WHITE PAPER

ASCRS Infectious
Disease Task Force
July 2007

Special Report:
Acanthamoeba Keratitis

eratitis can lead to severe visual disability and requires prompt diagnosis and treatment. Injury to the corneal surface and stroma allows
invasion of normal flora as well as organisms harbored by foreign
bodies. However, there are a select group of microbial pathogens that
can penetrate intact corneal epithelium, Acanthamoeba is felt to be in this class
of insidious pathogens.
Contact lens wear is an established risk factor for infectious keratitis. All types
of contact lenses can cause infection, with extended wear soft lenses conferring
greater risk than daily wear hard or soft lenses. Corneal changes from contact
lens use include an induced hypoxic and hypercapnic state promoting epithelial
cell desquamation and allowing microbial invasion. Contact lenses also induce
dry eye and corneal hypesthesia. Overnight rigid gas permeable lens use for
orthokeratology has also been associated with bacterial keratitis. Recently, the
competition for more comfortable and more consumer friendly contact lens
solutions have been identified as playing a key role in the increase in atypical
causes of microbial keratitis including Fusarium (B&L MoistureLoc) and
Acanthamoeba (AMO Complete MoisturePlus).

Diagnostic Techniques
ASCRS Infectious
Disease Task Force
Francis S. Mah, MD Chair
Eduardo Alfonso, MD
Tat-Keong Chan, MD
Eric D. Donnenfeld, MD
Terry Kim, MD
Terrence P. OBrien, MD

ASCRS Infectious
Disease Task Force
The American Society of Cataract and
Refractive Surgery established clinical
committees and task forces to better
identify and meet the needs of the
membership. The Infectious Disease
Task Forces goals are to broaden
awareness of infectious disease
occurrences and provide guidance for
diagnosis, treatment and management
of these conditions.

Routine culture of corneal infections is not the usual practice in the community.
A small peripheral ulcer may be treated empirically, but a large, purulent, central ulcer that extends to the middle to deep stroma should be cultured prior to
treatment. In addition, ulcers that are clinically suspicious for fungal, mycobacterial, or amoebic infections or are unresponsive to initial broad spectrum
antibiotics warrant cultures. Topical anesthesia with proparacaine hydrochloride
is preferred since it has fewer antibacterial properties than other topical anesthetics. A sterile platinum spatula is used to scrape the leading edge as well as
the base of the ulcer, while carefully avoiding contamination from the lids and
lashes.
In cases of deep stromal suppuration that is not readily accessible or a progressive microbial keratitis unresponsive to therapy, a corneal biopsy may be warranted. A round 2mm to 3mm sterile, disposable skin punch is used to incise
the anterior corneal stroma and lamellar dissection is performed with a surgical
blade. The specimen is then ground in a mortar with trypticase soy broth and
plated on media.
Acanthamoeba keratitis is a rare opportunistic infection that affects approximately 1.2 to 3.0 cases per million. Acanthamoeba are ubiquitous protozoa that
exist in 2 forms: trophozoites (the active form) and cysts (the inactive form).
Under unfavorable conditions, trophozoites transform into cysts that are resistant to extremes of temperature, pH, and desiccation. Cysts are notoriously difficult to kill and this is one reason why this infection is so difficult to eradicate.
Only one class of medications is known to have cystocidal activity, the
biguanides.

ASCRS Infectious Disease Task Force

The initial report of Acanthamoeba keratitis was in 1975

in a patient who sustained eye trauma outdoors. This was
followed by an epidemic of infections in soft contact lens
wearers in the late 1980s, largely attributed to homemade saline. Besides all types of contact lenses, additional risk factors include ocular trauma, corneal transplantation, and exposure to infected lake water, sea water, hot
tubs, tap water, or saliva. Recently, an alarming increase
in the rate of Acanthamoeba keratitis has been observed
prompting the CDC to investigate possible etiologies.
This has concluded in the first association being the contact lens solution, AMO Complete MoisturePlus, which
has been voluntarily pulled from the market by its manufacturer. The CDC is continuing its search into other possible connections for reasons into the increase.
Acanthamoeba infection presents with similar nonspecific
symptoms as bacterial and viral keratitis. Pain that is outof-proportion to clinical findings is characteristic, but not
universal. Early corneal infection manifests as epithelial
involvement, including elevated epithelial lines that may
appear as dendritic, punctuate epithelial erosions, microcycts, and epithelial haze ( FIGURE 1). Stromal findings,
which occur later, include single or multiple stromal infiltrates and nummular keratitis. Ring infiltrates or satellite
lesions usually suggest advanced disease (FIGURE 2).
Tropism of the Acanthamoeba organism for corneal
nerves causes radial keratoneuritis, the reason for the
extreme pain (FIGURE 3).
Diagnosis is typically delayed for a number of reasons.
Early infections are commonly treated as bacterial or herpetic keratitis. The disease can also be confused with
fungal keratitis. Delay in diagnosis makes it more difficult to treat since the infection becomes more deeply
seated.
Treatment of Acanthamoeba kratitis is long, involves
toxic medications, and may be unsuccessful in curing the
infection if the infection involves the posterior cornea. A
combination of topical anti-amoebic agents, including
biguanides (eg, PHMB and chlorhexidine), diamides (eg,
propamidine) and aminoglycosides (eg, neomycin) are
typically used. Of these, only the biguanides are active
against the cystic form of the disease. None of these medications are available commercially in the United States
and they must be compounded by a specialty pharmacy
before use. Medications must be used for months starting
at hourly intervals and tapered as the clinical situation
improves. The use of topical steroids is controversial. It
clearly improves patient comfort, but may potentiate the
infection by conversion of the cyst to trophozoites.

