Acanthamoeba keratitis incidence increases in some areas

Acanthamoeba keratitis (AK) is a protozoan infection associated with contact lens wear, particularly unhygienic storage and cleaning of contact lenses. The microscopic organism commonly exists in soil and dust, lakes, rivers, hot springs and hot tubs.

According to Joseph P. Shovlin, OD, FAAO, a Primary Care Optometry News Editorial Board member with the Northeastern Eye Institute in Scranton, Pa., the incidence of AK has increased in certain parts of the world, but has not significantly changed in others.

“There certainly seem to be upswings or insurgences in certain geographic areas. For example, in England and South Korea, several reports have surfaced during the past 5 years showing an increased prevalence,” he said in PCON interview. “However, it is not certain whether we are experiencing an environmental shift.”

Geographic-based increases

Shifts in the prevalence of AK during the past 5 years seem to vary based on geographic region, Dr. Shovlin said.

“In the United States, some areas hard hit by natural disasters have experienced an unusually high number of infections,” he said. “The Chicago area recently reported an exceedingly high number of confirmed cases following a reduction in chlorine levels in the municipal water supply.”

Dr. Shovlin said that during the past 15 years, his group has cared for six confirmed cases prior to last year. “In the past 18 months, we’ve had five confirmed cases of AK associated with contact lens wear,” he said.

EPA study on Acanthamoeba

A 2004 Environmental Protection Agency (EPA) study determined that it is not necessary to regulate Acanthamoeba in drinking water. Researchers Nena Nwachuku, PhD, and Charles P. Gerba, PhD, examined the health effects of Acanthamoeba and its potential for waterborne transmission.

According to the EPA Web site (www.epa.gov), the work reported in this paper provides the most up-to-date information on all aspects of public health risk and presence of Acanthamoeba in water. The study provided the scientific basis and helped the EPA administrator make the “Do Not Regulate” determination decision for Acanthamoeba on the Contaminant Candidate List.

According to the EPA’s decision, AK is not commonly spread through drinking water. “The critical control point identified for AK in contact lens wearers is personal hygiene, not drinking water,” the paper said. “Therefore, there is no meaningful opportunity for health risk reduction for the general population by regulating.”

Acanthamoeba risk factors

Dr. Shovlin said the risk factors for AK include contact lens wear, a significant epithelial micro-dehiscence, repeated inoculation with contaminated solution or water, host susceptibility with perhaps a defect in mucosal immunity or host defense mechanisms.

“AK is often confused with sterile keratitis secondary to contact lens wear and herpes simplex keratitis,” he said.

According to John E. Sutphin Jr., MD, a professor at the University of Iowa Hospitals and Clinics, Department of Ophthalmology and Visual Sciences, additional risk factors include eye trauma; exposure to hot tubs, lakes or cisterns; and exposure to soil.

The EPA study further examined the risks factors associated with contact lens wear and divided these risk factors into subcategories. Of the AK cases assessed in the study, 85% of patients wore contact lenses, according to the EPA Web site. Of these, 56% wore daily wear lenses, 19% wore extended wear lenses, 26% had a history of corneal trauma and 25% had a history of exposure to contaminated tap water.

The study also listed risk factors related to contact lens care and hygiene:

• using tap water to wet or store lenses
• using bottled water to wet or store lenses
• using nonsterile solutions to wet or store lenses
• wearing contact lenses during swimming
• wearing lenses in hot tubs
• lens swapping
• wetting lenses with saliva

Differential diagnosis

Dr. Shovlin said, due to increased awareness about Acanthamoeba since the 1980s, clinicians are now more likely to consider AK as part of their red eye (keratitis) differential diagnosis, particularly in contact lens wearers with pain.

“An early diagnosis is paramount and will often help minimize morbidity to the cornea,” he said. “Telltale signs can be divided into regions of the cornea that are affected. Epithelial signs include a patchy epithelial involvement, and a stellate or pleomorphic epitheliopathy is possible. A bull’s eye lesion, elevated corneal lines in a dendriform pattern and punctate erosions are also seen early in the infection,” he said.

Common stromal signs include granulomatous or nonsuppurative infiltrates and radial keratoneuritis (“lightning flash”), he said. “Radial nerve infiltrates are only found in Acanthamoeba keratitis or leprosy,” he said. “So, the former is the more likely diagnosis in contact lens wearers with this finding.”

