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A Vision for Vision
Making tomorrow’s sight-saving
treatments a reality today
Review of the NIHR Specialist Biomedical Research Centre for Ophthalmology
at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology,
and UCL Partners Eyes and Vision Theme
National Institute for
Health Research
The goal of the National Institute for Health Research
is to create a health research system in which the NHS supports
outstanding individuals, working in world-class facilities,
conducting leading-edge research focussed on the needs of
patients and the public.
This is the declared goal of the
National Institute for Health Research
(NIHR), which was established by the
Department of Health in 2006 to drive
forward a five-year strategic plan
entitled ‘Best Research for Best Health:
a new national health research strategy’.
To drive innovation in the prevention,
diagnosis and treatment of ill health
and to translate advances in biomedical
research into NHS practice, the NIHR
created 12 Biomedical Research Centres
(BRCs) nationwide through partnerships
between the NHS and universities.
The NIHR Biomedical Research Centre
(BRC) for Ophthalmology was founded
in April 2007, and is jointly run by
Moorfields Eye Hospital NHS Foundation
Trust and the University College London
(UCL) Institute of Ophthalmology. It is
the only national BRC that is dedicated
to vision and eye disease.
Contents
Together, we really make a difference
02
Our strategy
03
Overview of our research themes
04
Age-related macular degeneration
06
Diabetes
08
Glaucoma
10
Ocular repair, regeneration and pharmaceutics
12
Ocular surface disease
14
Paediatrics and inherited eye disease
16
Infrastructure support
18
Education and training
20
Patient and public involvement
22
The juxtaposition of a huge and
unique clinical resource at one of the
world’s largest and longest-established
eye hospitals with one of the largest
eye research institutions with over
40 academic staff, has led to a wide
range of ground-breaking biomedical
research firmly focussed on responding
to clinical challenges.
1
Together, we really make a difference
Professor Peng Tee Khaw
PhD FRCS FRCOphth FRCP FIBiol
FRCPath FMedSci
Professor Philip J Luthert
BSc MBBS FRCP FRCPath
FRCOphth
Director of Research and Development,
Moorfields Eye Hospital
Director of the UCL Institute of
Ophthalmology
Director of the NIHR Specialist BRC
for Ophthalmology
Professor of Pathology
Director of UCL Partners Eyes
and Vision Theme
Head of Pathology Clinical
Services Division
Professor of Glaucoma and Ocular Healing
and Consultant Ophthalmic Surgeon
Ocular repair, regeneration and
pharmaceutics theme leader
Moorfields Eye Hospital,
the largest specialist eye
hospital in the UK, has been
providing eye care and
treatment to the community
for over 200 years.
During this time our hospital has
developed a unique reputation for
high-quality and expert patient care,
as well as outstanding and groundbreaking research into eye disease
and therapeutic interventions. In
2009/10 we recorded more than
330,000 outpatient attendances in
our clinics and almost 70,000
attendances at our specialist Accident
& Emergency Department. Over
27,000 in-patient and day case
procedures were performed, and
around 8,500 laser treatments were
carried out.
We currently provide ophthalmic
care at our hospital in City Road in
central London, as well as at 12
other sites in and around the capital,
which means we are able to
provide care and expert treatment
closer to patients’ homes.
2 The UCL Institute of
Ophthalmology attracts
researchers of the highest
international calibre,
exploring fundamental
and applied questions in
the science of vision.
The mission of the UCL Institute of
Ophthalmology is to develop new
treatments for eye disease out of
a large and varied foundation of
basic research. The UCL Institute
of Ophthalmology is also part of
UCL Biomedicine, one of the largest
aggregates of biomedical expertise
in the world.
Moorfields Eye Hospital, the world’s
longest-established eye hospital
A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
The range of diseases we study extends
from inherited retinal degenerations
affecting young children to age-related
macular degeneration and glaucoma,
the most common causes of blindness in
the elderly. Currently we have groups
investigating every stage of the visual
process from the mechanics of rods and
cones to the brain’s interpretation of
complex visual scenes. Our researchers
are making progress in understanding the
basic mechanisms of blinding disease and
investigating new methods of treatment
by conventional pharmacology, gene
therapy and cellular therapy, including
stem cells.
Strength in partnership
Combined, our joint site has the highest
measure of scientific productivity and
impact in the world for ophthalmic
research activity. We continue to build a
strong team of academic, research and
clinical colleagues, to explore different
ways of finding better treatments, and to
help our patients access new procedures
and treatments as quickly and safely as
possible. In whatever capacity you may
be associated with our BRC, we hope you
find the following description of some
of our achievements as interesting and
inspiring as we do. Together, we can really
make a difference to people’s lives.
UCL Institute of Ophthalmology, one
of the largest eye and vision research
institutions in the world
Our strategy
Our strategy is based around six themes
defined by major common eye problems
or disease processes.
We target disease areas that are both clinically significant
and identified as important to patients and their relatives.
We continue to prioritise areas where there is an outstanding
existing track record of translational achievement (turning
laboratory discoveries into patient benefits) and expertise
at an international level.
We have built support and infrastructure around these
themes, growing strategic partnerships and collaborations
and building capacity to support and consolidate all the links of
the translational bridge. As a result, new treatment techniques
and practices that improve patient health are brought through
as quickly as possible, which benefits patients, as well as the
NHS, universities and the UK as a whole.
Our aim is to be the development site of choice for rapid-track
delivery of new diagnostic methods and therapies, developed
both internally and in partnership with companies and
charities entering at any stage of development.
