Download Ocular Surface Research in Singapore

Expert ophthalmologist Associate Professor Louis Tong explains
his role as a clinician and researcher investigating eye disease in
Asia, and discusses some of the issues affecting the field today
epithelial cell biology, inflammation and
meibomiam gland dysfunction; I am the only
faculty member that runs a dedicated clinical
service for dry eye and related ocular surface
inflammatory disorders.
What are the main areas of research
conducted by SERI and what types of
training and development opportunities are
available at the Institute?
To begin, can you provide a brief overview
of your academic background and
describe what initially attracted you to
ophthalmology and, more specifically,
corneal and external eye disease?
I am a principal clinician-scientist, Head
of the Ocular Surface Research Group
and co-Head of the Ocular Inflammation
and Immunology Research group at the
Singapore Eye Research Institute (SERI). I’m
also a senior consultant ophthalmologist at
the Corneal and External Eye Service of the
Singapore National Eye Centre, as well as
being tenured track Associate Professor at
the Office of Clinical, Academic and Faculty
Affairs at the Duke-National University of
Singapore (Duke-NUS) graduate medical
school. In addition, I am a senior clinical
lecturer and adjunct Associate Professor at
the Department of Ophthalmology, Yong Loo
Lin School of Medicine, NUS, and a clinical
physician on the faculty of the Singhealth
Residency Program for the Ophthalmology
Academic Clinical Program.
I received my PhD degree from NUS, and was
trained first in Singapore as an undergraduate
before further training and fellowships in
the UK and Baylor College of Medicine, USA.
My research interests are dry eye, corneal
SERI is Singapore’s premier eye research
institute, focusing on the understanding and
treatment of eye diseases, with particular
emphasis on those typical to Asia. Its goal
is to be a global centre of excellence in
eye and vision research in Asia, known
internationally for translating basic science
to clinical applications for the prevention and
treatment of sight-threatening disorders. It
aims to undertake innovative and outstanding
basic science and clinical research, with an
emphasis on translational research, and to
work closely with stakeholders and partners
both nationally and internationally.
SERI covers a diverse spread of eye research,
including ocular surface, cornea and refractive,
glaucoma, retina, neuro-ophthalmology,
paediatric ophthalmology and vision research,
epidemiology and health service research. It
is supported by platforms such as proteomics,
ocular genetics, animal models of disease,
imaging, and databases and statistics.
Why has there been such an increase in
demand for international ophthalmic
activities in recent years?
Firstly, an ageing population in many
countries results in increased patient load.
Ophthalmology is essentially a discipline
dealing with ageing problems such as senile
cataracts, glaucoma, age-related macular
degeneration, etc. Secondly, surgical
intervention in routine problems such as
cataracts has become highly effective
through recent advances such as the use of
phacoemulsification; more accurate refractive
correction has altered many people’s
lifestyles. Thirdly, increased government
investment in eye care programmes
and infrastructure has had an impact. In
Singapore, the establishment of the Singapore
National Eye Centre and later SERI was pivotal
to the success of ophthalmic programmes.
Fourthly, recent years have seen increased
lobbying from eye research institutes for
media publicity and increased funding
through endowments and special interest
groups. Via networking at large international
meetings and events, eyecare and research
have increased in reputation and prominence.
Finally, technological advances in lasers and
imaging technology, and breakthroughs in
basic sciences, have benefited eyecare and
research. Suddenly, people are realising that
problems in ophthalmology can be addressed
with state-of-the-art tools from other fields
such as cancer, rheumatology and radiology.
ASSOCIATE PROFESSOR LOUIS TONG
Roving eye
How is the Ocular Surface Research Group,
of which you are Head, so well placed to
conduct competitive research? Do you
collaborate with any other partners?
Apart from its work as part of the
Collaborative Research Initiative in
meibomiam gland dysfunction, the Group is
also collaborating with many other local and
overseas institutions; for example, the Victor
Chang Cardiac Research Institute in Sydney,
Australia, the University of California, USA,
and industry organisations such as Alcon
(now a Novartis company), Allergan Inc. and
Santen Pharmaceuticals.
You have been awarded a career support
research award from the National Medical
Research Council. Could you provide an
overview of what your research will entail?
I have been awarded the Clinician Scientist
Award in the category of senior investigator.
This is funding over five years to support me
and my research team, in terms of manpower,
equipment and consumables, to translate
diagnostic and treatment modalities in
ocular surface research for dry eye and eyelid
inflammation into clinical care.
