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SERI Overview

The Singapore Eye Research Institute (SERI) was conceived with the foresight of a visionary leader, Prof Arthur Lim, the founder and fi rst Medical Director of the Singapore National Eye Centre (SNEC), who had keenly pursued the idea of an eye research institute in a period of time when research was hardly in vogue in Singapore.

Established in 1997, SERI is Singapore’s national research institute for ophthalmic and vision research. SERI’s mission is to conduct high impact eye research with the aim to prevent blindness, low vision and major eye diseases common to Singaporeans and Asians. Over the last decade or so, SERI has conducted landmark research that has led to tangible outcomes, actual patient benefi t, and success stories. It has paved the way for signifi cant improvements in how eye diseases are treated and prevented, not just for Singaporeans or Asians but on a global scale.

At its inception, SERI saw a national remit in ophthalmic and vision research, and till today, despite the demarcations introduced by the healthcare clustering system, SERI bridges both entities with a presence in each cluster. SERI ensures that its facilities and resources are open to researchers across Singapore so that the greatest benefi t may be obtained from what is a relatively small clinical ophthalmology catchment area in Singapore.

SERI has grown from a founding team of five in 1997 to a faculty of more than 196 staff, encompassing clinician scientists, scientists, research fellows, PhD students and support staff. This makes SERI one of the largest research institutes in Singapore, as well as the largest eye research institute in the Asia Pacific region. SERI has also over 220 adjunct faculties from various eye departments, biomedical institutes and tertiary centres in Singapore. SERI has published an impressive array of 3,405 scientific papers, and has secured external peer-reviewed competitive grants worth more than $309 million. As of 31 December 2018, SERI’s faculty has been awarded with more than 506 national and international prizes and filed 123 patents.

As the research institute of the SNEC, and directly affiliated to the Yong Loo Lin School of Medicine, National University of Singapore, as well the Duke-NUS Medical School, SERI undertakes vision research in collaboration with local clinical ophthalmic centres and biomedical research institutions, as well as major eye centres and research institutes throughout the world.

SERI ranks first globally in terms of eye publications per capita, far ahead of the US, UK and Japan.

With its impressive publication track record, SERI is comparable to renowned eye institutes, both regionally and internationally.

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Publication

The US published the most number of papers. Singapore* published the most number of eye papers per capita *95% of papers from SERI

*All searches fi ltered for ‘ophthalmology’ related publications

rd Supplemental Table 1. Country of Origina Ranked 3 in proportion of 1042 Full Length Manuscripts Submitted papers accepted (success rate) and Accepted to the American Journal of Ophthalmology between October 1, 2009 in Ophthalmology* and September 20, 2010

th United States 273 88 Ranked 4 in number of papers Japan 141 49 accepted in American Journal China 91 4 Republic of Korea 63 13 of Ophthalmology* Spain 52 9 *95% of papers from SERI / NUS India 37 2 Germany 35 9 Singapore 33 10 Success rate (manuscripts received vs accepted) United Kingdom 29 7 for Ophthalmology Journal 2010 Success Rate Italy 29 7 Turkey 29 6 30% 28% 25% Brazil 24 4 23% While we may be relatively young and lean, SERI is proud to rank 25% 21% Taiwan 22 4 19% 18% 20% 15% France 21 9 above the global heavyweights, i.e. Singapore is Impact number 15% 13% 13% 12% 10% 9% 9% Israel 20 4 10% The Netherlands 17 7 one globally in terms of eye publications per capita, far ahead of 5% Australia 17 5 the US, UK and Japan. 0% 36 Other Countries 129 20 Total 1042b submitted 257 accepted Italy India Japan Taiwan Canada a Australia Germany Based on the location of the corresponding author

With its impressive publication track record, SERI is comparable Singapore Hong Kong b South Korea Netherlands Only the tip 17 countries with submitted or United States accepted manuscripts are listed here. to renowned eye institutes, both regionally and internationally. United Kingdom

Singapore (where 95% of the publications are generated via SERI) was ranked 3rd in the proportion of papers accepted (success rate) in the top-ranked eye journal, Ophthalmology, and further ranked 4th in success rate in another high Impact Factor eye journal, the American Journal of Ophthalmology.

Collaboration “Research is a team sport” SERI has cultivated a symbiotic network of people, including its team of scientists and researchers, trial coordinators and optometrists as well as ophthalmologists from public sector eye hospitals such as the Singapore National Eye Centre (SNEC), National University Health Systems (NUHS), Tan Tock Seng Hospital and so on. We work together in close collaboration to achieve a common goal - the generation of knowledge and/or technology that can potentially improve the clinical management and treatment of eye diseases. SERI has additionally initiated a steady stream of impactful research collaborations with peers at the A*STAR Research Institutes, Nanyang Technological University as well as other biomedical institutions and eye centres in Singapore.

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Today, SERI is recognized as a pre-eminent pacesetter of ophthalmology and vision research in Asia and the rest of the world. It is a strong advocate of strategic research alliances and collaborations. The SERI faculty has played key strategic advisory roles in the initiation and conceptualization of research ideas and technologies with renowned international institutions, including Stanford University and Johns Hopkins University in the United States, Moorfields Eye Hospital in England, the Centre for Eye Research Australia, University of Melbourne, the Centre for Vision Research, University of Sydney and the Lions Eye Institute in Australia, the Capital University and Zhongshan Ophthalmic Institute in China. This has enabled us to maintain a high level of research competency and skills transference. SERI has also forged important ongoing research alliances with major industry partners.

Local Collaborations

International/Industry Collaborations Global Academic Collaborations Industry Collaborations

• Aravind Eye Care System, India • Kirchhoff-Institute for Physics, • AcuFocus • Menicon • Aston University Birmingham University of Heidelberg • Advanced Medical Optics • Merlion Pharma • Australian National University School • Kyoto Prefectural University of • Advanced Medical • Network Medical of Biological Sciences, Australia Medicine, Japan Technologies • Neurovision • Center for Eye Research Australia, • Lions Eye Institute, Australia • Alcon • Northern Lipids University of Melbourne • Max Planck Institute, Germany • Allergan • Novartis • Centre for Vision Research, University • Narayana Nethralaya Foundation, India • Angioblast Systems • Ocular Therapeutix of Sydney • Oregon Health & Science University, • AqueSys • Oculex Asia • CHUV-Lausanne University Hospital, USA • Bausch & Lomb • Optique Paris Miki Lausanne, Switzerland • St. George’s University, USA • Bayer • ORA • City University London • Stanford University, USA • Canon • Oxigene • Cornea Research Foundation of • Tel Aviv University, Israel • Capital Optical • PARAXEL America • The First Affiliated Hospital of • Carl Zeiss International • Doshisha University, Kyoto, Japan Chongqing Medical University, China • Ceepro • Patsnap • Duke University Eye Centre, USA • Queen’s University Belfast, Canada • Celgene • Pfizer • East Valley Ophthalmology, USA • The University of Wisconsin-Madison, • Ellex • Pharmacia & Upjohn • Erasmus University Medical Center, USA • Essilor • Quark Rotterdam, Netherlands • The Weizmann Institute of Science, • Eyedetec Medical Pharmaceuticals • Ho Chi Minh Eye Hospital, Vietnam Israel • Frontier FMC • Quintiles • Hospital Kuala Lumpur, Malaysia • University of Aberdeen, Scotland • GlaxoSmithKline • Roche • Indiana University School of Medicine, • University of New South Wales, • i-Optics • Santen USA Australia • Johnson & Johnson Pharmaceutical • Institute of Ophthalmology, Moorfields • University of Pennsylvania, USA • Kendle International • SATA CommHealth Eye Hospital, London, United Kingdom • Vietnam National Institute of • Keravision • SkinEthic • Johns Hopkins University, Baltimore, Ophthalmology • Laserex • Technolas USA • West Virginia University Eye Institute • Lenticor • VisionEx • King Khaled Eye Specialist Hospital, • Zhongshan Ophthalmic Centre, • Mandarin Opto-Medic • Welch Allyn Saudi Arabia Sun Yat-Sen University, China

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Research Strategy

SERI’s success in eye and vision research can be attributed to our state-of- the-art facilities, a conducive and nurturing environment that encourages robust and dynamic interactions between clinicians and scientists, a systematic research governance structure, and a strategic talent development programme, all of the above complemented by the insightful vision of a strong leadership team. Interactions between Clinicians and Scientists A core underlying principle that furthered the robust interactions between our clinicians and our scientists was the inherent understanding that impactful research leads to enhanced clinical outcomes, clinical reputation and increase in patients, both locally and regionally. This served to nurture this symbiotic relationship between clinicians and scientists. Hence, our focus at SERI is geared towards applied translational research, where each research group has a few clinician drivers who present unmeet clinical needs, and pose the right clinical questions and challenges, which our scientists undertake to address.

What is SERI’s Strategy?

World-class high quality academic research

Close interaction between Clinicians, Long-term strategies Clinician Scientists (CS) & Scientists Robust systems & finances

Inter-disciplinary Collaborations Development of people collaboration with industry Succession planning

Focus on Translational Clinical Research

Broad impact on all aspects of ophthalmology & medicine

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Research Governance Structure SERI has a robust research governance structure that is designed for SERI’s multi-disciplinary eye research groups to strategically tackle major eye diseases, leveraging on multiple core platform technologies that support the entire spectrum of research-from bench to bedside, to population.

SERI currently has 16 research groups in the following disciplines of eye research: • Ocular Genetics Research Group • Ocular Therapeutics & Drug Delivery Research Group • Tissue Engineering & Stem Cell Research Group • Ocular Surface Research Group • Retina Research Group • Health Services Research Group • Anti-Infectives Research Group • Clinical & Ocular Imaging Research Group • Ocular Epidemiology Research Group • Glaucoma Research Group • Ocular Inflammation & Immunology Research Group • Myopia Research Group • Cornea & Refractive Research Group • Bioengineering & Devices Research Group • Cataract Research Group • Visual Neuroscience Research Group

This research structure is augmented by core research support platforms: • Experimental & Basic Sciences Platform • Technology Development & Commercialization • Clinical Research & Trials Platform • Administration, Research Affairs & Support Services Platform • Population Health Platform • Research Training & Development Platform • Translational Pre-Clinical Model Platform • Imaging Platform • Data Science and Data Management Platform

These platforms interact with and support our diverse research themes, including: • Ocular Therapeutics & Drug Delivery • Ocular Imaging • Genetics of Eye Diseases • Ocular Inflammation & Immunology • Tissue Engineering & Stem Cell research • Health Services Research • Ocular Surface (Anti-Infectives & Dry Eyes)

The interactions between platforms and themes collectively serve to test key hypotheses, answer major clinical questions and generate knowledge that will further augment the management and treatment strategies for all the major eye diseases, with particular relevance for Singapore and Asia, with emphasis on these major eye diseases: • Glaucoma, with emphasis on Asian glaucoma (e.g. angle closure glaucoma) • Myopia and other refractive errors • Corneal and ocular surface disease • Diabetic retinopathy and other retinal vascular diseases • AMD and other degenerative ocular conditions

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SERI: Platforms & Themes PLATFORMS

Experimental & Basic Sciences

Translational Pre-Clinical Model

Clinical Research & Trials

Imaging

Population Health Ocular Surface Ocular Imaging Statistics & Data Management Genetics of Eye Diseases Genetics of Eye Health Services Research Health Services Biomarkers of Eye Diseases of Eye Biomarkers Tissue Engineering & Stem Cell Tissue

Ocular Infl ammation & Immunology Ocular Infl Administration, Research Aff airs Ocular Therapeutics & Drug Delivery Ocular Therapeutics & Support Services

Technology Development & Commercialization

THEMES

Leadership SERI’s research strategy is complemented by the articulate mapping of SERI’s long-term vision by its leadership, who not only inspired, but imbued all at SERI and SNEC on the need for research as an integral aspect of our clinical mission and as the key to future eye therapeutics and interventional strategies. This vision which began with Prof Arthur Lim was distilled through SERI’s four Executive Directors - the late Prof Chew Sek Jin, Prof Donald Tan, Prof Wong Tien Yin and Prof Aung Tin. The reputation of SERI’s core leadership, in terms of both their clinical expertise and their distinguished track record and research know-how, has laid a solid foundation for SERI to attract top collaborators, advisors and industry partners to collaborate with SERI on strategic research initiatives.

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Talent Development

SERI as a Global Magnet

SERI recognizes that human talent is a key factor in the development of scientifi c and biomedical research in ophthalmology. This is why SERI aims to meet the requirements of the institute in the next decades by proactively seeking and nurturing the next generation of scientists, researchers and clinician scientists. This will ensure SERI’s longevity and continued progress in the fi eld of eye research. SERI adopts a holistic approach to the development of research manpower in eye research, focusing on translational and clinical sciences relevant to ophthalmology. Over the years, SERI has acted as a global magnet, attracting research talents from all over the world to Singapore, including professionals from Israel, Germany, the UK, US, Asia Pacifi c, Hong Kong, Korea, China, India, Netherlands and the ASEAN region. This has contributed to a dynamic expansion of SERI’s research capacity and capabilities, and contributed to a melting pot of research talents from diverse backgrounds, interacting closely and forming an incubator for the generation of ground breaking research.

Conclusion SERI’s desired outcome is the development of fundamental paves the way for the generation of knowledge that will have knowledge and intellectual property in the fi eld of ophthalmic a direct positive impact on treatment strategy and therapeutic and vision research, and the generation of scientifi c publications approaches to major eye diseases, specifi cally to Asia and of signifi cant impact that will lead to better management of eye beyond. diseases. We intend to further build upon the existing robust and In the new decade, SERI, a bona fi de “Singapore Inc” organization, fertile clinician–scientist ecosystem, as well as leverage on the has set its sights on being one of the top 5 eye research research environment in Singapore to develop a new generation institutes in the world. The achievement of this goal and the of clinician scientists. global recognition that it will bring will certainly be a milestone SERI’s focus is predominantly geared towards translational well worth the signifi cant commitment, passion and hard work research (research with a clinical focus), hence this certainly that has been the hallmark of the SERI faculty.

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Projects With Positive Impact and Clinical Applicability

Over the last 21 years, SERI has conducted several successful research projects with clearly positive outcomes in terms of impact and clinical applicability. This is a summary of 15 highly successful studies demonstrating tangible translational values:

Managing Myopia, Eye by Eye

Tooth In The Eye The SERI team, led by Professor Donald Tan, was c redited as being the first in Southeast Asia to perform the osteo-odonto keratoprosthesis (OOKP) artifi cial cornea procedure on a 19-year-old Thai patient in 2004, using the boy’s own canine tooth to SERI studies on the development of myopia in implant a plastic cornea into one eye. The team has Singapore’s children found that the use of atropine won 3 international awards for their work in this eye drops have achieved close to an 80% reduction area. This procedure may have signifi cant clinical in the worsening of myopia progression. Further impact as it restores sight in severe cases of studies, led by Professor Donald Tan and Adjunct blindness due to injuries (burns or acid attacks) that Assoc Professor Audrey Chia, are being carried previously had no therapeutic recourse. Currently, out to fi nd the optimal effi cacy and safety of this the team is embarking on the second phase of this procedure in order to help develop a treatment study in collaboration with NTU, which aims to routine that will manage childhood myopia. As explore the use of novel biomaterials to replace the Singapore has one of the world’s highest myopia tooth portion so as to make this procedure more rates, any form of prevention to stem the progress efficient, faster and accessible. of myopia would be signifi cant for children in Singapore.

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Pioneering Genetic Eye Therapies A SERI 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 signifi cant problem amongst the rapidly ageing population of Singapore. Professor Aung Tin, Assoc Professor Eranga Vithana and Dr C.C. Khor, supported by Professor Wong Tien Yin, had additionally 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 work was also the fi rst in the world to study PACG genetics using a genome-wide perspective, and was published in the prestigious scientifi c journal, Nature Genetics, on 26 August 2012. This discovery has led to further research to elucidate the full genetic architecture of PACG which will allow the development of a clinically useful genetic profi le for the identifi cation, risk stratifi cation 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 have the potential to culminate in new treatment modalities 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.

Eyes Provide Clues To Halting An Epidemic Of Stroke Risk Contact Lens Infection A team lead by Professor Wong Tien Yin, led The team of Professors Donald Tan, Roger Beuerman a major international study involving 1,500 and Aung Tin managed to place Singapore in the patients from Singapore and Australia with spotlight as the fi rst in the world to identify a major acute stroke. The study demonstrated that outbreak of fusarium keratitis (a serious fungal patients with retinal microvascular signs are infection of the cornea) associated with soft contact more likely to have “lacunar” or “small blood lens wear, and further proved the link between the vessel” strokes than without signs, providing outbreak and use of a specifi c contact lens cleaning important insights into the microvascular solution. The worldwide withdrawal of this product contribution to stroke. Retinal photography resulting from their fi ndings immediately prevented may thus eventually complement cerebral CT international escalation of blindness from this most and MR imaging in diagnosis, classifi cation serious form of eye infection globally. and risk stratifi cation of acute stroke. This This was a breakthrough fi nding, as this was the fi rst will have signifi cant implications on how time that such an outbreak had been reported among stroke is treated. contact lens wearers anywhere in the world. This resulted in a review of the international standards in contact lens care solutions and led to new standards being proposed.

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Invigorating our Medical Armory Knowing how proteins are constructed and how they interact is part of a relatively new field of study called proteomics. Defensins are a group of natural protein molecules found in mammals that are known to kill a wide range of germs and microbes, earning them the name of “natural antibiotics”. The SERI Defensins team, comprising Professor Beuerman and Dr 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. This has allowed us to develop new, natural anti-microbial drugs whose potential goes far beyond that of just the eye, as they may be able to provide a new set of powerful, yet safe disease fi ghting medicines.

Tan EndoGlide A SERI team headed by Professors Donald Tan and Jodhbir Mehta invented a new donor insertion device, known as the Tan EndoGlide, for the current form of EK surgery, Descemet’s Stripping Endothelial Keratoplasty (DSAEK), which has been patented, licensed and bulk manufactured by Network Medical Products (UK). This device is now commercially available worldwide. A paper in the American Journal of Ophthalmology (AJO) had demonstrated that the Tan Endoglide reduces corneal cell damage by more than 50% as compared to other methods. Patients in Singapore have had fi rst access to the device since 2009. The Tan Endoglide is now used for all patients in SNEC undergoing this new procedure, which is rapidly replacing conventional forms of corneal transplantation. SNEC now performs the largest number of these transplants in Asia and is one of the leading eye specialist centres worldwide, with the best results, largely due to the Tan EndoGlide device. The device is currently being used by over 50 corneal surgeons worldwide. The Tan Endoglide 2 is an enhancement of the original design, making it even easier and safer to perform this complex type of small-incision keyhole surgery. It has been refi ned 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.

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Use of Fibrin Glue to Develop New Frontiers in Corneal Transplants A SERI team headed by Professors Donald Tan and Jodhbir Mehta have also invented a new form of treatment for corneal transplants, using fibrin glue, which is a novel approach. A provisional patent for this treatment has been fi led. 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 the patients. This technology could also contribute to faster recovery and fewer follow-ups, and better cost savings in healthcare expenditure.

ReLEx and SMILE Another project led by Professors Donald Tan and The SERI team further came up with the concept of Jodhbir Mehta pioneered a new form of corneal making ReLEx potentially reversible (which would make refractive surgery in collaboration with Carl Zeiss, it safer than LASIK). Instead of discarding this lenticule, which may eventually rival LASIK. The team is now they developed the concept and technique of cryo- able to perform keyhole LASIK without making a full preserving (freezing in liquid nitrogen) and storing the corneal fl ap. This procedure, named the Refractive lenticule for the potential future use of the patient. This Lenticule Extraction (ReLEx), is an evolution of laser process has been patented. refractive surgery. Pre-clinical studies are currently underway. If this A modifi ed procedure known as SMILE (SMall Incision technique proves to be effi cacious, this will be a Lenticule Extraction) involves the creation of a much major advantage over conventional LASIK, as SERI smaller keyhole incision through which the lenticule would have pioneered the fi rst potentially reversible can be extracted – with a smaller wound. Due to the refractive surgery procedure. The current priority smaller wound, SMILE results in a stronger eye, less is the development of a sound commercialization immediate postoperative discomfort and tearing and strategy to target the biggest ophthalmic market, i.e. the potential for less dry eye problems, as compared to those suff ering from presbyopia. The team is currently LASIK. Reducing these side-eff ects and complications, exploring the concept of using the discarded lenticules normally associated with LASIK, may make SMILE a as intracorneal presbyopia implants. potentially safer option.

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Landmark Trilogy of Large-Scale Population-Based Eye Studies Professor Wong Tien Yin and his team, including Professors Aung Tin, Ecosse Lamoureux, Saw Seang Mei and Cheng Ching-Yu as well as Associate Professor Charumathi, 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 diff erent 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 origin from 2007–2009. • The Singapore Chinese Eye Study (SCES), the last of the three studies, examined 3,200 Singaporeans of Chinese origin in 2011. The Singapore Eye Disease Study (SEDS) - The Singapore Indian/ Chinese Cohort (SICC), initiated via funds from SERI’s pilot grant which then secured a $2.2 million 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 is an extension of the completed SiMES study. The SICC will therefore complete the trilogy of large-scale population-based eye studies in the three main ethnic groups in Asia i.e. the Chinese, Indians and Malays. These studies in totality provide, for the fi rst time, a powerful set of scientifi c data on the causes and impact of vision threatening diseases in 10,000 Asian people. The strengths and opportunities are unparalleled. Since these studies observed the same standardized protocol derived from benchmark studies in Western societies (US and Australia), hence it would facilitate the direct comparison of data not only among the three Asian ethnic groups in Singapore, but this data is comparable with data from the Western populations. The SICC, along with SiMES, therefore form the largest, most comprehensive population-based study on vision-threatening eye diseases aff ecting the three major ethnic groups in Asia, representing half of the world’s population.

