Microbiology:Acanthamoeba is a genus of protozoans that are ubiquitously present in various habitats, including water, air, soil, and dust. The most common species that cause AK are Acanthamoeba castellani and Acanthamoeba polyphaga
- Acanthamoeba species exist in two forms, an active trophozoite or a dormant cyst.
- Trophozoite form: Feeds on bacteria, algae, and yeasts. Trophozoites are also capable of slow locomotion and asexual reproduction.
- Cystic form: Exhibits minimal metabolic activity and is capable of surviving adverse environmental conditions such as severe changes in temperature or pH, high doses of UV-light, food deprivation, or desiccation.
Risk factors:Causes of AK appear to be multifactorial, but most cases have been linked to contact lens wear and their cleaning solutions.
- Contact lens wear (M/C cause)
- Corneal injury
- Exposure to dust, soil, or contaminated water
Acanthamoeba keratitis usually presents unilaterally but may rarely occur in both eyes.
Excruciating pain (PATHOGNOMIC)The characteristic finding of AK, even in the early stage, is pain out of proportion to clinical findings; there is a thought that this is due to the action of trophozoite-derived proteases.
Other features:Symptoms may wax and wane between mild and severe.
- Decreased vision
- Eye redness
- Foreign body sensation
- Tearing, and discharge
- Common complications: Glaucoma, iris atrophy, broad-based anterior synechiae, cataract, and persistent endothelial defect
- Rarer complications: Scleritis, sterile anterior uveitis, chorioretinitis, and retinal vasculitis
Approximately 75 to 90% of patients with early acanthamoeba keratitis are initially misdiagnosed; therefore, a diagnosis of acanthamoeba keratitis should merit special consideration in patients with several weeks of symptoms that have not improved despite compliance with a daily regimen of topical antibiotics or antivirals. The clinician should consider bacterial superinfection if symptoms worsen despite the initiation of appropriate treatment.
Comprehensive ocular examination is also necessary for patients with suspected ocular infection.
Slit-lamp examination:As many of these exam findings are non-specific, the clinician must have a high index of suspicion for AK in cases in which the history and other features are highly suggestive.
- Early findings:
- Epitheliopathy with punctuate keratopathy
- Epithelial or subepithelial infiltrates
- Perineural infiltrates (> 60% cases): Highly suggestive for AK
- Late-stage findings:
- Characteristic featuresL “Ring-like” stromal infiltrate & radial keratoneuritis
- Other findings: Satellite lesions, ulceration, abscess formation, anterior uveitis with hypopyon, and epithelial defects
- Advanced disease: Stromal thinning and corneal perforation
Plate culture technique:Gold standard for the detection of Acanthamoeba. Corneal scraping or biopsy is required to obtain a sample for culture. As Acanthamoeba trophozoites feed on bacteria, cultures will develop on 1.5% non-nutrient agar plates covered by E. Coli. The rate of positive culture result for Acanthamoeba in the setting of acanthamoeba keratitis is generally low, reported anywhere from 40-70%. Samples must be observed daily for up to one week before declaring a negative result.
Polymerase chain reaction (PCR):PCR has the advantages of being widely available, fast, and less labor-intensive. Thus, there is some reason to believe that PCR may become the new gold standard for the diagnosis of acanthamoeba keratitis in the near future.
- 18s rRNA region: M/C employed to detect Acanthamoeba in clinical samples
In vivo confocal microscopy (IVCM):IVCM is also an extremely useful tool that allows for the non-invasive examination of individuals cells of the cornea in real-time. IVCM will only reliably detect cysts, which will appear as well-defined, round, double-walled, hyper-reflective bodies. The pooled sensitivity and specificity of IVCM in one study were found to be 85.3% and 100%, respectively. IVCM may also be used to monitor disease progression and response to treatment. However, IVCM is expensive and often not readily available.
Cytology:Cytology smears is a viable method to detect Acanthamoeba cysts on corneal scrapings or biopsied tissue. Cytology smears have the advantage of being fast, easily performed, and readily available in most facilities. Cytology smears additionally do not require live organisms as with culture or intact DNA as required for PCR.
Newer diagnostic procedures:
- Loop-mediated isothermal amplification (LAMP)
- Novel, non-invasive imaging techniques:
- Heidelberg retina tomography II (HRT II)
- Nuclear magnetic resonance (NMR) spectroscopy
- Contact lens associated keratitis
- Dry eye
- Herpes simplex virus keratitis
- Recurrent corneal erosion
- Staph marginal keratitis
Acanthamoeba trophozoites are frequently sensitive to a variety of medications, including antibiotics, antiseptics, antifungals, and antiprotozoals. However, Acanthamoeba is resistant to most of the listed treatments in the cystic form, thereby allowing for prolonged infection. Both medical and surgical options may be considerations in the setting of treatment-resistant AK.
Antiamebics:The goals of medical therapy include the eradication of viable cysts and trophozoites and rapid resolution of the associated inflammatory response. Diamidines and biguanides are two classes of antiamebics that are often the first-line therapy for acanthamoeba keratitis due to their proven cysticidal effects. Topical treatment should continue for up to one year after PK.
- Epithelial debridement can be performed to allow for improved penetration of topical medications
Extra corneal manifestations:The development of extra corneal manifestations such as scleritis or limbitis indicates a worse outcome and warrants treatment with anti-inflammatory medications. These medications may warrant continuation for several months to control inflammation and eradicate the pathogen.
- NSAIDs: Oral flurbiprofen (50-100 mg, 2-3x daily)
- High-dose systemic steroids: Prednisolone 1 mg/kg/day
- Systemic immunosuppressants: Cyclosporine (3.0 to 7.5 mg/kg/day)
Surgical management:If acanthamoeba keratitis remains unresponsive to topical conservative treatment, various surgical options remain available. Notably, PK used to be the first-line therapy for AK before biguanides and diamidines. Now, PK is generally only for patients with significant cataract, fulminant corneal abscess, corneal perforation, or therapy-resistant ulceration with peripheral neovascularization.
- Penetrating keratoplasty (PK)
- Corneal cryoplasty
- Amniotic membrane transplantation
- Riboflavin-UVA crosslinking