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Acanthamoeba keratitis--implications for contact lens wearers.

Acanthamoeba keratitis can result in a devastating outcome for the patient but is fortunately a relatively rare clinical presentation. This article outlines the signs and symptoms of the condition and discusses strategies to minimise the risk for the patient.

Introduction

Acanthamoeba keratitis (AK) is rare--you are 20 times more likely to have a bacterial corneal infection while wearing contact lenses than an infection caused by Acanthamoeba. However, the condition is much more severe and is highly debilitating in the short and long term. The symptoms of Acanthamoeba keratitis are incapacitating, the condition waxes and wanes, usually requiring treatment for four to six months and only 75-85% of cases retain useful vision without the need for keratoplasty. (1)

With an estimated 130m contact lens wearers worldwide (2) and expected expansion of the market, (3) combined with the disease severity, it is imperative that contact lens wearers understand how to minimise the risk of AK and develop future strategies to limit the incidence and morbidity of this devastating condition.

Acanthamoeba organism

Acanthamoeba is a single-celled protozoa that is found mainly in contaminated water and soil, but also in dust and air. (4) It is sometimes called a parasite, however, this term is incorrect as Acanthamoeba does not require a host organism to survive. It is an extremely resilient organism that exists in two forms, the active trophozoite (see Figure 1) that moves by contractions of finger-like projections, and the dormant cyst that is encased in a double layer cellulose wall (see Figure 2). The cyst is able to withstand environmental extremes including temperature, pH and desiccation for long periods of time. (4) Acanthamoebafeeds on bacteria, fungi and algae and can host pathogenic organisms within its nucleus. (5) Acanthamoeba most often causes keratitis, however, some strains (not those that cause keratitis) can also very rarely infect the brain and skin. (6)

Corneal infection with Acanthamoeba

Clinical signs and symptoms

Contact lens associated AK is usually unilateral but can occur in both eyes, although this is rare. Early symptoms are typically pain, photophobia and watering, sometimes much exaggerated from the clinical picture. It is important to be aware that AK can also occur without pain and in non-contact lens wearers. (1)

In the early stages, AK is confined to the epithelium with punctate keratopathy and often pseudodendrites. Other early signs include 'perineural' infiltrates which occur in over 60% of UK cases. (1) As the disease progresses, the infection moves to the stroma and inflammation typically occurs centrally, impairing vision with a 'ground glass' type appearance to the cornea. Immunering ulcers and scleritis, thought to be sterile inflammatory reactions, tend to occur later in 15-20% of cases. (1) If scleritis develops, then very severe, persistent pain is usually reported. (1)

[FIGURE 1 OMITTED]

Laboratory investigations

The traditional laboratory techniques to detect Acanthamoeba are corneal culture or histopathology. A section of epithelium, which is usually very fragile due to the infection, is removed and half is placed on non-nutrient agar for culture and the other half is placed on a microscope slide for immunohistochemistry staining. For culture, in the laboratory the nonnutrient agar is washed with Escherichia coli (E. coli), a food source for Acanthamoeba. The plate is observed under a microscope periodically for up to 12 days. Trophozoites appear early, slowly moving through the agar with a contractile motion as they ingest the E. coli. (7) Cysts generally appear after several days as the food source depletes. Corneal culture in Acanthamoeba tends to be around 60% specific. (1) In histopathology, the epithelial section is fixed and stained for organisms which are visualised with a microscope. Trophozoites are difficult to visualise in histopathology as they tend to be damaged in this procedure. Polymerase chain reaction (PCR), a more recent molecular technique, assesses the DNA of microorganisms captured with a corneal swab. This technique is sensitive in up to 85% of cases. (1)

[FIGURE 2 OMITTED]

Confocal microscopy

A useful tool in the diagnosis of AK is the in vivoconfocal microscope in which cysts appear as highly reflective spheres. However, it is important to be aware that a study has shown that the technique is accurate only in the hands of an experienced user, as the cysts can be easily confused with the patient's immune cells. (8)

