Acanthamoeba Keratitis

Acanthamoeba keratitis is a rare, parasitic eye disease. It is caused by Acanthamoeba and may seriously impair vision.

  • Processes: infectious

Overview

Acanthamoeba keratitis (AK) is a rare eye disease caused by amoebae of the genus Acanthamoeba that colonize the cornea of the eye. If left untreated, permanent consequences and even blindness may result from it [1].

In industrialized countries, AK incidence is largely associated with contact lens use. It has been estimated that 85% of all AK cases correspond to individuals wearing contact lenses. Presumably, contact lens use results in numerous but minimal cornea lesions that facilitate tissue colonization by amoebae. If inadequate hygiene measures allow the parasite to reach the protective space between a contact lens and the cornea of the eye, it will invade the tissue through the aforementioned lesions and release proteases until it reaches the corneal stroma.

Symptoms related with AK are unspecific and involve pain, redness, excessive sensibility to light, blurred vision and foreign body sensation. In the advanced stages of the disease, the cornea becomes increasingly cloudy and pain augments. Diagnosis requires detection of parasite stages in histopathological examinations or cultures.

Treatment mainly consists in frequent and prolonged topical administration of antimicrobial agents. Generally, distinct compounds are combined in order to eliminate not only the infective parasite stages, but also the more resilient, permanent ones. After termination of therapy, patients have to be monitored closely for possible recurrences. If patients do not respond to medication, a corneal transplantation may be required.

Etiology

Causative agents of AK are distinct species of amoeba pertaining to the genus of Acanthamoebae. These parasites may trigger the disease while they exist as infective trophozoites, parasite stages that measure up to 50 μm in diameter and that present filamentous cellular processes called acanthopodia. Acanthamoebae may also exist as non-infective but resilient cysts. Such cysts may resist extreme conditions of temperature, humidity, pH and concentration of chemicals for years and may then give rise to infective trophozoites again [2].

Acanthamoebae may invade the cornea of the eye and this process is largely facilitated by pre-existing, small cornea lesions. There are isolated case descriptions regarding surgical procedures such as radial keratotomy as possible triggers of AK [3] [4]. In industrialized countries however, such lesions are largely associated with contact lens use. Indeed, the majority of AK patients in the United States wears contact lenses [5] [6]. The parasite may survive in the protected space between cornea and contact lens, will not be exposed to constant movements of the eyelid and can then invade the tissue. Inadequate hygiene measures concerning contact lens use increase the risk for AK. This is the case if contact lenses are not appropriately disinfected, if homemade solutions are used for this purpose or if contact lenses are not used as recommended by the manufacturer. AK has also been associated with contact lens use while swimming.

In other countries, however, AK may also be observed in patients who do not use contact lenses [7] [8].

Epidemiology

Considering the etiology of the disease, it is not surprising that AK incidence increased in the United States when disposable contact lenses became available to large parts of the population at the end of the last century [9]. This trend, however, apparently reversed when effective cleaning solutions were marketed.

Estimates regarding the overall incidence of AK range between 1 and 4 per million inhabitants. Among people who wear contact lenses, the incidence has been estimated to be about 1 per 10,000 individuals [10]. Thus, the risk for AK increases up to 100-fold when wearing contact lenses.

There are no reliable data regarding the incidence of AK complications such as systemic infection and amoebic encephalitis. They are considered to be very rare. With regards to amoebic encephalitis, only about 100 cases have been reported to date.

Pathophysiology

According to current knowledge, minimal cornea lesions greatly facilitate cornea invasion by Acanthamoeba. As it has been previously mentioned, such lesions may result from contact lens use and, in rare cases, from surgical interventions. There are several sources of causative pathogens that patients may be in contact with during everyday life. It is likely that amoeba reach the protective space between contact lens and cornea when contaminated cleansing solutions are used or when contact lenses are worn while swimming. In fact, if contaminated lenses are placed on the cornea, minimal abrasions may be formed on it and allow parasitic invasion. The circumstances of parasitic cornea invasion in individuals that do not wear contact lenses are not yet completely understood. Possibly, cornea lesions are present but result from other causes.

In vitro studies have proven that amoeba adhere significantly stronger to the cornea when protective, superficial cell layers are eliminated. Amoeba binding to molecular targets has been shown to be species specific and AK could only be detected in humans, rabbits, hamsters and pigs while other species seem to be resistant to infection. Upon adherence, parasites release proteases and thus clear the way to deeper layers, up to the corneal stroma.