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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 1979 Singapore children in 1999 and followed them for 10 years. The environmental and genetic risk factors (Genome- wide Association Scans) were identifi ed. This study identifi ed modifi able environmental risk and protective factors for myopia. It was demonstrated that near work, IQ and parental history increased the risk of myopia, while outdoor activities and breastfeeding were protective factors. This study further identifi ed several genetic susceptibility variants, which were replicated in other populations such as the STARS GWAS Family study. Potential genes are 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. Consequent from this study, the education of the public through the National Myopia Prevention Program, Ministry of Health has culminated in a decreased trend of myopia (spectacle wear) in the past few years. Thus, nation-wide economic costs attributed to myopia will decrease. Additionally, the identifi cation of minor genetic variants will facilitate the recommendation of interventions for children to decrease myopia progression.

Retinal Imaging for Disease Prediction: From Bench to Bedside Another high impact study led by Professor Wong Tien Yin and Dr Carol Cheung is based on research fi ndings which seem to indicate that an assessment of retinal vascular damage using non-invasive imaging technology will enable the prediction of one’s predisposition to certain eye problems and systemic diseases. This project demonstrated that retinal vascular (blood vessels at the back of our eye) changes can predict the risk of heart disease, stroke, diabetes, hypertension, dementia, kidney and other vascular conditions years before their development and independent of current diagnostic methods. The early identifi cation of such diseases will enable more targeted and eff ective intervention, ultimately translating into a signifi cant reduction in disability, morbidity and mortality. This would signifi cantly impact on the lives of millions in Singapore and around the world, leading to substantial savings in the nation’s long-term healthcare budget.

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Singapore Integrated Diabetic Retinopathy Programme (SiDRP) The SERI team led by Professor Wong Tien Yin established the Singapore Integrated Diabetic Retinopathy Programme (SiDRP), a national comprehensive diabetic retinopathy (DR) screening programme aimed at enhancing the current DR screening programme at the primary health care (polyclinic) level. SiDRP is based on Professor Wong Tien Yin’s concept of centralized assessment of DR from retinal photographs, leveraging on the capabilities of SERI’s ocular imaging research and its team of readers or graders at Singapore Ocular Reading Centre (SORC), supported by a tele-ophthalmology platform. SiDRP aims to provide real-time (1 hour turnaround) assessment of DR. SiDRP will facilitate a more eff ective and prompt service delivery of DR screening by streamlining and automating the entire process. SORC will function as a national-level centralized grading centre for DR, supporting all government polyclinics in the early phase, and thereafter will provide more comprehensive coverage for all patients by including private GPs, opticians and other relevant entities within SORC’s purview. The SiDRP initiative facilitates the early detection of DR, and thus allows for early intervention and the prevention of vision loss. It eliminates ineffi ciencies within the current DR screening workfl ow by providing a faster, more cost- eff ective and better disease diagnoses. In summary, the new SiDRP system serves as a major paradigm shift in the screening of DR in MOH, and refl ects investment in translational research with direct benefi t to patients, improved productivity and cost savings to the healthcare system.

Ocular Drug Delivery Platform A team lead by Associate Professor Tina Wong from SERI, together with collaborators from the Department of Materials Science and Engineering at Nanyang Technological University, has come up with a way to free patients from the need to administer frequent, daily eye drops for years or even indefi nitely. The use of nanotechnology allows the successful delivery of medication via specifi c bioengineered carrier platforms, which are applied to the eye. These nanocarrier systems enable a steady release of the drug over several weeks. This has immediate benefi ts to 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, the issues arising from non- compliance will be addressed and signifi cantly 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 after glaucoma fi ltration surgery, which is a major obstacle for long-term success of the surgery. The results have demonstrated the superiority of sustained-release drug delivery system in terms of clinical effi cacy when compared to conventional treatment. Work is progressing smoothly and successfully on these new sustained-release drug delivery systems. Early outcomes seem to indicate high potential as the next generation of ocular drug delivery systems, not only for glaucoma, but for all other ocular diseases, thus eliminating the need for frequent and long-term eye drops to control such conditions. The benefi ts to the patients will be the ability to cease carrying multiple bottles of eye drops, and to potentially reduce the signifi cant risk of disease progression. This will ultimately lead to a notably improved quality of life. The projects listed above serve as cross–spectrum of the cutting-edge research conducted by SERI over the last 21 years, in our quest to discover knowledge and technology that could improve the clinical management and treatment of eye diseases.

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Our Achievements

SERI has received numerous accolades for our impactful research over the years. An overview of these awards as follows:

Year Award Name Awardee

A/Prof Jodbhir Mehta 2009 AAO Achievement Award Prof Saw Seang Mei

2009 SingHealth GCEO Excellence Awards 2009 – Biomedical Research Prof Aung Tin

2009 NUS Outstanding Researcher Award Prof Wong Tien Yin

Prof Donald Tan 2009 Inaugural President's Science and Technology Award (PSTA) Prof Aung Tin Prof Roger Beuerman

2009 NMRC Clinician Scientist Award A/Prof Louis Tong

2009 Casebeer Award, American Academy of Ophthalmology, 2009 Prof Donald Tan

2009 Alcon Research Prize: Merit Prize (Senior Category) Dr Daniel Su

2010 ASCRS Howard Lieberman MD, Memorial Award 2010 Dr Leonard Yuen

2010 ARVO Basic Science Award Dr Anita Chan

2010 NRF-MOH Healthcare Research Scholarship Dr Marcus Ang

National Outstanding 2010 Prof Wong Tien Yin Clinician Scientist Award 2010

Duke-NUS Medical School – 2010 Prof Wong Tien Yin Tanoto Initiative for Diabetes Research Award

2010 NMRC Clinician Scientist Award A/Prof Tina Wong

2010 25th APAO Congress – Holmes Lecture Adj A/Prof Ho Ching Lin

2010 25th APAO Congress – De Ocampo Lecture Prof Wong Tien Yin

2010 APAO Achievement Award Prof Aung Tin

2010 NHG Eye Institute Novartis Research Prize Dr Veluchamy A Barathi

2010 President's Science Award (PSA) 2010 Prof Wong Tien Yin

2010 Singapore Prestigious Brand Award 2010 Singapore Eye Research Institute

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Year Award Name Awardee

AAO International 2011 A/Prof Jodbhir Mehta Ophthalmologist Education Award

2011 NUS Faculty Research Excellence Award Prof Donald Tan

2011 Australia and New Zealand Corneal Society - Doug Coster Award Prof Donald Tan

2011 Canadian Society of Ophthalmology - Bruce Jackson Award Prof Donald Tan

American Society of Cataract and Refractive Surgery (ASCRS) 2012 2012 Dr Chelvin Sng Symposium on Cataract, IOL and Refractive Surgery

2012 NMRC Transition Award Dr Sabanayagam Charumathi

2012 NMRC Clinician Scientist Award A/Prof Cheng Ching-Yu

2012 Global Ophthalmology Awards Program: VERDICT, Bayer Grant A/Prof Gemmy Cheung

2012 NUS Faculty Outstanding Researcher Award Prof Aung Tin

2012 AAO, Senior Achievement Award Prof Donald Tan

2012 NMRC Transition Award Dr Nobuyo Yawata

2012 NMRC Clinician Scientist Award (Senior Investigator) A/Prof Louis Tong

2013 APAO De Ocampo Lecture Prof Aung Tin

2013 APAO Nakajima Award A/Prof Jodbhir Mehta

2013 APAO Distinguished Service Award Adj A/Prof Lee Shu Yen

2013 APAO Outstanding Prevention of Blindness Award A/Prof Gemmy Cheung

2013 APAO Achievement Award Prof Wong Tien Yin

2013 APAO Achievement Award Adj A/Prof Doric Wong

2013 ARVO Fellow (Silver Award) Prof Wong Tien Yin

2013 ARVO Fellow (Gold Award) Prof Roger Beuerman

2013 Alcon Research Institute Awardee Prof Aung Tin

2013 Eisenhower Fellowship Prof Wong Tien Yin

2013 President’s Science and Technology Awards - Young Scientist Award Dr Khor Chiea Chuen

Global Ophthalmology Awards Program (GOAP) from Bayer, Research 2013 Dr Su Xinyi Award

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Year Award Name Awardee

Dr Jimmy Liu, Dr Damon Wong, Prof Wong Tien Yin, Prof Aung Tin, 2013 IES Prestigious Engineering Achievement Award Dr Baskaran Mani, A/Prof Cheng Ching-Yu, Dr Carol Cheung, Haslina Binte Hamzah

2013 2013 Chew Sek Jin Memorial Lectureship Award Prof Saw Seang Mei

Bangalore Ophthalmic Society (BOS) Submit 2013 - Lifetime Achievement 2013 Prof Roger Beuerman Gold Medal

2013 SingHealth Publish! Award (Outstanding) Dr Laurence Lim

2013 SingHealth Publish! Award (Outstanding) A/Prof Eranga Vithana

2013 SingHealth Publish! Award (Medical Research) Dr Monisha Nongpiur

2013 Excellence in Ophthalmology Vision Award (XOVA) Dr Marcus Ang

2013 Singapore Translational Research (STaR) Investigator Award Prof Wong Tien Yin

2014 The Macula Society 2014 Arnall Patz Medal Prof Wong Tien Yin

2014 Southeastern Chinese University of Technology Guest Professor Award Prof Roger Beuerman

2014 APAO Nakajima Award A/Prof Gemmy Cheung

2014 APAO Achievement Award A/Prof Cheng Ching-Yu

2014 APAO Outstanding Prevention of Blindness Award A/Prof Cheng Ching-Yu

2014 Singapore Translational Research (STaR) Investigator Award Prof Aung Tin

2014 NMRC Transition Award Dr Queenie Li

2014 NMRC Transition Award Dr Anita Chan

2014 AAO Academy's Achievement Award Dr Chan Tat Keong

2014 AAO Senior Achievement Award Prof Aung Tin

2014 Bombay Ophthalmology Society - Gold Medal in Ophthalmology A/Prof Jodhbir Mehta

The College of Optometrists 2014 Prof Saw Seang Mei College’s Research Excellence Awards - Bernard Gilmartin OPO Award

2014 Arthur Lim Professorship in Ophthalmology Prof Donald Tan

Andhra Pradesh Ophthalmological Society – 2014 A/Prof Jodhbir Mehta Dr. P Siva Reddy Oration Medal

Prof Wong Tien Yin 2014 President’s Technology Award (PTA) Prof Lee Mong Li Prof Wynne Hsu

A/Prof Tina Wong 2014 President’s Technology Award (PTA) Prof Subbu Venkatraman Prof Freddy Boey

2015 APAO Outstanding Service in Prevention of Blindness Award Prof Ecosse Lamoureux

2015 APAO Distinguished Service Award Adj A/Prof Audrey Looi

2015 APAO Distinguished Service Award Adj A/Prof Doric Wong

2015 ARVO Gold Fellow Prof Saw Seang Mei

2015 ARVO Gold Fellow Prof Wong Tien Yin

Prof Aung Tin 2015 IES Prestigious Engineering Achievement Awards Adj A/Prof Shamira Perera Dr Baskaran Mani

2015 SingHealth Publish! Award (Outstanding) A/Prof Eranga Vithana

2015 SingHealth Publish! Award (Medical Research) Dr Wong Chee Wai

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Year Award Name Awardee

XXXIII Congress of the ESCRS – 2015 Dr Liu Yu-Chi 1st prize, Refractive Poster Award

XXXIII Congress of the ESCRS – 2015 Dr Ronald Yeoh Best Video Award

2015 EMBO Young Investigator Award Dr Khor Chiea Chuen

2015 NMRC Transition Award Dr Danny Cheung

2015 NMRC Clinician Scientist Award-Senior Investigator A/Prof Tina Wong

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Our Values

Success Our success stories validate SERI’s legacy as a trailblazer of eye research

Innovation Our research is innovative, out-of-the-box and constantly challenging new boundaries

Global We stand tall among global heavyweights in eye research due to our impactful research

Heal We seek to heal and strive towards a cure for blindness & vision disorders

Translational Our research is geared towards tangible outcomes (from bench- bedside-population)

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The SERI Executive Leadership

A Legacy And Catalyst For SERI’s Pre-Eminent Success SERI’s success has no doubt been driven by strong leadership for over 21 years. They have imbued all at SERI/SNEC with the realization that research is integral and serves as the key to novel eye therapeutics and interventional strategies. Additionally, the reputation of SERI’s core leadership, as key opinion leaders has led the way for SERI to attract top collaborators and industry partners to work with SERI on strategic research initiatives. First SERI Executive Director: the late Prof Chew Sek Jin The late Professor Chew Sek Jin, the Visiting Scientist, Rockefeller University; a Clinical Professor of fi rst Director of Singapore Eye Research Ophthalmology, LSU Eye Centre, as well as an Anatomy Adjucator, Institute (SERI) was a pioneer of Association for Research in Vision and Ophthalmology.

ophthalmic research in Singapore and was He was a pioneer in myopia research and was the President of the undisputed driving force propelling the Myopia International Research Foundation and Director of vision research to greater heights, until its Asia-Pacifi c HQ. Prof Chew received his Ph.D. in Neuroscience his untimely and tragic death in 1998. from Rockefeller University and was the recipient of numerous A brilliant ophthalmologist and scientist, scientifi c and humanitarian awards. Despite suff ering from a the late Prof Chew played indispensable roles as a member of terminal illness, Prof Chew maintained his usual vigorous pace the Scientifi c Advisory Board of the Myopia Center, New England of research, teaching and patient care.

College of Optometry, as well as the Glaucoma Foundation. The late Prof Chew will always be remembered as one of the Prof Chew was also appointed as a Visiting Professor for the most promising research brains that Singapore had produced. City University of New York and New York Eye & Ear Infi rmary; a

Second SERI Executive Director: Prof Donald Tan Prof Tan is concomitantly the Lead Principal Investigator for two Prof Donald Tan is the Arthur Lim Professor major $25 million Translational Clinical Research programme in Ophthalmology at the Ophthalmology and grants i.e. the $25 million “Translational Research Innovations in Visual Sciences Academic Clinical Program, Ocular Surgery” (TRIOS) programme that ends in the third quarter Duke-NUS Medical School as well as a Senior of 2013, followed by the $25 million “Eye Surgery and Innovative Advisor with the Singapore National Eye Technologies (EyeSITe)” programme grant awarded in August Centre. He further holds a concurrent position 2013, that will leverage on the TRIOS grant’s past success, with as Senior Principal Clinician Scientist at the the ultimate aim to provide new clinical therapies and diagnostic Singapore Eye Research Institute (SERI). applications to aid in alleviating ocular morbidity from major eye

Prof Donald Tan, who was formerly Medical Director of SNEC, diseases, including corneal disease, infection, glaucoma, refractive was instrumental in introducing the SingHealth Duke-NUS errors and retinal disorders. Ophthalmology & Visual Sciences Academic Clinical Program which He is the recipient of over 20 awards, which include the APAO 2001 seamlessly integrates clinical care, education and research. He was De Ocampo Award, the AAO 2006 Distinguished Achievement Award, also the architect of SERI, globally recognised as a top eye research the ISRS/AAO 2009 Casebeer Award, the Saudi Ophthalmological institute, where he served as Chairman till 2013. Society 2010 Gold Medal, the Australia and New Zealand Corneal

Prof Tan is recognised internationally as a leading research pioneer Society 2011 Doug Coster Award, the Canadian Society of for his extensive work and innovations in corneal and stem cell Ophthalmology 2011 W. Bruce Jackson Award, the EuCornea 2012 transplantation, refractive surgery, myopia treatments and patented Medal, the Portland, Oregon Arthur Devers 2012 Lecture. He was surgical devices. Involved primarily in clinical and translational also part of the SERI team conferred the Inaugural President’s research in cornea, refractive surgery and myopia, he has published Science Award in 2009, the highest honor bestowed upon scientists over 330 peer-reviewed articles (h index = 55), contributed more and medical researchers in Singapore. In addition, he was been than 18 book chapters and holds 21 patents in stem cell culture, conferred the Arthur Lim Professorship in Opthalmology in 2014 myopia prevention, refractive corneal implants and surgical devices and is also the recipient of the the prestigious Binkhorst Medal at for endothelial keratoplasty, and has further trained more than 30 American Society for Cataract and Refractive Surgery Meeting 2015. corneal fellows from over 13 countries. One of his inventions i.e. Prof Tan established the Asia Cornea Society in 2007 and the the “Tan EndoGlide” - a disposable surgical device is the fi rst device Association of Eye Banks of Asia in 2009, and is currently President marketed in the world with both FDA and CE approval for selective of both societies. In 2012 he assumed the Presidency of the US tissue transplantation of the cornea. based Cornea Society as its fi rst International President.

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Third SERI Executive Director: Prof Wong Tien Yin

Prof Wong Tien Yin is currently Professor Medical Research Council, Singapore, and a Council member of and Medical Director of the Singapore the Asia Pacifi c Academy of Ophthalmology, and the Asia Pacifi c National Eye Centre, as well as concurrently Vitreo-Retinal Society and the Honorary Treasurer of the College the Chairman of the Singapore Eye of Ophthalmologists in Singapore.

Research Institute (SERI). He further For his illustrious career encompassing academic work, clinical serves as the Chair of the Ophthalmology service and research, he has been recognized nationally and and Visual Sciences Academic Clinical internationally with numerous awards, including the Ten Program, as well as the Vice-Dean, Offi ce Outstanding Young Person of the World award for “academic of Clinical Sciences, Duke-NUS Medical School. Prior to undertaking leadership in people younger than 40 years of age” (1999), the these roles, Prof Wong had served as Professor and Chair of Asia Pacifi c Academy of Ophthalmology Prevention of Blindness Ophthalmology, University of Melbourne, as well as the Managing Award (2003) and Distinguished Service Award (2005), the Sandra Director of the Centre for Eye Research Australia. He had thereafter Doherty Award from the American Heart Association (2004), the undertaken other roles including, Head of Ophthalmology, National Outstanding Researcher Award from the National University of University of Singapore, as well as the Group Director, Research, at Singapore (in 2004 and 2009), the Woodward Medal from the the Singapore Health Services. University of Melbourne in 2005, the Alcon Research Institute Prof Wong is a senior principal clinician scientist, who balances Award (in 2006), the Novartis Prize in Diabetes (Global Young clinical work and research focused on retinal and macular Investigator) in 2006 and the Australian Commonwealth Health diseases, including diabetic retinopathy, age-related macular Minister’s Award for Excellence in Health and Medical Research in degeneration and retinal vein occlusion. He directs a large multi- 2006. He further was the recipient of the 2007 Australian Society disciplinary research program combining imaging, epidemiology of Medical Research AMGEN Medical Research of the Year Award and clinical trials on retinal diseases, and the use of ocular imaging for “outstanding contributions to translational research”.

technologies to predict eye and cardiovascular diseases. He is cited In 2008, Prof Wong was awarded the $5 million Singapore as the current world leader in the fi eld of retinal vascular sign, and Translational Researcher Award (STaR), and in 2010, the National their prognostic signifi cance as markers of future cardiovascular Outstanding Clinician Scientist Award. In 2010 and 2014, he was and cerebrovascular risk, and in understanding the impact and conferred the highest national honour in Science and Technology eff ects of diseases like hypertension and diabetes on the retinal in Singapore, i.e. the President’s Science Award and the President’s microvasculature. Technology Award respectively. He was also a recipient of the He has published over 1000 papers, including papers in the 2013 Eisenhower Fellowship from the USA and was awarded New England Journal of Medicine, the Lancet, the Journal of the the Arnall Patz Medal from the Macular Society 2014 as well as American Medical Association (JAMA), Nature, Nature Genetics, inducted in as an ARVO Fellow (Gold) Class 2015. and Annals of Internal Medicine, and is named on 18 patents as a co-inventor. He has given more than 200 invited lectures around the world, and acts as the Principal Investigator for more than US$50 million in grant funding from the Biomedical Medical Research Council (BMRC) and National Medical Research Council (NMRC), Singapore, as well as overseas agencies, including the National Institutes of Health (NIH), USA, the National Health and Medical Research Council (NHMRC), Australia, and JDRF, USA.

He serves on Editorial Boards of Investigative Ophthalmology and Visual Sciences, Diabetes Care and many other journals. He was previously the Executive Editor of the American Journal of Ophthalmology. He further sits on several national and international committees, and is a Board member of the National

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Fourth SERI Executive Director: Prof Tin Aung Prof Tin Aung is currently the fourth programme grant awarded in 2008, and the $25 million “Eye Executive Director of Singapore Eye Surgery and Innovative Technologies (EyeSITe)” programme Research Institute and holds multiple grant awarded in August 2013.

pre-eminent appointments as Deputy He has an impressive record of more than 420 publications, Medical Director (Research), as well including articles in high impact factor journals i.e. JAMA and as Senior Consultant and Head of Nature Genetics. He has been cited as the fourth most productive Glaucoma department at Singapore researcher in the world for glaucoma research. He has been an National Eye Centre. He is a Professor invited lecturer to over 100 international conferences and has of Ophthalmology, as well as the Director of Research at the received numerous awards including the Singapore NMRC-BMRC National University Health System (NUHS), Department of Clinician Scientist Awards, the SingHealth GCEO Excellence Ophthalmology. Prof Aung is a highly accomplished clinician Award, the Nakajima Award and de Campo Award from the Asia and academic in ophthalmology concurrent with his role as Pacifi c Academy of Ophthalmology and the Alcon Research the Academic Vice-Chair (Research), Ophthalmology and Visual Institute Award. Sciences Academic Clinical Program, Duke-NUS Medical School. He was further bestowed with the highest accolade granted to Prof Aung is also a senior principal clinician scientist and his the scientifi c community in Singapore when he was part of the visionary and forward-looking approach has been instrumental in SERI team who was conferred the Inaugural President’s Science the establishment of a world leading research program on angle Award in 2009. closure glaucoma in Singapore, a disease that remains a major He is a member of the Editorial Boards of Ophthalmology, Journal cause of blindness across the world, and especially so in Asia. of Glaucoma, Eye, Graefe’s Archive for Clinical and Experimental His research program extends across a broad range of aspects Ophthalmology and six other journals. He is also currently a of treatment, from clinical phenotyping, genetics screening, member of the Board of Governors for the World Glaucoma and detailed imaging, right through to therapeutics, surgical Association. techniques and randomized trials. He is the leader of various global research collaborations spanning about 15 countries, Prof Aung has further endeavoured to develop national and among which he has directed an international consortium international collaborations with scientifi c and healthcare that was successful in identifying novel primary angle closure institutions and industry players so as to maximize the impact glaucoma (PACG) genes. He has further led major international of this research. He has also played a key role in providing the clinical trials related to PACG disease management. vision and leadership in SERI that has helped to establish SERI as an entity to be reckoned with globally. Prof Aung is recognized globally as one of the most In 2015, Prof Aung’s illustrious achievements, visionary outstanding and prolifi c leadership skills and eminent professional standing have clinician scientists in the culminated in his appointment as the President of the World field of glaucoma. His Glaucoma Association. impactful contributions to ophthalmology, with a research-specifi c focus on diseases endemic to Asia, has earned him international repute, and elevated the positioning of Singapore and the region on the global ophthalmology road-map. Of special note, he was featured in The Ophthalmologist as one of the 100 Most Infl uential People in Ophthalmology today.

