Over the last 18 years, SERI has conducted several successful research projects with positive outcomes for impact and clinical applications. This is a summary of 15 highly successful studies we did that demonstrated tangible translational values.
Tooth In The Eye
A SERI team led by Adjunct Professor Donald Tan was credited as being the first medical team in Southeast Asia to perform an artificial corneal procedure known as osteo‐odonto keratoprosthesis (OOKP) on a 19-year-old Thai patient in 2004. The procedure, which involved using the boy’s own canine tooth to implant a plastic cornea into one eye, has won three international awards for the team. This procedure may have significant clinical impact, as it restores sight in severe cases of blindness due to injuries (burns or acid attacks) that previously had no therapeutic recourse. Currently, the team is embarking on the second phase of this study in collaboration with Nanyang Technological University (NTU), which aims to explore the use of novel biomaterials instead of teeth to make this procedure more efficient, faster and accessible.
Gene Identification For Inborn Corneal Disease
SERI conducted a project that investigated the genetic basis of corneal dystrophies – and researchers working on this project managed to identify the gene that could potentially blind babies born with a severe form of congenital corneal blindness, known as congenital hereditary endothelial dystrophy (CHED). The team also discovered similar mutations in the same gene amongst adults with the most common form of premature ageing of corneas, known as Fuchs’ endothelial dystrophy. This discovery provides research opportunities to develop potential gene therapies to address corneal dystrophy - a significant problem amongst Singapore’s rapidly ageing population.
Eyes Provide Clues To Stroke Risk
Professor Wong Tien Yin, Associate Professor Kamran Ikram and Doctor Carol Cheung led a team that conducted a major international study, which involved 1,500 patients from Singapore and Australia with acute stroke. The study demonstrated that patients with retinal microvascular signs are more likely to have “lacunar” or “small blood vessel” strokes than patients without those signs, providing important insight into microvascular contribution to stroke. Retinal photography may thus eventually complement cerebral CT and MR imaging in the diagnosis, classification and risk stratification of acute stroke. This will have significant implications on how stroke is treated.
Novel Use Of Cord Blood For Stem Cell Transplantation
Most stem cells grown in labs for transplants are currently cultured with blood serum derived from cows. A Pilot Grant study conducted by SERI, titled “Ex vivo expansion of ocular surface epithelial cells for transplantation - novel use of cord blood and fetal fibroblasts and stem cells”, has successfully secured funding from Singapore’s Biomedical Research Council (BMRC) to access the use of human cord blood serum, as well as fetal fibroblast and ocular surface stem cells, to externally culture epithelial cells. This novel method can potentially reduce the risk of zoonosis (the transmission of infections from animals) and reduce the risk of transplanted tissue rejection. This study represents a major advancement in cell culture and bioengineering, as it allows for safer and more efficient means of growing cells and tissues for human transplantation, with improved long-term clinical results.
Exploring The Use Of Laser For "Bladeless" Refractive Surgery
We conducted a clinical trial to evaluate a new surgical method for Endothelial Keratoplasty (EK) - a common procedure surgeons use for corneal transplants. The procedure, known as Femtosecond Laser-Assisted Deep Lamellar Endothelial Keratoplasty (FLEK), involves the use of a femtosecond laser to perform “bladeless” EK surgery.
Femtosecond lasers have greater surgical precision and accuracy than a blade and can potentially result in better visual outcomes for patients. The laser also helps automate corneal surgery procedures, which simplifies the transplant operation and reduces surgical risks. This project has now evolved into a major collaborative study, with our industry partner Carl Zeiss, utilising their latest Visumax laser as the equipment of choice.
Managing Myopia, Eye by Eye
SERI's studies on the development of myopia in Singaporean children found that the use of atropine eye drops helps reduce myopia progression by 80%. Further studies, led by Professor Donald Tan and Doctor Audrey Chia, are being carried out to find the optimal efficacy and safety of this procedure, which will help them develop a treatment routine that effectively manages childhood myopia. As Singapore has one of the world’s highest myopia rates, any form of prevention to stem the progress of myopia would be significant for children in Singapore.