3
Overview of
our research themes
Our six core research areas are: age-related macular degeneration;
diabetes; glaucoma; ocular repair, regeneration and pharmaceutics;
ocular surface disease; and paediatrics and inherited eye disease.
Visual impairment and blindness can have a substantial impact on
a patient’s perception of their quality of life. Patients equate the impact
of loss of vision with suffering a stroke or having an advanced form
of cancer.
Our aim is to improve the treatments and ultimately the quality of life
of those who suffer from visual loss. We are making great advances
but there is still a tremendous amount of work to be done. Below, we
introduce our themes, and a summary of the objectives of each theme.
Age-related macular
degeneration
Diseases of the retina are the commonest
cause of blindness across all age groups.
The greatest research challenges lie with the diseases
that have limited options for treatment, affect many
people and/or are increasing in prevalence.
Age-related macular degeneration (AMD) qualifies
on all three counts and is therefore at the forefront
of our research strategy. AMD is responsible for over
half of blindness registrations in the UK. For more
information, see pages 6 and 7.
Diabetes
Diabetic retinopathy is the leading cause of
blindness in people under the age of 60 in
the UK. Visual loss has a devastating impact on
individuals’ quality of life and the socio-economic
cost is huge, estimated to be around £2 billion
4 per year. At Moorfields and the UCL Institute of
Ophthalmology we are committed to addressing
visual loss in diabetes in accordance with the St
Vincent Declaration (a set of goals for the medical
care of people with diabetes published following an
international conference in 1989) to enable people
with the condition to lead independent lives of high
quality. For more information, see pages 8 and 9.
A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
Glaucoma
Glaucoma is the most common neurodegenerative
disease in the world and the most common cause of
irreversible blindness. It affects more than 70 million
people, of whom more than 7 million are blind. If
detected early, through regular monitoring of pressure
in the eye (intraocular pressure), visual loss can usually
be stemmed.
Ocular repair, regeneration
and pharmaceutics
In our work to prevent scarring as a result of
surgery, we have been at the forefront of
translating several new treatments from basic
laboratory discovery through to large-scale
The ultimate goal is to reduce the burden on
the individual and on society of visual impairment
and blindness from glaucoma, and to lessen the
impact of the diagnosis of glaucoma and subsequent
treatments on the patient’s quality of life. Worldwide,
there is only a handful of centres with a comparable
expertise in the study of this group of complex
diseases and the molecular analysis of ophthalmic
genetics. For more information, see pages 10 and 11.
international trials and improved clinical treatments
for patients in the UK and around the world.
We are focussing on developing final dosage forms
of medicines used to control post-operative scarring
in the eye, and are moving towards clinical trials
for our tissue tablet. For more information,
see pages 12 and 13.
Ocular surface disease
Ocular surface disease covers diseases of the
conjunctiva and cornea. These range from minor
to sight-threatening and are the commonest reason
for patients seeking eye examination in primary and
secondary care settings in the UK. Moorfields Eye
Hospital and the UCL Institute of Ophthalmology
have a long track record in the investigation of ocular
surface disorders. We have focussed on diseases
that result in the dysfunction and death of limbal
epithelial cells that can lead to chronic corneal
ulceration. Current research is directed at improving
the results of corneal transplant therapy. For more
information, see pages 14 and 15.
Paediatrics and
inherited eye disease
The major causes of treatable childhood
blindness are inherited eye disease and
developmental abnormalities of the eye.
Our main priorities for research are to identify
the genetic basis of these disorders and, through
basic and translational research, develop new
and improved treatments for patients. We are at
the beginning of an exciting new era where
untreatable blinding genetic eye disease will be
amenable to treatment. For more information,
see pages 16 and 17.
5
Age-related macular
degeneration
Work within this theme includes new improved treatments
for ‘wet’ AMD and, based on basic laboratory understanding
and epidemiology studies, the development of novel
interventions and preventative strategies for the currently
untreatable forms of ‘dry’ AMD.
Age-related macular degeneration (AMD)
is the leading cause of severe visual loss in
Europe and North America and, with an
ageing population, the burden of this disease
is projected to increase dramatically.
As its name suggests, AMD predominantly
affects the macula, the centre of vision that
is important for reading and detailed vision.
It can be classified into early and late stages
based on specific clinical features. Early AMD
is characterised by the presence of drusen
(tiny yellowish deposits under the retina) and
is compatible with reasonable vision. However,
many patients with early AMD progress to
the vision-threatening late forms of AMD.
The late wet or neovascular form is
characterised by the growth and leak of
abnormal blood vessels beneath the macula,
causing severe loss of vision.
6 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
MR Adnan Tufail
Theme leader – Age-related
macular degeneration
Consultant ophthalmic surgeon at Moorfields
Eye Hospital and senior lecturer at UCL Institute
of Ophthalmology
Currently, we have treatments for late
neovascular AMD but these involve an intensive
intervention with frequent injections into the
eye and long-term monthly follow-up of the
patient, which is problematic to deliver, and
only a third of patients recover some of their
lost vision. We have no effective treatments for
the late dry atrophic form of AMD, or effective
interventions for early AMD.
“The challenge to develop effective treatments
for patients with AMD is having the right
spectrum of expertise to turn a novel idea into
The atrophic form of
AMD for which no
treatment exists. A trial
of a novel intervention
for this condition will
commence next year
Above left:
Optical coherence
tomography (OCT)
features of drusen.
Drusen are tiny yellow
or white deposits
that are seen in the
retina, and are a
characterisation of
macular degeneration
at an early age
a practical intervention. The team we have
includes experts in genetics, vascular and stem
cell biology and gene therapy as well as in
clinical trials and visual function measurement.