Prof Aung has received more than US$15 million in competitive research grant funding. He is additionally the Co-Lead Principal Investigator for two $25 million Translational Clinical Research programme grants awarded to SERI i.e. the $25 million “Translational Research Innovations in Ocular Surgery” (TRIOS)

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SERI Senior Scientific Advisor: Prof Roger Beuerman Prof Roger Beuerman In addition, he has authored 40 book chapters on subjects as is currently the Senior diverse as bioengineering to ophthalmology. Prof Beuerman Scientific Advisor of has also edited books in ophthalmology, and sits on several the Singapore Eye editorial boards, including as Executive Editor of Cornea, and as Research Institute, and an editorial board member of Ocular Surface. concurrently holds Prof Beuerman was inducted as an ARVO Fellow (Silver and positions as Professor Gold) Class of 2009 and 2013 respectively, and is additionally a of Neuroscience and Fellow of the Alcon Research Institute, and the Paolo Foundation Behavioural Disorders at Duke-NUS Medical School; Adjunct in Helsinki, Finland. In 2009, he was the proud recipient of the Professor of Ophthalmology, Yong Loo Lin School of Medicine Inaugural President’s Science Award together with Professors at the National University of Singapore; Adjunct Professor of Donald Tan and Aung Tin. He is also the recipient of the Lifetime Chemical and Biomedical Engineering at Nanyang Technological Achievement Award of the Bangalore Ophthalmic Society, 2013. University and Adjunct Senior Scientist at the Bioinformatics Institute.

He has more than 20 years of experiences in ophthalmology. His major research areas include the proteomic biomarkers of eye disease and development of new antimicrobial peptides for use in ophthalmology. He has worked to develop methods for analysing the microliter volumes of tears from the eye as a diagnostic source and looks to developing population based studies in proteomics.

Prof Beuerman has further contributed towards the development of experimental animal models in various areas of research including myopia and corneal research, which have served as an important platform in the elucidation of certain clinical hypothesis. He additionally has a long history of productive work in the area of ocular surface repair and stem cells and ocular surface regeneration. He has been instrumental in providing the basic science support during SERI’s pioneering years, and was part of the team involved in early conjunctival stem cell transplants in SNEC.

Prof Beuerman is further personally responsible for peer- reviewed grant funding exceeding $8,000,000, including grants from Singapore funding bodies i.e. NMRC, BMRC, SingHealth Foundation and Exploit as well as international funding bodies i.e. NIH. He has published more than 300 articles in international peer-reviewed journals, and has given more than 31 invited talks and over 500 presentations at international and local meetings.

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www.seri.com.sg 16 OrganizationalOrganizational Chart & ChartKey Contacts GOVERNANCE STRUCTURE (as of January 2014)

Senior Scientific Advisors EXECUTIVE DIRECTOR Adj Prof Donald Tan Prof Aung Tin Prof Paul Kaufman Prof Michael Belkin Prof Roger Beuerman

DEPUTY EXECUTIVE DIRECTOR Prof Jodhbir Mehta Scientific Director Prof Leopold Schmetterer

DIRECTOR DIRECTOR DIRECTOR DIRECTOR ADMINISTRATION, TECHNOLOGY LABORATORY CLINICAL DIRECTOR RESEARCH AFFAIRS, & DEVELOPMENT & TRANSLATIONAL TRANSLATIONAL POPULATION HEALTH SUPPORT SERVICES COMMERCIALIZATION RESEARCH RESEARCH Prof Ecosse Lamoureux Dr Vandana Ramachandran Dr Danny Belkin A/Prof Eranga Vithana A/Prof Tina Wong

RESEARCH GROUP

Ocular Cornea & Ocular Ocular Glaucoma Cataract Ocular Therapeutics & Refractive Retina Myopia Imaging Surface Genetics Drug Delivery

Co-Heads Head Head Co-Heads Head Head Head Head Head Adj Prof Donald Tan A/Prof Gemmy Prof Aung Tin Prof Saw Seang Mei Prof Leopold Prof Louis Tong Prof Chee Soon A/Prof Eranga A/Prof Tina Wong Prof Jodhbir Mehta Cheung A/Prof Audrey Chia Schmetterer Phaik Vithana

Ocular Tissue Engineering Anti- Bioengineering & Visual Inflammation & Health Services Ocular & Stem Cell Infectives Devices Neuroscience Immunology Research Epidemiology

Head Head Co-Heads Head Co-Heads Head Head Prof Jodhbir Mehta A/Prof Rajamani Dr Michael Girard Prof Dan Milea Prof Chee Soon Prof Ecosse Prof Cheng Ching- Lakshminarayanan A/Prof Shamira Phaik Lamoureux Yu Perera Prof Louis Tong

RESEARCH PLATFORM

Experimental Translational Experimental & Translational Pre- Clinical Research / Experimental Data Proteomics Genomics Molecular & Cell Ophthalmic Data Science Basic Sciences Clinical Model Trials Management Biology Pathology Microscopy

Head Head Head Head Head Head Head Head Head Head A/Prof Eranga Dr Amutha Barathi Prof Aung Tin Dr Zhou Lei A/Prof Eranga Dr Seet Li Fong Dr Anita Chan Dr Gary Yam Prof Ecosse Prof Cheng Ching- Vithana Vithana Lamoureux Yu

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Prof Executive Director, SERI Ophthalmic Genetics, Angle Closure aung.tin@ Aung Tin Head, Glaucoma Research, SERI Glaucoma, Glaucoma Imaging singhealth.com.sg Deputy Medical Director (Research), SNEC Prof Chairman, SERI Epidemiology of Eye Diseases, Population wong.tien.yin Wong Tien Yin Medical Director, SNEC Studies, Hypertensive Retinopathy, Age- @singhealth.com.sg Related Macular Degeneration, Clinical Trials, systemic reviews, Meta-Analysis, Ocular Imaging Prof Deputy Executive Director, SERI Femtosecond Laser Ablation, Selective jodhbir.s.mehta Jodhbir Mehta Head, Tissue Engineering & Stem Cell, Tissue Transplantation, Endothelial Cell @singhealth.com.sg SERI Transplanatation, Biological Tissue Glues, Co-Head, Cornea & Refractive, SERI Corneal Genetics, Ocular Head & Senior Consultant, Corneal & Defensins/Infectious Keratitis , Ocular Drug External Eye Disease Dept, SNEC Delivery, Corneal Imaging, Artificial Cornea, Dry Eye Studies Prof Scientific Director, SERI Imaging, Optical coherence tomography, leopold.schmetterer Leopold Schmetterer Head, Ocular Imaging, SERI Ocular blood supply, Clinical trials @seri.com.sg

Prof Director, Population Health, SERI Epidemiology of Eye Diseases, Impact, ecosse.lamoureux Ecosse Lamoureux Head, Health Services Research, SERI Adherence, Diabetic Retinopathy, Glaucoma, @seri.com.sg Head, Data Management, SERI & Quality of Life

A/Prof Director, Laboratory Translational Ophthalmic Genetics, Genetic Basis of eranga.nishanthie. Eranga Vithana Research, SERI Corneal Dystrophies, Retinal Dystrophies, [email protected] Head, Ocular Genetics, SERI Glaucoma & Myopia, Parametric & Non Head, Experimental & Basic Sciences, Parametric Linkage Analysis, Gene Knock SERI Out Models of Corneal Dystrophies, Gene Head, Genomics, SERI Replacement Therapy

A/Prof Director, Clinical Translational Cell Biology Of Wound Healing & tina.wong.t.l Tina Wong Research, SERI Mechanobiology, Ocular Drug Delivery @singhealth.com.sg Head, Ocular Therapeutics & Drug Systems, Epigenetics of Conjunctival Delivery, SERI Inflammation, Biomarkers In Glaucoma, Head & Senior Consultant, Glaucoma Wound Healing Dept, SNEC

Prof Senior Scientific Advisor, SERI Ocular Surface Disease, Myopia, Proteomics, roger.wilmer.beuerman Roger Beuerman Antimicrobials Peptide, Corneal in @seri.com.sg Reflective Surgery Adj Prof Senior Scientific Advisor, SERI Corneal Transplantation Research: Anterior donald.tan.t.h Donald Tan Co-Head, Cornea & Refractive, SERI Lamellar Keratoplasty, Endothelial @singhealth.com.sg Keratoplasty, Femtosecond Laser-Assisted Keratoplasty, DSAEK & DMEK Surgical Devices For Donor Delivery, Epidemiological Studies, Comparative Graft Survival Studies, Keratoprosthesis Research: OOKP & Boston Type 1 Trials, Synthetic OOKP Research, Tissue Engineering: Ocular Surface Epithelia & Endothelial Cell Culture/Transplantation, Refractive Surgery Research: Lasik, Acufocus Trials, Relex Trials, Infectious Keratitis Research: Asian Disease Outbreaks, Multicentre Clinical Trials, Pterygium Research: Surgical Trials, Ebm Studies, Epidemiology, Etiological Studies, Myopia Research: Epidemiology & Environmental Risk Factors, Clinical Trials on Myopia Retardation Therapies PI Designation Research Interests Email

Prof Head, Cataract Research, SERI Innate Inflammatory Responses Underlying chee.soon.phaik Chee Soon Phaik Co-Head, Ocular Inflammation & Various Ocular Conditions, Disease @singhealth.com.sg Immunology, SERI Mechanisms of Uveitis & Keratitis Head & Senior Consultant, Cataract Dept, SNEC

Prof Head, Ocular Epidemiology, SERI Glaucoma, Age-Related Macular Degeneration, cheng.ching.yu Cheng Ching-Yu Head, Data Science, SERI Myopia, Epidemiology & Genetic @seri.com.sg Senior Clinician Scientist, Glaucoma Epidemiology of Eye Diseases Dept, SNEC

Prof Head, Visual Neuroscience, SERI Clinical Neuro-Ophthalmology, General dan.milea Dan Milea Senior Clinician, Neuro-Ophthalmology Ophthalmology, Cataract and Anterior @snec.com.sg Dept, SNEC Segment Surgery, Clinical Research in Neurosciences (Cortical Control of Eye Movements, Hereditary Optic Neuropathies, Nonvisual Retinal Phototransduction, Retinal Imaging and Neurodegenerative Diseases) Prof Co-Head, Myopia Research, SERI Epidemiology & Gene-Environment saw.seang.mei Saw Seang Mei Interactions for Chronic Diseases, including @seri.com.sg Eye Diseases, Retinal Vessel Calibre & Myopia

Prof Head, Ocular Surface, SERI Ocular Surface Wound Healing, Cell Migration, louis.tong.h.t Louis Tong Head, Research Training & Adhesion, Inflammation, Cell Biology @singhealth.com.sg Development, SERI Associated with Pterygium (Matrix Co-Head, Ocular Inflammation & Dysregulation & Angiogenesis), Tear Immunology, SERI Biochemistry Senior Consultant, Corneal & External Eye Disease Dept, SNEC

A/Prof Head, Retina Research, SERI Imaging & Treatment of Retinal Disorders gemmy cheung.c.m Gemmy Cheung Head & Senior Consultant, Medical including Age-Related Macular Degeneration, @singhealth.com.sg Retina Dept, SNEC Idiopathic Polypoidal Vasculopathy, Diabetic Retinopathy & Retinal Dysfunction in Association with Ocular Inflammation (Uveitis) A/Prof Co-Head, Myopia Research, SERI Myopia, Strabismus, Retinopathy of audrey.chia.w.l Audrey Chia Head & Senior Consultant, Paediatric Prematurity, Amblyopia, Visual @singhealth.com.sg Ophthalmology & Adult Strabismus Electrophysiology Dept, SNEC Co-Clinical Director, Myopia Centre, SNEC

A/Prof Head, Anti-Infectives, SERI Antimicrobial Peptides, Protein Aggregation & lakshminarayanan. Lakshminarayanan Protein- Protein Interactions rajamani Rajamani @seri.com.sg

A/Prof Deputy Head, Ocular Epidemiology, Epidemiology of Chronic Kidney Disease, charumathi. Sabanayagam SERI Cardiovascular sabanayagam Charumathi Disease, Role of Sleep, Inflammation, Retinal @seri.com.sg Vascular Caliber & Diabetic Retinopath

A/Prof Co-Head, Bioengineering & Devices, Ocular Imaging, Cataract Surgery, Glaucoma, shamira.perera Shamira Perera SERI Lasers, Glaucoma Surgery @singhealth.com.sg Senior Consultant, Glaucoma Dept, SNEC PI Designations Research Interests Email Dr Head, Translational Ophthalmic Ophthalmic pathology and retinal anita.chan.s.y Anita Chan Pathology, SERI immunobiology research @singhealth.com.sg Head & Senior Consultant, Ocular Inflammation & Immunology Dept, SNEC Clinical Director, Ophthalmic Pathology Service, SNEC Dr Co-Head, Bioengineering & Devices, Diagnosis and Therapy for Biomechanically- mgirard Michael Girard SERI related Disorders, Ophthalmology, @nus.edu.sg Experimental and Computational Soft Tissue Biomechanics, Optical Coherence Tomography Theory, Developments and Applications

Dr Assistant Director, Laboratory Conjunctival Wound Healing after Glaucoma seet.li.fong Seet Li Fong Translational Research, SERI Filtration Surgery: Fibrosis, Epigenetic @seri.com.sg Head, Experimental Molecular & Cell Regulation, Mirna, Inflammation, Anti-Fibrotic Biology, SERI Drug Discovery & Testing. Cell Biology of Pterygium Dr Head, Translational Pre-Clinical Experimental Myopia, Biochemistry, Molecular amutha.b.veluchamy Velachamy A Barathi Model, SERI & Pharmacological Aspect of Muscarinic @seri.com.sg Acetylcholine Receptors & Transglutaminases, Animal Models of Ocular Diseases, Eye Growth Patterns & Mouse Optics, Corneal Wound Healing, Retina & Scleral Biology in Molecular Level Dr Head, Experimental Microscopy, SERI Ocular Surface Cell Biology, Stem Cell gary.yam.h.f Gary Yam Epigenetics, Reprogramming & Therapy, @seri.com.sg Protein Folding Disease, Protein Quality Control & Chaperone-Assisted Protein Correction Dr Head, Proteomics, SERI Ocular Proteomics, Biomarkers of Ocular zhou.lei Zhou Lei Diseases; Antimicrobial Peptide Design, @seri.com.sg Synthesis, Characterization & Purification. Ocular Drug Pharmacokinetics Prof Clinician Scientist, SERI/SNEC Vision regeneration and repair in glaucoma, jonathan.guy.crowston Jonathan Crowston Professor of Ophthalmology, Centre Functional assessment in glaucoma, @snec.com.sg for Vision Research, Duke-NUS Bioenergetics

Dr Clinician Scientist, SERI Glaucoma - Anterior & Posterior Segment baskaran.mani Baskaran Mani Director, Research Clinic, SERI Imaging Devices – Development & Evaluation, @seri.com.sg Epidemiology of Glaucoma, Angle Closure Glaucoma, IOP Correction Factors, Drug Trials, Yoga & Eye Dr Clinician Scientist, SERI Diabetic Retinopathy, Cell Replacement gavin.tan Gavin Tan Consultant, Surgical Retina Dept, SNEC therapy in Retinal Diseases, Retina imaging @singhealth.com.sg Co-Head, Ocular Imaging Dept, SNEC Telemedicine and Artificial Intelligence in Clinical Director, SNEC Ocular Reading Ophthalmology Centre (SORC)

Dr Clinician Scientist, SERI Retinal Disease, Ophthalmic Epidemiology, cheung.ning Danny Cheung Consultant, Surgical Retina Dept, SNEC Retinal Vessel Analysis @snec.com.sg

Dr Clinician Scientist, SERI Novel approaches toward the diagnosis and donny.hoang @singhealth.com.sg Donny Hoang Consultant, Surgical Retina Dept, SNEC treatment of pathologic myopia, Scleral collagen-crosslinking, Multimodal imaging (OCT, US, MRI) of staphylomatous pathologic myopia, In vivo measurement of scleral stiffness Stunting progression of short-sightedness Improvement of surgical outcomes in highly myopic eyes PI Designation Research Interests Email

Dr Clinician Scientist, SERI Corneal Transplantation, Refractive Surgery, liu.yu.chi Ophthalmic Epidemiology, and Drug Delivery @seri.com.sg Liu Yu-Chi Clinician Scientist, Corneal & External System Eye Disease Dept, SNEC

Dr Clinician Scientist, SERI Glaucoma- Imaging & Risk Factors, Ophthalmic monisha.esther. Monisha Nongpiur Genetics, Epidemiology nongpiur @seri.com.sg Dr Clinician Scientist, Ocular Epidemiology, Machine Learning, Big data analytics, tyler.rim Tyler Rim SERI Epidemiology, Medical Informatics @snec.com.sg Clinician Scientist, Medical Retina Dept, SNEC

Dr Junior Principal Investigator, Visual Visual and Non-Visual Photoreception, raymond.najjar Raymond Najjar Neuroscience, SERI Circadian Biology, Sleep, Pupillometry, Visual @seri.com.sg Neurosciences, Cognitive Neurosciences, Lighting design Dr Junior Principal Investigator, Tissue Cell Biology – Propagation of Primary Human gary.peh.s.l Gary Peh Engineering & Stem Cell, SERI Corneal Endothelial Cells (HCEnCs) @seri.com.sg Tissue-Engineering – Development of Alternative Graft Material using Cultivated HCEnCs Stem Cell Biology – Human Embryonic Stem Cells (Early Neural Differentiation) Dr Senior Clinical Research Fellow, Ocular Ocular Imaging, Primary Eye Care, jacqueline.chua.y.m Jacqueline Chua Imaging, SERI Epidemiology @seri.com.sg

Dr Senior Research Fellow, Ocular Surface, Molecular Pathogenesis of Human Pterygium hou.aihua Hou Aihua SERI @seri.com.sg

Dr Senior Research Fellow, Tissue Primary Angle Closure Glaucoma (PACG) lee.mei.chin Lee Mei Chin Engineering & Stem Cell, SERI @seri.com.sg

Dr Senior Research Fellow, Tissue Directed Differentiation of Human Pluripotent lovatt.matthew.jason Matthew Jason Lovatt Engineering & Stem Cell, SERI Stem Cells towards Corneal Endothelial Cells, @seri.com.sg Stromal Keratocytes via Neural Crest Induction Dr Senior Clinical Research Fellow, Clinical health services and translational eye man.eyn.kidd.ryan Ryan Man Heath Services Research, SERI research @seri.com.sg Ocular epidemiology Patient-centred outcomes in eye and metabolic disorders

Research Support Platform Contacts

Name Designation Email Dr Vandana Ramachandran Director, Administration, Research Affairs & Support [email protected] Services, SERI

Dr Danny Belkin Director, Technology Development & Commercialization, [email protected] SERI Title: Flyer 2 SIZE: 210mm X 297mm D:16-005 DH1601047 GP10B-CG

www.seri.com.sg Glaucoma Research Group

The Glaucoma Research Group is further divided into 3 subgroups:

Angle Closure Glaucoma Glaucoma Imaging and Glaucoma Genetics Clinical Research

Angle Closure Glaucoma Goal: To improve understanding and management of angle closure glaucoma (PACG)

Current research includes evaluation and phenotypic characterization of primary angle closure glaucoma patients, improved screening modalities for angle closure and better management of the disease. An ongoing clinical trial aims to compare laser iridotomy (LI) with no treatment in subjects with asymptomatic narrow angles, the anatomical trait that predisposes to PACG, in order to assess the eff ectiveness of prophylactic treatment in the prevention of blindness due to PACG. Glaucoma Imaging and Clinical Research Goal: To develop enhanced imaging modality and treatments for glaucoma

This group encompasses research that involves the evaluation of various imaging devices (e.g. Ultrasound Biomicroscopy (UBM), Optical Coherence Tomography, Retcam etc); studies on medical, laser and surgical management of glaucoma; epidemiological studies as well as new techniques in glaucoma such as pupillometry, motion detection perimetry, 24-hour IOP monitoring and Oxymap.

Several multi-centre randomized controlled trials were completed. These include: 1. RCT to evaluate the eff ectiveness of selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in patients with PACG, compared to prostaglandin analogues, the current fi rst choice IOP-lowering medical therapy. 2. RCT comparing goniosynechialysis with phacoemulsifi cation vs phaco alone in the management of synechial ACG. 3. RCT on laser iridoplasty in patients with persistent appositional PACG.

