Improved Eye Care Solutions and Medicines for the Prevention and Cure of Acanthamoeba keratitis
Submitting InstitutionUniversity of the West of Scotland
Unit of AssessmentAllied Health Professions, Dentistry, Nursing and Pharmacy
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Ophthalmology and Optometry, Pharmacology and Pharmaceutical Sciences
Summary of the impact
Dr Fiona Henriquez's research into the debilitating eye infection Acanthamoeba
keratitis (AK) has significantly impacted on the handling of contact
lenses and their cases to the benefit of the world's 125 million contact
lens users. Her research findings have been ground-breaking for the
research community and have featured widely in the media reaching
audiences from scientists, industry professionals, the general public and
individual contact lens users. The research has resulted in 2 patents and
there are 3 non-disclosure agreements in place with companies relating to
commercialisation projects. Related work on Acanthamoeba cysts has
resulted in a fourth commercialisation project.
Dr Fiona Henriquez's research interests focus on infections by
opportunistic eukaryotic pathogens and in particular, the Acanthamoeba
species. These microorganisms are difficult to treat due to the inefficacy
of current medicines and the resistance of Acanthamoeba to many
compounds. Some compounds that have been shown to be effective are also
highly toxic to human cells. This pioneering research, undertaken in
partnership with the University of Strathclyde (active since her
appointment at UWS in 2005), led to the initial steps taken to develop a
novel high-throughput assay system to assess the efficiency of the
inhibitory compounds (Ref 3.1). This assay has facilitated Dr Henriquez's
In 2008 Henriquez et al., published a study that clearly presented the
challenges faced in the treatment of Acanthamoeba keratitis (AK).
In this research, the resistance of Acanthamoeba to several
anti-tubulin compounds, including potent anti-neoplastics (paclitaxel,
vinblastine) is described, thus illustrating its resilience to the most
potent inhibitors to eukaryotic cells. This is despite the fact that
tubulin is one of the most conserved proteins between species and the high
resistance phenomenon was found to be due to different amino acids in
critical binding areas of the Acanthamoeba protein. Significantly,
these amino acid differences may be exploited in future studies to create
a specific compound that can target only Acanthamoeba tubulin,
thus reducing the toxic effects in the human host (Ref 3.2). This early
research was followed up with in 2009 when Henriquez et al., described the
characterisation of alternative oxidase (AOX), which is present in Acanthamoeba
but not in the human host. AOX is a mechanism through which Acanthamoeba
can overcome inhibitory pressures from toxic compounds and therefore it is
important to take this into consideration for future drug design (Ref
Dr Henriquez`s work has also focused on exploiting metabolic differences
between Acanthamoeba and the human host and she has directed three
UWS PhD students in this area. This work has characterised the histidine
biosynthesis and shikimate pathways present in Acanthamoeba but
absent from the human host. Her work has demonstrated that Acanthamoeba
growth can be inhibited by compounds that block either of the pathways and
has already been protected by two published patents.
In addition to the challenge of the development of an effective
treatment, investigation into contact lens user compliance highlighted the
issue that the contact lens end user must be adequately informed of the
potential risks of Acanthamoeba contamination of contact lenses.
For this reason, Dr Henriquez organised an event at the British Science
Festival in 2012 to highlight the potential risks of microbial
contamination in contact lenses to the public. She brought together a
multidisciplinary team of four experts; an optician who delivered
tutorials about the correct use of contact lenses; an engineer to explain
why contact lenses and their cases are ideal surfaces for microbial
growth: an immunologist with expertise in immune responses in the eye; and
a microbiologist (Dr Henriquez), who focused on the challenges faced in
treating Acanthamoeba infection (Ref 3.4).
References to the research
3.1 McBride J, Ingram PR, Henriquez FL, Roberts CW. Development of
colorimetric microtiter plate assay for assessment of antimicrobials
against Acanthamoeba. J Clin Microbiol. 2005 Feb;43(2):629-34.