This cross-cutting approach is delivering clinical
trials of new treatments in the next two years.”
Adnan Tufail
Examples of our research projects:
The London Project to Cure Blindness (AMD)
One of our approaches to treating AMD is
through the ground-breaking research of the
London Project to Cure Blindness, which is led
by Professor Pete Coffey at the UCL Institute
of Ophthalmology. Pete and his team aim to
replace the retinal pigment epithelium cells (RPE)
at the back of the eye that are affected in AMD,
using human embryonic stem cells (HES) that
have been transformed into RPE cells. They seek
to transplant these RPE cells into the patient on a
specially engineered patch that will be inserted
behind the retina.
Another important arm of the project is to
develop the technology by which HES cells
can be transformed into photoreceptors (lightdetecting cells) and transplanted into patients.
It is believed that the photoreceptors are lost after
the RPE have degenerated. We are now ready to
initiate the safety studies that we need to do prior
to clinical trials, and are on track to begin human
clinical trials during 2011. Considering that these will
be the first human embryonic stem cell trials in the
UK, the project really will be breaking new ground.
A novel intervention to treat geographic
atrophy (late dry AMD)
There is currently no effective therapy to prevent
progressive vision loss in patients with atrophic
AMD. In 2011 we will commence a pioneering
clinical trial of a novel intervention that prevents
the build-up of a key waste product that damages
the cells under the retina. As a precursor to this
trial, the study team at Moorfields and the UCL
Institute of Ophthalmology are developing new
ways of assessing atrophy disease progression, and
functional changes in patients with this disorder to
allow for more effective clinical trial design.
The ABC trial for wet AMD
Current strategies for the use of drugs to treat
neovascular AMD lead to gradual drop-off in vision,
which means that the benefits of these intensive
treatments are being lost with time. Moorfields was
the lead and coordinating centre of an important
randomised multi-centre trial. Using an anti-VEGF
drug (a substance that prevents the formation or
growth of new blood vessels) resulted in not only
the recovery of lost vision on average, but also the
development of an individualised retreatment
algorithm. This maintained benefit over time,
with a reduced treatment burden relative to
current interventions.
7
Diabetes
The programme of translational research for this
theme extends from the laboratory investigation of
the mechanisms of retinal disease to clinical trials
of new medical and surgical interventions.
Diabetes is the commonest cause of blindness
in young adults. The aim of the diabetes research
theme is to protect people from loss of vision
by improving the diagnosis and treatment of
diabetic retinal disease. We have a broad strategy
that integrates distinct but complementary
programmes of research to translate progress
in scientific research into effective new
interventions. These research programmes include
the development of highly sensitive diagnostic
imaging techniques and powerful new therapies.
“It is hugely rewarding to see how progress
in basic science can be translated into new
interventions that have a real impact on
people’s lives. The ability to observe individual
cells and molecules in the retina non-invasively is
tremendously exciting. This offers a unique
insight into the effects of diabetes on the retina
that is certain to lead to improved outcomes.”
James Bainbridge
8 MR James Bainbridge
Theme leader – Diabetes
Consultant ophthalmic surgeon at Moorfields
Eye Hospital and Wellcome Advanced Fellow
at UCL Institute of Ophthalmology
Diagnostic imaging techniques
The retina can be studied in unique detail because
it is accessible to optical imaging. We are using
high-resolution cellular and molecular imaging
techniques to study the effect of diabetes on the
retina and the impact of therapeutic interventions.
We are working to develop imaging and
psychophysical techniques to help us to understand
the relationship between changes in retinal structure
and function. As a ‘window’ to the brain, imaging of
the retina enables us to study mechanisms of disease
relevant to the central nervous system. Consequently,
we are collaborating with neurologists to identify
biomarkers of vascular disease in the retina that can
be used as tools for the prevention of stroke.
A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
“The work includes local, national
and international collaboration
and this is what makes the
Reading Centre an exciting
place in which to work.”
Dr Tunde Peto (right)
Head of Reading Centre
Above left:
Maintaining healthy
circulation in the retina
is critical for sight
Powerful new therapies
Recent scientific advances in our understanding
of the mechanisms involved in diabetic retinal
disease have led to the identification of new
targets for treatment. The first results of an
ongoing clinical trial demonstrate that
intraocular delivery of a VEGF inhibitor (a
substance that prevents the formation or growth
of new blood vessels) can improve visual outcome
in people with diabetes, benefiting five times
more people than conventional laser treatment.
We are also working to understand the impact
of diabetic retinal disease on people’s abilities
to perform the essential activities of daily life.
By offering hospital-based vision rehabilitation
services to people with diabetes, we will
investigate in detail the effect of diabetes on
people’s sight. The results of this work will
inform the future development of services
to enable people with diabetes to make the
most of their visual ability.
The Reading Centre
The Reading Centre provides vital objective
evaluation of images for clinical epidemiological
studies and clinical trials. It has a broad role within
the BRC that includes teaching and training,
research into the best methods of image analysis,
and validation of new imaging techniques.
Dr Jacob is a busy inner-city GP whose life has
changed as a result of recent translational research.
His story is typical of many for whom diabetes has
a devastating effect: despite conventional laser
treatment, his failing sight began to affect his ability
to work. Recent research led by Mr Phil Hykin at
Moorfields has helped to demonstrate that a new
injectable treatment targeting the VEGF molecule
can dramatically improve the outlook for people
with diabetic eye disease. Following a course of
injections, Dr Jacob was enormously relieved
to experience a substantial improvement in vision
and has been able to continue his work with
renewed confidence. “This has made a significant
difference,” he says. “I was struggling to read
but now my sight is back to normal.”
