Acanthamoeba keratitis

Acanthamoeba keratitis is a rare disease in which amoebae invade the cornea of the eye, and affects roughly 1.2 to 3 million people 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 Acanthamoeba keratitis (AK) may cause permanent visual impairment or blindness, due to damage to the clear portion of the front of the eye (called 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 effects of diverse drugs and biocides in AK. Acanthamoeba keratitis is a rare disease in which amoebae invade the cornea of the eye, and affects roughly 1.2 to 3 million people 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 Acanthamoeba keratitis (AK) may cause permanent visual impairment or blindness, due to damage to the clear portion of the front of the eye (called 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 effects of diverse drugs and biocides in 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. In fact, the first case of Acanthamoeba keratitis described was due to ocular trauma. Once on the contact lens, Acanthamoeba is able to survive in the space between the contact lens and the surface of the eye. 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. This increase in glycoprotein content, along with microtrauma to the corneal epithelial surface due to contact lens use increases the risk for infection. Once the organism has gained access to the surface of the eye, it is able to invade through the epithelium and Bowman's layer. It 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. The organism is also capable of invading deeper into the cornea; using metalloproteases it is able to penetrate deep into the stroma of the cornea. As the disease progresses, it may penetrate through cornea but very rarely causes infection inside the eye (endophthalmitis) due to a robust neutrophil response in the anterior chamber. While the vast majority of cases of Acanthamoeba keratitis occur in contact lens wearers, there have been many cases of Acanthamoeba described in those who do not wear contact lenses, especially outside the United States. 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. Beyond the route of inoculation into the eye and external risk factors, host factors are also likely to play a significant role in the development of Acanthamoeba keratitis. In fact, studies of contact lens users in the UK, Japan, and New Zealand found that 400 to 800 per 10,000 asymptomatic contact lens users had lens storage cases contaminated with Acanthamoeba spp. However, the rate of Acanthamoeba keratitis among these patients was only 0.01 to 1.49 per 10,000 contact lens users. Although the exact host factors have not been fully described, it is likely that corneal epithelial defects, tear film composition, eye surface pH, and level of anti-Acanthamoeba IgA antibodies in the tear film. Species within the genus, Acanthamoeba, are generally free-living trophozoites. These trophozoites are relatively ubiquitous and can live in, but are not restricted to, tap water, freshwater lakes, rivers and soil. 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 unnucleated 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 contact in 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. Another clinical feature that can distinguish Acanthamoeba from bacterial causes of keratitis is a lack of discharge from the eye. On physical exam, findings will depend on the stage of the disease. Early manifestations in the cornea can be seen as punctate keratopathy, pseudodendrites, and epithelial or subepithelial corneal deposits. These features can lead an examiner to confuse AK with a viral keratitis, such as that caused by Herpes zoster virus or Herpes Simplex Virus. As the disease progresses and infiltrates the corneal stroma, a classic 'ring infiltrate' may be present on examination (although this is only seen in about 50% of cases). Corneal ulceration, or in severe cases, perforation, can also occur and may be accompanied by hypopyon. 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 10-20X objective on an inverted microscope. Polymerase chain reaction 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.