Feature, Insight's Continuing Professional Development – NEW in 2022!, Report

A spotlight on Acanthamoeba keratitis: healthy contact lens wear

 

At the completion of this CPD activity, optometrists will have developed their knowledge of Acanthamoeba keratitis. Including:

  • Understand the prevalence, behaviour and risk factors associated with Acanthamoeba keratitis
  • Identify Acanthamoeba keratitis when it presents in the clinic and develop informed referrals for further treatment
  • Understand treatment protocols for Acanthamoeba keratitis
  • Develop intervention strategies that promote patient education and adherence on contact lens hygiene

NOTE: Optomery Australia members can enter their details at the bottom of this article to have it automatically added to their Learning Plan.

Acanthamoeba keratitis is a rare but debilitating infection found mostly in contact lens wearers. DR NICOLE CARNT discusses the critical role of optometrists in detection and informed referrals, as well as minimising the chances of infection in the first place.

A/Prof Nicole Carnt
BOptom (Hons) PhD GradCertOcThe  FAAO FBCLA
Scientia Associate Professor, Deputy Director of Research, School of Optometry and Vision Science, Faculty of Medicine and Health, UNSW, Sydney
Group Leader, Vision and Virus Immunology Collaboration, Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney
Associate Researcher, Institute of Ophthalmology, University College London 

Introduction to Acanthamoeba trophozoite

A contact lens wearer washes their face in the bathroom sink when water splashes up into their eye. They blink and clear the vision, but let’s put the contact lens under the microscope (Figure 1 above).

Acanthamoeba keratitis is rare; for the 140 million contact lens wearers globally, only around 750 develop Acanthamoeba keratitis each year.1 However, the impact of the infection is significant. Acanthamoeba keratitis patients have a 50% chance of losing significant vision and undergoing treatment over 12 months.2 As the infection waxes and wanes, vision-related quality of life is halved across reading, mobility and emotion domains.3 

Risk factors

Acanthamoeba keratitis is an opportunistic infection, and 85-90% of cases occur in contact lens wearers.1 The role of contact lenses in the infection is twofold: they act as a vehicle to deliver and maintain contact with the ocular surface and they increase the chance of ocular surface irritation. 

Most microbes in the tears, trapped behind or attached to contact lenses, don’t cause infection because of the remarkable defence the ocular surface has. However, when corneal cells are damaged, they produce mannose. Acanthamoeba expresses a ‘mannose-binding lectin’ on the surface, which enables corneal attachment and infection. 

Acanthamoeba is found everywhere, but the main avoidable risk factor is contact lenses mixing with water. In a recent UK study, it was shown that water activities were responsible for 62% of the population attributable risk of Acanthamoeba keratitis in that study. That means over half the cases could be eliminated if contact lens wearers avoided water.4 

Acanthamoeba exists in two forms, the feeding motile trophozoite (Figure 1) and the dormant resilient cyst. The cyst form can withstand extremes of temperature, pH and other stressors. It is also able to resist disinfection, antibiotics and other chemotherapy agents. Though misuse of contact lens disinfection products has been associated with outbreaks of Acanthamoeba keratitis,4,5 typically the cases do not return to baseline following withdrawal of the solution.5 In addition, cases seem to be increasing in severity.2 This suggests that Acanthamoeba is becoming more prevalent and virulent in the environment. 

When I asked a 1,500-participant strong Acanthamoeba keratitis Facebook Support group what they thought the major risk for Acanthamoeba keratitis in 2017 (Figure 2), the second highest risk factor, was “lack of information”. Optometrists are in a powerful position to minimise the risk of this rare but devastating disease.

Figure 2: ‘What is the major risk factor for Acanthamoeba keratitis?’ word cloud posted on the Acanthamoeba keratitis Facebook Group: Aug 2017.