Laser To Treat Asian Glaucoma
Primary Angle Closure Glaucoma (PACG) is one of the more prevalent forms of glaucoma in Singapore, as well as other Asian countries such as China and India. In patients with PACG, topical medications can control eye pressure but they do not treat the mechanism causing the problem, and there remains further risk of angle closure and eye pressure over time.
We conducted a study, “Argon Laser Peripheral Iridoplasty for Primary Angle Closure Glaucoma (PACG): A Randomized Controlled Trial” to determine the efficacy and safety of a procedure known as Argon Laser Peripheral Iridoplasty in the management of PACG. Iridoplasty is a therapy that addresses the mechanism of a persistent narrow drainage angle, and might be useful to help patients in the complete withdrawal of medical therapy, or reduce the number of eye drops they need to apply. The findings of this study will be largely relevant for glaucoma management in Singapore, China and India, and other countries with a high prevalence of PACG. This research may ultimately help us to prevent PACG-caused blindness.
Stopping Contact Lens Related Infections In Their Tracks
Our paper “Contact lens related infectious Keratitis’, was published in the Journal of the American Medical Association (JAMA), Impact factor 23.33, in June 2006. This paper revealed that a major outbreak of Fusarium keratitis, a type of fungal corneal infection, was associated with soft contact lens wear. The study also identified a link between the outbreak and the use of a certain brand of contact lens cleaning solution. This resulted in a review of then-current international standards in contact lens care solutions, followed by the proposal of new standards. This successful paper put Singapore in the spotlight as the first country in the world to identify the association between the Fusarium keratitis outbreak, soft contact lens wear and contact lens solutions.
Invigorating Our Medical Armory
Proteomics is a relatively new field of study that looks at how proteins are constructed and how they interact. One of the proteins studied under this field is defensins - a group of natural protein molecules found in mammals that are known to kill a wide range of germs and microbes. This quality of defensins has earned them the name, “natural antibiotics”. The SERI Defensins team, led by Professor Beuerman and Doctor Zhou Lei, has developed a new research platform using a multi-disciplinary approach to engineer new forms of anti-microbial molecules, based on their work on defensins. The platform has allowed us to develop new, natural anti-microbial drugs with potential applications beyond that of just the eye, as they may be able to provide a new set of powerful and safe disease-fighting medicines.
Pioneering Genetic Eye Therapies
A team of researchers led by Professor Aung Tin and Associate Professor Eranga Vithana managed to identify the gene that could potentially blind babies born with a severe form of congenital corneal blindness, known as congenital hereditary endothelial dystrophy (CHED). The team further discovered similar mutations in the same gene amongst adults with the most common form of premature ageing of corneas, known as Fuchs’ endothelial dystrophy. This discovery provides research opportunities to develop potential gene therapy to address corneal dystrophy, a significant problem amongst the rapidly ageing population of Singapore.
Professor Aung Tin, Associate Professor Eranga Vithana and Doctor C.C. Khor, supported by Professor Cheng Ching-Yu, have also led an international consortium that discovered three genes linked to primary angle closure glaucoma (PACG), a type of glaucoma predominantly found in Asian patients. This team was also the first in the world to study PACG genetics using a genome-wide perspective, and their findings were published in the prestigious scientific journal, Nature Genetics, on 26 August 2012. The discovery of these genes have led to further research to elucidate the full genetic architecture of PACG, which will allow the development of a clinically useful genetic profile for the identification, risk stratification and treatment of PACG patients in the future. This was a major achievement for the Singapore team, and this information on the genes involved in PACG has now opened up new and exciting research areas that can result in potential new treatment methods for angle closure glaucoma in the future.
As these novel medical treatments come close to implementation, a coordinated basic and clinical research base is essential. Further investment to support this work will translate into treatment and, hopefully, the eventual eradication of many degenerative and hereditary eye diseases.
SCORM - Identifying The Risk Factors For Myopia
The Singapore Cohort Study of the Risk factors for Myopia (SCORM), led by Professor Saw Seang Mei, recruited 1,979 Singapore children in 1999 and followed their development for 10 years. Through genome-wide association scans, environmental and genetic risk factors for childhood myopia were identified. This study identified modifiable environmental risk and protective factors for myopia: doing near work, IQ and parental history increased the risk of myopia, while outdoor activities and breastfeeding protected the children against myopia.
