Mohammad Elkossi

Introduction

Acanthamoeba keratitis (AK) is uncommon, but missing the diagnosis can have devastating consequences. The early clinical picture is often non-specific, and the disease can closely mimic herpes simplex keratitis (HSK). For any clinician assessing a contact lens wearer with keratitis, keeping Acanthamoeba a part of the differentials is therefore essential.

The clinical presentation

The typical patient is a contact lens wearer presenting with unilateral red, painful and photophobic eye, often with reduced vision. Pain out of proportion to the clinical findings is a classic clue, although it is not typically present in every case.

A thorough contact lens history is important. Risk factors include overnight/extended wear, poor lens hygiene and exposure of lenses to tap water, swimming pools or other contaminated water.

The early examination may be surprisingly unremarkable. Punctate epithelial changes, epithelial defects and pseudodendritic lesions can occur, while stromal disease may initially be subtle. As the infection progresses, radial keratoneuritis, multifocal stromal infiltrates and eventually the characteristic ring infiltrate may develop (1).

The major diagnostic pitfall is presumed HSK in a contact lens wearer. A dendritic or pseudodendritic epithelial lesion does not necessarily mean herpes. Severe pain, radial keratoneuritis, stromal infiltrates, an atypical course or failure to respond to appropriate antiviral treatment should prompt reconsideration of the diagnosis.

This is particularly important before starting topical corticosteroids. Prior steroid use before the diagnosis of AK has been associated with poorer visual outcomes, and misdiagnosis as HSK is a recognised reason for inappropriate steroid exposure (2).

Confirming the diagnosis

When AK is suspected, corneal scraping should be performed where appropriate and samples sent for microscopy and culture, specifically for Acanthamoeba. PCR can provide an additional diagnostic route, particularly when conventional microbiology is negative. No single investigation should, however, be regarded as definitive in isolation (1,3).

The role of confocal microscopy

In vivo confocal microscopy (IVCM) can be particularly helpful when the clinical suspicion is high but microbiology is inconclusive.

Acanthamoeba cysts appear as highly reflective, rounded structures, classically with a double-walled appearance. Trophozoites may also be seen, although they are more difficult to identify reliably.

A 2023 systematic review and meta-analysis found pooled sensitivity of 94% and specificity of 87% for confocal microscopy in AK (4). Other studies have similarly demonstrated good diagnostic performance, particularly when IVCM is interpreted by experienced clinicians (5).

However, IVCM is an adjunct rather than a replacement for corneal sampling. Interpretation is operator-dependent, and structures such as bright spots are not specific to Acanthamoeba (6). A negative scan should therefore not completely exclude AK when the clinical picture remains suspicious. In practice, combining clinical assessment, microbiological investigation and IVCM provides the best opportunity for an early diagnosis.

Treatment: act early

Once AK is strongly suspected, treatment should not be delayed while awaiting microbiological confirmation.

The mainstay of therapy is topical biguanide treatment, traditionally PHMB or chlorhexidine, often combined with an aromatic diamidine such as propamidine or hexamidine. Treatment is initially intensive and is subsequently reduced according to clinical response (1,7).

The recent Orphan Drug for Acanthamoeba Keratitis (ODAK) trial provides important evidence for the use of higher-concentration PHMB monotherapy. The trial compared PHMB 0.08% with PHMB 0.02% plus propamidine 0.1% and found similar 12-month medical cure rates: 86.7% and 86.6%, respectively (7). This suggests that PHMB 0.08% monotherapy is a reasonable evidence-based option, although treatment protocols vary between centres and availability of preparations remains an important practical consideration.

Treatment is prolonged. Acanthamoeba can exist as trophozoites and highly resistant cysts, meaning that apparent clinical improvement does not necessarily indicate eradication. Therapy may need to continue for many months, with gradual reduction in frequency under specialist supervision (1,7). Contact lens wear should cease immediately, with the lenses, case and solutions discarded.

The role of topical corticosteroids remains controversial. They should not be started in untreated or inadequately treated AK. If significant inflammation persists once effective anti-Acanthamoeba therapy has been established, corticosteroids may occasionally be considered under specialist supervision (2,8).

Refractory disease may require additional therapies such as systemic miltefosine or topical agents including voriconazole, although the evidence for these approaches remains considerably less established than for biguanides (1).

What happens in the long term?

AK is often a prolonged disease. Patients may continue to experience pain, photophobia and fluctuating vision even after the infection is coming under control. Treatment should therefore be tapered cautiously, with prolonged follow-up.

The visual outcome depends heavily on the stage at diagnosis. Early disease treated appropriately can have a good outcome, whereas advanced stromal involvement may leave significant corneal scarring, irregular astigmatism or permanent visual impairment. Therapeutic keratoplasty may be required for progressive infection, perforation or disease refractory to medical treatment (1,7).

Once the infection has been eradicated, residual corneal opacity or irregular astigmatism can be addressed with optical rehabilitation, including consideration of corneal transplantation in selected patients.

The take-home message

The most important intervention in AK may be thinking of it early enough.

A contact lens wearer with presumed HSK should prompt a second look if the pain is disproportionate, the clinical findings are atypical or the response to antiviral treatment is not as expected. Corneal sampling and, where available, IVCM can help establish the diagnosis.

Most importantly, do not let the presence of a dendritic-looking epithelial lesion close the diagnostic process. In the contact lens wearer, Acanthamoeba needs to remain firmly on the list.

References

1. Dart JKG, Saw VPJ, Kilvington S. Acanthamoeba keratitis: diagnosis and treatment update 2009. Am J Ophthalmol. 2009;148(4):487-499.e2.
2. Robaei D, Carnt N, Minassian DC, Dart JKG. The impact of topical corticosteroid use before diagnosis on the outcome of Acanthamoeba keratitis. Ophthalmology. 2014;121(7):1381-1386.
3. Tappeiner C, et al. Comparison of culture, confocal microscopy and PCR in routine hospital use for microbial keratitis diagnosis. Br J Ophthalmol. 2022;106(6):830-836.
4. Moshtaghion SM, Abolhosseini M, Yaseri M, Hosseini SB, Rezaei Kanavi M. Diagnostic accuracy of confocal scan in detecting Acanthamoeba keratitis and fungal keratitis: a systematic review and meta-analysis. Int Ophthalmol. 2023;43(8):3011-3022.
5. Vaddavalli PK, et al. Role of confocal microscopy in the diagnosis of fungal and Acanthamoeba keratitis. Ophthalmology. 2011;118(1):29-35.
6. Hau SC, Dart JKG, Vesaluoma M, et al. Diagnostic accuracy of microbial keratitis with in vivo scanning laser confocal microscopy. Br J Ophthalmol. 2010;94(8):982-987.
7. Dart JKG, et al. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (polihexanide) and placebo versus PHMB 0.02% and propamidine 0.1%. Ophthalmology. 2024;131(2):145-155.
8. Kappagoda S, et al. Advances in the management of Acanthamoeba keratitis: a review of the literature and synthesized algorithmic approach. Surv Ophthalmol. 2022.