Ongoing RCTs include: 1. RCT comparing SLT vs prostaglandin analogues in POAG, including Quality of Life and cost-eff ectiveness assessments. 2. RCT on Trabeculectomy vs Tube implant in POAG. Glaucoma Genetics Goal: To identify gene(s) underlying glaucoma

Current research involves the identifi cation of novel loci for PACG and POAG, both monogenic and polygenic, by traditional family-based linkage, candidate gene and genome wide association analyses. Recently, we identifi ed three novel genetic loci in PACG and we will be following up patients at risk to evaluate these and other loci in profi ling genetic and anatomical risks for progression. Further, we are characterizing the genetic loci in PACG in cell lines and hope to identify molecular targets of importance in pathogenesis and management of PACG. Biomechanics and Glaucoma Goal: To develop biomarkers using biomechanical properties of tissues in the anterior segment and Optic nerve head, related to glaucoma

Research related to biomechanics of optic nerve head and anterior segment tissues is the main focus of a team of scientists from NUS and SERI. Several studies in primates and humans are being conducted to evaluate these properties and eff orts are made to fi nd their association to diagnosis of the types of glaucoma and prognosis related to progression and management.

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Research Doctors

Name Designation Contact Us: Prof Aung Tin at [email protected] Executive Director, SERI Prof Aung Tin Head, Glaucoma Senior Consultant, SNEC Selected Publications Adj A/Prof Ho Ching Lin Senior Consultant, SNEC 1. Trikha S, Saff ari E, Nongpiur M, Baskaran M, Ho H, Li Z, Tan PY, Allen J, Khor CC, Perera SA, Cheng CY, Aung T, Vithana E. A Genetic Variant in TGFBR3-CDC7 Is Co-Head, Bioengineering & Associated with Visual Field Progression in Primary Open-Angle Glaucoma Patients A/Prof Shamira Perera Devices from Singapore. Ophthalmology. 2015 Sep 14. Senior Consultant, SNEC 2. Thakku SG, Tham YC, Baskaran M, Mari JM, Strouthidis NG, Aung T, Cheng CY, Girard MJ. A Global Shape Index to Characterize Anterior Lamina Cribrosa Morphology Adj A/Prof Rahat Husain Senior Consultant, SNEC and Its Determinants in Healthy Indian Eyes. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3604-14. Dr Boey Pui Yi Consultant, SNEC 3. Baskaran M, Foo RC, Cheng CY, Narayanaswamy AK, Zheng YF, Wu R, Saw SM, Foster PJ, Wong TY, Aung T. The Prevalence and Types of Glaucoma in an Urban Chinese Dr Desmond Quek Consultant, SNEC Population: The Singapore Chinese Eye Study. JAMA Ophthalmol. 2015 May 14. Co-Head, Bioengineering & 4. Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, Mani B, Chen LJ, Kee C, Garway- Dr Michael Girard (NUS) Devices Heath DF, Sripriya S, Fuse N, Abu-Amero KK, Huang C, Namburi P, Burdon K, Perera SA, Gharahkhani P, Lin Y, Ueno M, Ozaki M, Mizoguchi T, Krishnadas SR, Osman EA, Co-Head, Ocular Epidemiology Lee MC, Chan AS, Tajudin LS, Do T, Goncalves A, Reynier P, Zhang H,Bourne R, Goh D, Prof Ching-Yu Cheng Head, Statistics Broadway D, Husain R, Negi AK, Su DH, Ho CL, Blanco AA, Leung CK, Wong TT, Yakub A, Liu Y, Nongpiur ME, Han JC, Hon DN, Shantha B, Zhao B, Sang J, Zhang N, Sato R, Dr Baskaran Mani Clinician Scientist Yoshii K, Panda-Jonas S, Ashley Koch AE, Herndon LW, Moroi SE, Challa P, Foo JN, Bei JX, Zeng YX, Simmons CP, Bich Chau TN, Sharmila PF, Chew M, Lim B, Tam PO, Dr Monisha Esther Nongpiur Clinician Scientist Chua E, Ng XY, Yong VH, Chong YF, Meah WY, Vijayan S, Seongsoo S, Xu W, Teo YY, Cooke Bailey JN, Kang JH, Haines JL, Cheng CY, Saw SM, Tai ES; ICAARE-Glaucoma Dr Tin Aung Tun Clinical Research Associate Consortium; NEIGHBORHOOD Consortium, Richards JE, Ritch R, Gaasterland DE, Pasquale LR, Liu J, Jonas JB, Milea D, George R, Al-Obeidan SA, Mori K, Macgregor S, Hewitt AW, Girkin CA, Zhang M, Sundaresan P, Vijaya L, Mackey DA, Wong TY, Research Optometrists/ Coordinators/ Assistants Craig JE, Sun X, Kinoshita S, Wiggs JL, Khor CC, Yang Z, Pang CP, Wang N, Hauser MA, Tashiro K, Aung T, Vithana EN. A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet. 2015 Apr 10. Name Designation 5. Narayanaswamy A, Leung CK, Istiantoro DV, Perera SA, Ho CL, Nongpiur ME, Serena Ting Manager (Genetics Team) Baskaran M, Htoon HM, Wong TT, Goh D, Su DH, Belkin M, Aung T. Effi cacy of selective laser trabeculoplasty in primary angle-closure glaucoma: a randomized Teo Soh Chin Senior Clinical Research Coordinator clinical trial. JAMA Ophthalmol. 2015 Feb;133(2):206-12. 6. Nongpiur ME, Haaland BA, Friedman DS, Perera SA, He M, Foo LL, Baskaran M, Stella Ng Senior Clinical Research Coordinator Sakata LM, Wong TY, Aung T. Classifi cation Algorithms Based on Anterior Segment Optical Coherence Tomography Measurements for Detection of Angle Closure. Ooi Ya Ying Senior Clinical Research Coordinator Ophthalmology 2013; 120(1):48-54. 7. Narayanaswamy AK, Zheng C, Perera SA, Htoon HM, Friedman DS, Tun TA, He M, Anna Sim Senior Clinical Research Coordinator Baskaran M, Aung T. Variations in Iris Volume with Physiological Mydriasis in Subtypes of Primary Angle Closure Glaucoma. Invest Ophthalmol Vis Sci 2013; 54: Cheryl Tan Senior Clinical Research Coordinator 708-13. Cynthia Ong Clinical Research Coordinator 8. Zheng C, Guzman CP, Cheung CY, He Y, Friedman DS, Ong SH, Narayanaswamy AK, Chew PT, Perera SA, Aung T. Analysis of Anterior Segment Dynamics using Anterior Segment Optical Coherence Tomography Before and After Laser Peripheral Iridotomy. Arch Ophthalmol/JAMA Ophthalmol 2013; 131: 44-9. Genetics Team 9. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, Do T, Abu-Amero K, Huang CK, Low S, Tajudin LS, Perera SA, Cheng CY, Xu L, Jia H, Ho CL, Sim KS, Wu R, Name Designation Tham CC, Chew PT, Su DH, Oen FT, Sarangapani S, Soumittra N, Osman EA, Wong HT, Tang G, Fan S, Meng H, Huong DT, Wang H, Feng B, Baskaran M, Shantha B, Director, Laboratory Translational A/Prof Eranga Vithana Ramprasad VL, Kumaramanickavel G, Iyengar SK, How AC, Lee KY, Sivakumaran TA, Research Yong VHK, Ting SML, Li Y, Wang YX, Tay WT, Sim X, Lavanya R, Cornes BK, Zheng YF, Wong TT, Loon SC, Yong VK, Waseem N, Yaakub A, Chia KS, Allingham RR, Hauser Dr Khor Chiea Chuen (GIS) Adjunct Clinician Scientist MA, Lam DSC, Hibberd ML, Bhattacharya SS, Zhang M, Teo YY, Tan DT, Jonas JB, Tai ES, Saw SM, Hon DN, Al-Obeidan SA, Liu JJ, Bich Chau TN, Simmons CP, Bei JX, Zeng Dr Lee Mei Chin Senior Research Fellow YX, Foster PJ, Vijaya L, Wong TY, Pang CP, Wang N, Aung T. Genome-wide association analyses identify three new susceptibility loci for Primary Angle Closure Glaucoma. Dr Wu Mei Hui Research Fellow Nat Genet 2012 Oct;44(10):1142-6. Victor Yong Senior Research Officer 10. How AC, Baskaran M, Kumar RS, He MG, Foster PJ, Lavanya R, Wong HT, Chew PTK, Friedman DS, Aung T. Changes in anterior segment morphology after laser Ng Xiao Yu Senior Research Officer peripheral iridotomy: An anterior segment optical coherence tomography study. Ophthalmology 2012; 119: 1383-7. Li Yuan Han (Allan) Research Associate Chong Yaan Fun Research Officer

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www.seri.com.sg Ocular Genetics Research Group

Research is focused on understanding the genetic basis and biochemical mechanisms of hereditary eye diseases, including the study of inherited glaucoma subtypes, corneal dystrophies, retinal dystrophies and myopia. Particular attention is given to eye diseases and phenotypes common to Asia such as primary angle closure glaucoma and myopia. Both parametric and non parametric locus/gene mapping methods are carried out to identify novel disease genes disease susceptible loci as well as quantitative traits of ocular diseases. Candidate genes and novel genes are screened to identify novel mutations and to carry out genotype-phenotype correlations for ocular diseases more prevalent within the main racial groups of Asia. One of the main goals is to establish ethnic/race specifi c disease database that contain both clinical and genetic information for identifi cation of genetic markers with diagnostic, prognostic or pharmacological value.

Hereditary Eye diseases studied Glaucoma (PACG, NTG, POAG), Retinal degenerations (RP, AMD) Corneal dystrophies (FECD, CHED) Myopia

For mendelian diseases collect large families and identify the chromosomal location of the Form clinically well defi ned patient panels gene by linkage analysis (Chinese, Malay, Indian)

Use for GWA studies to identify Identify the disease gene by screening susceptibility loci for complex genes in the defi ned chromosomal interval disorders i.e. PACG, (Myopia)

Functionally characterize gene mutations Develop markers for Clinical Diagnosis Create and study animal models of disease and Prognosis to understand the molecular pathology of disease

Screen known candidate genes to identify novel mutations unique to Develop and test treatment modalities Chinese (Malay and Indian) populations

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Current Research Areas Glaucoma At SERI we study primary open angle glaucoma (POAG), primary angle-closure glaucoma (PACG), pseudo exfoliation glaucoma (PXG) and congenital glaucoma. In order to elucidate the full allelic spectrum for both POAG and PACG, we plan to conduct large scale GWAS, exome arrays, whole genome sequencing and interrogate related quantitative traits. For the development of a diagnostic and prognostic risk stratifi cation model for POAG and PACG we plan to incorporate genomic as well as demographic, environmental and endophenotypic (clinical and imaging parameters) information. We also aim to investigate whether the recently identifi ed PACG genetic variants are also associated with early stages of angle closure disease or are involved in susceptibility to disease progression. In addition, we plan to characterize the function of the newly identifi ed PACG susceptibility genes to provide insights into disease pathogenesis that will enable future development of novel eff ective therapies. In order to adequately power genomic discoveries and conduct large scale meta-analyses we have entered into several regional and international collaborations to share data from GWASs on glaucoma and related quantitative traits. The International Glaucoma Genetics Consortium (IGGC) has been established for POAG, while for PACG we are leading a global PACG genetic consortium with investigators from across the globe. Additionally we have conducted GWAS studies on PXG and have identifi ed further genetic variants for the condition. Corneal diseases To study genetic basis of numerous corneal dystrophies including Congenital Hereditary Endothelial Dystrophy (CHED), more frequently occurring Fuch’s Corneal Dystrophy (FCD), keratoconus and Bowman’s membrane and Stromal Corneal Dystrophies (SCD).

Since 2004 the Ocular Genomics Group has produced more than 90 peer-reviewed papers in leading journals in Genetics and Ophthalmology such as Nature Genetics, Plos Genetics, Human Molecular Genetics and Ophthalmology.

Head: A/Prof Eranga Vithana Key Team Members: Prof Aung Tin, Prof Saw Seang Mei, Prof Wong Tien Yin, Prof Jodbhir Mehta, Dr Khor Chiea Chuen (GIS), Prof Cheng Ching-Yu Contact Us: A/Prof Eranga Vithana at [email protected]

Selected Publications 1. Vithana EN*, Chen Y*, Lin Y*, Jia L*, … Khor CC, Pang CP#, Sun X#, Yang Z#. Common genetic variants near the ABCA1 gene and in the PMM2 gene are associated with primary open-angle glaucoma. Nat Genetics (*Joint fi rst authors). Nat Genet. 2014; Oct;46(10):1115-9 2. Hysi PG*, Cheng CY*, Springelkamp H*, Macgregor S*, Bailey JNC*, Wojciechowski R*, Vitart V, Nag A, Hewitt AW, Höhn R, Venturini C, Mirshahi A, Ramdas WD, Thorleifsson G, Vithana E, Khor CC, Stefansson AB, ……………… Wong TY, BMES GWAS Group, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium, Viswanathan A*, Mackey DA*, Craig JE*, Wiggs JL*, van Duijn CM*, Hammond CJ*‡, Aung T*‡. Genome-wide Analysis of Multiethnic Cohorts Identifi es Four New Loci Infl uencing Susceptibility to Increased Intraocular Pressure and Susceptibility to Glaucoma. Nat. Genet 2014 3. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R , Chen LJ, Do T, Huang CK, Abu-Amero K, Low S, Tajudin LSA, Perera SA, Simmons CP, Bei JX, Zeng YX, Foster PJ, Vijaya L, Wong TY, Pang CP, Wang N, Aung T. Genome-wide association analyses identify three new susceptibility loci for Primary Angle Closure Glaucoma. Nat Genet 2012 Oct; 44(10):1142-6 4. Vithana EN, Morgan P, Sundaresan P, Ebenezer ND, Tan DT, Mohamed MD, Anand S, Khine KO, Venkataraman D, Yong VH, Salto-Tellez M, Venkatraman A, Guo K, Hemadevi B, Srinivasan M, Prajna V, Khine M, Casey JR, Inglehearn CF, Aung T. Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2). Nat Genet. 2006 Jul;38(7):755-7 5. Li Z, Allingham RR, …... Wiggs JL, Khor CC, Yang Z, Pang CP, Wang N, Hauser MA, Tashiro K, Aung T, Vithana EN. A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet. 2015 Jul 1;24(13):3880-92 6. Cornes BK, Khor CC, Nongpiur ME, Xu L, Tay WT, Zheng Y, Lavanya R, Li Y, Wu R, Sim X, Wang YX, Chen P, Teo YY, Chia KS, Seielstad M, Liu JJ, Hibberd ML, Cheng CY, Saw SM, Tai ES, Jonas JB, Vithana EN, Wong TY, Aung T. Identifi cation of Four Novel Variants That Infl uence Central Corneal Thickness in Multi-Ethnic Asian Populations. Hum Mol Genet. 2012; 21(2):437-45 7. Khor CC*, Ramdas WD*, Vithana EN*, Cornes BK, Sim X, Tay WT, Saw SM, Zheng Y, Lavanya R, Wu R, Wang JJ, Mitchell P, Uitterlinden AG, Rivadeneira F, Teo YY, Chia KS, Seielstad M, Hibberd M, Vingerling JR, Klaver CCW, Jansonius NM, Tai ES, Wong TY, van Duijn CM, Aung T. Genome-wide association studies in Asians confi rm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus infl uencing optic disc area. Hum Mol Genet. 2011; 20(9):1864-72. 8. Nongpiur ME*, Khor CC* , Jia H*, …. Pang CP#, Vithana EN#, Wang N#, and Aung T#. ABCC5, a gene that infl uences the anterior chamber depth, is associated with primary angle closure glaucoma. Plos Genet. (# Joint last authors) 2014; Mar 6; 10(3):e1004089 9. Trikha S, Saff ari E, Nongpiur M, Baskaran M, Ho H, Li Z, Tan PY, Khor CC, Perera SA, Cheng CY, Aung T*, Vithana E*. Genetic variant in TGFBR3-CDC7 is associated with visual fi eld progression in primary open angle glaucoma patients from Singapore. Ophthalmology. 2015 Dec;122(12):2416-22 10. Lee MC*, Chan AS*, Goh SR, Hilmy MH, Nongpiur ME, Hong W, Aung T, Hunziker W, Vithana EN. Expression of the primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in endothelial and epithelial cell junctions in the eye. Invest Ophthalmol Vis Sci. 2014; May 6;55(6):3833-41

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www.seri.com.sg Anti-Infectives Research Group

Antimicrobials against Ocular Pathogens (AMOP) Millions of people suff er from infectious diseases each year, unfortunately morbidity is also in the millions and healthcare costs soar in the presence of infections that are not susceptible to the available antimicrobials. The unchecked emergence of antimicrobial resistance is a phenomenon that could potentially transport us back to the pre-antibiotic era if proper measures are not taken. Mortality and morbidity associated with infection by antibiotic-resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and extensively drug-resistant tuberculosis (XDR-TB) is on the rise. Untreatable, multiple drug resistant Gram-negative bacteria in particular will pose the greatest public health threat in the coming decade. Antibiotic resistance is a world-wide critical healthcare issue. South East Asia is particularly at risk for eye infections that aff ect thousands of people annually. Of particular signifi cance is the prevalence of fungal infections of the eye and Fusarium as a primary culprit. Even TB and pneumonia are common in developed and emerging countries. Despite these concerns, the antibiotic drug development pipeline is depleted and many big pharmaceuticals have long opted out of antibiotic discovery and development. Becoming more recognized is the emergence of resistance of fungus and yeast to existing drugs which is exacerbated by the very few drugs available for fungus and yeast. Candiasis and aspergilliosis are becoming common in Europe and fungal infections are major healthcare issues in Asia. AMOP joins in this eff ort through our validated ElucidatusTM technology platform and promising drug development pipeline of antimicrobial compounds, targeting ophthalmic, resistant Gram-negative infections, as well as Gram-positive pathogens especially MRSA, and fungus which are currently underserved segments of clinical need.

Core Competencies Aside from the list of patents fi led, and know-how, AMOP has developed a portfolio of compounds in the area of antimicrobial discovery through the use of a multi-disciplinary platform (Figure 1). The research and development capability of AMOP has been developed through a series of outstanding collaborations among several institutions in Singapore (Singapore National Eye Centre, Bioinformatics Institute, Genome Institute of Singapore, National University of Singapore and School of Engineering, Singapore General Hospital, Pathology, Nanyang Technological University), China (South China University of Technology, South China Botantical Garden {State Key Laboratory}), and Switzerland (University of Geneva) and is fortunate to have the support of the Agency for Science, Technology and Research (A*STAR) and SERI in our spin-off quest.

Program Organization and Emphasis

Antibiotics Antimicrobials against Antifungals Ocular Pathogens (AMOP) Small Molecules Molecular Microbiology Chemical Synthesis SERI Dynamics SERI Peptides SERI GIS SCBG BII SNEC PLATFORM TECHNOLOGIES NUS UG SCUT SGH NTU

Cell and Molecular Animal Models Biology-Toxicology Biophysics

Pre-IND Mechanisms of Delivery and Bacteria Fibrosis Biofi lims studies Resistance Release Biosensors

SPECIFIC AREAS OF EMPHASIS

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Educational Programs

AMOP off ers educational programs at all levels from fi nal year projects in undergraduate programmes to PhD and post-graduate level studies. A distinct advantage of working in a multi-disciplinary environment is that the student becomes familiar with all aspects of infections from the chemistry of therapeutics to the clinical and all stages of antimicrobial development.

Head: References A/Prof Rajamani Lakshminarayanan, PhD 1. Hanxun Zou, Jun-Jie Koh, Jianguo Li, Shengxiang Qiu, Thet Tun Aung, Rajamani Lakshminarayanan, Xiaoping Dai, Charles Tang, Fang Hui Lim, Lei Zhou, Ai Ling Tan, Chandra Verma, Donald T. H. Tan, Hardy Sze On Chan, Key Personnel: Padmanabhan Saraswathi, Derong Cao, Shouping Liu, Roger W. Beuerman, • Prof Roger Beuerman , PhD, SERI, Singapore Design and Synthesis of Amphiphilic Xanthone Based Membrane Targeting Antimicrobials with Improved Membrane Selectivity, J Med Chem, 2013; • Chandra Verma, PhD, Bioinformatics Institute, Singapore 56(6): 2359-73. • Saraswathi Padmanabhan, PhD, SNEC, Singapore 2. Bai Y, Liu S, Li J, Lakshminarayanan R, Pasmanabhan S, Tang C, Ho D, Verma C, Beuerman RW, Pervushin K. Progressive structuring of a branched antimicrobial peptide on the path to the inner membrane target. J Biol Collaborators: Chem. 2012 Jun 14. • Donald TH Tan, MD, SNEC 3. Koh JJ, Qiu S, Zou H, Lakshminarayanan R, Li J, Zhou X, Tang C, Saraswathi P, Verma C, Tan DT, Tan AL, Liu S, Beuerman RW. Rapid bactericidal action • Konstatin Pervushin, PhD, Biological Sciences, NTU of alpha-mangostin against MRSA as an outcome of membrane targeting. Biochim Biophys Acta. 2012 Sep 13 . • Jodhbir Mehta, MD, SERI/SNEC 4. Tan XW, Lakshminarayanan R, Liu SP, Goh E, Tan D, Beuerman RW, Mehta • Swaine Chen, MD, PhD, Singapore NRF Fellow, GIS, Infectious JS. Dual functionalization of titanium with vascular endothelial growth Diseases, NUS, School of Medicine factor and ß-defensin analog for potential application in keratoprosthesis. J Biomed Mater Res B Appl Biomater 2012 Nov Epub 2012 Jul 23. Ai Ling Tan, MD, Pathology, SGH • 5. Li J, Lakshminarayanan R, Bai Y, Liu S, Zhou L, Pervushin K, Verma C, • Howard Reizman, PhD, Department of Microbiology, Beuerman RW. Molecular dynamics simulations of a new branched antimicrobial peptide: A comparison of force fi elds. J Chem Phys. 2012 Dec University of Geneva 7;137(21):215101 • Thomas Dick, PhD, Department of Microbiology, NUS 6. Bai Y, Liu S, Jiang P, Zhou L, Li J, Tang C, Verma C, Mu Y, Beuerman RW, Seeram Ramakrishna, FREng, VP-Research Strategy, NUS, Pervushin K. Structure-dependent charge density as a determinant of • antimicrobial activity of peptide analogues of defensin. Biochemistry. Mechanical Engineering, NUS 2009 Aug 4;48(30):7229-39. • Derong Cao, PhD, Department of Chemistry, South China 7. Liu S, Zhou L, Chen L, Dastidar SG, Verma C, Li J, Tan D, Beuerman R. Eff ect of structural parameters of peptides on dimer formation and highly oxidized University of Technology side products in the oxidation of thiols of linear analogues of human beta- • Timothy Barkham, Laboratory Medicine, TTSH defensin 3 by DMSO. J Pept Sci. 2009 Feb;15(2):95-106. 8. Liu S, Zhou L, Li J, Suresh A, Verma C, Foo YH, Yap EP, Tan DT, Beuerman • Josh Granek, PhD, Lab of Microbial Genomics, Duke RW. Linear analogues of human beta-defensin 3: concepts for design of Univeristy antimicrobial peptides with reduced cytotoxicity to mammalian cells. Chembiochem. 2008 Apr 14;9(6):964-73. • Takashi Suzuki, Eihme Graduate School of Medicine, Japan 9. Seebah S, Suresh A, Zhuo S, Choong YH, Chua H, Chuon D, Beuerman R, Verma C. Defensins knowledgebase: a manually curated database and Research Fellows: information source focused on the defensins family of antimicrobial • Thet Tun Aung, MBBS, MS peptides. Nucleic Acids Res. 2007 Jan;35(Database issue):D265-8. Epub 2006 Nov 7. database has had over a million hits. Contact Us: Prof Rajamani Lakshminarayanan at [email protected]

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www.seri.com.sg Ocular Therapeutics & Drug Delivery Research Group

The need for controlled, sustained-release drug delivery systems has been recognized by the ophthalmic community and industry. Recent advances in technology have enabled the rapid progression in this fi eld of research and product development. Sustained drug delivery platforms are designed to meet the varying specifi c duration of eff ects, ranging from weeks to months to meet the therapeutic indications of diff erent ophthalmic conditions. Drug delivery not only encompasses the various platforms for achieving the sustained drug release eff ect, but also the mode of delivery of the delivery platform e.g. intravitreal, contact lens, subconjunctival, punctual, intrascleral and intracameral. Sustained release encompasses small protein molecules, drugs, antibodies and nucleic acid entities. The Ocular Drug Delivery Research Group is based at the Ocular Therapeutics and Engineering Centre at the School of Materials Science and Engineering, Nanyang Technological University.