Prevention of Acanthamoeba keratitis 

My team at UNSW has been looking just where in the environment and our bathrooms Acanthamoeba is. We have found that around 30% of Sydney bathroom sinks harbour Acanthamoeba.6 

Most of the organisms we found are from the T4 group, which is the most prevalent strain that infects the eye. Furthermore, we and others have found the exact same genotype in people’s eyes as in the environment.7 We have also found Acanthamoeba in 38% of samples taken from lakes and rivers across northern NSW, and the major dam feeding Sydney has around the same proportion of isolation. 

It has been shown that, following flooding, there are increases in cases of Acanthamoeba.8 As the water recedes, the microbes multiply, and so does Acanthamoeba, which feeds on this concentration of microbes. We don’t swim in the ocean after flooding, so let’s remind our contact lens wearers to take a bit more care of their eyes and contact lenses then too.

Changing your patients’ behaviour

Contact lens wearers might equate drinking water and washing with water as safe – and don’t realise the dangers of mixing water with contact lenses. This is what prompted Acanthamoeba patient and advocate, Ms Irenie Ekkeshis, to design the concept of ‘no water’ graphic for contact lens packaging. She lobbied the British Contact Lens Association, and they produced the first version of the graphic in 2014 (Figure 3). 

Figure 3: ‘No-water’ design courtesy of the Cornea and Contact Lens Society of Australia.

Since then, it has been adopted in the US and in 2021 it was launched in Australia by the Cornea and Contact Lens Society of Australia. (https://www.cclsa.org.au/tap/). 

In 2020, we published a 200-contact lens wearer randomised controlled trial that demonstrated an improvement in water avoidance behaviour and less gram-negative toxins (like those produced by Pseudomonas, another water dwelling microbe) in contact lens cases.9 

Optometrists looking for ways to persuade their patients to do the right thing can draw on the twin sciences of psychology and marketing which offer ‘gain-framing’ as one of the best ways to change behaviour.

With ‘gain-framing,’ your message is communicated in terms of its positive consequences. For example: “Did you know that tap water contains specific germs that like to live on your contacts? If you are about to swim or take a shower – remove your lenses first. This helps keep your eyes healthy and should allow you to safely wear contacts.”

Repeated messaging is also crucial, so look for opportunities at each aftercare appointment.

Another important role of the optometrist in preventing Acanthamoeba keratitis is providing optimal fitting contact lenses. Aftercare provides not only an opportunity to educate contact lens wearers to adopt sensible attitudes to mixing tapwater and contact lenses but to review contact lens performance and make adjustments and upgrades.

Diagnosing Acanthamoeba keratitis

In the early stages of Acanthamoeba keratitis, epitheliopathy occurs appearing as a grey-dirty, fragile epithelium. There might be pseudodendrites and/or perineural infiltrates (Figures 4a and 4b). The classic ring infiltrate, with its ground glass stromal infiltrate appearance and scleritis are indications of later stage disease (Figures 4c and 4d).  

In early disease, pain may or may not be present, but photophobia is usually experienced. Acanthamoeba keratitis is usually monocular, although in rare cases, patients are affected in both eyes. It is not thought to be transmitted from one eye to the other, but rather bilaterally through dual inoculation.

Acanthamoeba keratitis is misdiagnosed in 30-50% of cases, most often, as Herpes Simplex keratitis due to pseudodendrites and/or the stromal infiltrate.1 Perineural and ring infiltrates can occur in severe bacterial keratitis, but these are rare and so for Acanthamoeba keratitis, these signs are considered pathognomic. 

Misdiagnosis not only delays treatment, but the treatment may also be detrimental to the outcomes. Corticosteroids are likely to be prescribed in stromal Herpes Simplex keratitis, but their use in Acanthamoeba keratitis prior to antiamoebic treatment is associated with a five times worse outcome (see Treatment section).10 Arguably the global expert on Acanthamoeba keratitis, Professor John Dart, says Acanthamoeba keratitis needs to be ruled out in a contact lens wearer before Herpes Simplex keratitis is diagnosed. 