“Anti-VEGF injections significantly improved the
outcome compared to conventional laser treatment.
We expect that anti-VEGF injections will supersede
laser as the optimal therapy for certain kinds of
diabetic eye disease in the next few years.”
Phil Hykin
9
Glaucoma
Glaucoma affects 2% of those over 50 years old, but 5% of
those over 80 years. Therefore, with an increasingly ageing
population, glaucoma is becoming a much more common
condition, with half of glaucoma cases being undetected
until the disease has caused some loss of vision.
Early detection is thus essential to prevent blindness,
and appropriate strategies should be adopted to
manage glaucoma once a diagnosis has been
confirmed. The key areas of research are: diagnosis;
monitoring and measuring disease progression;
establishing risk factors for glaucoma; and
evaluating the impact of disease on the individual.
“Our research strategy is focussed on patients’
needs. My research team has expertise across
many fields, from diagnostic tests to measuring
the impact of vision loss on everyday activities.
Much of my research programme is translational,
turning laboratory discoveries to patient benefit.”
David Garway-Heath
Professor David Garway-Heath
Theme leader – Glaucoma
Consultant ophthalmic surgeon at Moorfields Eye
Hospital and International Glaucoma Association
Professor of Ophthalmology and Allied Studies
at UCL Institute of Ophthalmology
affected by the presence of cataract and refractive
error. Moorfields patient Carol Bronze describes
her impressions of the Moorfields MDT:
“I have been involved with the MDT testing at
Moorfields Eye Hospital, where I am a patient,
for several years now. I assisted as one of the trial
patients when the testing was being pioneered and I
Our key areas of study include:
found the equipment and procedure incredibly easy
to use. Both the explanation of how to use the
The Moorfields Motion Displacement Test
programme and the functionality made the whole
(MMDT)
testing experience easy and quick. Testing of the
This is a new test for glaucoma diagnosis that has
arisen as a result of 20 years’ work. It is affordable, eyes can be distressing, tiring and lengthy. I found
the MDT test so easy to use, I was happy to return to
portable, easily understood by patients and is not
10 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
“Since I was diagnosed with glaucoma six years
ago, Moorfields has played a huge part in my life
– from regular appointments every week to
numerous different operations. At some points,
it seemed as if I would never return to school
full time, or lead a ‘normal’ life, but thanks to
Moorfields and their research I have been able
to do so. Without their treatment, help and
support, my life would have been very different,
and I cannot thank them enough for what they
have done for me and my family.”
Julia Margetts, Moorfields patient
Above left:
A glaucomatous
optic disc
help refine it whenever I was needed. Indeed, I
would be happy to take part in further testing as
all patients should have an opportunity to use a
procedure that makes life easier for them.”
Combining visual fields and imaging for
glaucoma diagnosis
Imaging is used to monitor the structure of the
optic nerve while a visual field test measures its
function. Recently, we have investigated the
use of information obtained through imaging
to supplement that obtained through visual field
testing, with the aim of diagnosing glaucoma
earlier and reducing the variability of current tests.
Monitoring intraocular pressure
Intraocular pressure (IOP) is the major risk factor
for glaucoma development. We are constantly
evaluating new devices to measure IOP and are
also developing better-performing devices.
he UK Glaucoma Treatment Study and
T
the UK Glaucoma Risk Factor Study
Our main clinical trial is the UK Glaucoma
Treatment Study (UKGTS), which is the first and
only randomised placebo-controlled trial in the
medical treatment of glaucoma. We are now
extending the trial to the UK Glaucoma Risk
Factor Study (UKGRIFS).
The EPIC Norfolk Study – eye and vision module
The European Prospective Investigation of Cancer
(EPIC) investigates the effect of diet on long-term
health and over 6,000 participants have been
examined to date. The eye module is a key
component of this study.
UK Biobank Eye Study
We are responsible for the eye component of
the nationwide UK Biobank project, which aims
to shed light on many of the most common
debilitating diseases by studying genetic and
molecular information from samples obtained
from over 100,000 people around the UK.
Impact of glaucoma on the individual
This important field of research provides insight
into how vision impairment caused by glaucoma
impacts on the patient’s daily activities. We aim
to determine the effect of binocular visual field
damage (taken from both eyes) on daily activities
(driving, mobility, reading, everyday tasks, face
recognition). We have already shown how
everyday tasks like reaching and grasping are
affected by glaucoma. Future work will look at
balance; we know that glaucoma is related to
an increased risk of falling over, which can lead
to fractures – a major health problem.
11
Ocular repair, regeneration
and pharmaceutics
Work within this theme includes new surgical techniques to
improve surgery based on basic laboratory understanding of
biological responses; the role of growth factors and their effect
on ocular scarring; the cellular and molecular basis of cell motility
(spontaneous movement) and scarring; and ocular stem cells
– basic biology and therapeutic use including prevention of
scarring, tissue reconstruction and regeneration.
Why scarring is important
Our focus is the efficient development of new
clinical treatments to control scarring (fibrosis)
after surgery and disease. The causes of fibrosis are
complex and contribute to many human diseases,
including every major blinding disease. There is a
large unmet need for anti-scarring therapies that
can be used for disease treatment and to manage
healing after surgery. Preventing scarring also helps
the body to regenerate, and encourages stem cells
to restore the eye.