Mission To deliver new and improved drug delivery solutions to the clinic for use in all disciplines in ophthalmology

Goal To be recognized as the fi rst ocular drug delivery research centre in Singapore and in the surrounding region

To achieve this, a team of dedicated bioengineering scientists, material scientists and clinician scientists work together to develop, design and evaluate novel drug delivery platform solutions for a wide range of ophthalmic medications encompassing glaucoma, corneal and vitreoretinal infl ammation, fi broproliferative disorders and ocular infections. Sustained delivery carriers for existing topical drugs commonly prescribed in the clinic such including anti-glaucoma, anti-scarring, anti-angiogenic and anti-infl ammatory drugs are currently pipeline products being developed.

Examples of current areas of research and emerging technologies are as follows: • A sustained release of 5-fl uorouracil (5FU) for the treatment of post-operative scarring following glaucoma surgery. Commercialisation of this product, HA5FU gel, is now in progress. • A sustained release carrier for Latanoprost (LipoLat) is in clinical trials to establish safety and effi cacy in lowering intraocular pressure in glaucoma patients. Lipolat is the fi rst sustained drug delivery system that has been developed in Singapore for the medical treatment of glaucoma. • A new sustained release ophthalmic implant of prednisolone acetate for the indication of anterior segment infl ammation and post cataract surgery is expected to commence clinical trials in the near future. • Evaluation of diff erent carriers suitability for the sustained delivery of proteins and drugs to treat vitreoretinal disorders outside of intravitreal injection is a major focus for the team.

New drug delivery formulations developed in our laboratory will provide an alternate therapeutic solution for ophthalmic patients worldwide. This will improve quality of life through freedom from eye drop instillation and from associated complications from Prednisolone sustained release implant in rat eye eye drop allergy and challenges of patient compliance to any given treatment regime.

Head: A/Prof Tina Wong Contact Us: [email protected]

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Tissue Engineering and Stem Cell Research Group

Tissue Engineering and Stem Cell Program is focused on: • Understanding and investigate the reconstruction and replacement of the cornea by the use of novel biomaterials • Investigating the principles of corneal tissue engineering in order to improve surgical outcomes • Understanding the principles of in-vivo expansion of stem cells for the reconstruction of the cornea Our Goals • Innovate in corneal tissue engineering and stem cell reconstruction from both a basic science and primarily a translational research point of view Some of the key research areas of the group are as follows:

1. Femtosecond Laser-Assisted Ocular Surgery The use of femtosecond laser has revolutionized the way clinicians perform refractive and cataract surgery. The laser has become an important tool to perform accurate and fi ne dissections with minimal collateral damage in ocular tissues. The main work to date in this area of study has been focused on investigation on the laser-ocular tissue interactions, optimization of the laser technology in performing myopic ReLEx (refractive lenticule extraction), analyzing the eff ects of laser in cataract surgery and various keratoplasties, as well as tissue engineering the extracted lenticule from ReLEx as corneal inlay to correct presbyopic errors.

(A) Whole-mount ß3-tubulin staining of cornea after 2. Corneal Endothelial Cell Research undergoing LASIK procedure. (B) Helium ion micrograph of a crater on corneal The human corneal endothelium (CE) is perhaps the physiologically most important stromal bed, created by a cavitation bubble during femtosecond laser photodisruption process. layer of the cornea. Although cells of the CE are unable to undergo any functional (C) In-vivo confocal micrograph of femtosecond laser photodisrupted plane (refl ective layer) and regeneration within the eye, studies have demonstrated the capacity for primary side cut (refl ective line). human CECs to proliferate within a laboratory setting. We have since further improved (D) Topography of rabbit cornea captured by handheld videokeratographer. the cultivation of isolated human CECs using a patented dual media culture system. The cultivated human CECs can be consistently propagated to the third passage, retain characteristic cellular morphology and expression markers indicative of the human CE layer. This has enabled down-stream development of potential graft alternatives through tissue-engineering. Currently, we are looking at the use of various constructs, both synthetic and biological, as potential scaff old for tissue-engineering, and characterizing the growth of the cultivated human CECs on each of these constructs. We are also looking at ways to improve the culture of human CECs using diff erent small molecules that have shown potential in improving the adherence, and/or the proliferation of cultivated human CECs.

Culture of Human Corneal Endothelial cells for transplant

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3. Anterior Segment Drug Delivery Systems We have developed a biodegradable, prednisolone acetate-loaded microfi lms made of poly (d,l-lactide-co-∑-caprolactone) (PLC). This drug delivery system is capable of delivering sustained and therapeutic drug levels to the anterior segment over 4 weeks and therefore eliminates patient compliance and dependency on a frequent dosing regimen after surgery. It also circumvents the limitations of the conventional eye drops, such as low bioavailability and short duration of action. We have demonstrated that this novel microfi lm has good biocompatibility and surgical feasibility in animal models. The implantation of the microfi lm into the subconjunctival space is a single, simple and non-invasive procedure. The microfi lm degrades to non-toxic metabolites with time hence no extra procedure is needed to remove the implant after the depletion of the drug. Furthermore, the microfi lm has the capacity to be customized to deliver diff erent drug release profi les depending on diff erent clinical scenarios.

Slit lamp biomicroscopy photo showing the subconjunctivally- Corneal allograft control (A) and corneal allograft treated with predinisolone acetate (PA)- implanted predinisolone acetate-loaded microfi lm. loaded microfi lm (B). The PA microfi lm signifi cantly reduced the graft opaque, edema and neovascularization, prolonging the graft survival.

4. Ocular Surface Stem Cell Reconstruction The presence of a smooth ocular surface is vital for normal vision. The corneal epithelium is the outermost region of the cornea and has a primary protective function. Its renewal relies on limbal stem cells. Their destruction is a major debilitating cause of ocular morbidity. Transplantation to replace the damaged corneal epithelium can principally restore the vision, however allogeneic transplants in patients with bilateral disease do not have satisfactory long-term treatment due to the persistent use of immunosuppression. As a long-term goal, we are examining the role of other autologous cell sources to develop a safe, stable, eff ective and functional tissue engineered construct for patients with bilateral ocular surface disease.

5. Artifi cial Cornea Artifi cial corneas (or keratoprostheses) currently in common use, are preferred for chronic infl ammatory and ocular surface diseases. However, keratoprosthesis technology is still lacking – both these devices utilize older polymers and outdated designs. The Osteo-odonto keratoprosthesis (OOKP) is reserved for the more severe ocular surface diseases, and has a high rate of device retention, but involves highly complex surgery requiring removal of an autologous tooth. Our team’s goal is the development of a synthetic OOKP-type device not requiring a tooth will signifi cantly improve the time to visual rehabilitation for patients requiring this surgery and simplify the surgical procedure tremendously. Our previous work shows that TiO2 has excellent biocompatibility as a substrate to support cornea fi broblast integration, enhanced surface cell spreading and adhesion. We are developing a semi-fl exible carbon mesh skirt for a synthetic OOKP artifi cial cornea.

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6. Protein Aggregation and TGFBI Related Corneal Dystrophy Stromal corneal dystrophies (CDs) are characterized as a group of bilateral, heterogeneous inherited disorders. The majority of these CDs in the stromal layer of the cornea have been attributed to mutations found on the TGFßI gene coding for a 683-amino acid transforming growth factor-induced protein (TGFßIp). Defects in this gene lead to progressive accumulation of protein aggregates in the cornea that can result in loss of corneal transparency and hence vision. At present, 63 distinct pathogenic mutations have been identifi ed in TGFßI that are associated with diff erent clinical phenotypes. Though TGFßIp is present in various other tissues, only cornea-specifi c aggregation is triggered by the occurrence of these mutations. Current treatment relies on laser/surgical intervention, which often involves high recurrence rates. Since there are no eff ective medical treatments of TGFßI-associated CDs, this research project aims to look into the mechanism of the disease and develop viable therapeutic strategies to treat these dystrophies. Biophysical, biochemical and structural aspects of the mutations will be analyzed. The present study will involve the development of in-vitro models of protein aggregation and evaluating the role of pharmacological chaperones (PCs) capable of inhibiting or dissolving the aggregates. This will allow us to develop a novel therapy for these stromal dystrophies. Slit lamp photography shows the multiple radially oriented linear opacities in the anterior to midstromal depth of the central cornea with subepithelial and anterior stromal scarring in the right (A) and left eye (B) with a novel A620D mutation. Slit lamp photograph showing radially oriented linear opacities in the cornea (C) of a H626R mutation, which are more clearly seen on retroillumination (D).

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Contact Us: Head: Prof Jodhbir Mehta at [email protected]

Selected Recent Publications 1: Liu YC, Peng Y, Lwin NC, Wong TT, Venkatraman SS, Mehta JS. Optimization of subconjunctival biodegradable microfi lms for sustained drug delivery to the anterior segment in a small animal model. Invest Ophthalmol Vis Sci. 2013 Mar 21. doi:pii: iovs.12-11466v1. 10.1167/iovs.12-11466. [Epub ahead of print] PubMed 2: Chung HW, Mehta JS. Fibrin glue for gundersen fl ap surgery. Clin Ophthalmol. 2013;7:479- 84. doi: 10.2147/OPTH.S42105. Epub 2013 Mar 6. 23493670; 3: Ang M, Mohamed-Noriega K, Mehta JS, Tan D. Deep anterior lamellar keratoplasty: surgical techniques, challenges, and management of intraoperative complications. Int Ophthalmol Clin. 2013 Spring;53(2):47-58. doi: 10.1097/IIO.0b013e31827eb746. 4: Khor WB, Teo KY, Mehta JS, Tan DT. Descemet stripping automated endothelial keratoplasty in complex eyes: results with a donor insertion device. Cornea. 2013 Feb 26. [Epub ahead of print]

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The SERI Retina group comprises of clinicians, clinician-scientists and scientists with a broad focus and expertise in basic, translational and clinical research in characterizing molecular mechanisms and pathways, epidemiology, imaging and management of retinal disorders. Particularly, the group emphasizes on Asian Age-related Macular Degeneration (AMD), including polypoidal choroidal vasculopathy (PCV), diabetic retinopathy (DR) and other retinal disorders such as central serous chorioretinopathy (CSR). Strengths • CLINICAL EXPERTISE in management of Asian retinal diseases • CLINICAL COHORTS on > 2,000 patients with AMD and DR • EPIDEMIOLOGICAL AND GENETIC DATABASE on >10,000 patients • State-of-the-art ANIMAL FACILITY with animal models for retinal diseases • World Class RETINAL IMAGING & OCULAR GRADING Centre • SIPRAD-an industry standard platform in retinal angiogenic diseases Selected Projects Does Genetic Variation in the CFH region of age-related macular degeneration patients allow 1. Prof Wong Tien Yin bacteria to trigger the disease? 2. Singapore Diabetic Retinopathy Epidemiology, Biomarkers and Imaging (DREAM) Program Prof Wong Tien Yin Phenotyping Asian Macular Diseases – a prospective functional and angiographic study of 3. A/Prof Gemmy Cheung the clinical course of three common acquired retinal conditions in an Asian population 4. Detailed choroidal sub-layer analysis of age-related macular degeneration A/Prof Yasuo Yanagi Pathophysiology of diabetic retinopathy and novel drugs for diabetic retinopathy using DR 5. Dr V A Barathi mouse model 6. Screening of novel drugs in laser-induced CNV model in rodents and non-human primates Dr V A Barathi & A/Prof Gemmy Cheung 7. Genome-wide association studies on diabetic retinopathy in Asians Dr Gavin Tan PI: A/Prof Gemmy Cheung 8. Ocular Biomarker Study for Retinal Angiogenic Diseases (OBSRAD study) Co-I: Dr Danny Cheung 9. Identifi cation of novel targets for macular degeneration and macular edema Dr Raj Patil 10. Investigation of LGR5 as a bonafi de retinal stem cell marker Dr Shweta Singhal PI: Dr Shweta Singhal 11. Investigation into the use of Dental Pulp Stem Cells (DPSC) as a source of retinal stem cells Co-I: Dr Gary Yam & Dr Goh Bee Tin (NDC) Team Members Head SERI Research Team A/Prof Gemmy Cheung, Head & Senior Consultant, Medical 1. Dr V A Barathi, Head, Translational Pre-Clinical Model Retina Department Platform 2. Prof Ching-Yu Cheng, Head, Ocular Epidemiology Research Group and Data Science Platform SNEC/SERI Clinical Team 3. Prof Ecosse Lamoureux, Director, Population Health 4. A/Prof Charumathi Sabanayagam, Deputy Head, Ocular 1. Prof Wong Tien Yin, Medical Director Epidemiology 2. A/Prof Gemmy Cheung,, Head, Medical Retina Department 5. Dr Carol Cheung, Adjunct Research Scientist 3. Adj A/Prof Doric Wong, Head, Retina Centre 4. A/Prof Ian Yeo, Deputy Medical Director (Education) 5. Dr Edmund Wong, Deputy Medical Director (Clinical Services) Contact Us 6. Adj A/Prof Lee Shu Yen, Deputy Head, Surgical Retina Department and Clinical Director, Retinal Service A/Prof Gemmy Cheung at [email protected] 7. Dr Ranjana Sanjay Mathur, Clinical Director, PEC and Visual Electrodiagnostic Service 8. Dr Chan Choi Mun, Senior Consultant 9. Dr Gavin Tan, Co-Clinical Director, Ophthalmic Imaging Services 10. A/Prof Yasuo Yanagi, Clinician Scientist 11. Dr Danny Cheung, Clinician Scientist 12. Dr Anna Tan, Consultant 13. Dr Shweta Singhal, Registrar

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www.seri.com.sg Ocular Surface Research Group

SERI’s ocular surface research group engages in international level highly competitive research related to the ocular surface. The main focus is on the diagnosis and treatment of ocular surface diseases such as dry eye, meibomian gland dysfunction and pterygium, and understanding the molecular basis of these diseases. The type of research ranges from epidemiology, health service, biochemical, cell- and animal-based research to imaging and human clinical trials. In recent years the group has performed research related to ocular surface T cells, induction of ocular surface infl ammation in animals, the epigenetics of pteryigum, infl ammatory signaling such as the NFkB signaling, the eff ects of S100 calcium-binding proteins and the regulation of wound healing by molecules such as SPARC and transglutaminase-2. In particular, they have investigated molecular cell adhesion mechanisms as well as biomechanics of cell movement relevant to the ocular surface. The group is dedicated to the evaluation and use of state-of-the-art technologies in dry eye, such as non-invasive meibography, tear evaporimetry, thermopulsation treatment, and comprehensive lipid analysis by mass spectrometry. The group is currently very active in various projects with commercial potential such as the establishment of an image analysis software for meibography, tear protein markers for evaluation of ocular surface infl ammation and development of anti-infl ammatory drugs. As part of the eff ort to translate research fi ndings to clinical care, the ocular surface research group has published in topics such as selection of eyedrops for dry eye based on acidity, use of patient logs for activities in dry eye and use of autologous plasma drops for recalcitrant dry eye. Our research audience includes diverse groups of people, including for example, optometrists and ophthalmologists in the International Dry Eye Workshop 2, ocular surface scientists in a report of the Meibomian Gland Dysfunction International Workshop, and general medical practitioners, in a paper published in British Medical Journal. Emphasis is therefore not only in innovative research, but the promotion of education of public and health professionals, and championing the healthcare of patients with ocular surface diseases.

Manpower The ocular surface research team is led by a principal clinician scientist, A/Prof Louis Tong, and currently comprises a post- doctoral research fellow, two graduate students, two research optometrists, one project coordinator and one research assistant. The group is dedicated to nurturing post- and undergraduate medical students, undergraduate fi nal year project students as well as polytechnic students who are welcome to join the lab for long or short term attachments.

Equipment The ocular surface research lab houses cutting edge facilities and equipments, such as centricollation system (Prospect Biosystems), fl ow cytometry facility (BD), cell impedence tracking device (xCELLigence, Roche), microscopy imaging station and basic laboratory setups including qPCR machines (Roche), fi lm development and cell culture facilities.

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Grant support Our research is supported by national competitive grants (National Medical Research Council) including two clinician-scientist awards, one individual research grant and the Biomedical Research Council Translational Clinical Research Project grant, two international awards, as well as various sources of industrial fundings.

Head: Prof Louis Tong Contact Us: [email protected]

Selected Publications 1. Tong L, Seow G, Tan J, Thumboo J. Dry eye practice pointer. BMJ. 2012; 345:e7533. 2. Tong L et al. The eye: A window of opportunity in rheumatoid arthritis? Nature Reviews Rheumato.2014 Jun 10. 3. Waduthantri S, Yong SS, Htoon HM, Tong L. Randomised controlled trial of Systane Ultra® vs Refresh Tears® in Asian dry eye patients. Optom Vis Sci. 2012; 89: 1647-53. 4. Lam SM, et al. Extensive characterization of human tear fl uid collected using diff erent techniques unravels the presence of novel lipid amphiphiles. J Lipid Res. 2014 Feb;55(2):289-98. doi: 10.1194/jlr.M044826. 5. Koh YW, Celik T, Lee HK, Petznick A, Tong L. Detection of meibomian glands and classifi cation of meibography images. J Biomed Opt. 2012; 17(8):086008. 6. Tong L, Png E, Hou AH, Yong SS, Yeo HL, Riau A, Mendoze E, Charausia SS, Lim CT, Yiu TW, Iismaa SE. Molecular Mechanism of Transglutaminase-2 in Corneal Epithelial Migration and Adhesion. BiochimBiophysActa 2013;1833:1304-1315. 7. Png E, Samivelu GK, Yeo SH, Chew J, Chaurasia SS, Tong L. Hyperosmolarity mediated mitochondrial dysfunction requires transglutaminase-2 in human corneal epithelial cells. J Cell Physiol. 2011; 226: 693–699. 8. DA Schaumberg, JJ Nichols, EB Papas, L Tong, M Uchino, KK Nichols. The international workshop on meibomian gland dysfunction: Report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011; 52 (4): 1994-2005. 9. Lan, Wanwen; Chen, Silin; Tong, Louis. MicroRNA-215 Regulates Fibroblast Function: Insights from a Human Fibrotic Disease. Cell Cycle. 2015 Jun 18;14(12):1973-84. 10. Riau AK, Wong TT, Finger SN, Lan WW, Chaurasia SS, Hou AH, Chen SL, Yu SJ, Tong L. Aberrant DNA methylation of matrix remodeling and cell adhesion related genes in pterygium. PLOS One. 2011; 6(2): e14687. 11. Selva KJ, Liu YC, Siak JK, Lan WW, Tong L, Yawata M, Mehta JS, Yawata N, Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection. Mucosal Immunol 2015 Jun 17. 12. Gong L, Sun XH, Ma ZZ, et al, Tong L. A Randomized, Parallel-Group Comparison Study of Diquafosol Ophthalmic Solution in Patients with Dry Eye (Comparison with 0.1% sodium hyaluronate ophthalmic solution) in China and Singapore. Br J Ophthalmol. 2015 Jul; 99(7):903-8.

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www.seri.com.sg Myopia Research Group

The Myopia Research Group at the Singapore Eye Research Institute, in conjunction with the Singapore National Eye Centre and National University of Singapore, has been involved in various aspects of myopia research over the last 20 years. The group’s research focus is on fi ve sub-themes: Genetics, animal experimental models, epidemiology and community-based interventions, treatments to retard myopia progression and visually-disabling pathologic myopia. The aims of our group are to better understand the epidemiology, genetics, pathogenesis and public health implications of myopia, to develop and evaluate novel interventions to prevent or slow myopia progression in young children, and to formulate better management strategies for myopia-related complications in older adulthood. The multi-disciplinary team will address important key questions to tackle the epidemic of myopia.