Urgent referral to a hospital eye service with experience in diagnosing and managing Acanthamoeba keratitis is crucial. Often contact lens wearers with acute eye disease will present to the GP or non-ophthalmic emergency departments who do not have ready access to slit lamps. Creating a red eye triage at your practice or practices in your area enables a pathway for less misdiagnosis. 

We have found that late referral to hospital eye services experienced at managing Acanthamoeba keratitis is associated with poor outcomes related to misdiagnosis and mismanagement.2 On the referral include the contact lens history and water risk factors as well as documenting the signs and symptoms.  

The gold standard for Acanthamoeba keratitis diagnosis is corneal scrape for culture, but it is only positive in 50-60% of confirmed clinical cases.11 Increasingly PCR swabs are being used, but PCR is not always definitive and is not available in all centres. In vivo confocal microscopy, which is only available in large referral eyecare centres such as Sydney Eye Hospital, can be very informative as the cysts of Acanthamoeba can be visualised. However, the cysts can be confused with white blood cells, and it is difficult to diagnose Acanthamoeba keratitis based on in vivo confocal alone. 

There are several groups globally working on better diagnostic techniques. In my lab, PhD student Mr Hari Peguda is working with Professor Mark Willcox from the UNSW School of Optometry and Vision Science and Dr Sophia Gu from UNSW Chemical Engineering. We are using nanoparticles to label Acanthamoeba – in a test tube now – but the goal is to do this with patients in the clinic. We and others have used hyperspectral imaging to show that Acanthamoeba has a different spectral profile compared to bacteria.12 

Treatment challenges and best practice

Rarely Acanthamoeba also causes skin lesions and fatal encephalitis, but greater than 95% of disease occurs in the cornea. Acanthamoeba are eukaryotic which are the same as human cells and have been likened to macrophages in the active form. 

In the cornea, Acanthamoeba can encyst and escape the host immune and drug treatment regime. The most successful agents are biguanides (0.02-0.08% polyhexanide, PHMB or chlorhexidine 0.02-0.2%, compounded) used in monotherapy or in combination with diamidines used off label (Brolene, May and Baker, UK and Desmodine, Chauvin, France).1 

The diamidines are not effective against cysts and cannot be used alone. A clinical trial in Europe has just concluded and an application is being made for the first licensed product for Acanthamoeba keratitis (PHMB 0.08%). Up to now, patients have had to use compounded PHMB without the provision of product information, supplied in glass containers with stoppers that are easily tipped over, expire within a month and are subject to raw material supplies. 

The outcomes of Acanthamoeba keratitis tends to be bimodal. Around 50% resolve in a three-month period, while the others go on to have a waxing and waning disease process that can last more than 12 months and up to four years.2 

The severe cases are driven by inflammation, with ring infiltrates and scleritis (which is very painful) common. Retinal necrosis occurs in a small proportion of patients. In these severe cases, topical and systemic steroids are usually required for the pain and to dampen the inflammation.1 

Although steroids should not be used prior to diagnosis, we have shown that concurrent with anti-amoebic treatment steroid use is not associated with worse outcomes.13 It is recommended not to start concurrent steroids in the first two weeks of anti-amoebic treatment. Persistent epithelial defects, fixed dilated pupils, glaucoma and cataracts are side effects of the intense and prolonged treatment. 

My group at the UNSW has found that some patients with genetic variation in inflammatory genes are more susceptible to severe outcomes, and this is partially replicated in proteins in their tears.14 It is hoped that in the future, topical drops that dampen the action of these inflammatory proteins will be available as a more targeted, gentle way to manage inflammation with less side effects.

Other treatments are in the pipeline including antimicrobial peptides (AMPs).15 AMPs are expressed on the corneal surface in response to Acanthamoeba and synthetic versions may be effective as a topical treatment and/or in contact lens solutions/coatings.

