiply, which can worsen the infection.

Inconsistency has also been seen in studies. Some studies indicate that applying corticosteroids after using an antiamoebic doesn't worsen outcomes. This suggests that well-centred and initiated treatments may lessen stromal inflammation as macrophages attack dead cysts in the cornea. 

Corticosteroid use before diagnosis and appropriate therapy is associated strongly with failure in treatment. The reason is that this seems to indicate an immunosuppressed state, in which the amoeba can grow without hindrance. This makes corticoids early and inappropriately very undesirable. In mild cases, or where there is no associated inflammation beyond the cornea, NSAIDs like flurbiprofen (50 to 100 mg, two to three times daily) will often do quite well. Flurbiprofen has anti-inflammatory, analgesic, and antipyretic properties.³

Antifungals

Antifungals, such as miconazole and clotrimazole, have been used as eye drops for treating Acanthamoeba keratitis. Voriconazole has also been reported, in both the topical and oral forms, for this condition. Laboratory studies showed that natamycin was more effective than propamidine isethionate and polyhexamethylene biguanide against the cyst form of Acanthamoeba. However, there is yet inconclusive clinical data regarding natamycin's efficacy in patients.⁴

Antibacterials

Neomycin can kill the trophozoite stage of Acanthamoeba but lacks high cysticidal action like other drugs. It cannot be utilised alone against cyst resistance; neomycin is capable of inducing hypersensitivity to itself as well as creating neomycin-resistant temperature-sensitive mutants. Treatment with neomycin in a "triple therapy", e.g., together with propamidine and dibromopropamidine, has successfully treated large numbers of AK patients. This is because neomycin indirectly affects Acanthamoeba by reducing trophozoite bacterial food and bacterial superinfection.³

Surgical interventions: a last resort

Therapeutic penetrating keratoplasty (TPK) was once the major form of therapy for Acanthamoeba keratitis (AK). The use of previous treatment advances in early diagnosis and medical therapy has, however, left some uncertainty regarding the timing and rationale for using this surgical option. One clear indication for TPK is nearing corneal perforation (development of a hole). In other cases, it can be considered when the disease moves to the centre part of the cornea despite the application of the strongest antiamoebics. 

Performing surgery early while the infection is localised might help by removing the infected area along with some healthy surrounding tissue. This gives the donor cornea a better chance of survival in a healthier ocular environment. After surgery, medical treatment should continue for several months to ensure that no Acanthamoeba organisms have survived. The chances of surgery being successful are markedly diminished if the infection penetrates too far to the edge of the cornea. In such cases, months of medical therapy may be indicated before surgery, but the prognosis is usually poor. This shows why, often, early surgical intervention is better. 

Other new forms of treatment, like conjunctival flap (CF) and amniotic membrane graft (AMG), have also proved valuable in the healing of the cornea and restoration of its surface. However, in cases of large corneal perforation, TPK is so far the only effective surgical treatment to save the eye.⁵

Challenges in eradicating Acanthamoeba keratitis

Delayed diagnosis

Acanthamoeba keratitis (AK) is hard to diagnose early, as its nonspecific presentation imitates other forms of keratitis. Between 90–93% of cases are wrongly diagnosed at the onset, particularly in non-contact-lens wearers when suspicion is minimal. Diagnosis consequently remains delayed by months, making prognosis worse and prolonging therapy.

Lack of standardised diagnostic protocols

The absence of uniform diagnostic tests for Acanthamoeba keratitis (AK) impedes significantly early and reliable detection. Diagnostic tests like confocal microscopy, PCR, and culture are employed intermittently, and there is no single tool that acts as a globally accepted gold standard. Further, the clinical presentation of AK, particularly in its early stages and among non-contact-lens wearers, tends to be subtle or unusual, leading to low diagnostic specificity and common misdiagnosis of the condition.⁶

Lengthy and complex treatment regimens

Treatment of Acanthamoeba keratitis (AK) is typically protracted and multifaceted, with treatment for less severe forms taking 3–4 months to complete and taking over 8 months in patients with deep stromal involvement. Having the T4 genotype, which is virulent and likely to be drug-resistant as well, makes eradication even more challenging. Moreover, the heavy burden of treatment punctuated by high-frequency dosing, adverse effects, and long duration can substantially weaken patient compliance and overall outcomes.

Severe visual and structural damage

Acanthamoeba keratitis (AK) has the potential to cause extensive visual and structural destruction, especially in advanced cases affecting stromal layers of the cornea, with a high likelihood of resulting in permanent damage. Advanced disease may require surgical therapy, such as therapeutic penetrating keratoplasty (PK), which is inherently risky and variably successful. Delayed treatment increases the probability of irreversible vision loss dramatically, with most patients having significantly diminished final visual acuity.

Initial inappropriate treatment

Inappropriate initial management is a frequent problem in the treatment of Acanthamoeba keratitis (AK). The inappropriate use of corticosteroids before a definitive diagnosis can worsen the disease by inhibiting the immune response and stimulating the growth of Acanthamoeba. Moreover, misdiagnosis often leads to the application of antiviral or antibacterial therapy, which is not effective against the amoeba and postpones the start of adequate antiamoebic treatment, worsening the prognosis in the end.⁷

FAQs

What is acanthamoeba keratitis (AK)?

AK is a serious eye infection caused by the Acanthamoeba species, mostly in contact lens wearers, resulting in pain, vision loss, and possible corneal scarring.

What are common causes of Acanthamoeba keratitis?

Common causes are poor hygiene of contact lenses, biofilms, trauma to the cornea, exposure to contaminated water, and surgical complications such as LASIK.

What is the best way to treat Acanthamoeba keratitis?

Early diagnosis and treatment with amoebicidal agents like propamidine, PHMB, and chlorhexidine are essential. Combination therapies are often used for better results.

What are the difficulties in treating Acanthamoeba keratitis?

Challenges are delayed diagnosis, absence of standardised diagnosis tests, complex and lengthy treatment regimens, and misdiagnosis or inappropriate treatment at the beginning.

Summary

Acanthamoeba keratitis (AK) is a serious eye disease predominantly in users of contact lenses, causing pain, loss of vision, and possible corneal scarring. Early detection and immediate treatment with amebicides such as propamidine, PHMB, and chlorhexidine is important. Neomycin can kill trophozoites, but it needs combination therapy to be effective. Corticosteroids will control inflammation but aggravate the infection if applied improperly. In more advanced cases, surgery such as therapeutic penetrating keratoplasty can be required. Treatment challenges include delayed diagnosis, absence of standardised tests, lengthy treatment regimens, and initial mismanagement.