Picture of people Myopia Research Program The Epidemiology Studies Several large population-based studies have helped determine the prevalence of myopia in children, including the School Cohort of Refraction Myopia (SCORM) cohort which followed children aged 7-9 years for a period of 10 years, and the Strabismus Amblyopia and Refractive Error Singaporean preschool children (STARS), a cross-sectional study of children aged 6 months to 6 years. Data are also available from several adult studies including the Singapore Malay, Indian and Chinese eye studies (SIMES, SINDI, SCES) which provide information of myopic prevalence in Singaporeans aged >40 years. Early life data are available from the GUSTO birth cohort involving 1200 children in whom refractive status is measured at aged 3 years. Together, these studies provide us with great detail of the size of the myopic problem in Singapore, and an opportunity to study risk factors associated with myopia.

Ongoing work include an SAF study assessing pathologic lesions in 700 myopic individuals and controls; and a SEED study looking at the impact of pathologic myopia on quality of life in Singapore adults. Pilot studies investigating the 10-year longitudinal pathologic changes from the teenage to young adulthood in SCORM and the 10 year follow-up visit of the STARS study to evaluate role of outdoors (using wristband outdoor light meter), near work and genes on myopia.

As active members of the Meta-PM International Consortium, an international group formed to evaluate the natural history of pathological myopia, we hope to help develop new pathologic myopia grading guidelines and clinical practice guidelines for the screening of pathologic myopia lesions adults with very high myopia with early treatment of ocular problems when present, and visual rehabilitation when required. Myopia and Genetics Genetic studies in myopia show a complex interaction of multiple genetic infl uences. Our work with the international Consortium for Refractive Errors And Myopia (CREAM) has uncovered several novel genetics variants by meta-analyzing genome-wide association studies (GWAS) from more than 30 population-based studies in Europe, Asia, United States and Australia. The challenge now is to consolidate information to see if we could identify high risk children with genetic susceptibility for extreme myopia with the Singaporean Chinese population who will benefi t from early interventions to retard the progression of myopia.

Manhattan plot of top snps for axial length identifi ed in the CREAM consortium

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The Biology of Myopia Over the years, we have also studied the factors that infl uence myopia in mouse and chick models. Our studies show that atropine reduces myopia progression in both pigmented and non-pigmented mice eyes, and that atropine may act on one or more muscarinic receptors to diff erentially regulate expression levels of specifi c receptors which in turn infl uence axial length and vitreous depth, the main morphological parameters associated with myopia.

Our muscarinic receptor knockout mouse study has provided in vivo evidence to support an important role for the M2/M3 muscarinic receptor in myopia development. The data indicate that the actions of the M2 receptor are mediated by changes in the expression of key extracellular matrix proteins, linking the functional role of M2 with scleral remodeling in myopia. The study also highlights the utility of the mouse as a model for myopia, particularly in conjunction with new technologies that can measure ocular dimensions and optical properties with high precision. Further mouse studies are needed to pinpoint and validate the downstream targets of M2 and to investigate the role of the M3 receptor subtype in myopia development.

More recently, we have also shown that manipulation of the chromaticity of light can also infl uence myopia progression with chicks raised in red/green environment becoming more myopic while those in blue/green light became more hyperopic. We intend to see if similar chromatic manipulation could also slow myopic progression in children.

Interventional Studies: Slowing, Stopping and Reversing Myopia Researchers at SERI/SNEC have been exploring ways of slowing or stopping myopia using optical (e.g. progressive add, bifocal and myopic defocus glasses) and pharmacological (eg. pirenzepine and atropine) interventions. Of these, results from the Atropine Treatment of Myopia (ATOM) studies have been most promising. There are 2 major ATOM studies, ATOM1 and ATOM2, involving a total of 800 subjects and testing a variety of doses of atropine over a 3-5 year periods. These studies suggest that even a low dose of atropine (0.01%) could slow myopia progression by 60% with no/minimal side-eff ects. This has translated into clinical practice with many clinicians locally and worldwide now converting to lower doses. More work still needs to be done to better understand the exact pharmacological mechanism of the medication, and to determine the best possible treatment regime. Low-dose atropine, however, has been one of the more exciting new developments in myopia management for some time.

There are, however, other novel optical (eg. peripheral defocus optics or corneal modifying contact lenses) and pharmacological treatments which need to be explored. The role of diff erent treatment modalities (either on its own or in combination) is still unclear and much work still needs to be done on the subject.

We do also know that environmental factors (such as the lack of outdoor activity and too much near work) may infl uence myopia onset and progression. Reasons for this are uncertain but it is believed that levels of light intensity, chromatics and frequency may be important. The FIT outdoor trial evaluated a weekend Park outdoor program. Novel school or family-based outdoor programs could help to stop or slow myopia onset and progression in our local Singaporean context. Steps have been made to undertake an exploratory randomized controlled study both locally and in conjunction with collaborators overseas.

Clinical Myopia Eventually, the importance in this research is how it can be used clinically to prevent or slow myopia in childhood, minimize the subsequent impact on quality-of-life and quality-of-vision in adulthood (eg. through optical and surgical correction) and to manage any myopia-related complications which may occur in mid to late adulthood.

The myopic epidemic in Singapore started in the 1980s, and individuals from that generation of Singaporeans, with a prevalence of high myopia of 20-30%, are now entering their 5th decade when myopic complications (such as retinal detachment, macula neovascularization, schisis or atrophy, early cataracts and glaucoma) start to manifest.

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Directions of Myopia Research Our plans of the future include programs encompassing fi ve sub-themes: genetics, animal experimental models, epidemiology and community-based interventions, treatments to retard myopia progression and visually-disabling pathologic myopia to cover diff erent aspects of myopia research. The epidemiological studies have already led to modifi cation of behavior in the community and changes in national policies. Our proposed outdoor physical activity program will be integrated in schools and rolled out nationwide in conjunction with the Ministries of Education and Health (Health Promotion Board). The ATOM studies have led to changes in our clinical management of children with progressive myopia. There is still much that needs to be learnt and our hope is that we can continue in discover ever better ways to control and manage myopia and to evaluate the predictors and natural history of pathologic myopia.

Co-Heads: Contact Us: Prof Saw Seang Mei at [email protected] A/Prof Audrey Chia at [email protected] Key Team Members: • Prof Donald Tan • Prof Cheng Ching-Yu • Dr Victor Koh • Prof Roger Beuerman • Dr Velachamy A Barathi • Dr Qiao Fan • Prof Wong Tien Yin • Prof Terri Young • Dr Pavan K Verkicharla Prof Saw Seang Mei A/Prof Audrey Chia • Prof Wallace Foulds • Dr Dharani Ramamurthy • Dr Khor Chiea Chuen • Dr Suan Pu

Selected Publications 1. Samarawickrama C, Mitchell P, Tong L, Gazzard G, Lim L, Wong TY, Saw SM. 13. Chia A, Lin XY, Mohamed D, Guzzard G et al. Risk factors for strabismus and Myopia-related optic disc and retinal changes in adolescent children from amblyopia in young Singapore Chinese children. Ophthalmic Epidemiology Singapore. Ophthalmol. 2011;118:2050-7. 2013;20(3):138-47. 2. Morgan IG, Ohno-Matsui K, Saw SM. Myopia. Lancet. 2012; 379(9827):1739-48. 14. Zheng YF, Pan CW, Chay J, Wong TY, Finkelstein E, Saw SM. The economic 3. Fan Q, Zhou X, Khor CC, Cheng CY, Goh LK, Sim X, Tay WT, Li YJ, Ong RT, Suo cost of myopia in adults aged over 40 years in Singapore. Invest Ophthalmol C, Cornes B, Ikram MK, Chia KS, Seielstad M, Liu J, Vithana E, Young TL, Tai ES, Vis Sci. 2013;54(12):7532-7. Wong TY, Aung T, Teo YY, Saw SM. Genome-wide meta-analysis of fi ve Asian 15. Fan Q, Wojciechowski R, Ikram KM, Cheng CY, Chen P, Zhou X, Pan CW, cohorts identifi es PDGFRA as a susceptibility locus for corneal astigmatism. Khor CC, Tai ES, Aung T, Wong TY, Teo YY, Saw SM. Education infl uences the PLoS Genet. 2011; 7(12):e1002402. association between genetic variants and refractive error: a meta-anlaysis 4. Low W, Dirani M, Gazzard G, Chan YH, Zhou HJ, Selvaraj P, Au Eong KG, Young of fi ve Singapore studies. Human Molecular Genetics. 2013. TL, Mitchell P, Wong TY, Saw SM. Family history, near work, outdoor activity, 16. Foulds WS, Barathi VA, Luu CD. Progressive myopia or hyperopia can be and myopia in Singapore Chinese preschool children. Br J Ophthalmol. induced in chicks and reversed by manipulation of the chromaticity of 2010;94(8):1012-6. ambient light. Invest Ophthalmol Vis Sci. 2013;54(13):8004-12. 5. Lim W, Kwan JL, Goh LK, Beuerman RW, Barathi VA. Evaluation of gene 17. Barathi VA, Kwan JL, Tan QS, Weon SR, Seet LF, Goh LK, Vithana EN, expression profi les and pathways underlying postnatal development in Beuerman RW. Muscarinic cholinergic receptor (M2) plays a crucial role in mouse sclera. Mol Vis. 2012;18:1436-48. the development of myopia in mice. Dis Model Mech. 2013;6(5):1146-58. 6. Barathi VA, Weon SR, Tan QS, Lin KJ, Tong L, Beuerman RW. 18. Chia A, Li W, Tan D, Luu CD. Full-fi eld electroretinogram fi ndings in children Transglutaminases(TGs) in ocular and periocular tissues: eff ect of muscarinic in the atropine treatment for myopia (ATOM2) study. Doc Ophthalmol. agents on TGs in scleral fi broblasts. PLoS One. 2011;6(4):e18326. 2013;126(3):177-86. 7. Barathi VA, Beuerman RW. Molecular mechanisms of muscarinic receptors 19. Chang L, Pan CW, Ohno-Matsui K, Lin X, Cheung GC, Gazzard G, Koh V, in mousescleral fi broblasts: Prior to and after induction of experimental Hamzah H, Tai ES, Lim SC, Mitchell P, Young TL, Aung T, Wong TY, Saw SM. myopia with atropine treatment. Mol Vis. 2011;17:680-92. Myopia-related fundus changes in Singapore adults with high myopia. Am J 8. Sng CC, Lin XY, Gazzard G, Chang B, Dirani M, Chia A, Selvaraj P, Ian K, Drobe Ophthalmol. 2013;155(6):991-999.e1. B, Wong TY, Saw SM. Peripheral refraction and refractive error in Singapore 20. Chia A, Chua WH, Wen L, Fong A, Goon YY, Tan D. Atropine for the treatment Chinese children. Invest Ophthalmol Vis Sci. 2011 Feb 28;52(2):1181-90. of childhood myopia: changes after stopping atropine 0.01%, 0.1% and 9. Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, Tan D. Atropine 0.5%. Am J Ophthalmol 2014;157(2):451-457. for the treatment of childhood myopia: safety and effi cacy of 0.5%, 0.1%, 21. Ngo CS, Pan CW, Finkelstein EA, Lee CF, Wong IB, Ong J, Ang M, Wong TY, Saw and 0.01% doses (ATOM2). Ophthalmol. 2012;119(2):347-54. SM. A cluster randomised controlled trial evaluating an incentive-based 10. Dharani R, Lee CF, Theng ZX, Drury VB, Ngo C, Sandar M, Wong TY, Finkelstein outdoor physical activity programme to increase outdoor time and prevent EA, Saw SM. Comparison of measurements of time outdoors and light myopia in children. Ophthalmic Physiol Opt. 2014. levels as risk factors for myopia in young Singapore children. Eye (Lond). 22. Chia A, Li W, Chua WH, Goon YY, Fong A, Tan D. Changes after cessation of 2012;26(7):911-8. atropine: ATOM2. Am J Ophthalmol 2014; 157(2):451-7. 11. Chang L, Pan CW, Ohno-Matsui K, Lin X, Cheung GC, Gazzard G, Koh V, 23. Verkicharla PK, Ohno-Matsui K, Saw SM. Current and predicted Hamzah H, Tai ES, Lim SC, Mitchell P, Young TL, Aung T, Wong TY, Saw SM. demographics of high myopia and an update of its associated pathological Myopia-related fundus changes in Singapore adults with high myopia. Am J changes. Ophthalmic and Physiological Optics 35.5 (2015): 465-475. Ophthalmol. 2013;155:991-9.e1. 24. Ramamurthy D, Chua L, Yu S, Saw SM. A review of environmental risk factors 12. Verhorven VJM, Hysi PG, Wojciechowski R, Fan Q, Guggenheim JA, Hohn R, for myopia during early life, childhood and adolescence. Clinical and MacGregor S, Saw SM, Bailey-Wilson J, Stambolian D, Klaver C, Hammond Experimental Optometry. 2015 Nov 1;98(6):497-506. C. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nature Genetics 2013, 45(3): 314-317.

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www.seri.com.sg Ocular Infl ammation & Immunology Research Group

Infl ammation of the ocular surface following injury, infection or from chronic conditions such as Stevens-Johnson syndrome takes a toll in the work place and in visual morbidity. Chronic infl ammation associated infections is a major problem in Asia which often result in corneal blindness. Intraocular infl ammation is another commonly seen condition associated with various other eye diseases. The Ocular Infl ammation and Immunology Research group seeks to unveil the mechanisms and markers of major ocular infl ammatory diseases with the goal of improving current diagnostic and therapeutic approaches. The group is interested in both infectious and sterile infl ammation as well as ocular autoimmune disorders of the anterior and posterior segments of the eye, such as keratitis, pterygium, dry eye, uveitis, retinitis and infl ammation associated with glaucoma and retinal diseases.

VISION Our scientists and clinicians work at the forefront of ocular infl ammation, furthering the understanding of infl ammatory mechanisms and developing new diagnostics and therapeutics. Infl ammation plays a signifi cant role in many ocular diseases. Understanding how dysregulation of innate and adaptive immune responses leads to diseased ocular conditions is key. To combat infl ammatory diseases in the eye, identifi cation of diagnostic and predictive biomarkers and of potential targets for new therapeutics is underway with genetic-, proteomic- and cell-based approaches using human samples.

Role of defensins on ocular surface protection. Upon pathogen attack, tissue wounding or the presence of infl ammatory cytokines, the secretion of ß-defensins from epithelial cells increases. Infection and proinfl ammatory cytokines also brings neutrophils to the site and increase HNP concentration locally. Defensins stimulate the secretion of selective cytokines from epithelial cells and the proliferation of both epithelial cell and stroma fi broblasts. Both defensins and cytokines will recruit more immune cells to the site and thus mark the progression of infl ammation.

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Ocular Surface Infectious Diseases Intraocular Infectious Diseases (Epidemic Keratoconjunctivitis, CMV keratitis) (CMV-related Uveitis, Tuberculosis associated Uveitis) Ocular Surface Non-Infectious Diseases Intraocular Non-Infectious Diseases (Corneal Injury, Dry Eye, Stevens-Johnson syndrome) (Diabetic Retinopathy, Uveitis)

Clinical Data In-vivo confocal microscopy Laser Flare Photometry

Human Sample Analysis qPCR DNA sequencing Multiplex protein analysis High dimensional fl ow cytometry

In-vitro analysis In-vivo Animal models Human primary cells Knockout mice Human cell lines Disease models Imaging

Infl ammatory Mechanisms Diagnostic Development Therapeutics Development

Ongoing Projects 1. Targeting the infl ammatory mechanisms in adenovirus infection and epidemic keratoconjunctivitis - Dr Nobuyo Yawata 2. Development of biomarkers for corneal transplantation wound healing and severe corneal chemical and other injuries - Prof Jodhbir Mehta, Dr Nobuyo Yawata 3. Ocular surface infl ammation: The role of T cells in dry eye - Prof Louis Tong 4. Ocular surface infl ammation: Animal models - Prof Louis Tong 5. Use of autologus plasma eye drops therapy for severe dry eye in Singapore - Prof Louis Tong 6. Identifi cation of the infl ammatory mechanisms in fi brosis - Prof Roger Beuerman 7. Proteomics study on ocular surface infl ammatory diseases; S100 protein family as potential biomarkers - Prof Roger Beuerman 8. Understanding the innate and adaptive immune mechanisms of CMV-related anterior uveitis - Prof Chee Soon Phaik, Dr Jay Siak, Dr Nobuyo Yawata 9. Immunogenetics of CMV-related anterior uveitis - Prof Chee Soon Phaik, Dr Jay Siak, Dr Nobuyo Yawata 10. Development of new diagnostics for TB-related uveitis - Prof Chee Soon Phaik, Dr Jay Siak, Dr Nobuyo Yawata 11. Standardisation of uveitis nomenclature for disease entities-formation of database for classifi cation criteria for specifi c disease entities - Prof Chee Soon Phaik 12. Validation of a Novel Micro-fl uid Cytokine Analysis Platform for aqueous and vitreous humour in normal and eyes with Diabetic Retinopathy - Dr Kelvin Teo, Dr Marcus Ang, Dr Nobuyo Yawata

Co-Heads: Prof Chee Soon Phaik, Prof Louis Tong Team Members: Prof Chee Soon Phaik, Prof Louis Tong, Dr Siak Jyh Kuen, Prof Roger Beuerman, Prof Jodhbir Mehta, A/Prof Tina Wong, Dr Li Fong Seet, Dr Yu-Chi Liu Contact us: Prof Chee Soon Phaik at [email protected], Prof Louis Tong at [email protected]

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www.seri.com.sg Ocular Epidemiology Research Group

Overview The Ocular Epidemiology Research Group, led by Prof Ching-Yu Cheng, conducts epidemiological studies and population-based projects under the Singapore Epidemiology of Eye Diseases (SEED) programme. Our strategic vision is to provide novel knowledge in the population eye health to enable dissecting, detecting and preventing the most important eye diseases in both our children and ageing populations in Singapore and Asia, and also to promote ADULTS & THE ELDERLY & ADULTS and improve global eye health.

Our Vision CHILDREN A world-leading research programme focusing specifi cally on the epidemiology and impact of eye diseases in Asia • Provide a one-stop “data portal” and information source on epidemiology of Asian eye diseases • Cover an entire spectrum of prevalence, incidence, risk factors and impact of Asian eye diseases in 3 major racial/ethnic groups (Chinese, Malays, Indians) Aims • To document the prevalence, incidence, risk factors and public health signifi cance of blinding eye diseases in Singapore and Asia through the conduct of large scale epidemiological studies • To foster international collaborations with other public health and ophthalmic institutes in Asia and worldwide • To provide research expertise, training and consultation to other researchers and ophthalmic institutions in Singapore and Asia SEED Population Cohorts The SEED programme includes more than 25,000 adult and children participants from 7 large population-based studies, with a focus on studying major eye diseases, including diabetic retinopathy, age-related macular degeneration, glaucoma, refractive errors and cataract.

Study name Age range Ethnicity Number Data Collected

Singapore Malay Eye Study (SiMES) 40-80 years Malays 3280 Prevalence, environmental and genetic risk factors, and Singapore Indian Eye Study (SINDI) 40-80 years Indians 3400 impacts of visual impairment and major eye diseases Singapore Chinese Eye Study (SCES) 40-80 years Chinese 3353

Chinese, Prevalence, environmental and genetic risk factors, and The Singapore Prospective Study 24-95 years Malays, and 5000 impacts of cardiovascular and metabolic diseases (e.g., Programme (SP2) Ancillary study Indians hypertension, dyslipidemia, obesity, and diabetes mellitus)

Chinese, Singapore Consortium of Cohort Genetic and lifestyle risk factors for ocular and systemic 21-75 years Malays, and 6000 Studies – Multiethnic Cohort diseases (e.g., cancer and heart disease) Indians

Chinese, Singapore Cohort Study of the Risk Prevalence, incidence rates, progression and risk factors of 7-9 years Malays, and 1600 Factors for Myopia (SCORM) myopia in children Indians

STrabismus, Amblyopia, and 6 to 72 Magnitude and causes of refractive errors and other ocular Refractive Error study of preschool Chinese 3000 months diseases Singapore children (STARS)

Research Competencies & Expertise The Ocular Epidemiology Research Group and SEED Programme bring together innovative and cutting-edge epidemiological research for a focus and theme-oriented strategy, with multi-disciplinary expertise in all aspects of clinical and epidemiological research. Our group has developed upon the following major focus areas:

• Basic & Advanced Epidemiology • Genetic Epidemiology • Infrastructure of Population Health

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We provide data towards public health planning and resource allocation in the region. The data collected from our group has been used widely by national and international agencies (e.g., the Ministry of Health Singapore, WHO, the Global Burden of Disease program) and clinical guidelines (e.g., 2014 Ministry of Health Diabetes Guidelines). Furthermore, we have established Singapore as a leading hub of ophthalmic epidemiology, clinical and genetic research in Asia through particular focus on diseases that are prevalent in this region. We also provide research expertise, resource, and consultation to other research centres, hospitals and ophthalmic institutions in Singapore and Asia, and conduct training programmes for clinicians, research fellows, and graduate students interested in ophthalmic epidemiology. Head Prof Ching-Yu Cheng Team members Deputy Head: A/Prof Charumathi Sabanayagam Investigator & Fellow: Dr Yih Chung Tham, Dr Simon Nusinovici, Dr Yijin Tao Research Associate: Dr Shivani Majithia, Dr Sahil Thakur Clinical Team: Cong Ling Teo, Cynthia Ong, Binu Thapa, Rosesita Binte Shaikh, Manivannan Udayaraj Biobank Laboratory: Miao Ling Chee, Michelle Ng Research Admin: Ho Kee Ka, Angelina Lee, Riswana Banu, Munirah Naser

Contact us: Prof Ching-Yu Cheng at [email protected]

Selected Publications 1. Sabanayagam C, et al. Retinal microvascular caliber and chronic kidney disease in an Asian population. Am J Epidemiol 2009;169:625-32. 2. Fan Q, et al. Education infl uences the association between genetic variants and refractive error: a meta-analysis of fi ve Singapore studies. Hum Mol Genet 2014; 23:546-54. 3. Tham YC, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology 2014;121: 2081-90. 4. Wong WL, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta- analysis. Lancet Glob Health 2014;2:e106-e116. 5. Liao J, et al. Meta-analysis of genome-wide association studies in multiethnic Asians identifi es two loci for age-related nuclear cataract. Hum Mol Genet 2014;23:6119-28. 6. Hysi PG, Cheng CY, et al. Genome-wide analysis of multi-ancestry cohorts identifi es new loci infl uencing intraocular pressure and susceptibility to glaucoma. Nat Genet 2014;46:1126-30. 7. Cheng CY, et al. New loci and coding variants confer risk for age-related macular degeneration in East Asians. Nat Commun 2015;6:6063. 8. Tham YC, et al. Aggregate eff ects of intraocular pressure and cup-to-disc ratio genetic variants on glaucoma in a multiethnic Asian population. Ophthalmology 2015;122:1149-57. 9. Chua J, et al. Prevalence, risk factors, and visual features of undiagnosed glaucoma: the Singapore Epidemiology of Eye Diseases Study. JAMA Ophthalmol 2015;133:938-46. 10. Gupta P, et al. Relationship between peripapillary choroid and retinal nerve fi ber layer thickness in a population-based sample of nonglaucomatous eyes. Am J Ophthalmol 2016;161:4-11.