This publication is in a highly ranked journal in the subject area
(number 3 in citations and number 7 ranked by Eigenscore). It has
revolutionized how Acanthamoeba viability is assessed. Before this
publication Acanthamoeba assessment was slow and reliant of the fact
that Acanthamoeba can feed on bacteria. This new method is suited for
high through put assays without the need for a co culture of organisms.
Since its publication in a subject focused journal it has been cited 37
times and it is now routinely used in laboratories worldwide, including
3.2 Henriquez FL, Ingram PR, Muench SP, Rice DW, Roberts CW. Molecular
basis for resistance of Acanthamoeba tubulins to all major classes
of antitubulin compounds. Antimicrob Agents Chemother. 2008
This publication is in the number 1 journal in pharmacology and
pharmacy for both citations and by Eigenfactor score ranking. It is the
first study into genetic factors in Acanthamoeba that influence its
resistance to toxic molecules that are used as herbicides,
anti-neoplastics and anti-helminthics. Since its publication it has been
cited 15 times in journals concerning medicinal chemistry and
biotechnologies at an international level.
3.3 Henriquez FL, McBride J, Campbell SJ, Ramos T, Ingram PR, Roberts F,
Tinney S, Roberts CW. Acanthamoeba alternative oxidase genes:
identification characterisation and potential as antimicrobial targets.
Int J Parasitol. 2009 Nov;39(13):1417-24. doi:
10.1016/j.ijpara.2009.04.011. Epub 2009 May 21. PubMed
This publication is in a highly respected journal for parasitology
(ranked 6 out 63, Eigenscore). It is specific to Acanthamoeba research
and at the time of publication offered a unique insight into the makeup
of the Acanthamoeba genome, including intron mapping and the existence
Evidence of participation at BSF and this itself was an investigative
research project to increase understanding of the public's knowledge of
Details of the impact
There are 125 million contact lens wearers worldwide and potentially all
are at risk of Acanthamoeba infection and therefore this research
has a global impact.
Following publication of her research findings on the Acanthamoeba
keratitis in 2008, Dr Henriquez actively engaged in dialogue with the
commercial arm of the world famous Moorfields Eye Hospital NHS Foundation
Trust, Moorfields Pharmaceuticals. The company specialises in the
manufacture and development of sterile liquid products and Ophthalmic
Specials products. Moorfields agreed to conduct a survey amongst
Ophthalmologists, which confirmed the unanimous agreement that an
effective pharmaceutical product was required to treat Acanthamoeba
The impact of this research has been in 4 areas:
a) Commercialisation and Industry Impacts: Through
publication of patents and participation in industry-focused conferences,
Dr Henriquez has been involved in discussions with several eye care
companies. To date, non-disclosure agreements (NDA) have been signed by 3
separate companies: Boots Technical Centre for Boots Opticians, which has
almost 700 UK ophthalmic and dispensing optician stores and circa 5000
staff; Viopti, which is a small to medium sized enterprise (SME),
registered as a company in May 2009; Sauflon Pharmaceuticals Ltd, a global
manufacturer of contact lenses and solutions, offering the widest range of
contact lenses and aftercare products anywhere in the world. Sauflon's
high-quality contact lenses and aftercare products reach Opticians,
Optometrists, Eye Doctors and Eye Care Professionals in over fifty
b) Patents Awarded: Dr Henriquez's research has resulted in
Patent awards for both Antimicrobial and Antiprotozoal compounds (See
Section 5.1). The patents protect the use of the inhibitory compounds
glyphosate and 3-amino-triazole that block the shikimate pathway and
histidine biosynthesis pathway in Acanthamoeba, respectively.
Patents were awarded in Europe and in the patent covering the shikimate
pathway has also been awarded in the USA.
c) Sauflon, who have signed a NDA, have seen the patent and have already
tested the shikimate pathway inhibitor, glyphosate, with their contact
lens solution "All-In-One Light". This resulted in an increased efficiency
of this contact lens solution to eliminate Acanthamoeba
trophozoites from contact lenses. Investigations are now focusing on
elimination of the highly resistant cyst form within 6 hours.
