Medical interventions for acanthamoeba keratitis: Cochrane systematic review



Acanthamoeba are microscopic, free-living, single-celled organisms which can infect the eye and lead to Acanthamoeba keratitis (AK). AK can result in loss of vision in the infected eye or loss of eye itself; however, there are no formal guidelines or standards of care for the treatment of AK.


To evaluate the relative effectiveness and safety of medical therapy for the treatment of AK.

Search methods

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), PubMed (1948 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 2015), the metaRegister of Controlled Trials (mRCT) (, ( and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) ( We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 9 January 2015.

Selection criteria

We included randomized controlled trials (RCTs) of medical therapy for AK, regardless of the participants’ age, sex, or etiology of disease. We included studies that compared either anti-amoeba therapy (drugs used alone or in combination with other medical therapies) with no anti-amoeba therapy or one anti-amoeba therapy with another anti-amoeba therapy.

Data collection and analysis

Two authors independently screened search results and full-text reports, assessed risk of bias, and abstracted data. We used standard methodological procedures as set forth by the Cochrane Collaboration.

Main results

We included one RCT (56 eyes of 55 participants) in this review. The study compared two types of topical biguanides for the treatment of AK: chlorhexidine 0.02% and polyhexamethylene biguanide (PHMB) 0.02%. All participants were contact lens wearers with a median age of 31 years. Treatment duration ranged from 51 to 145 days. The study, conducted in the UK, was well-designed and had low risk of bias overall.

Outcome data were available for 51 (91%) of 56 eyes. Follow-up times for outcome measurements in the study were not reported. Resolution of infection, defined as control of ocular inflammation, relief of pain and photosensitivity, and recovery of vision, was 86% in the chlorhexidine group compared with 78% in the PHMB group (relative risk (RR) 1.10, 95% confidence intervals (CI) 0.84 to 1.42). In the chlorhexidine group, 20 of 28 eyes (71%) had better visual acuity compared with 13 of 23 eyes (57%) in the PHMB group at final follow-up (RR 1.26, 95% CI 0.82 to 1.94). Five participants required therapeutic keratoplasty: 2 in the chlorhexidine group compared with 3 in the PHMB group (RR 0.55, 95% CI 0.10 to 3.00). No serious adverse event related to drug toxicity was observed in the study.

Authors' conclusions

There is insufficient evidence to evaluate the relative effectiveness and safety of medical therapy for the treatment of AK. Results from the one included study yielded no difference with respect to outcomes reported between chlorhexidine and PHMB. However, the sample size was inadequate to detect clinically meaningful differences between the two groups as indicated by the wide confidence intervals of effect estimates.


Alkharashi Majed, Lindsley Kristina, Law Hua Andrew, Sikder Shameema


Medical interventions for acanthamoeba keratitis

Review question
We reviewed the evidence about medical treatments for Acanthamoeba keratitis.

Acanthamoeba are microscopic, free-living, single-celled organisms. Infection of the eye by these organisms is known as Acanthamoeba keratitis (AK). Although very rare, if left untreated AK can lead to the loss of vision in the eye or, in extreme cases, loss of the eye itself. Contact lens wear is the most common risk factor for AK. The most common symptom of AK is severe pain, which is out of proportion to the clinical signs and associated with sensitivity to light, blurry vision, and tearing.

Study characteristics
We found one eligible study of 55 participants from the UK. All participants in the study had a history of contact lens wear. The study randomly assigned people with AK to one of two medical treatment options: chlorhexidine eye drops or polyhexamethylene biguanide (PHMB) eye drops. Participants in the study were treated for 51 to 145 days.

Key results
In the one study identified, similar results were seen between the chlorhexidine and PHMB groups in terms of resolution of infection, changes in vision, or need for surgery. However, the number of participants in the study was small and the results uncertain; thus, we cannot be confident that there are really no differences between these treatments. No serious side effect was observed with either treatment in the study.

Quality of the evidence
Although the study was well-designed with no suggestion of bias, the results must be interpreted carefully because of the small number of participants.

Reviewer's Conclusions

Implications for practice

This review identified a paucity of evidence to inform robust conclusions for treating AK in practice. One study of 55 participants with AK randomized to one of two topical biguanides resulted in insufficient evidence of any difference between chlorhexidine and polyhexamethylene biguanide with respect to resolution of infection, changes in visual acuity, or need for keratoplasty. The results should be interpreted cautiously as these data represent a small sample of the population.

Implications for research

There is a need for well designed and adequately powered RCTs to determine 1) which anti-amoebic therapy is favorable over another anti-amoebic therapy in treating AK and 2) whether adjunctive treatments to anti-amoebic therapy, such as antibiotics, are beneficial compared with anti-amoebic therapy alone. Important outcomes for sample size calculations should include resolution of infection, improvement in vision (20/40 or better), and reduction in patient-reported symptoms, especially pain. In order to enroll a sufficient sample size, RCTs should be multi-centered with a central coordinating center to ensure methodological standards and consistency of protocols are maintained across all study sites. Participants, study personnel, and outcome assessors should remain masked from the participant treatment assignment until the trial ends and data have been analyzed. These studies also should prespecify times for outcome measurements with follow-up of six to 12 months.

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