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ASSOCIATE PROFESSOR LOUIS TONG
Clear vision
A prominent research group working as part of the Singapore Eye Research Institute has been conducting promising
studies into diseases of the ocular surface, and so contributing to the research of a small but world-leading organisation
OF ALL THE faculties natural selection has
endowed the human body, one of the most
precious is sight. The development of forwardfacing eyes is a landmark in human evolution as
much as the opposable thumb and the ability
to walk erect, and this mode of vision is an
innovation around which the human body has
been shaped. To a large extent it is a feature that
defines humans as a species, and it is certainly
one of the most integral sensory tools people
use to interact with their environment on a
continual moment-by-moment basis.
Blindness, in part because of these considerations,
must be among the most feared medical
conditions humans can be affected by, as well
as being difficult to cope with on a psychological
and practical level. The fourth most common
form of the condition worldwide is corneal
blindness: functional sight loss that occurs when
the cornea, the clear membrane that covers
the eye, becomes scarred or vascularised to the
extent that it is no longer clear. The result is
that a patient can have eyes that are otherwise
perfect, but be blinded by the cornea alone.
SIGHT AND SINGAPORE
Cornea-related blindness accounts for 10 per
cent of sight loss in Asia, and is therefore a
frequent focal point for ophthalmological
research. The condition develops over time
through episodic inflammations caused by
88INTERNATIONAL INNOVATION
conditions such as dry eye syndrome, allergic
keratoconjunctivitis and autoimmune scarring,
or injuries including chemical damage and
microbial infection. The multilayered epithelium
in the ocular surface superficially resembles the
skin and the special innate immune defence –
the eye associated lymphoid tissue – is located
here to interact with the external environment,
including microbes. A key feature that has
developed with evolution is its ability to react
with inflammation. This limits further damage
and is fine-tuned to prevent an unwarranted
destructive immune response. The recruitment
of immune cells to the eye and other processes
relevant to systemic health is therefore governed
by sensing and regulatory systems at the ocular
surface. Consequently, measures which tackle
inflammation and reduce corneal damage over
time could have an impact on visual loss.
One team hoping to achieve just such an impact
is Dr Louis Tong’s Ocular Surface Research
Group at the Singapore Eye Research Institute
(SERI), a young organisation that nonetheless
accounts for 95 per cent of Singapore’s eye
publications. Through numerous collaborations,
ready access to clinical populations and their
own extensive expertise, Tong and his fellow
scientists tackle some of the most prevalent
eye diseases in Singapore, and Asia more widely.
Working with the surface of the eye is an area
that has its advantages, points out Tong: “The
accessibility of the structure for collection
Biochemical and imaging tools
can be used to select dry eye
patients suitable for different
treatments, and even to suggest
adjunctive treatments
of biological materials and for surgical
intervention, and consequently the opportunity
to make groundbreaking collaborations are
major benefits”.
COLLABORATING THROUGH CORIM
Recently, some of the Singapore scientist’s
most influential work has been conducted
alongside the Collaborative Research Initiative
in Meibomian gland dysfunction (CORIM).
Previous studies have shown that lipids are
important for the proper function of the
tear, and that imbalances result in unstable
tear dynamics and dry eye. The consortium
brings together four of Singapore’s leading
research institutes, including SERI, in an effort
to investigate the role of complex lipids in
the human tear film, and the oil-secreting
meibomian gland’s role in maintaining them.
INTELLIGENCE
A vision of the future
The Singapore Eye Research Institute (SERI) Graduate Academy offers
numerous programmes and scholarship opportunities, including:
• Research internships with universities and polytechnics
• Medical undergraduate research attachments
• PhD studentships in conjunction with various universities and the National Medical Research
Council, Singapore
OCULAR SURFACE
RESEARCH IN SINGAPORE
OBJECTIVES
To conduct ocular surface clinical
and translational research at an
internationally competitive level
that aims to understand underlying
mechanisms and improve treatments of
ocular surface diseases.