d) British Contact Lens Association new warning labels on
contact lens cases: In September 2012, Dr Henriquez organised
the event `Microbes in contact lens' at the British Science Festival in
order to highlight the dangers of contact lens negligence and poor care
and that finding effective medicines for Acanthamoeba keratitis is
a considerable challenge as they are eukaryotic (as are humans) and thus
many treatments are toxic to humans. This research into finding new
protective measures and treatments, through public engagement and media
discussion and consequent correspondence (Section 5), encouraged an
artist/patient to design dedicated warning labels for contact lens
solution boxes and cases to inform users to avoid water exposure of their
contact lenses (Section 5). These `no water' sticker labels have been
endorsed by the British Contact Lens Association (Section 5.1). The BCLA
are distributing these labels to their members and the stickers are also
available to purchase. Dr Henriquez has received letters and emails from
members of the public endorsing the research, or seeking information and
advice on contact lens handling and care (Section 5.3). This is evidence
of changing behaviour and perception in the end user of their own use of
contact lenses and thus significant impact on improving public health.
e) In 2012 Dr Henriquez received a Scottish Funding Council Innovation
Voucher Scheme award to work with the microbiological biocide testing
company, Blutest. Currently, there is no international standard (ISO)
specifically detailing procedure to assess the efficacy of
biocides/contact lenses solutions against Acanthamoeba. Therefore,
the aim of this project was to develop a rapid test to assess biocides on
highly resistant protozoan cysts. Cysts are notoriously difficult to test
since they have extremely low metabolic activity and do not replicate. The
test, which is based on monitoring excystation by a colourimetric assay,
has been validated through testing several biocides and can now be used to
evaluate the efficacy of biocides, which is already of commercial impact
for Blutest (See Section 5.1).
2. Media Article Impacts: Relevant ophthalmic professional bodies
have sought interviews with Dr Henriquez, with resulting articles in
specialist industrial journals in Ophthalmology, such as `Optician'
magazine, a key reference for Optician practitioners. There has also been
significant public dissemination through national and international media
portals, including The Daily Telegraph, The Daily Mail, MSN and yahoo
news. (See Section 5.2). The public have responded to these articles
through online discussions, some highlighting their own experiences with
the disease and some calling for more awareness of this pathogen.
Sources to corroborate the impact
5.1. COMMERCIALISATION/INDUSTRY IMPACTS
- PATENT: Roberts, C.W. Ingram, P.R. HENRIQUEZ, F.L. & Roberts, F.
(2006). Antimicrobial Compounds PCT/GB2006/000875.
This patent describes the utilization of the shikimate pathway in Acanthamoeba
as a target to stop Acanthamoeba growth. It protects the use of
glyphosate in contact lens solutions and as a therapeutic agent.
- PATENT: HENRIQUEZ, F.L & Roberts, C.W. (2008). Antiprotozoal
compounds. UK patent application PCT/GB/2009/051197.
This patent protects the use of the histidine biosynthesis pathway in Acanthamoeba
as a target to inhibit Acanthamoeba. It protects the use of
3-amino-triazole in contact lens solutions.
- BCLA Adoption of new "no water" labeling and letter from the Artist,
who was inspired to design these labels from the `Microbes in contact
lenses' event at the British Science Festival 2012.
- Boots Technical Centre
Non-disclosure agreement and letter of interest 2009
Non-disclosure agreement, SeeKIT innovation voucher and letter of support
- Sauflon Pharmaceuticals Ltd
- Blutest -SFC IVS voucher scheme report on work leading to successful
rapid assay development.
Letter of support
5.2. MEDIA ARTICLE IMPACTS
All media articles are also available online and this has stimulated
public discussion about Acanthamoeba and its devastating effects.
5.3. GENERAL PUBLIC IMPACTS
Example Quote from member of public dated 8th September 2012 `My
wife was the second reported case in the United States approx 26 years
ago. We assume she contacted it from the water in a Hot Tub. She also
wore contacts at the time. She did have to have a Cornea Transplant — It
was done out of UCLA. I found this article very similar to the symptoms
she (my wife) had. She is doing well now, has lost some peripheral
vision and will most likely go blind in her one eye. Good luck and
continue success with your studies. Please feel free to contact me if we
can help in anyway'