Course and management

While trophozoites are sensitive to many chemotherapeutic agents, cysts are mostly resistant. Biguanides (polyhexidine biguanides, PHMB 0.02%-0.06%, and chlorhexidine 0.02%-0.2%) and diamidines (propamidine Isethionate 0.1%, Brolene, May and Baker, UK and hexamidine 0.1%, Desmomedine, Chauvin, France) are the most effective cystocidal agents. (9) None of the treatments are licensed but there is good evidence from case series that they are effective in vivo. (1) Some resistant strains have been reported for the diamidines, (10) and so they are generally not recommended for monotherapy. Epitheliopathy, pseudodendrites and stromal inflammation in AK can be easily confused with herpes simplex keratitis (HSK). In a recent audit of nearly 200 cases of AK at Moorfields Eye Hospital, mainly from the period 2000-2012, 50% of AK cases were initially diagnosed as HSK. (11) When these patients develop stromal inflammation, they are often placed on topical corticosteroids. In this recent audit, it was found that use of corticosteroids before the initiation of anti-amoebic drugs is independently associated with poorer treatment outcomes. (11) Older age and delay in anti-amoebic treatment (11,12) are also associated with poorer outcomes.

While steroids are contraindicated prior to anti-amoebic treatment, there is debate as to whether steroids can be introduced safely to limit scarring and preserve vision in AK. A survey of prescribing trends in the US showed that 70% of ophthalmologists use topical corticosteroids in the treatment of AK. (13) In laboratory tests, steroids have been shown to aid excystment into trophozoites, rendering them more susceptible to therapy. (14) However, animal models show that the early immune response, which would be dampened by steroids, has potent activity against Acanthamoeba. (15) As around 15% of those treated with topical steroids will develop increased intraocular pressure, it is essential to undertake tonometry at every follow-up visit. (1)

Compared to bacterial keratitis, AK disease process is much more protracted and most cases take four to six months to resolve. It is common for the condition to escalate from a quietened state or recur after treatment has been withdrawn. This may stem from the difficulty of eliminating cysts from the cornea and/or be evidence of an inflammatory reaction to dead cyst walls. If scleritis develops oral steroids and immunosuppressive therapy such as ciclosporin is often necessary. (16) Corneal perforation can occur in a small proportion of cases, usually when there is a concomitant superinfection, and keratoplasty may need to be performed. Persistent epithelial defect is common in severe disease and amniotic membranes may be therapeutic when combined with keratectomy. (17) Keratoplasty is primarily carried out for visual rehabilitation but can also be used to eliminate persistent organisms, although there is less success in these cases. (1,18) Pain from scleritis was a principle cause of enucleation in the past, but this outcome is rare with current immunosuppressive therapy. (19)

The protracted and uncertain course of the disease can be very difficult to deal with, especially for young, normally healthy individuals and counselling may be required during this period. With vision compromised due to the central location of corneal inflammation, patients often lose visual function including the stereopsis needed for depth perception. Fear of falling may result and simple tasks, such as reading normal size print become difficult. (20)

Despite the hardship, it is common for sufferers to ask when they can return to contact lens wear. Once the condition has resolved, daily disposable wear is commonly recommended. Although there have been reports of AK in daily disposable wearers, it is reasonable to expect the risks to be less and there is evidence in bacterial disease that microbial keratitis events are less severe. (21,22)

If corneal irregularity results from the scarring and vision is improved with rigid gas permeable contact lenses, a trial is generally advised and may avoid visual rehabilitation with keratoplasty.

Who is at risk?

In industrialised countries, around 85% of cases occur in contact lens wearers, whereas in more rural countries, trauma in non-contact lens wearers is the most common cause of AK. (1) There is wide regional variation in the incidence of AK ranging from two per million wearers in the US to greater than 20 per million in some parts of the UK, thought to be due to environmental differences, such as water quality, and patterns of contact lens use. (23)

Centres in the US and UK, including Moorfields Eye Hospital have noted an increase in the number of cases in recent years. (24-26) The cause at this stage is not clear. Since April 2013, a case control research study at Moorfields Eye Hospital has been investigating risk factors, and results will be available later this year. A British Ophthalmic Surveillance Unit study, which is tracking cases across the entire UK is also being conducted.