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www.seri.com.sg Health Services Research (HSR) Group

The Health Services Research (HSR) is the translational eye research unit at SERI. Headed by Prof Ecosse Lamoureux, the unit is focused on the epidemiology and risk factors of major eye diseases in Singapore; patient-centered outcomes research; low vision outcomes and rehabilitation; and translational clinical research in eye diseases, particularly in diabetic retinopathy and glaucoma.

About the HSR Unit: Established in April 2009, the HSR Unit is strategically placed to interface with health research, clinical practice and health policy, and therefore able to improve the utilization of research knowledge and best evidence to effi ciently and eff ectively inform on: i. Eye health care practices ii. Implementation of complex interventions to improve self-effi cacy and quality of life iii. Guidelines and ocular program development iv. Policies development related to improving eye care in Singapore

Members

Dr Preeti Gupta Dr Pauline Soh Dr Ryan Man Research Research Eyn Kidd Research Fellow Fellow Prof Ecosse Lamoureux Fellow • Director, Population Health • Head, Health Services Research Group • Head, Data Management Platform • Deputy Director, Academic Medical Research Institute (AMRI) • Professor, Duke-NUS and NUS

Dr Eva Fenwick Amudha Alfred Gan Research Fellow Aravindhan Senior Research Statistician Associate Major Projects: • An Innovative and Patient-Centric Research Program Targeting the Ageing Singaporeans: The PRevention Of and interVentIon for eye Diseases in the Elderly (PROVIDE) programme • Singapore Diabetic Retinopathy Screening Programme (SiDRP) • Evaluating the Feasibility and Short-term Eff ectiveness of a Novel Diabetic Retinopathy-Specifi c Integrated Care Model (DR-ICM) for poorly controlled patients with diabetic retinopathy: A Pilot Study • Improving Diabetes and Health Outcomes: Enhancing Health Literacy in Patients with Diabetes and Diabetic Retinopathy • The Clinical and Economic Impact of Extending Screening Intervals for Diabetic Retinopathy and Macular Edema in Singapore • Improving the measurement of vision-specifi c quality of life in Singaporeans using item banking and computer adaptive testing: The ‘VisBank’ study • Investigating the Prevalence and Impact of Vision Impairment, Hearing Loss and Dual Sensory Impairment in Residential Care Facilities in Singapore • Developing a Predictive Model for Non-compliance to Tertiary Ophthalmological Referrals in Persons with Diabetic Retinopathy (PM-DR)

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Others: • Understanding the impact of unilateral and bilateral glaucoma on QoL • Acceptance and attitudes of patients and family members towards an implant for glaucoma drug delivery • Accelerometer-based measurement of physical activity in Singaporean adults before and after cataract surgery • Development of Glaucoma Utility Index-S (GUI-S) in Singapore • Evaluating a novel eye care model for visually impaired people in various communities in Singapore

Collaborations: • Health Services System Research SRP, Duke-NUS Medical School • Centre of Quantitative Medicine, Duke-NUS Medical School • Lions Home for the Elders • SingHealth and National Healthcare Group Polyclinics • The Singapore Advanced Imaging Laboratory for Ocular Research (SAILOR) • Yong Loo Lin School of Medicine, National University of Singapore • Singapore National Eye Centre (SNEC) • Department of Family Medicine and Continuing Care, Singapore General Hospital • Centre for Eye Research Australia, University of Melbourne, Australia • Aging Centre, Duke University, USA • University of Sydney, Australia • Queensland University of Technology, Australia • Gloucestershire Eye Unit, UK

Contact Us: Prof Ecosse Lamoureux at [email protected]

Publications (Selected from 250+) 1. Rooney D, Lye WK, Tan G, Lamoureux E.L., Ikram MK, Cheng CY, Kumari N, Zheng YF, Mitchell P, Wang JJ, Wong TY, Sabanayagam C. Body mass index and retinopathy in Asian populations with diabetes mellitus. Acta Diabetol. 2015 Feb; 52(1):73-80. 2. Chan EW, Chiang PP, Liao J, Rees G, Wong TY, Lam JS, Aung T, Lamoureux, E.L. Glaucoma and Associated Visual Acuity and Field Loss Signifi cantly Aff ect Glaucoma- Specifi c Psychosocial Functioning. Ophthalmology. 2015 Mar; 122(3):494-501. 3. Sabanayagam C, Khoo EY, Lye WK, Ikram MK, Lamoureux, E.L., Cheng CY, Tan ML, Salim A, Lee J, Lim SC, Tavintharan S, Thai AC, Heng D, Ma S, Tai ES, Wong TY. Diagnosis of Diabetes Mellitus using HbA1c in Asians: Relationship between HbA1c and Retinopathy in a Multi-Ethnic Asian Population. The Journal of Clinical Endocrinology & Metabolism (JCEM). 2015 Feb;100(2):689-96. 4. Man RE, Sasongko MB, Wang JJ, MacIsaac R, Wong TY, Sabanayagam C, Lamoureux, E.L. The Association of Estimated Glomerular Filtration Rate With Diabetic Retinopathy and Macular Edema. Invest Ophthalmol Vis Sci. 2015 Jul 1;56(8):4810-4816. 5. Fenwick EK, Ong PG, Sabanayagam C, Rees G, Xie J, Holloway E, Cheng CY, Wong TY, Lim B, Tan PC, Lamoureux, E.L. Assessment of the psychometric properties of the Chinese Impact of Vision Impairment questionnaire in a population-based study: fi ndings from the Singapore Chinese Eye Study. Qual Life Res [Accepted 23 September 2015]. 6. Fenwick EK, Xie J, Man RE, Lim LL, Flood VM, Finger RP, Wong TY, Lamoureux, E.L. Moderate consumption of white and fortifi ed wine is associated with reduced odds of diabetic retinopathy. J Diabetes Complications. 2015 Nov-Dec;29(8):1009-14. 7. Wah W, Earnest A, Sabanayagam C, Cheng CY, Ong ME, Wong TY, Lamoureux, E.L., Composite Measures of Individual and Area-Level Socio-Economic Status Are Associated with Visual Impairment in Singapore. PLoS One. 2015 Nov 10; 10(11):e0142302. doi: 10.1371/journal.pone.0142302. eCollection 2015. 8. Ansah JP, Korne DD, Bayer S, Chong P, Thiyagarajan J, Matchar DB, Lew N, Phua A, Koh V, Lamoureux, E.L., Quek D. Future requirements for and supply of ophthalmologists for an aging population in Singapore. Human Resources for Health. (2015) 13:86 DOI 10.1186/s12960-015-0085-4. 9. Sasaki M, Kawasaki R, Rogers S, Man RE, Itakura K, Xie J, Flood V, Tsubota K, Lamoureux, E.L., Wang JJ. The Associations of Dietary Intake of Polyunsaturated Fatty Acids With Diabetic Retinopathy in Well-Controlled Diabetes. Invest Ophthalmol Vis Sci. 2015 Nov 1;56(12):7473-9. 10. Man RE, Sabanayagam C, Chiang PP, Li LJ, Noonan JE, Wang JJ, Wong TY, Cheung GC, Tan GS, Lamoureux, E.L. Diff erential Association of Generalized and Abdominal Obesity With Diabetic Retinopathy in Asian Patients With Type 2 Diabetes. JAMA Ophthalmol. 2015 Dec 17. doi: 10.1001/jamaophthalmol.2015.5103.

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www.seri.com.sg Bioengineering & Devices Research Group

Biomedical Engineering (often used synonymously with Bioengineering) is a relatively modern fi eld that has made a considerable impact on global healthcare by producing translational advances from research. The fi elds of cardiovascular research and orthopedics represent excellent examples whereby biomedical engineering solutions are used routinely in clinical practice. Currently, there are several opportunities for biomedical engineers to make a similar impression in Ophthalmology as this arena is ripe for development.

The Bioengineering & Devices Research Group was established as a new initiative at SERI in January 2014. It aims to foster knowledge exchange and collaborations between biomedical engineers from the various biomedical engineering institutions in Singapore (e.g. NUS Biomedical Engineering, NTU Bioengineering, A*STAR, SUTD) and clinician scientists at SERI. Our mission is to drive translational impact by

1) Identifying current and imminent clinical needs that require biomedical engineering solutions 2) Attracting and inspiring early stage biomedical engineers to pursue careers in Ophthalmology 3) Enhancing networking among clinicians, clinician-scientists, basic scientists, and biomedical engineers 4) Actively leading and seeking large research grant funding 5) Aiding patent fi ling and commercialization of outputs born from new collaborations 6) Reporting on current collaborations Biomedical Engineering Areas of Interests: • Development, verifi cation and validation of novel ophthalmic devices • Advanced ophthalmic imaging solutions • Biomechanics • Biomaterials • Cell and Tissue Engineering • Bioelectronics Example of a custom-designed and 3D printed glaucoma drainage • Bioelectricity device (NUS Biomedical Engineering – BN3101: Course on Biomedical Engineering Design) • Robotic microsurgery

Interests for Biomedical Engineers Developed devices and techniques that can be applied to wider domains. We are interested to hear about novel developments and can help you rapidly maximize your exposure through its application to Ophthalmology.

Interests for Clinicians There are still several achieveable unmet needs and opportunities within Ophthalmology requiring a BME solution: in fact the 2015 Institute of Engineers Singapore-Prestigious Engineer award was won by a collaboration between A*STAR and SERI/ SNEC team involving Prof Tin Aung, Dr Baskaran Mani and Assoc Prof Perera.

Dr Girard has been teaching the Biodesign class at NUS for 2 years, where biomedical engineering students designed and developed working prototype medical devices within 12 weeks. Clinicians may be interested in proposing and co-supervising projects to help these projects evolve to their highest potential. However, the focus on commercialization means that only the most promising projects are carried through.

Serving on SERI’s Patent review committee, a reviewer for several innovation grants and as a member of A*STAR’s Diagnostic Development hub, have led to a deep commitment to advancing commercialization in Singapore for Adj Assoc Prof Perera. His work with TouchSurgery in creating a successful Cataract Surgery training app has opened up important routes of collaboration in new pastures.

Together, both co-heads work to facilitate projects between Clinicians and Engineers via networking events and in conjunction with third party stakeholders for funding and mentorship.

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Current Projects and Collaborations An early prototype for the LensGun – A tool to facilitate IOL insertion during cataract surgery 1) Development of Novel Intraocular Lens Injectors

2) Development of Smart Pupil Expanders

Novel smart pupil expander 3) Improved Diagnosis of Age-related Macular Degeneration using Novel Protein Multiplexing Technology Dr Dieter Trau, co-founder of AYOXXA Biosystems Pte Ltd, and Dr Marcus Ang are currently validating AYOXXA’s multiplexing technology to improve the diagnosis of age-related macular degeneration.

4) Development of Novel Engineering Tools to Characterize Ocular Biomechanics In Vivo Dr Michael Girard is currently developing novel engineering tools that will allow clinicians to quantify scleral, retinal, choroidal, corneal, iris, and optic nerve head biomechanics in vivo. These tools help the diagnosis and treatment of multiple ophthalmic disorders including myopia, glaucoma, corneal disorders and AMD.

Co-Heads:

Contact Us: Dr Michael J.A. Girard at [email protected] Assoc Prof Shamira Perera at [email protected]

Dr Michael J.A. Girard Assoc Prof Shamira Perera

Selected Publications Mari JM, Park SC, Strouthids NG, Girard MJA. Enhancement of Lamina Cribrosa Visibility in Optical Coherence Tomography Images Using Adaptive Compensation. Invest Ophthal and Vis Sci. 2013; 54(3):2238-47. Girard MJA, Strouthidis NG, Desjardins A, Mari JM, Ethier CR. In Vivo Optic nerve Head Biomechanics: Performance Testing of a 3D tracking algorithm. Journal of the Royal Society Interface. 2013; 10(87):20130459. Lamina cribrosa visibility using optical coherence tomography: comparison of devices and eff ects of image enhancement techniques. Girard MJ, Tun TA, Husain R, Acharyya S, Haaland BA, Wei X, Mari JM, Perera SA, Baskaran M, Aung T, Strouthidis NG. IOVS 15;56(2):865-74.

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www.seri.com.sg Visual Neurosciences Research Group

The Visual Neurosciences Research Group is interested in the neurobiological interactions between the eyes and the brain and aims to translate fundamental scientifi c knowledge into clinical settings. More specifi cally, our group is investigating the visual, and non-visual behavioral and physiological consequences of clinical conditions aff ecting the retina and the optic nerves, including glaucoma, as well as other infl ammatory, compressive, hereditary optic neuropathies. Through our collaboration with the Neuroscience and Behavioral Disorders group at Duke-NUS, we also aim to study the non-visual cerebral responses originating from the eye, using modern techniques in a sleep-lab, as well as functional neuro-imaging.

Projects: 1. Dysfunction of the intrinsically photosensitive retinal ganglion cells in ophthalmic conditions. Our initial pupilometric studies (Rukmini et al, Ophthalmology, 2015) have shown dysfunction in the melanopsin expressing retinal ganglion cells (ipRGCs) system in primary open angle glaucoma, and significant correlations with the severity of the disease. In collaboration with the Glaucoma group (Prof Tin Aung, Dr Baskaran Mani, Adj A/Prof Shamira Perera) we are currently evaluating the efficiency of chromatic pupillometry with a novel photic stimulation paradigm (implemented with Dr J Gooley, Duke-NUS), for detecting early and pre-perimetric glaucoma. We also aim to assess the functions of the intrinsically photosensitive retinal ganglion cells in other neurodegenerative and inflammatory conditions, affecting the visual pathways and the central nervous system.

2. Retinal Neurobiology of Myopia. We are currently exploring (in collaboration with Prof Wallace Foulds, Dr Veluchamy Amutha Barathi, Dr Rajamani Lakshminarayanan and Dr Ouria Dkhissi Benyahya (INSERM Unit 846, France), the impacts of dopamine and different light exposures stimulating different photoreceptors on the progression and devolvement of acquired myopia, in different animal models.

3. Cerebral Projections of the intrinsically photosensitive retinal ganglion cells. explored with functional MRI. Collaborative work with Dr Brown Hsieh (Duke-NUS) and Prof Francoise Vienot (CNRS and Museum d’Histoire Naturelle, France).

4. Hereditary optic neuropathies. Our group has recently identified patients with genetically confirmed Autosomal Dominant Optic Atrophy in Singapore, a condition which is only rarely reported in South-East Asia. Collaborations with a group of geneticists in Angers, France, have allowed identification of novel genetic mutations in the OPA1 gene, responsible not only for visual loss due to optic atrophy, but also deafness. Various other mitochondrial genetic mutations affecting the optic nerves are explored through collaborations with a team of geneticists in Angers, France, lead by Prof Reynier and Prof Procaccio.

5. Ocular motor dysfunctions associated with conditions of the afferent pathways. Evaluation of the patterns and consequences of disrupted ocular motor behaviour, studied with infrared oculography, associated with various retinopathies and optic neuropathies.

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From left to right, collaborators and group’s members: E Atalay, S Sharma, AV Rukmini, RP Najjar, D Milea, JJ Gooley, B Mani, ZL Jing

Head: Prof Dan Milea Contact Us: [email protected]

Selected Recent publications 1. Annweiler C, Milea D, Whitson HW, Cheng CY, Wong TY, Ikram K, Lamoureux EL, Sabanayagam C. Vitamin D insuffi ciency and cognitive impairment in Asians: a multi- ethnic population-based study and meta-analysis. Journal of Internal Medicine, 2016, in press. 2. Najjar RP, Zeitzer JM. Temporal integration of light fl ashes by the human circadian system. Journal of Clinical Investigations, 2016, in press. 3. Rukmini AV, Milea D, Baskaran M, How AC, Perera SA, Aung T, Gooley JJ. Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity. Ophthalmology. 2015;122(9):1777-85. 4. Milea D, Aung T. Flavonoids and glaucoma: revisiting therapies from the past. Graefes Arch Clin Exp Ophthalmol. 2015;253(11):1839-40. 5. Uro M, Beauchet O, Cherif M, Graff e A, Milea D, Annweiler C. Age-Related Vitamin D Defi ciency Is Associated with Reduced Macular Ganglion Cell Complex: A Cross- Sectional High-Defi nition Optical Coherence Tomography Study. PLoS One. 2015 Jun 19;10(6):e0130879. 6. Nissen C, Rönnbäck C, Sander B, Herbst K, Milea D, Larsen M, Lund-Andersen H. Dissociation of Pupillary Post-Illumination Responses from Visual Function in Confi rmed OPA1 c.983A > G and c.2708_2711delTTAG Autosomal Dominant Optic Atrophy. Front Neurol. 2015 Feb 4. 7. Ebran JM, Milea D, Trelohan A, Bonicel P, Hamel JF, Leftheriotis G, Martin L. New insights into the visual prognosis of pseuoxanthoma elasticum. Br J Ophthalmol , 2014. 8. Najjar RP, Wolf L, Taillard J, Schlangen LJM, Salam A, Cajochen C, Gronfi er C. Chronic Artifi cial Blue-Enriched White Light Is an Eff ective Countermeasure to Delayed Circadian Phase and Neurobehavioral Decrements. PLoS ONE.2014 Jul 29;9(7): e102827. 9. Ronnbaeck C, Milea D, Larsen M. Imaging of the macula indicates early completion of structural defi cit in autosomal-dominant optic atrophy. Ophthalmology, 2013 Dec;120(12):2672-7. 10. Herbst K, Sander B, Lund-Andersen H, Wegener M, Hannibal J, Milea D. Unilateral anterior ischemic optic neuropathy: chromatic pupillometry in aff ected, fellow non- aff ected and healthy control eyes. Front Neurol. 2013 May 10.

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www.seri.com.sg Translational Pre-Clinical (Animal) Model Platform

The animal models of ocular diseases continue to be an important experimental tool for SERI with the fundamental knock-out mice becoming an integral part of SERI’s research. The animal facility at the Singapore Experimental Medicine Centre (SEMC) is well-equipped with instrumentation necessary for ocular research and is an essential adjunct facility utilized extensively by SERI scientists. This group involves a multi- disciplinary team that provides expertise and instrumentation facilitating translational and basic ocular disease research using animal models. The group works with all SERI project teams that require the use of disease-specifi c animal models. They provide technical support, as well as expert guidance on the selection of the appropriate animal to be utilized as an experimental model for human ocular disease study. Many animal models are currently being explored for ongoing SERI studies. Future SERI plans involve shifting the focus to understanding the cellular, genomics, proteomics and molecular levels of major ocular diseases in both anterior and posterior segments. This will be greatly aided by both the in-vitro and in-vivo models of disease studies that would facilitate the SERI team to explore new therapeutics that are currently being developed.

First Lab Equipped With Femto-Second Laser & Technolas Excimer Laser System For Corneal Surgery Femtosecond-laser surgery on rabbit

Ocular Imaging Facilities

In-vivo Confocal Microscopy Keratometry Corneal Topography AS-OCT Slit-lamp Microscopy

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www.seri.com.sg

The animal lab is shared with SingHealth Experimental Medical Centre (SEMC) of Singapore General Hospital. SERI has 4 rooms in SEMC, which are fully equipped with ophthalmological instruments (see listing below) to aid in ocular translational research and pre-clinical testing. SERI provides comprehensive translational research expertise and facilities within the confi nes of a single institution. SERI has a highly skilled and competent personnel group. It has a well-established infrastructure to orchestrate and support research projects in accordance to the highest international standards. A team of professional staff (scientifi c, veterinarian, clinician and technical) helps support a broad range of in-vitro and in-vivo animal research. SEMC became the fi rst academic animal research facility in Singapore to be fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) in 2006.

