Acanthamoeba Keratitis
   HOME

TheInfoList



OR:

''Acanthamoeba'' keratitis (AK) is a
rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, the term orphan disease describes a rare disease whose rarity results in little or no funding or research for treatments, without financi ...
in which
amoebae An amoeba (; less commonly spelled ameba or amœba; : amoebas (less commonly, amebas) or amoebae (amebae) ), often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and r ...
of the genus ''
Acanthamoeba ''Acanthamoeba'' is a genus of amoeboid, amoebae that are commonly recovered from soil, fresh water, and other habitat (ecology), habitats. The genus ''Acanthamoeba'' has two stages in its life cycle, the metabolically active trophozoite stage a ...
'' invade the clear portion of the front (
cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...
) of the
eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...
. It affects roughly 100 people in the United States each year. ''Acanthamoeba'' are
protozoa Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...
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.


Pathogenesis

In the United States, ''Acanthamoeba'' keratitis is nearly always associated with
soft contact lens Contact lenses, or simply contacts, are thin lens (optics), lenses placed directly on the surface of the Human eye, eyes. Contact lenses are ocular prosthetic devices used by over 150 million people worldwide, and they can be worn to correct ...
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.JOHN D.T. (1993) Opportunistically pathogenic free-living amebae. In: J.P. Kreier and J.R. Baker (Eds.), ''Parasitic Protozoa. Vol. 3''. Academic Press, New York, pp. 143–246. 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
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
s 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. 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 Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
, 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 the cornea but very rarely causes infection inside the eye (
endophthalmitis Endophthalmitis, or endophthalmia, is inflammation of the interior cavity of the eye, usually caused by an infection. It is a possible complication of all intraocular surgeries, particularly cataract surgery, and can result in loss of vision or l ...
) due to a robust neutrophil response in the
anterior chamber The anterior chamber ( AC) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Hyphema, anterior uveitis and glaucoma are three main pathologies in this area. In hyphema, ...
. 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 United Kingdom, 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 the level of anti-''Acanthamoeba'' IgA antibodies in the tear film play a role in the development of ''Acanthamoeba'' keratitis.


Life cycle

Species within the genus, ''Acanthamoeba'', are generally free-living
trophozoite A trophozoite (G. ''trope'', nourishment + ''zoon'', animal) is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing ''Plasmodium falciparum'' and those of the ''Giardia'' group. The complementary form of the t ...
s. 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 non-nucleated and reproduce by the means of
binary fission Binary may refer to: Science and technology Mathematics * Binary number, a representation of numbers using only two values (0 and 1) for each digit * Binary function, a function that takes two arguments * Binary operation, a mathematical o ...
.


Diagnosis

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 Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...
), 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
varicella zoster virus Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles (herpes zos ...
or
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two members of the Herpesviridae#Human herpesvirus types, human ''Herpesviridae'' family, a set of viruses that produce Viral disease, viral infections in the majority of humans. Both HSV-1 a ...
. 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 A perforation is a small hole in a thin material or web. There is usually more than one perforation in an organized fashion, where all of the holes collectively are called a ''perforation''. The process of creating perforations is called perfor ...
, can also occur and may be accompanied by
hypopyon Hypopyon is a medical condition involving Inflammation#Cellular component, inflammatory cells in the anterior chamber of the human eye, eye. It is an exudate rich in white blood cells, seen in the anterior chamber, usually accompanied by redness ...
. 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 Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. It may also be used to diagnose a fungal infection. The name comes ...
and
Giemsa stain Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups o ...
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 ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
''. 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 The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
(PCR) can be used to confirm a diagnosis of ''Acanthamoeba'' keratitis, especially when contact lenses are not involved.
Confocal microscopy Confocal microscopy, most frequently confocal laser scanning microscopy (CLSM) or laser scanning confocal microscopy (LSCM), is an optical imaging technique for increasing optical resolution and contrast (vision), contrast of a micrograph by me ...
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.


Treatment

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.