This study further identified several genetic susceptibility variants, which were replicated in studies of other populations, such as the STARS GWAS Family study. Potential genes are also currently being investigated in the SCORM, SIMES, SICC, SP2 and STARS Family populations. Additionally, genes from SERI’s myopia mouse and chick model will be replicated in the human population.
As a consequence of this study, public health education through the National Myopia Prevention Program by the Singapore Ministry of Health has culminated in a decreased trend of myopia (spectacle wear) in the past few years. This will reduce the nation-wide economic burden of myopia in Singapore. The identification of minor genetic variants will also facilitate the recommendation of interventions for children to decrease myopia progression.
STARS – INVESTIGATING MYOPIA IN CHILDREN
We conducted a study, ‘STrabismus, Amblyopia and Refractive Error Study’ (STARS), which involved 3000 children aged between 6 to 72 months. The study demonstrated that very early-onset myopia is influenced primarily by parental history of myopia, and that environmental factors have a smaller effect as compared with later-onset myopia. As a result of this study, health promotion measures are being targeted at older school-age children to modify environmental factors for “school myopia”. For early myopia, the genes will be investigated in the STARS family study.
Tan Endoglide
A SERI team headed by Adjunct Professor Donald Tan and Associate Professor Jodhbir Mehta had invented a new corneal donor insertion device, known as the Tan EndoGlide. This device was created for the most current form of endothelial keratoplasty (EK) surgery, Descemet’s Stripping Endothelial Keratoplasty (DSAEK), which has been patented, licensed and bulk manufactured by Network Medical Products in the UK - and is now commercially available worldwide.
The Tan Endoglide is the only donor insertion device in the world that is FDA-approved by the U.S Food and Drug Administration (FDA). All other competing devices, which are mostly designed in the US, are still at the clinical trial stage and have yet to be approved by the FDA. A recent paper in the American Journal of Ophthalmology (AJO) has demonstrated that the Tan Endoglide reduces corneal cell damage by more than 50% when compared to other methods. Patients in Singapore were the first to use the device since it was produced in 2009. The Tan Endoglide is now used for all patients in SNEC undergoing the DSAEK procedure, which is rapidly replacing conventional forms of corneal transplantation.
SNEC now performs the largest number of DSAEK transplants in Asia and is one of the leading eye specialist centres in corneal transplants worldwide, largely due to the Tan EndoGlide device. The device is currently being used by over 50 corneal surgeons worldwide.
The original Tan Endoglide has since been improved. The Tan Endoglide 2, an enhancement of the original design, makes it even easier and safer to perform this complex type of small-incision keyhole surgery. It has been refined in part from information derived from outcomes of SERI’s clinical trials with the Endoglide, which has the best published clinical results of any device in corneal transplantation.
Use Of Fibrin Glue To Develop New frontiers In Corneal Transplants
A SERI team headed by Adjunct Professor Donald Tan and Associate Professor Jodhbir Mehta has invented a new form of treatment for corneal transplants using fibrin glue. A provisional patent for this treatment has been filed. The new technique of enzymatic wound closure could potentially replace the need for surgical sutures in many ocular surgeries, thus achieving a better standard of ocular tissue repair for patients. This technology could also contribute to faster recovery and fewer follow-ups after corneal surgeries, as well as better cost savings in healthcare expenditure.
ReLEx and SMILE
A project led by Adjunct Professor Donald Tan and Associate Professor Jodhbir Mehta is pioneering a new form of corneal refractive surgery in collaboration with Carl Zeiss, which may eventually rival LASIK. With the new procedure, keyhole LASIK surgery can be performed without making a full corneal flap. This procedure, named the Refractive Lenticule Extraction (ReLEx), is an evolution of laser refractive surgery.
A modified procedure known as SMILE (Small Incision Lenticule Extraction) involves the creation of a much smaller keyhole incision through which the lenticule – a disc-shaped piece of corneal tissue - which can be extracted with a smaller wound. Due to the smaller wound, SMILE results in a stronger eye, less immediate post-operative discomfort and tearing, as well as a smaller potential for dry eye problems when compared to LASIK. Reducing these side-effects and complications, normally associated with LASIK, may make SMILE a potentially safer option.