Modifiable risk factors

Water exposure

In the UK, water is often stored in tanks in the roof space, which can become contaminated. (27) Limescale, which builds up on surfaces in contact with hard water supplies, harbour gram negative bacteria on which Acanthamoeba feeds. (27) Southern regions in the UK that have hard water supplies have a nine-fold increase in AK compared to the north and the midlands where softer water without lime scale exists. (23) Swimming in contact lenses, particularly in chlorinated water, has also been associated with AK. (23)

In 1998, the US Environmental Protection Agency lowered the level of carcinogenic disinfectant by-products allowed in water supply. Treatment plants altered the levels and timing of disinfectant to comply. In Chicago, AK incidence increased the further away contact lens wearers lived from the water treatment facility, indicating a possible association with increased microbial load and biofilm. (28) Biofilms are polysaccharide conglomerates of microorganisms that become more resistant to disinfection and environmental extremes and can harbour Acanthamoeba.

In 2010, the Center for Disease Control (CDC) in the US was contacted about two unusual clusters of AK cases in New York and Georgia. (26) In response, the CDC launched a US multistate case control investigation over the period 2008-2011 in conjunction with the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA). Control lens wearers were matched to 110 cases based on the state of residence, the type of eye care provider and contact lens use during this period. When controlling for other risk factors, storing lenses in water was associated with a 5.5 fold increase in risk. In a matched analysis, handling lenses with wet hands and rinsing the case in tap water before storing lenses was also associated with an increased risk. The CDC presented preliminary information on the subset of RGP wearers, as tap water rinsing of conditioning solution is recommended on many RGP solutions. (29) In the CDC analysis around half (18/37) of the cases of AK usually or always used tap water to store lenses, while 16/17 control RGP wearers never used tap water to store lenses. (26)

Contact lens solutions and their use

In 2007, an outbreak of AK occurred (30) which was linked to a contact lens solution, Complete MoisturePlus (AMO, Santa Ana, CA) that was subsequently withdrawn from sale. Laboratory investigations later revealed that a component of the solution induced encystment of Acanthamoeba rendering the organism more resistant to disinfection. Following the recall of Complete MoisturePlus, there was a drop in the number of cases in the US, however, this decrease did not reach the low level prior to the product launch. (31) There seemed to be some residual increased risk that was not present in the early 2000s. A study published in 2008, indicated that many of the marketed multipurpose solutions at that time were not effective against clinical and tap water strains of Acanthamoeba. (32) They found that the Chicago tap water strain was particularly virulent. (32)

Recent reports in Bristol and Manchester indicate an increase in cases seemingly related to a contact lens solution. (24, 25) While these reports may indicate trends, they may be affected by market forces or particular environment issues in that area and only a case control study across a more broad section of the contact lens community that measure exposure in both groups, will give definitive risk factors.

The CDC investigations did not show a specific risk associated with a particular type of lens care solution, but they did find 'topping off' rather than using fresh solution, increased the risk by four times. (26) Topping off promotes biofilm formation and dilutes the disinfection activity of the solution. (33)

Non-modifiable risk factors

Younger (less than 26 years) and older age (more than 55 years) wearers are also at increased risk of disease as are new wearers and those wearing lenses less than 12 hours/ day as revealed in the CDC analysis. This may be an example of the 'survivor' effect. Robin Chalmers has shown that extended wearers that could not achieve 30 nights of wear were more prone to adverse events. (34) It was thought there were other factors preventing this level of wear that may increase the susceptibility to adverse events and this could be the case with this group.

What should our advice be to wearers to limit the risk of disease?

Topping off solution should be avoided and rubbing and rinsing the contact lens with disinfectant is advised to remove microorganisms and tear debris along with ensuring adequate disinfection at each use. It would be prudent, especially in hard water areas in the UK, to restrict tap water contact with all contact lenses, including RGPs. This includes drying hands after washing with soap, limiting exposure while showering and not storing lenses or rinsing lenses or cases in water. It is recommended that cases should be rubbed and dried with a tissue and laid face down and replaced regularly to limit biofilm and contamination. (35)

Contact lenses are an important lifestyle feature and in many water activities, spectacles can potentially limit enjoyment and may at times result in injury. Goggles have been shown to reduce microbial contamination on contact lenses when swimming in pools (36, 37) and it is reasonable to recommend tight fitting goggles or prescription goggles to swimmers.

