Acanthamoeba keratitis

A problem for contact lens users that is here to stay

Keratitis due to acanthamoeba infection has now been recognised in Europe, Asia, Australia, the Americas, and parts of Africa. The cause is a free living protozoan found not only in soil and pond water but also in mains water supplies. It survives in adverse conditions by forming resistant cysts, which may contain legionellas and other bacteria. These cysts are impervious to inorganic chlorine at up to 50 ppm. The trophozoites are sensitive to chlorine at 2 ppm, but even this concentration is well in excess of that in public water supplies (<1 ppm). A strength of between 3 and 8 ppm is found, however, in chlorine generating disinfecting solutions for contact lenses.1

The cysts, so difficult to destroy, may be incorporated in the biofilm within water pipes and on contact lenses and may be cultured from both sites. Enhancement techniques may be required--especially when cultures are made from corneal scrapings or biopsy specimens--because earlier drug treatment may have induced temperature sensitivity and a shift into a “dormant” cyst stage.

Infection of the cornea with acanthamoeba without a contact lens as a vector is now well recognised in India2 3 but was first identified in the United States and Britain only 20 years ago.4 The cause may be trauma followed by application of contaminated water5 or contamination of the eye by mud, especially if the eye has been compromised by earlier infection with herpes virus or trachoma or other diseases causing breaks in the protective mucus and the integrity of the surface epithelium.

Acanthamoeba keratitis is increasingly being recognised among people who wear contact lenses, especially those who wear soft lenses. The chain of events is thought to begin with contamination of the contact lens storage case with acanthamoeba in household or mains water supplies. If bacterial contamination is also present (and it is found in up to 40% of storage cases) then these amoebas can multiply, ingesting the bacteria as a food source. If the contact lens is then immersed in the storage case and inadequately disinfected--as often occurs--acanthamoeba can adhere to it and so to the corneal epithelium. As many as 7% of storage cases are contaminated with acanthamoeba,6 but only one in 250000 wearers develops an active, invasive infection. The explanation for this disparity is not clear. Infection may develop in immunocompetent hosts by invasion through epithelial gaps, though there is debate whether motile trophozoites can penetrate between healthy intact epithelial cells, because of their size, unless they cause proteolysis.7 Penetration through such gaps would explain the increased microbial infection rates with extended wear of contact lenses: the corneal oedema that occurs with extended wear causes separation of epithelial bridges and disruption of mucus.

The earliest sign of infection is at the epithelial level, with patchy oedema. This causes an irregular dendritiform ulceration, which is often misdiagnosed as keratitis due to Herpes simplex virus. There is, however, less branching and a wider base. The clue to the correct diagnosis is that the patient is young and wears contact lenses; herpetic ulceration is rare in this group. Superficial infiltrates then appear in the underlying stroma. The epithelium may heal but appears oedematous and is easily debrided. At the same time linear infiltrates may be observed along one or more corneal nerves, and this is believed to be the cause of severe pain--out of proportion to the signs. If left untreated the amoebas penetrate the full depth of the cornea, forming a ring abscess, which may eventually lead to perforation. Most patients have antibodies to acanthamoeba, but the immune system alone seems unable to halt progressive corneal infection.

Successful medical treatment, with propamidine and neomycin, was first described 10 years ago,8 but for treatment to be effective early diagnosis is required. Resistance, associated with temperature sensitivity,9 and failure of treatment may both occur. Recent work has shown acanthamoebas to be sensitive to the biguanide antiseptic chlorhexidine and to polyhexamethylene biguanide, which is sold as a disinfectant for swimming pools.10 Both biguanides have been combined with propamidine and used successfully to treat acanthamoeba keratitis.4 11 This combination gives a more rapid therapeutic response than neomycin (to which cysts are usually resistant). While polyhexamethylene biguanide has been applied topically in an artificial tear complex, chlorhexidine has been applied in physiological saline; neither is ideal for topical ocular treatment, and more research is needed.

Preventing acanthamoeba keratitis occurring because of infection from natural sources remains impossible,2 but early recognition and treatment with 0.02% chlorhexidine (ideally with propamidine as well) should prevent blindness. Preventing infections associated with contact lenses is theoretically possible but will be difficult to achieve. It depends on the use of an effective amoebicidal disinfectant. Among the many marketed only two cold chemical disinfectants (hydrogen peroxide and chlorhexidine) are effective against acanth-amoeba cysts and most bacteria found in storage cases.12 Both should be used as sterile solutions and not dissolved in tap water. While also effective, thiomersal is not recommended because it can induce hypersensitivity. Storage cases should be washed daily with boiled-cooled water (at 70°C) and kept dry when not in use to prevent amoebic and bacterial multiplication. This procedure needs to be explained to both the people who fit contact lenses and their patients. Finally, compliance is required by those who wear contact lenses--but is often lacking in young people, who buy “disposable lenses” and then wear them for 14 days. The future development of sterile contact lenses that are disposed of properly each day may be expected to reduce the occurrence of this infection. In addition, extended wear of any contact lens overnight should be avoided.