Improving anti-scarring treatments
Administration of anti-cancer agents directly
into the eye after glaucoma filtration surgery to
control fibrosis, and therefore manage healing,
is currently the best clinical treatment available.
There are many side effects because repeat
injections of high doses that are naturally and
12 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
Professor Peng Tee Khaw
Theme leader – Ocular repair, regeneration
and pharmaceutics
Professor of Glaucoma and Ocular Healing at
UCL Institute of Ophthalmology and consultant
ophthalmic surgeon at Moorfields Eye Hospital
rapidly cleared in some regions of the eye
(eg the conjunctiva) are nevertheless toxic locally
and systemically.
To address toxicity, we have discovered that repeat
injections of a drug called metalloprotease inhibitor
(MMPI) have a markedly beneficial effect on scarring
reduction without the toxicity of anti-cancer agents.
“Research has, so far, saved my sight. It could help me
and many other children in the future.”
Rhiannon Willis, Moorfields patient
“Rhiannon’s story shows how research really changes
lives. She lost her sight from inflammation and
scarring but we managed to restore her sight
using new techniques and treatments developed
through research. Her story inspired most of
the donations for the new children’s hospital,
and she fittingly laid the foundation stone.” Peng Khaw
Above left:
The size of the
tissue tablet relative
to a pound coin
You can see
Rhiannon’s story at
http://www.nihr.ac.uk/
about/Pages/about_
transforming_health_
research_video.aspx
New methods of drug delivery
“The NIHR has helped to bring scientists like
To address tissue-specific pharmacokinetics
me together with clinicians to help change lives.
(what the body actually does to the drug, as
Our research into scarring and new drug delivery
opposed to what the drug does to the body),
will benefit other conditions where scarring causes
we have developed a novel, small, resorbable
blindness. This work is also important for training
tissue tablet to release MMPI locally at the fibrotic
the next generation of clinician scientists.”
site. Our results support a clear pathway to develop Professor Steve Brocchini, Professor of Chemical
the MMPI tablet to treat post-surgical fibrosis that
Pharmaceutics at the School of Pharmacy in
has a very good chance of success. If post-surgical
London, and a major researcher in the ocular
scarring can be controlled and the surgery is
repair, regeneration and pharmaceutics theme
successful long term, we have shown in large
trials that it is possible to halt the progression
of glaucoma.
We have also developed a prolonged dosage
form of an antibody, a protein-based medicine.
Antibodies are usually administered as injections,
but we have developed a tablet form, whereby a
single tablet can be placed at the site of surgery,
and remain biologically active over an extended
period of time. A recent study has shown this new
antibody tissue tablet to be more efficacious than
any treatment now used clinically.
Since glaucoma is the second leading cause of
blindness worldwide, the development of these
new medicines will allow simplification during
surgery and in post-surgical procedures. This will
potentially allow glaucoma filtration surgery to be
conducted more widely to halt progression of
glaucoma in a greater number of patients.
Peng Khaw examining a young patient’s eye prior to surgery
13
Ocular surface disease
Ocular surface diseases include several blinding disorders
that affect the cornea and conjunctiva at the front surface
of the eye. As a national referral centre, Moorfields has
relatively large numbers of patients whose ocular surface
disease is so severe that they have lost their sight.
Much of our time in clinics and operating
theatres is spent treating these patients with
immunosuppressive drug treatment, or corneal
or stem cell transplantation. We are focussing on
three areas of translational research that will lead
to new treatments for patients with ocular
surface diseases.
Direct molecular quality enhancement
of donor corneas
We aim to prolong the lifespan of donor cornea
cells following transplantation in patients with
blinding corneal disease (about 500 corneal
transplants are undertaken in Moorfields each
year). We are developing a method to do this
by modifying donor cornea cells in the laboratory
before transplanting them into patients’ eyes.
This should reduce – and possibly remove – the
need to replace transplants and, in the future,
the need for a transplant may be eliminated
altogether by treating the patient’s own cornea
with this type of technique.
14 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
MR Frank Larkin
Theme leader – Ocular surface disease
Consultant ophthalmic surgeon at
Moorfields Eye Hospital and senior lecturer
at both UCL Institute of Ophthalmology
and at Imperial College School of Medicine
at Hammersmith Hospital
Stem cell transplantation for limbal failure
The Cells for Sight Transplantation and Research
Programme is at the forefront of using stem cells
to tackle eye diseases that were previously
untreatable. Where previously permanent
blindness occurred, we can now help some
patients with genetic disorders, eye inflammation
or chemical burns who have scarring and opacity
of the cornea. We are developing the optimum
process to provide a graft with the highest possible
stem cell content. Successfully transferring such
The Cells for Sight Transplantation
and Research Programme
Dr Julie Daniels directs the Cells for Sight
Transplantation and Research Programme and is the
scientific lead for ocular surface stem cell therapy at
the NIHR BRC for Ophthalmology. In 2004, the Cells
for Sight Tissue Bank was the first stem cell bank in
the UK to obtain approval from the MHRA to treat
patients with cultured stem cells (stem cells grown
in the laboratory). Around 60% of the patients
treated have experienced improved vision and
reduced pain. This year, a new, expanded state-ofthe-art stem cell therapy research unit will be
opened. This unit will not only continue to provide
therapy for ocular surface disease but will also
support clinical trials of stem cell-based therapies
for other blinding eye diseases, including macular
degeneration and possibly optic nerve repair.
a graft from the laboratory to the surface of a means that if we have innovative treatments to
patient’s eye in the operating theatre has been an
translate from the laboratory to patient care, we
obstacle that we are overcoming by developing a
can research their effectiveness fairly quickly. Most
novel bioengineered substance to carry the cells.