The SERI team further came up with the concept of making ReLEx potentially reversible (which would make it safer than LASIK). Instead of discarding the lenticule, they developed the concept and technique of cryo-preserving (freezing in liquid nitrogen) and storing the lenticule to be re-inserted into the patients’ eye if needed. This process has been patented, and pre-clinical studies are currently underway.
The success of a reversible ReLEx technique will be a major advantage over conventional LASIK, and SERI would be the pioneer of the first reversible refractive surgery procedure. The current priority of ReLEx development is a sound commercialization strategy to target the biggest ophthalmic market, namely patients suffering from presbyopia (long-sightedness). The team is currently exploring the concept of using patients’ discarded lenticules as intracorneal presbyopia implants.
Landmark Trilogy Of Large-Scale Population-Based Eye Studies
SNEC director Professor Wong Tien Yin and his team - Professor Aung Tin, Professor Ecosse Lamoureux and Professor Saw Seang Mei, as well as Professor Cheng Ching-Yu and Associate Professor Charumathi Sabanayagam, have conducted a series of three landmark, community-based studies to systematically document the frequency, causes and impact of low vision and major eye diseases in the three different ethnic groups in Singapore.
The Singapore Malay Eye Study (SiMES) successfully looked at 3,280 individuals from Singapore’s Malay population from 2004–2006.
The Singapore Indian Eye Study (SINDI), the second of the studies, examined 3,400 Singaporeans of Indian descent from 2007–2009.
The Singapore Chinese Eye Study (SCES), the last of the three studies, examined 3,353 Singaporeans of Chinese descent from 2009-2011.
The Singapore Eye Disease Study (SEDS) - The Singapore Indian/ Chinese Cohort (SICC), initiated via funds from SERI’s pilot grant but which then secured a $2.2 million Biomedical Research Council (BMRC) grant, is an important population-based, cross-sectional, epidemiological study aimed at determining the prevalence and risk factors of visual impairment, blindness and major eye conditions in adult Indian and Chinese Singaporeans. This project extended from the SiMES study and completed the trilogy of large-scale population-based eye studies in the three main ethnic groups in Singapore: the Chinese, Indians and Malays.
These studies provide a powerful set of initial scientific data on the causes and impact of vision-threatening diseases in 10,000 Asians. The strengths and opportunities presented by these findings are unparalleled. As these studies observe the same standardized protocol derived from benchmark studies conducted among Western populations (US and Australia), they would facilitate the direct comparison of data not only among the three major ethnic groups in Singapore, but with Western populations as well. The SICC and the SiMES form the largest, most comprehensive population-based study on vision-threatening eye diseases affecting three major ethnic groups in Asia, which represent half of the current world population.
From Bench To Bedside: Retinal Imaging For Disease Prediction
Professor Wong Tien Yin and Doctor Carol Cheung led a high-impact study which indicates that an assessment of retinal vascular damage using non-invasive imaging technology will be able to predict a patient’s predisposition to certain eye problems and systemic diseases.
The project demonstrated that changes in the retinal vascular system (blood vessels at the back of our eye) can predict the risk of heart disease, stroke, diabetes, hypertension, dementia, kidney and other vascular conditions years before they develop, and independent of current diagnostic methods. The early identification of such diseases will enable more targeted and effective intervention, ultimately translating into a significant reduction in disability, morbidity and mortality. This would significantly impact the lives of millions in Singapore and around the world, leading to substantial savings in the nation’s long-term healthcare budget.
Singapore Advanced Imaging Laboratory For Ocular Research (SAILOR)
Spearheaded by Professor Wong Tien Yin, the Singapore Advanced Imaging Laboratory for Ocular Research (SAILOR) is a collaboration between SERI and A*STAR’s Institute of Infocomm Research (I2R). SAILOR is our first clinical translational research unit in Fusionopolis and an exemplary symbol of the excellent potential that can be created in translational research via prolific cross-disciplinary collaborations. Clinicians, scientists, computer scientists, and other experts make up the symbiotic pool of research talent at SAILOR, and they are a talent pool that represents the symbolic marriage between Science and Information Technology. This integration of talent enables SAILOR to further serve as a Tele-Ophthalmic Ocular Imaging Centre, a hub that ensures better and prompt service delivery by streamlining and automating the entire image capture process, the elucidation of images and result generation.