In the UK, a motivated patient with AK, Ms Irenie Ekkeshis, conceptualised and designed a 'No water' sticker for contact lens packaging that is endorsed and produced by the British Contact Lens Association (BCLA). She was concerned that there was little awareness amongst contact lens patients about domestic tap water as a risk factor for this severe disease and those wearers were taking unnecessary risks. It is hoped that eventually this symbol could be incorporated into contact lens packaging, but in the meantime, the stickers, which feature R and L markers, are available from the BCLA. (38)

At the recent BCLA Clinical Conference in Birmingham in June, 2014, Irenie Ekkeshis and the author hosted an exhibition stand promoting healthy contact lens wear that was donated by the BCLA and endorsed by the Moorfields Biomedical Research Centre (BRC). Short videos of 'Witless contact lens wearers' were presented to engage practitioners in different communication strategies to educate wearers. These will soon be available to view on the BRC website. (39) In the US, the CDC has teamed with the contact lens research and industry community to promote The Healthy Contact Lenses Program. This program has developed a website and infographics that can be displayed or circulated on social media. (40) In November 2014, the CDC will promote a social media campaign targeting 18-22 year olds in particular. Moorfields Eye Hospital will link with this campaign and hope to expand the reach of the program to increase the safety of contact lenses.

What does the future hold?

More stringent testing for contact lens solutions is expected to come to the market in the near future. Now that we have more experience with managing the condition, we can assess the efficacy of steroid use to preserve vision. We have better microbial analysis knowledge and techniques to assess the different strains of Acanthamoeba and correlate in vitro testing with clinical outcomes and novel formulations and vehicles for antiamoebic drugs are in the pipeline. (41)

In addition, there is a lot of solid information from laboratory and animal models on how the immune system responds to this disease although not all human manifestations are replicated in animals. (15) In our current research program at Moorfields Eye Hospital we are profiling the human host response, looking at genetic mutations that might affect how the eye responds and verifying those differences with biomarkers in the tears and from corneal lesions. Through this research we hope in the future to be able to give practitioners guidance for how to tweak current and emerging treatments to limit the severity of this disease.

Exam questions

Under the enhanced CET rules of the GOC, MCQs for this exam appear online at www.optometry.co.uk/cet/exams. Please complete online by midnight on September 19, 2014. You will be unable to submit exams after this date. Answers will be published on www.optometry.co.uk/cet/exam-archive and CET points will be uploaded to the GOC every two weeks. You will then need to log into your CET portfolio by clicking on 'MyGOC' on the GOC website (www. optical.org) to confirm your points.

References

Visit www.optometry.co.uk/clinical, click on the article title and then on 'references' to download.

Course code: C-37320 | Deadline: September 19, 2014

Learning objectives

To be able to explain to patients about the implications of Acanthamoeba keratitis (Group 1.2.4)

To be able to use appropriate techniques to identify signs of Acanthamoeba keratitis (Group 3.1.2)

To be able to give appropriate advice to reduce the risk of Acanthamoeba keratitis (Group 5.1.2)

Learning objectives

To be able to understand the signs and symptoms of Acanthamoeba keratitis (Group 5.2.2)

To be able to recognise and respond appropriately to ocular emergencies (Group 8.1.6)

Learning objectives

To be able to understand the natural progress of Acanthamoeba keratitis and how to assess its severity (Group 1.1.1)

To be able to assess cases of Acanthamoeba keratitis appropriately (Group 2.1.2)

Learning objectives

To be able to explain to patients about the implications of Acanthamoeba keratitis (Group 1.2.4)

To be able to use appropriate techniques to identify signs of Acanthamoeba keratitis (Group 3.2.2)

To be able to give appropriate advice to reduce the risk of Acanthamoeba keratitis (Group 5.2.1)

Reflective learning

Having completed this CET exam, consider whether you feel more confident in your clinical skills--how will you change the way you practice? How will you use this information to improve your work for patient benefit?

Nicole Carnt BOptom PhD, FAAO, FBCLA

Optometrist, Nicole Carnt graduated from University of New South Wales in 1989 and worked in private practice before taking a position with the Brien Holden Vision Institute in Sydney in 1999, where she held a variety of roles, including principal investigator on contact lens clinical trials. She completed a PhD on Epidemiology of Contact Lens Related Infection and Inflammation in 2012. She is currently a post-doctoral research optometrist at Moorfields Eye Hospital NHS Foundation Trust, funded by the Australian Government.
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Title Annotation:1 CET POINT
Author:Carnt, Nicole
Publication:Optometry Today
Geographic Code:4EUUK
Date:Aug 22, 2014
Words:3246
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