patients with blinding ocular surface disease have
If the disease occurs in both eyes, stem cells from
otherwise healthy eyes. This means that when we
a patient’s own eyes cannot be used and we have
can restore a healthy ocular surface, e.g. in corneal
previously had to rely on donor tissue. However,
transplantation, remarkable improvement in vision
we have now developed methods of isolating stem can result.”
cells from a variety of human tissues, such as the
Frank Larkin
mouth, and hair follicles from the scalp, to provide
a source of cells that will regenerate the surface of Christina had sight-restoring corneal transplantation
the eye but will not be a target for immune rejection. four years ago and still has excellent vision in the
eye concerned. Left almost totally blind after an eye
Treating blinding scarring conjunctival
infection many years previously, she became
diseases by selective new treatments
housebound and lost all her confidence, so when
Blinding scarring conjunctival diseases are
Moorfields told her she was a suitable candidate for
immune-mediated – they result from abnormal
a corneal transplant, she was delighted. She received
activity of the body’s immune system. We are
a new treatment to prevent her immune system
currently investigating the genetics and specific
rejecting the transplant, developed as a result of our
proteins in the ocular surface that are the targets
ongoing research on transplant rejection.
for the immune response. At present, very potent
She could not believe the improvement. “It was
immunosuppression drugs are necessary to stop
immediate and just amazing to be able to see
disease progressing in most patients and we are
again,” she says. When asked for examples of how
evaluating new drugs and drug combinations that
her newly restored vision had affected her day-toare more effective but also more specific, in order
day life, she reported being able to recognise her
to reduce the incapacitating or life-threatening
son’s face and to see the food she was eating.
side-effects of the drugs in current use.
“ I can’t praise the clinical and research staff at
“Most patients with ocular surface disorders
Moorfields enough. They are really doing a great
have been referred from their local department,
job and pioneering work that is transforming
and if their blinding disease cannot be treated in
people’s lives.”
Moorfields, there is nowhere else to go. Thus we
have quite large numbers of such patients: this Christina, Moorfields patient
15
Paediatrics and
inherited eye disease
Inherited disorders of the retina are one of the leading causes of
childhood blindness and for the most part there are no effective
treatments. Loss of vision is caused by the gradual death of the
light-sensitive cells in the retina. We are investigating several
different approaches to developing effective treatments.
Gene therapy for childhood blindness
professor Anthony Moore
First, a group led by Professor Robin Ali are trying
Theme leader – Paediatrics and
to improve the function of the light-sensitive cells and
inherited eye disease
prevent their death using gene therapy – the
introduction of a normal copy of the gene into the
Duke Elder Professor of Ophthalmology at UCL
retina to replace the faulty gene. This new human
Institute of Ophthalmology and consultant
gene is inserted into a harmless virus which then
ophthalmologist at Moorfields Eye Hospital and
transports the gene into the retinal cells, where the
Great Ormond Street Hospital for Sick Children
gene is able to function normally. In 2008 we
performed the first gene therapy clinical trial for
noticed a significant improvement in his night-time retinal disease in man, treating a rare form of
vision. Jacob can now cope much better in
infantile onset retinal disease. We have shown that
lowlight environments and feels more confident
the treatment is effective in improving sight and we
and independent when he goes out at night, and
are currently investigating the optimal dose to use
can now make his way through a pub or club
and the optimal age for treatment to be given.
unaided, something for which he previously
Jacob, 23, was born with a form of Leber’s
had to rely on friends.
congenital amaurosis, a condition in which the
“Before, I might have become completely blind by the
light-detecting cells at the back of his eyes were
time I was 40,” he says.“I am very grateful that I could
damaged and slowly degenerating. In June 2009
participate in this trial. The alternative for me was simply
he took part in our ground-breaking gene therapy
to wait and do nothing, so I am really very lucky.”
trial and within four weeks of his right eye being
injected with working copies of the faulty gene, he Jacob, Moorfields patient
16 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
“They said ‘let there be light’, and there was
Jacob (left) with
light. For 30 years I’ve seen absolutely nothing Dr Scott Robbie of
NIHR BRC for
at all, it’s all been black, but now light is coming the
Ophthalmology
through. It is truly amazing. They’re wonderful
people these scientists. It’s exciting. And after
you’ve seen nothing for 30 years but darkness,
suddenly to be able to see light again is truly
wonderful… My one ambition at the moment
is to see the moon, to go out on a nice clear
evening and to be able to pick up the moon.
Whether I’ll be able to do it or not, I don’t
know, but I’m relying on these scientists.”
Moorfields patient involved in the
retinal implant trial
Above left:
The Argus II
retinal implant
in situ
Artificial retina
A second approach is to replace the retinal cells
that have died. This requires a source of healthy
retinal cells but this is currently not available. We
have a team of scientists working towards developing
retinal cells from human stem cells. This is a complex
process, but we have made major advances over the
last few years and this form of treatment is a realistic
possibility within the next five years.
When the light-sensitive cells in the retina have
died completely, the retina fails to function and
the patient is blind, even though the nerves that
transmit information from the eye to the visual part
of the brain still work. This has led to the idea of
developing an artificial retina that will stimulate the
nerves within the eye directly and convey visual
information to the brain. Moorfields is one of a few
centres internationally involved in a multicentre
clinical trial of one form of retinal implant, the Argus
II retinal implant. Since 2008 our surgeons, led by
Mr Lyndon da Cruz, have carried out seven
successful operations to insert the Argus II retinal
implant into the eyes of seven blind patients
suffering from severe retinitis pigmentosa.