Singapore Integrated Diabetic Retinopathy Programme (SIDRP)
A team led by Professor Wong Tien Yin established the Singapore Integrated Diabetic Retinopathy Programme (SiDRP), a national comprehensive diabetic retinopathy (DR) screening programme at the primary health care (polyclinic) level. SiDRP is based on a concept developed by Professor Wong Tien Yin which allows the centralised assessment of DR from retinal photographs, and leverages the capabilities of SERI’s ocular imaging research and its team of readers or graders at the SNEC Ocular Reading Centre (SORC) - supported by a tele-ophthalmology platform.
SiDRP aims to provide real-time assessment of DR with a 1-hour turnaround. SiDRP will facilitate a more effective and prompt service delivery of DR screening by streamlining and automating the entire process.
SORC will function as a national-level centralised grading centre for DR, supporting all government polyclinics in the early phase, and eventually providing more comprehensive coverage for all patients by including private general practitioners (GPs), opticians and other relevant entities within SAILOR’s purview.
The SiDRP initiative will facilitate the early detection of DR, which leads to early intervention and the prevention of vision loss. It will eliminate inefficiencies within the current DR screening workflow by providing faster, more cost-effective and better disease diagnosing. SiDRP will be a major paradigm shift in the screening of DR in Singapore, and reflects the benefits of investment in translational research directly to patients. It will also usher in improved productivity and cost savings to Singapore’s healthcare system.
Ocular Drug Delivery Platform
A team lead by Associate Professor Tina Wong, together with collaborators from the Department of Materials Science and Engineering at Nanyang Technological University (NTU), has come up with a way to free patients from the need to administer frequent, daily eye drops for years - or even indefinitely.
The use of nanotechnology allows the successful delivery of medication via specific bioengineered carrier platforms, which are applied to the eye. These nanocarrier systems enable a steady release of the drug over several weeks, which directly benefits glaucoma patients who need to use eye drops every day to control their disease. With the emergence of sustained-release drug delivery systems for common glaucoma drugs, issues arising from missed applications can be addressed and significantly reduced.
SERI has completed a pilot clinical trial on a sustained-release drug delivery system, developed in collaboration with NTU. It is aimed at preventing scarring, which is a major obstacle for the long-term success of glaucoma filtration surgery. The results have demonstrated the superiority of the sustained-release drug delivery system, in terms of clinical efficacy, when compared to conventional treatment.
Work is progressing smoothly and successfully on these new sustained-release drug delivery systems. Early outcomes seem to indicate the system’s high potential as a next-generation ocular drug delivery system for glaucoma and all other ocular diseases, thus eliminating the need for frequent and long-term eye drops to control such conditions. By using this new system, patients don’t have to carry multiple bottles of eye drops wherever they go, which significantly reduces their risk of disease progression and lead to a notably improved quality of life.
Transforming Growth Factor Beta Induced (TGFBI) Test
A team led by Associate Professor Jodhbir Mehta and Associate Professor Eranga Vithana collaborated with a team from A*STAR’s Personalised OMIC Lattice for Advanced Research and Improving Stratification (POLARIS) to develop the Transforming Growth Factor beta Induced (TGFBI) test. The TGFBI test is a genetic test designed to aid in the diagnosis and management of patients with Stromal Corneal Dystrophies (CDs), and to identify family members of TGFBI-mutated patients who may also be at risk for CD. The successful determination of a patient’s TGFBI mutation status can facilitate clinical care by providing patients with personalised diagnoses, which will impact future disease progression and aid in the selection of mutation-specific topical therapies. TGFBI testing is also useful for providing genetic counseling to the family members of affected individuals, and screen family members who want to undergo eye surgeries like LASIK for potential genetic risks.
The projects listed above serve as a cross–spectrum overview of the cutting-edge research conducted by SERI, in its efforts to further its goal towards the generation of knowledge and/or technology that could potentially improve the clinical management and treatment of eye diseases.
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