Figure 1

Figure 2

Figure 3

ASCRS Infectious Disease Task Force RECOMMENDATIONS

1. Remove and return any AMO Complete
MoisturePlus Solution from offices/places of work.
2. Advise all patients, and especially contact lens wearers, of the association of ACA with the contact lens
solution, AMO Complete MoisturePlus Solution so
they may dispose of remaining solutions.
3. Recommend that all contact lens wearers rub their
lenses with an alternate cleaning solution and avoid
the 'no rub' technique advocated by manufacturers.
4. Although suspicion should be kept high due to the
increased risk of ACA keratitis, bacterial infectious
keratitis is still the most common etiology and should
remain on top of the list of differential diagnoses.
5. Be on the lookout for the early signs of ACA keratitis
and use vital dyes (fluorescein, lissamine green, rose
bengal) to help differentiate these lesions from those
caused by herpes simplex keratitis.
6. With cases of acute keratitis, unless it is of an abnormal appearance, larger than 2mm in size, moderate to
deep stromal melting, or is central or paracentral,
treatment should begin with intensive application of a
topical broad spectrum antibiotic(s).

7. If the keratitis does not respond, or has any of the

above unusual characteristics, corneal scrapings for
vital stains (Gram, Geimsa, etc) and cultures should be
obtained to identify the pathogen. Confocal
microscopy can aid in the diagnosis of ACA.
8. For any contact lens patient with a suspected infection,
contact lenses, cases, and cleaning solutions should be
collected for culturing.
9. Steroids should be used with caution in the above concerning situations, and preferably only if the organism
has been identified, and the patient is clinically
responding to the treatment.
10. Early diagnosis is the key to improved outcomes so
consider earlier referral to a specialist than usual.
11. Treatment involves extended and frequent dosing of at
least one of the cystocidal biguanides (PHMB 0.02%
and/or chlorhexidine 0.02%), and at least one other
agent - neomycin, propamidine, and/or clotrimazole,
for weeks to months. In addition, the treating clinician
may consider judicious use of oral itraconazole as an
adjunct to topical therapy.

References
1. Chang et al. Multistate outbreak of Fusarium keratitis
associated with use of a contact lens solution. JAMA 2006
Aug 23;296(8):953-63.
2.

Dixon, J.M., et al., Complications associated with the

wearing of contact lenses. Jama, 1966. 195(11): p. 901-3.

3.

Alfonso, E., et al., Ulcerative keratitis associated with contact

lens wear. Am J Ophthalmol, 1986. 101(4): p. 429-33.

4.

Schein, O.D., et al., The incidence of microbial keratitis

among wearers of a 30-day silicone hydrogel extended-wear
contact lens. Ophthalmology, 2005. 112(12): p. 2172-9.

5.

6.

Driebe, W.T., Jr., Present status of contact lens-induced

corneal infections. Ophthalmol Clin North Am, 2003.
16(3): p. 485-94, viii.
Mah-Sadorra, J.H., et al., Trends in contact lens-related
corneal ulcers. Cornea, 2005. 24(1): p. 51-8.

7.

Liesegang, T.J., Contact lens-related microbial keratitis:

Part I: Epidemiology. Cornea, 1997. 16(2): p. 125-31.

8.

Liesegang, T.J., Contact lens-related microbial keratitis:

Part II: Pathophysiology. Cornea, 1997. 16(3): p. 265-73.

9.

Hsiao, C.H., et al., Infectious keratitis related to overnight

orthokeratology. Cornea, 2005. 24(7): p. 783-8.

10. McDonnell, P.J., et al., Community care of corneal ulcers.

Am J Ophthalmol, 1992. 114(5): p. 531-8.
11. Charukamnoetkanok, P. and R. Pineda, 2nd, Controversies in
management of bacterial keratitis. Int Ophthalmol Clin, 2005.
45(4): p. 199-210.
12. Badenoch, P.R. and D.J. Coster, Antimicrobial activity of topical anaesthetic preparations. Br J Ophthalmol, 1982.
66(6): p. 364-7.
13. Alexandrakis, G., et al., Corneal biopsy in the management of
progressive microbial keratitis. Am J Ophthalmol, 2000.
129(5): p. 571-6.
14. Radford, C.F., et al. Acanthamoeba keratitis: multicentre survey
in England 1992-1996, National Acanthamoeba Keratitis Study
Group. Br J Ophthal 1998;82:1387-1392.
15. Tauber J. and Jehan F. Parasitic keratitis and conjunctivitis,
In: Smolin and Thoft's The Cornea Scientific Foundations &
Clinical Practice, 4th edit. Lippincott, Williams & Wilkins;
2005:427-430.
16. Thebpatiphat N. et al. Acanthamoeba at Wills eye hospital:
a parasite on the rise. Invest Ophthalmol Vis Sci 2006:
47:E-356.

ASCRS

AMERICAN SOCIETY OF CATARACT AND REFRACTIVE SURGERY

The mission of the American Society of Cataract and Refractive Surgery is to advance the
art and science of ophthalmic surgery and the knowledge and skills of ophthalmic surgeons.
It does so by providing clinical and practice management education and by working with
patients, government, and the medical community to promote the quality of eyecare.

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