The Argus II system uses a spectacle-mounted
camera to feed visual information to electrodes in the
eye. The electrical pulses emitted induce responses in
the retina that travel to the brain via the optic nerve.
The brain is then able to perceive patterns of light
and dark spots corresponding to the electrodes
stimulated, and the implants generate consistent
visual perceptions for the patients. The early results
of the trial are very promising. As the technology
improves, the next generation of these retinal
implants will revolutionise the treatment of
patients who are blind due to retinal disease.
Genetics of human retinal disease
Another aspect of research within the theme is to
identify the specific genetic changes causing retinal
disease within families, and then to carry out detailed
investigation of retinal function using electrophysiology
and psychophysics and correlate this with the structure
of the retina. We have access to state-of-the-art
imaging, so it is now possible to image the different
layers of the retina and even the light-sensitive cells
themselves. We use the same approach to study the
effects of novel therapies such as gene therapy.
The testing and imaging of young children is
especially challenging. Young patients cannot
follow instructions or sit patiently through long
testing sessions, so we need to use specially
developed child-friendly methods to measure their
vision accurately. We have recently recruited a new
research group, led by Dr Marko Nardini, who have
expertise in measuring vision in infants and young
children. They are developing novel methods of
testing using state-of-the-art ‘eye tracking’
equipment that records where on a screen the child is
looking. By displaying specially designed patterns
and measuring the child’s eye movements towards
them, we can test how well children can see. These
methods work even with very young infants.
17
Infrastructure support
The presence of an integrated, comprehensive set of support
facilities is critical to our success. The following facilities enable
all our discoveries, progress and achievements.
Gene therapeutics
Eye bank
The BRC programme of research has
provided infrastructure support, such as a
Vector Core Facility, and focus groups for
researchers investigating the genetic
causes of blinding eye diseases.
Donations by members of the public of
human tissue to researchers to facilitate
the development of new approaches in
the treatment of blinding eye diseases.
Genotyping and phenotyping facility
Technical and senior research support
in genotyping and phenotyping to
underpin the research conducted by
all research themes.
Imaging and psychophysics
Combining the expertise of optometrists, senior
academic psychophysics researchers and senior
NHS clinicians. Imaging takes a number of
forms, of which microperimetry is just one.
Cells for Sight Tissue Bank
A facility for the development of limbal
epithelial stem cell transplantation in patients
with blinding ocular surface failure.
18 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
Microperimetry allows us to map visual
sensitivity by displaying small spots of light at
precise locations on the retina. This allows us to
track the progression of the patient’s vision loss,
and to map any improvements in visual
sensitivity following new treatments.
Ocular electrophysiology
Expertise underpinning the assessment
of patients who have been treated with
novel therapies.
NIHR Research and Treatment
Centre for Eyes and Vision
This centre is being developed as part of
the BRC to include expanded phenotyping
facilities, advanced imaging, a novel treatments
unit, and functional vision assessment before
and after administration of novel therapies.
This new centre has quadrupled our existing
clinical research area.
Joint strategic infrastructure
and management
Reading Centre
Image grading to identify eye disease pathology
and progression and development of novel
research methods.
The BRC supports the continued integration and
development of strategic and research support
systems across the whole site to facilitate the
development of better patient management.
The Richard Desmond Children’s
Eye Centre at Moorfields
The Richard Desmond Children’s Eye Centre at
Moorfields houses the Fight For Sight paediatric
research floor.
Moorfields Pharmaceuticals
Development of new pharmaceutical approaches
to the treatment of disease including delivery of
new medicines to patients.
19
Education and training
Training future leaders in academic medicine. We fully support
the tenets established by the NIHR Trainees Coordinating Centre
(TCC), which means that we seek ways of developing research
careers and research leaders whose work focusses on people
and patient-based applied health research.
Clinical lecturers
We have six NIHR Integrated Academic Training
(IAT) clinical lecturers on our joint site. These
new posts, introduced through the NIHR TCC,
represent a significant investment by the NIHR and
the London Deanery in securing our future leaders
in clinical academic ophthalmology.
Clinical lectureships are specialty training posts
that incorporate research with clinical specialty
training. These posts are aimed at doctors who
have completed a research doctorate or equivalent
and show outstanding potential for continuing
a career in academic medicine or dentistry.
Mr Rizwan Malik, clinical lecturer in Ophthalmic
Translational Research
“I am immensely fortunate to have the opportunity
to pursue an academic career in ophthalmology as
an NIHR clinical lecturer; such opportunities were
not available to my predecessors just a few years
ago. The joint set-up of a premier research
institution and world-class clinical establishment
makes the BRC an unrivalled place to undertake
translational research. The foundation of this
research is underpinned by a patient-centred
approach: the research needs are
identified by potential areas of
improved clinical care whilst the
outcomes are designed to have
a measurable impact on the lives
of the patients we treat.”
Rizwan Malik
Alongside our clinical lecturers we are very fortunate
to have a strong base of clinical research fellows
and associates, post-doctoral research associates,
research fellows, clinical research optometrists, PhD
and MD students, research orthoptists, technicians,
and genetic nurses and counsellors.
20 Director of Education, UCL Partners Eyes
and Vision Theme
Professor Peter Shah has taken up the role
of Director of Education, UCL Partners (UCLP)
Eyes and Vision Theme, for which he is based
part-time at the NIHR BRC for Ophthalmology.