Prognosis

AK usually responds well to treatment. Early detection and adequate treatment is important to avoid permanent visual impairment.

Presentation

There are no pathognomonic symptoms of AK. Generally, patients report pain, excessive sensibility to light, blurred vision and foreign body sensation. The affected eye is usually reddened. The cornea may be cloudy, but during early stages of the disease only epithelial irregularities may be noted. Scleritis and anterior uveitis may be observed. If left untreated, eye pain will aggravate and corneal perforations may develop. Symptoms may last for months and finally result in blindness if therapeutic measures are delayed for any reason.

Because symptoms of AK are very similar to those observed in other forms of viral or bacterial keratitis, patients that have recently been diagnosed with such a disease and do not respond to therapy may be suspicious for AK.

Workup

A detailed medical history should be obtained. With regards to the Western world, AK is unlikely but not excluded in patients that do not use contact lenses. The patient should be questioned regarding their contact lens hygiene. Special attention should be given to the periods of time during which contact lenses are worn, to the frequency of changes, to cleansing solutions utilized and to any habits that may increase the risk for AK.

AK can only be verified when amoeba trophozoites and/or cysts are identified in histopathologic examinations or in corneal cultures. Such findings are highly specific, but little sensitive. Therefore, negative histopathologic or culture results do not rule out the presence of amoeba. More sensitive diagnostic approaches such as confocal microscopy and molecular biology methods may be required to confirm AK in these cases.

Treatment

AK requires aggressive surgical and pharmacological treatment [11] [12]. The existence of resilient cysts on the patient's cornea often complicates their treatment and causes frequent relapses.
The mainstays of medical treatment are topical antimicrobial agents. This way, achieved compound concentrations are higher than with systemic therapy. Combined treatment with two or more antimicrobials, e.g. 0.02% chlorhexidine and 0.02% polyhexamethylen biguanide is generally recommended to eliminate both trophozoites and the above mentioned cysts [12]. Propamidine and hexamidine may be used as alternative options but are not readily available.

Before topical treatment is started, corneal debridement should be realized. Initially, antimicrobials should be administered every hour. If the patient responds well to treatment, the frequency of applications may then be gradually reduced. After two weeks, antimicrobials should still be administered every three hours. Therapy should not be stopped before four weeks of uninterrupted treatment, sometimes it is even recommended to continue treatment for up to one year. After termination of treatment, close monitoring is required to detect possible relapses.

There is no evidence regarding potential benefits of steroid therapy. In fact, there are studies indicating that steroid therapy does not change the outcome, but rather worsens it [13] [14]. Steroid therapy may increase the risk for secondary bacterial infections. Thus, steroids should not be used to treat AK.
If patients do not respond to medical therapy, the infected cornea needs to be replaced. After thorough corneal debridement, a keratoplasty may be realized.

Prevention

Appropriate hygiene measures for contact lens use largely contribute to AK prevention. In this context, the manufacturers’ recommendations concerning minimal and maximal periods of time to wear lenses should be followed. Also, contact lenses should never be cleaned with homemade solutions, saliva or any fluids that are not specifically produced for contact lens cleansing. Cleansing solutions should not be reused. If contamination is suspected, the whole bottle should be discarded. Before contact lenses are handled, the hands should be thoroughly washed with water and soap. Before showering, taking a bath or swimming, contact lenses should be removed. While contact lenses are not used, they should be stored in the appropriate case that, in turn, should be cleaned regularly and replaced every three months.

If any problems regarding vision or eye sensation are experienced, a general practitioner or ophthalmologist should be consulted in order to avoid possible exacerbations of the disease.

Research is currently conducted to assess the possibility of immunization against AK. Animal studies have provided promising results, but the method has not been validated in men yet.

Patient Information

Acanthamoeba keratitis (AK) is a rare eye disease. Causative agents of AK are distinct species of the genus Acanthamoeba that invade the cornea of the eye and cause tissue damage, with possibly permanent consequences if not treated in a timely manner.

Causes
Acanthamoeba are very small parasites that are not visible to the naked eye. They live on even smaller microorganisms and may be present in different aqueous solutions.

In industrialized countries, AK is largely associated with contact lens use. When hygiene recommendations are ignored, contact lenses are cleaned with homemade solutions or other inappropriate fluids or are handled with dirty hands, they may easily be contaminated with amoeba. If a contaminated lens is placed on the cornea of the eye, amoeba gets trapped between the lens and the cornea. They are able to survive in this protected space, to invade the cornea and cause AK.