Conclusion

Optometrists are in a powerful position to educate contact lens wearers about Acanthamoeba keratitis. They play a vital role in teaching them how to minimise their chances of contracting the disease; they provide increased clinical care by ensuring healthy contact lens fitting and they are critical in the detection of the infection and the provision of informed referral.

References 

  1. Dart JK, Saw VP, Kilvington S. Acanthamoeba keratitis: diagnosis and treatment update 2009. Am J Ophthalmol. 2009; 148 (4): 487-99 e2.
  2. Carnt N, Robaei D, Minassian DC, Dart JKG. Acanthamoeba keratitis in 194 patients: risk factors for bad outcomes and severe inflammatory complications. Br J Ophthalmol. 2018; 102 (10): 1431-5
  3. Carnt N, Man R, Fenwick E, Keay L, Lamoureux E. The impact of Acanthamoeba Keratitis on the vision-related quality of life of contact lens wearers. Cornea. 2021; Oct 2021.
  4. Carnt N, Hoffman JM, Verma S, Hau S, Radford CF, Minassian DC, et al. Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors. Br J Ophthalmol. 2018; 102 (12): 1621-8.
  5. Yoder JS, Verani J, Heidman N, Hoppe-Bauer J, Alfonso EC, Miller D, et al. Acanthamoeba keratitis: the persistence of cases following a multistate outbreak. Ophthalmic Epidemiol. 2012; 19 (4): 221-5.
  6. Carnt NA, Subedi D, Lim AW, Lee R, Mistry P, Badenoch PR, et al. Prevalence and seasonal variation of Acanthamoeba in domestic tap water in greater Sydney, Australia. Clin Exp Optom. 2020; 103 (6): 782-6.
  7. Carnt NA, Subedi D, Connor S, Kilvington S. The relationship between environmental sources and the susceptibility of Acanthamoeba keratitis in the United Kingdom. PloS one. 2020; 15 (3): e0229681.
  8. Meier PA, Mathers WD, Sutphin JE, Folberg R, Hwang T, Wenzel RP. An epidemic of presumed Acanthamoeba keratitis that followed regional flooding. Results of a case-control investigation. Arch Ophthalmol. 1998; 116 (8): 1090-4.
  9. Arshad M, Carnt N, Tan J, Stapleton F. Compliance behaviour change in contact lens wearers: a randomised controlled trial. Eye (Lond). 2021; 35 (3): 988-95.
  10. Robaei D, Carnt N, Minassian DC, Dart JK. The impact of topical corticosteroid use before diagnosis on the outcome of Acanthamoeba keratitis. Ophthalmology. 2014; 121 (7): 1383-8.
  11. Hoffman JJ, Dart JKG, De SK, Carnt N, Cleary G, Hau S. Comparison of culture, confocal microscopy and PCR in routine hospital use for microbial keratitis diagnosis. Eye (Lond). 2021.
  12. Peguda HK, Mahbub SB, Sherpa TD, Subedi D, Habibalahi A, Anwer AG, et al. The Autofluorescence Patterns of Acanthamoeba castellanii, Pseudomonas aeruginosa and Staphylococcus aureus: Effects of Antibiotics and Tetracaine. Pathogens. 2021; 10 (7).
  13. Carnt N, Robaei D, Watson SL, Minassian DC, Dart JK. The Impact of Topical Corticosteroids Used in Conjunction with Antiamoebic Therapy on the Outcome of Acanthamoeba Keratitis. Ophthalmology. 2016; 123 (5): 984-90.
  14. Carnt NA, Pang I, Burdon KP, Calder V, Dart JK, Subedi D, et al. Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis. Invest Ophthalmol Vis Sci. 2021; 62 (3): 33.
  15. Tummanapalli SS, Willcox MD. Antimicrobial resistance of ocular microbes and the role of antimicrobial peptides. Clin Exp Optom. 2021; 104 (3): 295-307.

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