Acanthamoeba keratitis

Eye infection caused by a protist

Acanthamoeba keratitis (AK) is a rare disease in which amoebae of the genus Acanthamoeba invade the clear portion of the front (cornea) of the eye. It affects roughly 100 people in the United States each year. Acanthamoeba are protozoa found nearly ubiquitously in soil and water and can cause infections of the skin, eyes, and central nervous system. Infection of the cornea by Acanthamoeba is difficult to treat with conventional medications, and AK may cause permanent visual impairment or blindness, due to damage to the cornea or through damage to other structures important to vision. Recently, AK has been recognized as an orphan disease and a funded project, orphan diseases Acanthamoeba keratitis (ODAK), has tested the effects of a diverse range drugs and biocides on AK.

In the United States, Acanthamoeba keratitis is nearly always associated with soft contact lens use. Acanthamoeba spp. is most commonly introduced to the eye by contact lenses that have been exposed to the organism through the use of contaminated lens solution, using homemade saline based solution or tap water, or from wearing contact lenses while bathing or swimming. However, it may also be introduced to the eye by exposure to soil or vegetation, or by trauma. Soft contact lenses are more adherent to the corneal surface than hard lenses, which allows the Acanthamoeba organism to bind to mannosylated glycoproteins on the corneal surface. Expression of these proteins on the corneal surface is increased by contact lens use. Once the organism has gained access to the surface of the eye, it is able to invade through the epithelium and Bowman's layer. In some cases, the infection can then group around corneal nerves, producing radial deposits (radial keratoneuritis), and causing extreme pain. These are features also seen in viral and bacterial keratitis, and may be misleading. In non contact lens users, the greatest risks for developing Acanthamoeba infection are trauma and exposure to contaminated water. Further predisposing factors include contaminated home water supply, and low socioeconomic status. Infection is also more commonly seen in tropical or sub tropical climates. In addition to the trophozoite stage, the organism can also form a double walled cyst which may also be present in the environment, and can be very difficult to eradicate through medical treatment. Both of these stages are usually non nucleated and reproduce by the means of binary fission.

Due to the relative rarity of Acanthamoeba keratitis (AK) compared to other causes of keratitis (bacterial, viral, etc. ), it is often misdiagnosed, especially in the early stages of the disease. AK should be considered in all patients who use contact lenses, and following corneal abrasions or trauma. A thorough history should be obtained, especially relating to contact lens use and any recent changes in contact lens solution, exposure of the eyes to water or foreign objects, and symptoms that the patient is experiencing. The symptoms classically attributed to AK include decreased or blurred vision, sensitivity to light (photophobia), redness of the eye (conjunctival hyperemia), and pain out of proportion to physical exam findings. In cases of keratitis, diagnosis is typically achieved through evaluation of corneal scrapings. Scrapings are taking from the cornea, and plated on agar for culture, and also can be stained using Gram stain and Giemsa stain to differentiate between bacterial keratitis and AK. To culture Acanthamoeba, scrapings are placed on a non nutrient agar saline plate seeded with a gram negative bacteria such as E. coli. If Acanthamoeba are present, they will reproduce readily and become visible on the plate under 10–20 times objective on an inverted microscope. Polymerase chain reaction (PCR) can be used to confirm a diagnosis of Acanthamoeba keratitis, especially when contact lenses are not involved. Confocal microscopy is a non invasive technique that allows visualization of Acanthamoeba in vivo in cases in which corneal scraping, culture, and cytology do not yield a diagnosis.

Once Acanthamoeba keratitis is diagnosed, initiation of timely and appropriate treatment will have a significant impact on visual outcomes. Medical therapy aims to eradicate both trophozoite and cystic forms of Acanthamoeba and also control the inflammatory response.

Multiple classes of drugs have been found to be effective in killing the trophozoite form of Acanthamoeba, including anti bacterial, anti fungal, anti protozoal, and anti neoplastic agents. However, no single therapy has been found to eliminate both trophozoite and cystic forms, and to eradicate corneal infection. Due to the efficacy of these drugs against the Acanthamoeba, as well as their low toxicity to the cornea, they are commonly used as the first line medications in the treatment of AK. A limitation of diamidine use is relative corneal toxicity with long term use. Due to the potential for negative longterm visual outcomes with AK, therapy is usually started with a combination of a biguanide and a diamidine. Early use of high dose dual therapy helps to eliminate both trophozoite and cyst forms of the organism, while also preventing deep penetration of cysts into the corneal stroma. Cysts that are not eradicated from the cornea will cause recurrence. Therefore it is typically recommended that steroids be used briefly to aid in symptom resolution, and that anti amoebic agents be used both during, and for several weeks after topical steroid use.