Medical therapy

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. One class of medications used in treatment is the
biguanide Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give a highly basic solution. These solutions slowly hydrolyse to ammonia and urea. Synthesis Biguanide can be obtained fro ...
s, which include polyhexamethylene biguanide (PHMB) 0.02% to 0.06% drops, and
chlorhexidine Chlorhexidine is a disinfectant and antiseptic which is used for skin disinfection before surgery and to disinfect surgical instruments. It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and ...
0.02 to 0.2% drops. These medications disrupt the cell wall of the trophozoite organism, leading to its death. However, these agents have shown limited efficacy against the cystic forms. 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. Biguanides have also been found to act synergistically when used in combination with diamidines, with propamidine isethionate and hexamidine being the most commonly used. A limitation of diamidine use is relative corneal toxicity with long term use. A combined regimen of propamidine,
miconazole Miconazole, sold under the brand name Monistat among others, is an antifungal medication used to treat ring worm, pityriasis versicolor, and yeast infections of the skin or vagina. It is used for ring worm of the body, groin (jock itch), a ...
nitrate, and
neomycin Neomycin, also known as framycetin, is an aminoglycoside antibiotic that displays bactericidal activity against Gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against ...
has also been suggested. 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. The treatment is often initiated by instilling drops onto the surface of the eye every hour, 24 hours a day, for at least the first 48–72 hours. If an appropriate response to therapy, this may be reduced to hourly administrations during the day only, which is continued for several weeks to months. Beyond anti-amoebic therapies, there is also a role for topical steroids of anti-inflammatory medications in the treatment of ''Acanthamoeba'' keratitis. During infection, severe inflammation in the cornea and anterior chamber can cause more severe symptoms including pain and visual disturbance. Topical
steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...
s may be used to reduce this inflammation and thereby alleviate symptoms. However, the role of steroids is typically very limited, because their dampening of the immune response may lead to worsening of the infection. Additionally, steroids can increase the number of trophozoites in the cornea by inducing excystation. 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.


Surgical treatment

Surgical debridement of an infected cornea can also be used to reduce organism load and excise devitalized tissue from the cornea. It may also improve the efficacy of medical therapy by promoting penetration of medication into deeper layers of the cornea. In cases of corneal ulceration or perforation, or if corneal scarring is severe,
corneal transplant Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by Corneal button, donated corneal tissue (the graft). When the entire cornea is replaced it is known as penetrating ...
may be required. This typically involves full thickness transplantation of the cornea from a healthy donor eye. The size of the graft should be kept as small as possible, as larger grafts carry a great risk of host rejection, and due to the possibility of graft revision surgery. While surgery is capable of restoring vision by replacing a damaged cornea, it also carries risks of recurrent ''Acanthamoeba'' infection or graft failure. For this reason, anti-amoebic medications should be started prior to surgery, and continued for several weeks afterward. If there is suspicion or evidence of recurrent infection, cultures should be sent. If cultures are positive, anti-amoebic therapy should be continued for 6 months. Outcomes following surgery are typically much better for patients who receive surgery for vision improvement following infection resolution, and therefore all efforts should be made to maximize medical management before attempting surgery.


Epidemiology

A study in Austria reported a total of 154 cases of ''Acanthamoeba'' keratitis over a 20-year period. The age of those with AK ranged from 8 to 82 years old and 58% of the people were female. The data showed that 89% of the infected patients were contact lens wearers, almost all cases occurred only in one eye, and 19% required a corneal transplant. A study in 2023 calculated the incidence of acanthamoeba keratitis to be approximately 2.9 cases per million people.


References

* Shandilya VK, Parmar LD, Shandilya AV. Functional ambulation with bent knee prostheses for an adult with bilateral 90 degrees knee flexion contractures—A case report. J Family Med Prim Care erial online2020 ited 2020 Jun 29:2492-5. Available from
Journal of Family Medicine and Primary Care


External links

* /www.cdc.gov/parasites/acanthamoeba/ ''Acanthamoeba'' keratitis-
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
* /www.cdc.gov/parasites/images/acanthamoeba/acanthamoeba_lifecycle.gif Picture reference of the life cycle of ''Acanthamoeba'' {{DEFAULTSORT:Acanthamoeba Keratitis Discosea Amoebozoa species Disorders of sclera and cornea Rare infectious diseases Protozoal diseases