Acanthamoeba Keratitis

Signs and Symptoms: Acanthamoeba keratitis can occur in

patients of any age, sex or race, but mostly manifests in young, healthy adults. The list of risk factors is long: corneal foreign body, contact with non-sterile water, bullous keratopathy, neurotrophic keratopathy, herpes simplex keratitis, radial keratotomy, swimming and scuba diving, basement membrane dystrophy, contact lens wear and bacterial keratitis. Cases sometimes arise with no identifiable risk factors. Essentially, any event that disrupts the corneal epithelium is a potential risk factor for Acanthamoeba keratitis.

Acanthamoeba keratitis.

Patients with Acanthamoeba keratitis typically present with a unilateral, red, painful eye. Initially, there is typically a non-specific epitheliopathy which can progress to ulceration with infiltration. Limbititis occurs as 1-3 the initial finding in 94% of early stage cases and in 84% of late-stage cases. Another common finding is radial keratoneuritis, or perineuritis; this involves irregularly thickened corneal nerves in the anterior to mid-stroma with shaggy borders. Other clinical signs of Acanthamoeba keratitis include irregular epithelial defect, corneal microcysts, punctate keratopathy, bullous keratopathy, disciform stromal keratitis, pseudodendritic keratitis, anterior uveitis and a granulomatous stromal reaction. While Acanthamoeba keratitis has historically been associated with stromal ring infiltrate formation, only 6% of early cases and 1-3 16% of late cases actually present in this manner clinically. About half of patients report significant pain, the rest experience only mild irritation and foreign-body 4,5 sensation. Those who do report pain often present a degree much worse than the clinical appearance suggests. Rarely is Acanthamoeba keratitis correctly diagnosed in the early stage. It typically follows a chronic course that waxes and wanes over weeks to months and never fully heals despite seemingly appropriate therapy. In fact, the diagnosis is often finally made when all other treatments fail.

Pathophysiology: Acanthamoeba keratitis occurs from Acanthamoeba castellani, an opportunistic

free-living soil amoeba that is most commonly associated with incorrect contact lens handling and exposure to unsanitary conditions. While rare, the incidence of recognized Acanthamoeba keratitis is rising, due mostly to correct diagnoses in cases of non-specific keratitis as well as increased use of confocal microscopy. This noninvasive diagnostic modality readily identifies Acanthamoeba cysts in the cornea. Unortunately, this technology is not widely available. As we said previously, few correctly diagnose Acanthamoeba keratitis early on. Clinicians have mistaken Acanthamoeba keratitis for herpetic, fungal and bacterial keratitis. Acanthamoeba keratitis is partially amenable to non-protozoan treatments, and can wax and wane for years before a correct diagnosis is made. Certain antibiotics as well as preservatives in topical medications create a hostile environment for the microbe; in response, Acanthamoeba will encyst and become dormant, reducing the symptoms and clinical signs. So Acanthamoeba may seem partially responsive to other treatments, assuming a chronic course prior to the correct diagnosis. Acanthamoeba keratitis can present initially as a dendritic keratitis similar to herpes simplex keratitis (HSK), with this exception: there are no herpetic terminal end bulbs in Acanthamoeba keratitis. There probably have been cases of Acanthamoeba keratitis that clinicians have mistakenly treated for HSK. And, there have been reports of coexistent infections of both HSK and Acanthamoeba keratitis, with the Acanthamoeba presenting as a secondary, opportunistic infection. The Acanthamoeba organism nestles in the thickened border of the epithelium. Consider Acanthamoeba infection in cases of presumed or actual herpes simplex keratitis that does not respond to standard antiviral therapy. Corneal scrapings of Acanthamoeba may be cultured for diagnosis. This calls for non-nutrient agar with overlay of either Escherichia coli or Enterobacter. Culturing can take 1-9 days, sometimes longer. Unfortunately, the diagnostic yield is low and cultures are often falsely negative. Cultures often will reveal

the presence of bacteria, because Acanthamoeba frequently coexists with bacterial colonies upon which it feeds. Acanthamoeba often accompanies other corneal diseases, and may not be the primary or most active disease process in a combined keratitis.

Management: Treatment of Acanthamoeba keratitis is difficult due to the organism's ability to encyst
with the use of topical medications. Effective medications include topical polyhexamethylene biguanide (PHMB), propamidine isethionate (Brolene), chlorhexidine digluconate 0.02%, polymixin B, neomycin and clortrimazole 1%. In one series of 10 patients, the combination of Brolene and PHMB successfully cured all cases of Acanthamoeba keratitis. Cautious introduction of topical steroids along with anti-amoebic therapy helped resolve the inflammation and provided symptomatic relief.

Clinical Pearls:
Strongly suspect Acanthamoeba keratitis in chronic keratitis that does not respond to treatment. While ring infiltration has historically been associated with Acanthamoeba keratitis, it is a relatively rare finding and typically occurs late in the disease. Non-specific epitheliopathy is typically the presenting feature. As Acanthamoeba feeds upon bacteria, it frequently accompanies bacterial ocular infections. Acanthamoeba play a part in coinfections, sometimes explaining why other corneal infections do not respond to conventional therapy.