KEY PARTNERS
• Short-term overseas fellowships with the National Medical Research Council and
Ministry of Health
Singapore Eye Research Institute (SERI)
• Singhealth fellowship awards
• Singapore National Eye Centre education awards
Yong Loo Lin School of Medicine;
Singapore Lipidomics Incubator,
National University of Singapore (NUS)
• Postdoctoral training fellowships
NUS
• Research training programmes for ophthalmic residency
Singapore National Eye Centre
Duke-NUS Graduate Medical School
Nanyang Technological University
• Various visiting professorships
Ngee Ann Polytechnic, Ministry
of Education
The SERI Academy has also played a pivotal role in the recent establishment of the Arthur Lim
Professorship in Ophthalmology, a PhD scholarship, as well as a clinician-scientist residency
research programme.
Bioinformatics Institute (BII); Institute
of Molecular and Cell Biology; Institute
of Medical Biology; Institute of
Materials Research and Engineering,
Agency for Science, Technology and
Research (A*STAR)
SERI’s responsibility within the project has been
the clinical characterisation of dry eye and the
pursuit of clinical trials for potential treatments,
while the other institutes have analysed lipids,
thermographic images of tear evaporation and
meibomian gland structures. This approach
has so far proved beneficial in clinical care,
producing some intriguing results. For instance,
based on the study, it seems that biochemical
and imaging tools can be used to select dry eye
patients suitable for different treatments, and
even to suggest adjunctive treatments.
A UNIQUE RESOURCE
SERI was established in 1997 as part of the
Singapore National Eye Centre, a medical
facility that sees 60 per cent of the ophthalmic
patients in the country. In addition to his
research position, Tong runs the Centre’s
dedicated dry eye service clinic, which is a
referral destination for many patients in the
region and beyond with challenging dry eye
conditions, and serves as a recruitment point
for clinical trials and studies including those
performed with CORIM. Since its establishment
in 2006, the clinic has gathered a database of
over 1,000 dry eye patients, complete with
detailed prospective clinical assessments – the
largest of its kind worldwide.
It is with the help of this facility that Tong and
his collaborators have been able to achieve so
many notable advances in the field over the
last few years, including publication of the
most detailed profile of ocular surface lipids to
date, and helping SERI become a world leader
in published papers on pterygium, a puzzling
benign growth of the conjunctiva over the
cornea; popularly known as ‘surfer’s eye’. They
have also seen their research rapidly translated
into actual therapy on a number of occasions,
with projects involving the selection of eyedrops
based on acidity, autologous plasma treatment
for dry eye, tea tree oil therapy for demodex
mite infestation and lipiflow thermopulsation
treatment, among others.
TG2
Equally important has been the team’s work
on transglutaminase-2 (TG2) in the corneal
epithelium. Just as the surface of the eye must
stay moist, the corneal stroma must always be
dehydrated in order to remain transparent; when
the epithelial layer that protects it is breached
through disease or injury, it becomes hazy and
obscures vision. Hence, epithelial migration is
a crucial process to maintain this first line of
defence, and TG2 has an indispensable role in
this migration. Tong’s team has been responsible
for investigating just how it helps cells adhere to
the extracellular substrate, or move, depending
on necessity.
In a study completed last year, the Singapore
researchers investigated the role of TG2 in a
murine corneal wound-healing model, as well
as examining in detail its action as a regulator
of related processes such as cell adhesion
and migration in a culture of human corneal
epithelial cells. In both models, the investigation
showed that TG2 knockdown delayed wound
closure – and in the human cell culture, the
scientists observed that the absence of TG2 had
a knock-on effect on other molecular processes,
implicating other elements that may be crucial
in healing. In the future, it may be studies like
this that provide the key to eradicating corneal
blindness and its associated morbidity.
FUNDING
National Medical Research Council
Biomedical Research Council of Singapore
CONTACT
Associate Professor Louis Tong
Head, Ocular Surface Research Group
Co-Head, Ocular Immunology and
Inflammation Research Group
Head, Research Training and Development
Singapore National Eye Centre
11, Third Hospital Avenue
Singapore 168751
Singapore
T +65 62 277 255
E [email protected]
ASSOCIATE PROFESSOR LOUIS TONG
graduated in 1993 from NUS, registered
as a medical practitioner in 1994 and
achieved accreditation with the Singapore
Medical Council as an ophthalmologist in
2004. Apart from holding a tenure track
regular faculty position at Duke-NUS
graduate medical school and an adjunct
appointment at the Yong Loo Lin School
of Medicine, NUS, he currently holds
several appointments at SERI, and runs a
dry eye service at the Singapore National
Eye Centre, focusing on tear dysfunction
and meibomian gland disease, and a
general eye clinic for cataract surgery.
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