Dr. Shovlin said ring infiltrates are not pathognomonic, but very diagnostic in this patient population. However, he said, these tend to be a late presentation.

“Nonspecific findings include pseudo-guttate, hyphema, hypopyon, pseudomembrane, anterior or posterior scleritis, episcleritis, adenopathy and decreased sensation (initially),” he said. “Once an accompanying continuous scleritis ensues, the patient often experiences significant pain. There is a remarkable lack of corneal visualization in Acanthamoeba keratitis until medication toxicity occurs.”

According to Dr. Shovlin, differential diagnoses can be narrowed early by clinical suspicion, corneal scrapings, superficial keratectomy/biopsy, paracentesis, confocal microscopy and soft lens inspection.

“The most commonly employed techniques from the laboratory include plating on non-nutrient agar with an overlay of heat-killed Escherichia coli looking for growth of amoebae, immunofluorescent tests (direct and indirect) for capsid or nuclear staining, and confocal microscopy that is not only valuable for detection but also to monitor for clinical care,” he said.

Dr. Sutphin said AK is now being detected earlier, as much because of the technology as because of heightened awareness and early suspicion. “Patients with keratitis thought to be bacterial or viral who do not respond within 4 to 7 days should be evaluated for Acanthamoeba as well as fungus,” he said in an interview. “The confocal exam is very specific for Acanthamoeba and is easier to perform than with earlier microscopes.”

Acanthamoeba: An early diagnosis will help minimize corneal morbidity.

Treatment options

Dr. Sutphin said early recognition and treatment with topical chlorhexidine 0.02% or PHMB 0.02% are currently the first-line treatment for AK. “Treatment with Brolene (propamidine isethionate 0.1%, Aventis Pharma) or hexamidine is more controversial, and neomycin is only minimally effective,” he said. “For deeper lesions, one of the oral azoles, such as itraconazole or fluconazole, has been used in combination.”

Dr. Sutphin said this treatment is “intense”: hourly for 96 hours. Once the frequency is reduced, the duration is prolonged for at least 30 days, but usually longer.

According to Dr. Shovlin, first-line treatment for AK has been refined during the past 10 to 15 years, following a series of treatment trials for this relentless disease.

“Limitations in treatments during the past years relate to the paucity of effective medications, toxicity that results from their use and generally poor penetration deep into the stroma by the medications available,” he said. “The limited number of cases makes it difficult to design a clinical trial to determine effective treatment.”

He said a meta-analysis by Seals and colleagues has shown reasonable cure rates using 0.1% propamidine isethionate (Brolene) and 0.02% chlorhexidine digluconate (40/42), and McCulley and Wilhelmus found reasonable cure rates using 0.02% polyhexmethylene biguanide (PHMB/Bacquacil) and 0.1% propamidine isethionate (113/121).

“Armed with this information, most clinicians will use a dual therapy of an aromatic diamidine (anti-parasitic) such as propamidine to inhibit DNA synthesis and a biocide (PHMB) or cationic antiseptic (chlorhexidine) to inhibit membrane function,” Dr. Shovlin said.

“PHMB is available from Leiter’s pharmacy in California, and Brolene can be secured online from England or New Zealand pharmacies,” he said. “Additional adjuncts include cycloplegia, pain medications and judicious use of corticosteroids. However, the role for corticosteroid usage is controversial, because deterioration can occur and adverse events can develop while patients are on steroid therapy.”

For more information:

• Joseph P. Shovlin, OD, FAAO, can be reached at Northeastern Eye Institute, 200 Mifflin Ave., Scranton, PA 18503; (570) 342-3145; fax: (570) 344-1309; e-mail: jshovlin@aol.com.
• John E. Sutphin Jr., MD, can be reached at 200 Hawkins Dr., Iowa City, IA 52242-1091; (319) 356-2861; fax: (319) 356-0363; e-mail: john-sutphin@uiowa.edu.

References:

• Nwachuku N, Gerba C P. Health effects of Acanthamoeba spp. and its potential for waterborne transmission. Rev Environ Contam Toxicol. 2004;180:93-131.
• The study can also be found at www.waterquality.crc.org.au/hsarch/HS33g.htm.