Peter is a consultant ophthalmic surgeon and the
Supra-regional Glaucoma Specialist at University
Hospital Birmingham NHS Trust, where he
continues his clinical work.
“I passionately believe that education
is one of the key drivers for clinical
excellence, and is the gear which
allows us to translate research
and innovation into improved
care for the diverse communities
we serve.”
Peter Shah
Peter and his team will be working hard to make
UCLP Eyes and Vision the recognised world leader
for ophthalmic education, focussing on clinical
excellence and patient safety, and strengthening
the learning culture throughout the organisation.
Integration of the NIHR BRC with UCL Partners
academic health science centre strategy
Using the impetus provided by the tenets of the
academic health science centre, Peter will be
responsible for delivering a new MSc programme
at the heart of the community for health
science professionals, such as optometrists and
community nurses, including communicating
research developments, trials information and
new technologies, with a particular interest in
deprived communities. He will also be looking
into ways of developing new courses for clinical
ophthalmologists, incorporating clinical practice
and research development.
A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
Our successes at the 2010 NIHR
Experimental Medicine Summer School
Miss Megan James, PhD student, is pictured here
with Professor Dame Sally Davies, Director
General for Research and Development at the
Department of Health, receiving an award for best
poster presentation for her work on ‘Optimisation
of Cellular Scaffolds for Neural Retinal Cell
Replacement using Human Muller Stem Cells’.
The summer school was open only to doctoral
students nominated by all 12 national Biomedical
Research Centres. Seventy delegates attended
the event and all submitted an abstract for oral
or poster presentations. Of those only three were
selected to present orally and 25 by poster.
Dr Clemens Lange, one of our clinical research
associates, and a PhD student, is seen here
presenting his work on ‘Intraocular Oxygen
Distribution in Advanced Proliferative Diabetic
Retinopathy’, for which he received a ‘highly
commended’ award for his oral presentation.
“As a graduate student involved in translational
research at the NIHR BRC for Ophthalmology,
I am grateful for the support I receive from the
NIHR, without which I would not be able to carry
out research towards my PhD. To work in an
environment where science and clinical practice
are so intertwined is truly inspirational, and this
has led me to consider applying for a medical
school place in the future.”
Megan James
“The NIHR supports me to work with outstanding
scientists and clinicians, in world-class facilities,
to conduct leading-edge research focussed on the
needs of patients. Working within the NIHR BRC
for Ophthalmology provides an ideal opportunity
for people with an interest in translational research
and has reinforced my goal to pursue a career as
a clinician scientist.”
Clemens Lange
21
Patient and public involvement
Our patients help us to determine the important questions that need
to be answered through research, and increasing numbers of patients
are becoming involved in the design of research trials. We are also
organising more combined patient/researcher days, which we have
found to be remarkably mutually beneficial. Recent examples include
‘Glaucoma, Genes and Me’, and the ‘Birdshot Patient Day’.
Events
Glaucoma, Genes and Me
Since 2006, Mr Paul Foster and Dr Sancy Low
have been involved in a research project looking
at the genes involved in or responsible for primary
angle-closure glaucoma (PACG). Over 80 families
from the UK were involved in their project.
In September 2009, we held an event in central
London to bring together the research participants,
genealogy volunteers, charitable sponsors and
experts in the field of PACG. We were supported
by UCL under the Beacons for Public Engagement
programme - funded by the UK Higher Education
Funding Councils, Research Councils UK and the
Wellcome Trust.
This event was a superb opportunity to discuss
topics related to angle-closure glaucoma, and
the PACG patients and their families were able
to gain information on the aspects of PACG that
were most important to them. As researchers,
we benefited from gaining insights from patients
about how best to communicate with the public
about disease and research.
“The feedback we received
was exceptionally positive and
participants indicated great
enthusiasm for more events
of this nature.”
Dr Sancy Low
22 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
Participants in our ‘Glaucoma,
Genes and Me’ event
Birdshot Patient Day
In September 2010, after months of careful
planning, we held a patient day for sufferers
of Birdshot Chorioretinopathy. Birdshot is an
autoimmune disease, a rare and chronic form
of posterior uveitis that is potentially blinding,
particularly if left untreated.
We worked with the Birdshot Uveitis Society
to make this event possible and were again
supported by UCL under the Beacons for
Public Engagement programme.
The Birdshot Patient Day provided an opportunity
for people to meet fellow sufferers who understand
the difficulties of living with this disease, talk to the
experts, hear about innovations in treatment, and
to know that there is a strong support network
available to them. Clinical researchers were able
to discuss treatment regimens with patients, and
current research into the disease. Through these
discussions, patients identified issues that are of
key importance to them, which will inform the
development of research proposals in the future.
“ I am no longer scared of my
future and I feel less isolated
and powerless.”
Patients and staff at our Birdshot
Patient Day – an opportunity for all
to learn more
Rea Mattocks, Birdshot patient, co-founder
of Birdshot Uveitis Society and co-organiser
of the Birdshot Day
23
24 A Vision for Vision Making tomorrow’s sight-saving treatments a reality today
New tests are being developed to measure
vision in infants and children using specially
designed displays and an ‘eye-tracker’ device
that measures where on the display the child
is looking.
NIHR Biomedical Research Centre for Ophthalmology
Moorfields Eye Hospital NHS Foundation Trust
and UCL Institute of Ophthalmology
162 City Road
London
EC1V 2PD
Tel: (+44) (0)20 7253 3411
www.brcophthalmology.org
www.nihr.ac.uk/about/Pages/about_transforming_health_research_video.aspx
National Institute for
Health Research