Other Infectious Diseases
Acanthamoeba Keratitis
Nicky R. Holdeman
THE DISEASE
Pathophysiology
Acanthamoeba keratitis (AK) is a rare, sight-threatening disease, which results from colonization of the cornea with the free-living, microscopic, ubiquitous protozoa Acanthamoeba. These organisms have been isolated from treated and untreated tap water, swimming pools, salt water, air-conditioning units, air, dust, soil, vegetables, and animal waste.
Acanthamoeba inflammation is intensified by the release of proteolytic enzymes and stimulation of the immune system within the cornea. The organism is capable of existing in two forms: a free-living trophozoite, which is mobile and proliferates and feeds on bacteria and other unicellular organisms, and a double-walled cyst form that develops in response to a hostile environment, such as drugs, chemicals (chlorine), temperature, or other adverse stimuli. The cyst form is very hardy and can survive freezing temperatures and desiccation.
Etiology
AK results from exposure and subsequent infection of the cornea with Acanthamoeba. An epithelial break or bacterial infection may be necessary for Acanthamoeba infection, since the Acanthamoeba organism will initially sustain itself by ingesting bacteria. Contact lenses (CLs) may increase the ability of Acanthamoeba to bind to epithelial cells by altering the expression of certain proteins on the ocular surface.
The Patient
Clinical Symptoms
Symptoms commonly include pain, redness, foreign body sensation, photophobia, tearing, and decreased vision. The pain is often severe and out of proportion for the size of the corneal lesion and the extent of the inflammation. The accentuated pain (and decreased corneal sensitivity) may be a result of corneal nerve inflammation. However, in early cases, especially in the absence of keratoneuritis, pain may not be a significant symptom.
Clinical Signs
The keratitis may begin as an epithelial haze accompanied by epithelial breakdown, punctate staining, pseudodendrites, and elevated epithelial lines. The early presentation may be confined to the epithelium and is often a dendritiform epithelial pattern. Later in the infection, the more classic findings of a central stromal infiltrate, ring infiltrate, or satellite infiltrates may develop. Deep stromal involvement and presence of a ring infiltrate at presentation are often associated with a worse visual outcome.
Radial keratoneuritis—linear, branching infiltrates in the mid-stroma along the corneal nerves—which is considered the most specific sign for Acanthamoeba, may occur in less than 50% of patients.
Other conditions such as iritis, limbitis, scleritis, hypopyon, increased IOP, preauricular lymphadenopathy, and
conjunctival follicles may be present. There is typically an absence of neovascularization.
conjunctival follicles may be present. There is typically an absence of neovascularization.
A cataract may occur and progress during the management of AK. If left untreated, Acanthamoeba can potentially spread to the retina and cause serious chorioretinitis.
Note: Making the diagnosis is challenging, as AK is often misdiagnosed as a CL-related corneal epitheliopathy or the more common fungal or viral form of keratitis. The presence of conjunctival follicles, epithelial dendritiform pattern, PA nodes, and corneal hypothesia frequently leads to a misdiagnosis of herpes simplex keratitis. The lack of terminal end bulbs, typical in an HSV infection, is a good indicator that a patient may have AK.
Demographics
AK was first reported in the United States in 1973—an estimated 5,000 cases of AK have since occurred as of 2006; however, AK is so commonly misdiagnosed that the number could be much higher.
Although AK can occur in any age group, it is most often found in young adults who are immunocompetent.
CL wear has repeatedly been identified as a major risk factor for the development of AK. However, the condition is still very rare, affecting about 1.65 to 2.0/million CL wearers per year in the United States. Soft CL wearers are at 9.5 times greater risk of AK than rigid lens wearers.
The use of homemade saline and poor disinfection habits have been strongly associated with the condition.
Significant History
A history of corneal trauma, CL wear, and use of multipurpose solutions is important and comprises the primary risk factors for AK. CL wearers account for approximately 85% to 90% of cases, but AK can and does occur in non-CL patients.
Acanthamoeba has been found in contaminated CL cases and solutions. Inappropriate use of solutions, including homemade saline or rinsing of lenses in tap water or bottled water, puts a patient at significant risk.
A number of cases of AK have been reported in association with overnight orthokeratology and in patients swimming in a hot tub.
Ancillary Tests
Acanthamoeba can sometimes be cultured from corneal scrapings when plated on nonnutrient agar that has been overlaid with Escherichia coli. Samples should be incubated at approximately 37°C. Trophozoites feed on the bacterial overlay and usually appear within 3 days but can take up to 3 weeks. Cultures typically offer the most definitive means of diagnosis but are only positive in about 50% of clinically suspected cases.
The organism can be stained directly with Gram, Giemsa, methenamine silver, or Wright stain; however, identification is difficult. The chemofluorescent dye, calcofluor white, is often used to visualize the cysts and trophozoites. Periodic acid Schiff or acridine orange may also aid in the diagnosis.
PCR can be used as a diagnostic tool when very few cells are available for visual determination. This test has a reported sensitivity of 84% and specificity approaching 100%. Unfortunately, PCR techniques are expensive and require skilled technicians, which limit their usage.
Real-time fast-duplex TaqMan PCR (f-d-real-t PCR) appears to have a higher sensitivity and specificity than other techniques and may simultaneously detect ten different genotypes of Acanthamoeba. Future studies are needed to confirm the usefulness of this technique for disease management of AK.
In vivo corneal confocal microscopy is a rapid, noninvasive method for the diagnosis of Acanthamoeba. If performed and analyzed by an experienced clinician, this instrument offers high sensitivity and specificity (-90%) compared with smear and culture. It may also be helpful in excluding fungal or Acanthamoeba-like structures in cases with negative bacteriologic results.
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