Symptoms
AK may cause redness and pain of the eye, excess sensibility to light, tearing and blurred vision. Some patients experience the sensation of a foreign body in the eye. In advanced stages of the disease, the cornea may become cloudy. While the infection advances, pain and visual impairment will continuously increase.

Diagnosis
An ophthalmologic examination will confirm keratitis, but the physician is usually not able to distinguish between parasitic, viral and bacterial infections. In order to do so - and to be able to choose the appropriate treatment - they will need to obtain small tissue samples that can be examined microscopically. It may also be necessary to prepare cultures or to realize molecular analyses before the presence of Acanthamoeba can be confirmed.

Treatment
In order to prepare topical treatment, the affected cornea needs to be cleaned from debris. Afterwards, topical antimicrobials may be administered. Certain forms of Acanthamoeba are very resistant to antimicrobials, which is why usually two or three compounds are applied in a combined therapy. Antimicrobial treatment has to be administered very often, initially every hour, and for several weeks or months. The patient's response to treatment will determine when treatment can be stopped. Premature discontinuation of antimicrobial treatment is likely to cause recurrences.

In severe cases, extensive cornea damage may require cornea transplantation.

Appropriate hygiene measures regarding contact lens use are the best option to prevent AK. Additionally, it is recommended to consult an ophthalmologist if any of the above mentioned symptoms are experienced. Early diagnosis significantly improves the patient's chances for successful treatment.

References

  1. Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite. 2015; 22:10.
  2. Biddick CJ, Rogers LH, Brown TJ. Viability of pathogenic and nonpathogenic free-living amoebae in long-term storage at a range of temperatures. Appl Environ Microbiol. 1984; 48(4):859-860.
  3. Kurbanyan K, Hoesl LM, Schrems WA, Hamrah P. Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study. Eye (Lond). 2012; 26(1):126-132.
  4. Nazar M, Haghighi A, Niyyati M, et al. Genotyping of Acanthamoeba isolated from water in recreational areas of Tehran, Iran. J Water Health. 2011; 9(3):603-608.
  5. Auran JD, Starr MB, Jakobiec FA. Acanthamoeba keratitis. A review of the literature. Cornea. 1987; 6(1):2-26.
  6. Badenoch PR, Adams M, Coster DJ. Corneal virulence, cytopathic effect on human keratocytes and genetic characterization of Acanthamoeba. Int J Parasitol. 1995; 25(2):229-239.
  7. Sharma S, Garg P, Rao GN. Patient characteristics, diagnosis, and treatment of non-contact lens related Acanthamoeba keratitis. Br J Ophthalmol. 2000; 84(10):1103-1108.
  8. Bharathi JM, Srinivasan M, Ramakrishnan R, Meenakshi R, Padmavathy S, Lalitha PN. A study of the spectrum of Acanthamoeba keratitis: a three-year study at a tertiary eye care referral center in South India. Indian J Ophthalmol. 2007; 55(1):37-42.
  9. Lorenzo-Morales J, Martin-Navarro CM, Lopez-Arencibia A, Arnalich-Montiel F, Pinero JE, Valladares B. Acanthamoeba keratitis: an emerging disease gathering importance worldwide? Trends Parasitol. 2013; 29(4):181-187.
  10. Schaumberg DA, Snow KK, Dana MR. The epidemic of Acanthamoeba keratitis: where do we stand? Cornea. 1998; 17(1):3-10.
  11. Oldenburg CE, Acharya NR, Tu EY, et al. Practice patterns and opinions in the treatment of acanthamoeba keratitis. Cornea. 2011; 30(12):1363-1368.
  12. Clarke B, Sinha A, Parmar DN, Sykakis E. Advances in the diagnosis and treatment of acanthamoeba keratitis. J Ophthalmol. 2012; 2012:484892.
  13. Rabinovitch T, Weissman SS, Ostler HB, Sheppard JD, Teikari J. Acanthamoeba keratitis: clinical signs and analysis of outcome. Rev Infect Dis. 1991; 13 Suppl 5:S427.
  14. Park DH, Palay DA, Daya SM, Stulting RD, Krachmer JH, Holland EJ. The role of topical corticosteroids in the management of Acanthamoeba keratitis. Cornea. 1997; 16(3):277-283.

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