“Understand the disease processes at the cellular and molecular level in order to design better, innovate methods and dosage for the treatment of human ocular diseases” - Research Goal

• Carl Zeiss Femtosecond Laser Suite • Heidelberg HRT Posterior Segment OCT • Retinoscopy • Baush & Lomb Technolas Excimer laser • Carl Zeiss Anterior Segment OCT • A-Scan Ultrasound for Biometry Suite • Topcon Purepoint Laser Slit lamp measurements • Heidelberg HRT in-vivo Confocal Delivery System • Carl-Zeiss OLCI AC-Master for mouse Microscope • Micron IV comprehensive suite for rodent biometry measurements • Topcon Slit-lamp microscopy with video eye research • Automated Infrared Photorefraction Set- captures function • Autorefractor up for mouse & chicken • Specular Microscope for in-vivo • Real-Time IOP device • Vitrectomy and Indirect Ophthalmoscope endothelial cell count • Tonopen for both large and small animals • ESPION & Roland ERG set-up for small • Topcon Fundus Microscope • Dissecting/Surgical Microscope and large animals

SERI has staff who are well versed in the principles of Good Lab Practice (GLP) that attributes to the quality of our animal model research. The strength of SERI Experimental & Translational / Pre-Clinical has a team mainly: Principal Investigators (18); Veterinarians (4); Clinician Scientists/Fellows (14); Research Associates (5); Research Offi cers (6); Research Assistants (6)

Head: Dr Velachamy A Barathi Contact us: [email protected]

Selected Publications 1. Lai CM, Barathi A, et al. Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys. Mol Ther 2005; 12(4):659-668. IF = 6.825. 2. Lei Zhou, Amutha Barathi, et al. Proteomic analysis of rabbit tear fl uid: Defensin levels after an experimental corneal wound are correlated to wound closure. Proteomics 2007; 7(17): 3194-3206. IF = 5.5. 3. Barathi VA, et al. Two models of experimental myopia in the mouse. Vision Res. 2008 Mar;48(7):904-16. IF = 2.2. 4. Barathi VA, Beuerman RW and Schaeff el F. Eff ects of unilateral topical atropine on binocular pupil responses and eye growth in mice. Vision Research, 2009,Mar;48(7):904-16. IF = 2.2. 5. Barathi VA, et al. Transglutaminases (TGases) in Ocular and Periocular Tissues: Eff ect of Muscarinic Agents on TGases in Scleral Fibroblasts. PLOS One. 2011 Apr 6;6(4):e18326. IF = 4.56. 6. Remya Robinson, Barathi VA, et al. Fluvastatin Downregulates VEGF-A Expression in TNF-∂ –Induced Retinal Vessel Tortuosity, 2011 Sep 27;52(10):7423-31 IOVS. IF: 3.431. 7. Remya Robinson, Barathi VA, et al. Current update on animal models of diabetic retinopathy. 2012. Dis Model Mech. 2012 Jul;5(4):444-56. IF: 4.584. 8. Fan Q, Barathi VA. et al. Genetic variants on chromosome 1q41 infl uence ocular axial length and high myopia. PLoS Genet. 2012 Jun;8(6):e1002753. Epub 2012 Jun 7. IF: 9.543. 9. Lai CM, Barathi VA, et al. Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates. Gene Ther. 2012 Oct;19(10):999-1009. IF: 4.5. 10. Khanh-Nhat Tran-Viet, Barathi VA, et al. Identifi cation of a Novel Gene for Autosomal Dominant High-Grade Myopia Using Whole Exome Sequencing. Amr J Hum Genet, 2013 May 2;92(5):820-6. IF: 11.202.

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www.seri.com.sg Ocular Proteomics Support Platform

The Ocular Proteomics Laboratory is a core platform in Singapore Eye Research Institute (SERI) and provides expertise and instrumentation in cutting-edge proteomics and metabolomics research. Established in 2004, the Ocular Proteomics Laboratory has focused on application of proteomics to clinical samples from the eye to fi nd new biomarkers and understand the disease. Additionally, we collaborate with other research groups within Singapore Eye Research Institute/Singapore National Eye Centre and off er a broad range of proteomics/metabolomics and biological mass spectrometry (MS) services, including protein identifi cation, quantitative proteomics (iTRAQ, high resolution - MRM, SWATH, etc.), characterization of post-translational modifi cations (PTMs), MS-based non-targeted and targeted metabolomics, and drug analysis. Recently we have been asked to participate in the Human Proteome Organisation (HUPO) Eye Proteome project which aims to establish the human eye proteome database.

Facility Capability • AB SCIEX TripleTOF 5600 Mass • Protein identifi cation (identify proteins from a gel band, or whole proteome) Spectrometer • Quantitative proteomics and proteomic profi ling (iTRAQ, mTRAQ, high-resolution • Dionex UltiMate 3000 RSLCnano MRM, SWATH, etc.) system • Post-translational modifi cation discovery (glycosylation, phosphorylation, • AB SCIEX API 2000 MS/MS system acetylation, methylation, etc.) • Waters 2695 HPLC system • MS-based metabolomics • Waters Acquity UPLC I-Class system • Small molecule quantitation (drug level, targeted metabolomics, etc.)

OCULAR PROTEOMICS IN SERI

2 PATENTS 3 PATENTS

Developing Developing Biomarkers for Clinical Antimicrobial Peptides Diagnosis

Cornea Wound Cornea Infections Rabbit Model Human Dry Eye Human

Keratoconus Human Myopia PROTEOMICS Mouse Model PLATFORM

Lacrimal Gland Tumor Human

Diabetic Retinopathy Glaucoma Medication Human LASIK Human Human

Thyroid Eye Disease Human

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www.seri.com.sg

One of our focuses is on tear fl uid proteomics and metabolomics. We believe that tear fl uid is a useful source for discovering biomarkers associated with the various components of the lacrimal functional unit because of the close relationship of tears to the disease sites. Recent studies by our group showed that more than 1500 proteins and 60 small molecule metabolites were identifi ed in healthy human tears using the latest proteomics and metabolomics technology. This comprehensive tear composition repertoire can be served as a background for future biomarker research of ocular diseases. The current biomarker research projects which use tears as the source are: • Validation study of tear biomarkers for dry eye • Epidemiologic studies of tear proteomics in normal Chinese, Malay and Indian population • Tear proteomic profi les in post-LASIK (Laser in-situ keratomileusis) dry eye • Eff ect of glaucoma medication on tear protein profi les and use them as biomarkers to predict the risk of glaucoma surgical failure • Tear biomarkers in lacrimal gland tumor • Tear proteomic profi les in thyroid eye disease • Tear proteomic profi les in keratoconus Other important proteomics/metabolomics projects include: • Integrated “Omics” in ocular important drug-resistance pathogens • Circulating biomarkers in diabetic retinopathy using a metabolomics approach • Molecular mechanism of myopia and atropine treatment in a mouse model using quantitative proteomics • Vitreous proteomic profi le in diabetic retinopathy

Head: Dr Zhou Lei Contact Us: [email protected]

Selected Recent Publications 1. Chen L, Cheng CY, Choi HW, Ikram MK, Sabanayagam C, Tan GS, Tian DC, Zhang L, Venkatesan G, Tai ES, Wang JJ, Mitchell P, Cheung CM, Beuerman RW, Zhou L*, Chan ECY*, Wong TY*. Plasma Metabonomic Profi ling of Diabetic Retinopathy. Diabetes. 2016, Accepted. (IF = 8.474). * Corresponding author. 2. Chen L, Li J, Guo T, Ghosh S, Koh SK, Tian D, Zhang L, Jia D, Beuerman RW, Aebersold R, Chan EC, Zhou L*. Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress. Journal of Proteome Research. 2015, 14, 3982-3995. (IF = 5.001). *Corresponding author. 3. Tong L, Zhou XY, Jylha A, Aapola U, Liu DN, Koh SK, Tian D, Quah J, Uusitalo H, Beuerman RW, Zhou L*. Quantitation of 47 Human Tear Proteins using High Resolution Multiple Reaction Monitoring (HR-MRM) Based-Mass Spectrometry. Journal of Proteomics. 2015, 115, 36-48. (IF =5.080). *Corresponding author. 4. Barathi VA, Chaurasia SS, Poidinger M, Koh SK, Tian D, Ho C, Iuvone MP, Beuerman RW, Zhou L*. Involvement of GABA transporters in Atropine-treated Myopic Retina as revealed by iTRAQ Quantitative Proteomics. Journal of Proteome Research. 2014, Nov. 7; 13(11): 4647-4658. (IF = 5.001). *Corresponding author. 5. Zhou L*, Wei Ruihua, Zhao Ping, Koh Siew Kwan, Beuerman Roger W, Ding Chuanqing, Proteomic Analysis Revealed the Altered Tear Protein Profi le in a Rabbit Model of Sjögren’s Syndrome-Associated Dry Eye. Proteomics, 2013, 13(16), 2469-2481. *Corresponding author. 6. Zhou L, Beuerman RW. Tear analysis in ocular surface diseases. Progress in Retinal and Eye Research, 2012, 31(6), 527-550. (IF = 11.207). 7. Zhou L*, Zhao SZ, Koh SK, Chen L, Vaz C, Tanavde V, Li XR, Beuerman RW. In-depth analysis of the human tear proteome. Journal of Proteomics, 2012, 75(13), 3877-3885. (IF = 5.080). *Corresponding author. 8. Chen L, Zhou L*, Chan E, Neo J, Beuerman, RW, Characterization of The Human Tear Metabolome by LC-MS/MS. Journal of Proteome Research. 2011, Oct 7;10(10):4876-82. (IF = 5.617). *Corresponding author. 9. Wong TT, Zhou L, Li J, Tong L, Zhao SZ, Li XR, Yu SJ, Koh SK, Beuerman RW, Proteomic profi ling of infl ammatory signaling molecules in the tears of patients on chronic glaucoma medication, Invest. Ophthalmol. Vis. Sci. 2011, Sep 22;52(10):7385-91. (IF = 3.933). 10. Zhou L, Liu SP, Li J, Ong LB, Guo L, Wohland T, Tang C, Lakshminarayanan R, Mavinahalli J, Verma C, Beuerman RW. The structural parameters to antimicrobial activity, human epithelia cell cytotoxicity and killing mechanism of 10-AA synthetic analogues and covalent dimer derived from hBD3 C-terminal. Amino Acids. 2011 Jan;40(1):123-33. (IF = 4.106).

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www.seri.com.sg Experimental Microscopy Support Platform

The newly established Experimental Microscopy Sub-platform provides collaborative and advisory assistance for scientists in Singapore Eye Research Institute/Singapore National Eye Centre to use high resolution imaging for their research programs. To conduct fundamental and advanced research relating studies of morphological and expression characteristics to biological and material properties, the platform is equipped with “state of the art” light, stereo and confocal microscopes, including

Facilities • Carl Zeiss AXIOVERT 200 Motorized Microscope (AxioVision 4.8) • Carl Zeiss AXIOPLAN 2 Imaging Microscope (AxioVision 4.8) • Carl Zeiss AXIO Imager System with ApoTome (AxioVision 4.7.1) AXIO Imager System • Nikon C2 Confocal Laser Point Scanning System (NIS-Elements Ar-4) • BioRad ZOE Fluorescence Cell Imager AXIOVERT Motorized Microscope System • Nikon SMZ1500 Stereomicroscope • Nikon Eclipse TS100-F Stereomicroscopes (NIS-Elements D)

Most of them are outfitted with digital imaging to allow investigator to quickly use images for manuscripts, presentations and grants.

C2 Confocal Microscope System ZOE

Capabilities • Live cell and time-lapse imaging (cellular dynamics for biological functions) • Fluorescence microscopy (target protein expression in sub-cellular structures and single molecule tracking and quantification) • Phase contrast/differential interference contrast DIC microscopy (contrast-enhanced topographic imaging) • Confocal microscopy (high-resolution point scanning imaging for 3D image reconstruction) • Polarized light microscopy (anisotropy, birefringence composition) • Stereomicroscopy (for close work and micro-dissection) Manpower This platform has a team supported by Scientists, Research Offi cers and Laboratory Executives, who are committed to ensuring a high standard of research excellence and facility support.

Collaborators • Advanced Bio-imaging Core Platform, Academia, SingHealth • Electron Microscopy Unit, National University of Singapore (transmission and scanning electron microscopy, atomic force microscopy, cryosectioning and immunoelectron microscopy) • NanoCore, National University of Singapore (helium ion microscopy) • Institute of Molecular and Cell Biology, A*STAR Singapore (laser capture micro-dissection)

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www.seri.com.sg

Head: Dr Gary Yam Contact Us: [email protected]

Selected Recent Publications 1. Lee MC, et al. Expression of the primary angle closure glaucoma susceptibility gene PLEKHA7 in endothelial and epithelial cell junctions in the eye. Invest Ophthalmol Vis Sci. 2014 May 55(6):3833-41. 2. Yam GH, et al. Ex vivo propagation of human corneal stromal “activated keratocytes” for tissue engineering. Cell Transplantation 24(9), 1845-61 (2015). 3. Chaurasia SS, et al. Hevin plays a pivotal role in corneal wound healing. PLoS One. 2013 Nov 26;8(11):e81544. 4. Zhang T, et al. The eff ect of amniotic membrane de-epithelialization method on its biological properties and ability to promote limbal epithelial cell culture. Invest Ophthalmol Vis Sci. 2013 Apr 30;54(4):3072-81. 5. Tan XW, et al. In vivo biocompatibility of two PEG/PAA interpenetrating polymer networks as corneal inlays following deep stromal pocket implantation. J Mater Sci Mater Med. 2013 Apr;24(4):967-77. 6. Chaurasia SS, et al. Eff ect of fi brin glue on biomechanical properties of human Descemet’s membrane. PLoS One. 2012;7(5):e37456. 7. Seet LF, et al. Involvement of SPARC and MMP-3 in pathogenesis of human pterygium. Invest Ophthalmol Vis Sci. 2012 Feb 2;53(2):587-95. 8. Peh GS, et al. Cultivation of human corneal endothelial cells isolated from paired donor corneas. PLoS One. 2011;6(12):e28310. 9. Riau AK, et al. Nanoscale helium ion microscopic analysis of collagen fi brillar changes following femtosecond laser dissection of human cornea. J Biomed Nanotechnol. 2014 Aug;10(8):1552-62.

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www.seri.com.sg Data Science and Data Management Platform

Both data science and data management units serve to support all research themes across SERI that requires data collection, database management, statistical analysis, inference and reporting. Data Science Platform The data science team in SERI consists of a group of experienced statisticians with background in epidemiology, clinical trials and genetics analysis. What we do? The data science team is essential in the support of research platforms across all themes that require planning and analysis of experiments. The overall coordination and assignment of statisticians to research projects from various research themes will be managed by the statistics manager who will also monitor research projects and workload. Principal investigators, clinician scientists, research fellows from all research platforms are able to tap onto the statistics expertise of the team: 1. Study design and planning: Discussion with principal investigators/clinician scientists/research fellows to understand their research aims and to assist in the planning and design of their research study. Sample size and power calculations will be performed. Statistical analysis plans and statistical sections for grant application will be drafted by statisticians. 2. Statistical analysis and reporting: Primary and secondary analysis will be conducted to investigate research aims. Statisticians will collaborate in the writing of reports, abstracts and manuscripts as well as assist in reviews. Further insights and sub-group analysis will be investigated. 3. Statistical consulting: Provide an avenue to discuss and resolve ad-hoc statistical questions or post-hoc analysis for researchers in all themes. 4. Statistics workshop: Introductory statistics sessions could be conducted for researchers who would like to learn statistical software to perform their own analysis. The data science team have been actively involved in large population based studies such as Singapore Eye Epidemiology Disease (SEED) programme, and have established good collaboration within SERI, SNEC and other academic and research institutes such as NUHS, TTSH and Duke-NUS. In order to further upgrade the capability within the team, internal research meetings are conducted regularly to learn, share and discuss on statistical methods, problems and new methods with mentorship from statistics professors in NUS and Duke-NUS.

Contact Us Head: Prof Cheng Ching-Yu at [email protected] Contact Details: Prof Cheng Ching-Yu at [email protected] Team Members: Dr Htoon Hla Myint (Research Scientist) Mr Nguyen Duc Quang (Biostatistician) Dr Marco Yu (Senior Statistician) Ms Chee Miao Li (Biostatistician)

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www.seri.com.sg

Data Management Platform Data Management Unit (DMU) serves to support all research and clinical studies across SERI and SNEC that requires complete data management starting from Case Report Form designing to preparation of cleaned datasets. DMU is fully trained for • Best DM practices, Data Management policies and procedures • Programming and computerized system validations to ensure high quality and well organized databases with thorough documentation. At present, DMU is working on numerous SERI and SNEC projects from database design to data entry, quality checks and maintenance. DMU consists of Assistant Director, Database Programmer, Data Coordinator, Data Management Offi cers along with Temporary Data Management Assistants working on large population based epidemiological cross- sectional studies, cohort studies, clinical trials, genome- wide association studies, laboratory data and other projects with various organizations such as NUHS, NUS and overseas projects besides SERI and SNEC. Besides clinical research projects, DMU is involved in developing robust electronic data capture system (EDC) required for various departments in SERI and SNEC using object-oriented programming languages.

Overview of Data Management Workfl ow

PI / Co-PI Discussion with Edit Checks & Data Archive & DB Manager Final QC Backup

Data Cleaning Final Dataset to CRF Design & Final Query PI/Statistician Resolution

Develop DB, Query Data Dictionary Resolution & Report Generation & DM Plan Data Updating

QC Document QC on Data CRF Filing into Preparation & Study Collection and Data Complete DM MRO DM Orientation Entry Documentation

Contact Us Team Members: Ms Anandaraj Anita Ms Sophia Man She Yunn Head: Prof Ecosse Lamoureux Ms Farjana Begum Email: [email protected] Ms Habibah Banu binte Zakir Hussain Assistant Director: Ms Sangeetha Nagarajan Ms Nurul Huda binte Ramli Email: [email protected] Ms Fatimahtul Zuhra bte Yacob Marican

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www.seri.com.sg SERI Graduate Academy

SERI Graduate Academy is an education collaboration of Singapore Eye Research Institute with various local and international research institutions, universities and industrial partners forming specialized education centres that propels SERI’s vision in academic ophthalmology. As SERI recognizes that human talent is the key factor in the development of scientifi c and biomedical research in vision and the ocular realm, the Academy aims to meet the requirements of the eye research institute of the next decades by launching and supporting quality education initiatives in eye research.

SERI Graduate Academy’s Strategic Initiatives The Academy has a comprehensive approach in the development of manpower in eye research, focusing on translational and clinical sciences relevant to ophthalmology. As of 2018, SERI has a full time staff more than 196, excluding the adjunct research and clinical staff . It has supported the development and training of more than 100 students and fellows in the last 21 years. SERI Graduate Academy taps into a network of potential trainees and applicants from research and health centres from Singapore and all over the world, via its education brochure and recently enhanced website, to identify the critical talent of tomorrow.

Fellowships, Traineeships and Attachments In line with its eff orts to develop scientifi c talent for SERI, the Academy off ers a variety of programs and scholarships to nurture people from young students and undergraduates to postdoctoral fellows. This includes research internships with education centres such as polytechnics and universities, medical undergraduate research attachments, PhD studentships in conjunction with various universities and National Research Foundation, short term overseas fellowships with National Medical Research Council and Ministry of Health, SingHealth fellowship awards and Singapore National Eye Centre education awards, post-doctoral training fellowships, research training programmes for ophthalmic residency and various visiting professorships. Recently SERI Academy has played pivotal roles in setting up a PhD scholarship as well as a clinician-scientist residency research program.

SERI Graduate Academy Partners SERI Graduate Academy collaborates with universities such as the National University of Singapore, the Duke-NUS Medical School, and the Nanyang Technological University. It is also involved in major partnerships with prestigious research institutes such as the A*STAR research institutes and various industrial partners such as Pfi zer, Novartis, Allergan and Alcon.

International Advisory Panel (IAP) SERI has an IAP which consists of several prominent academic staff from internationally renowned universities, and the role of the IAP is to advise SERI on its education and development programmes, to ensure that these meet an internationally competitive standard.

Head: Prof Louis Tong Contact Us: [email protected]

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www.seri.com.sg Research Clinic

Conducting Clinical Trials at SERI The Singapore Eye Research Institute (SERI) is pre-eminent in its position as a centre for leading ophthalmic and vision research in Asia- Pacifi c. Our multiple collaborations with renowned local and international research and academic institutions, pharmaceutical, biotechnology, as well as other industry organizations, serve as a testament to the quality and credibility of the research conducted at SERI. The SERI Research Clinic is a research facility that houses several consultation rooms with specialist “state-of-the-art” equipment and “cutting-edge” tools to conduct comprehensive clinical trials and research studies. This is further supported by a symbiotic network of research personnel, including a dedicated team of research fellows, optometrists, coordinators, nurses, imaging technicians, data entry personnel and statisticians, as well as ophthalmologists from the various public-centre eye hospitals i.e. SNEC, NUHS, TTSH etc. This research team is able to conduct a wide range of long and short term studies, encompassing the entire spectrum of FIM (First -In-Man) phase I to phase IV clinical trials for drugs, implants and devices. Since its inception in 1997, the SERI Research Clinic has performed more than 500* clinical and epidemiology studies (including more than 100* random controlled trials) and evaluating visual impairment in the community. Today, the SERI Research Clinic typically has more than 100* on-going studies (encompassing clinical trials and research studies, epidemiology studies, ocular imaging studies, Health Services Research studies etc.) at any one time.

Facility Description Located over one fl oor of the Singapore National Eye Centre (the largest eye specialist centre in Singapore) and with a well-equipped and patient-friendly environment, our facility includes: • 6 consultation rooms including refraction rooms, all equipped with phoropters and slit-lamp biomicroscopes with applanation tonometers. • An in-house pharmacy and an Investigational Products (IP) room with the appropriate and secure drug storage refrigerators and cabinets. • Ample and secure storage facility with freezers for biological samples/ specimens. • State-of-the-art equipment such as the Optical Coherence Tomography (e.g. Spectralis, Cirrus and CASSIA OCT for posterior segment imaging, Visante OCT for anterior segment imaging), Ultra Biomicroscopy (UBM), Confocal Microscopy, Heidelberg Retinal Tomography (HRT II) and HRT III, Specular Miscroscopy, IOL Master, Dynamic Vessel Analyser, Humphrey Visual Field Analysers, Ocular Response Analyzer (ORA), Pneumatonometer, RAPDx pupilometer, Retcam, CORVIS, LipidView, LipidFlow and digital ophthalmic cameras such as the slit lamp and retinal cameras (e.g. Fundus Fluorescein Angiography (FFA) and Indocyanine Green Angiography (ICG)) are also available. • A robust and systematic schedule of equipment inspection and maintenance, to ensure the smooth and eff ective conduct of all trial-related activities. Manpower Resources Committed to ensuring a high standard of research excellence, our more than 50 study personnel, includes clinical research fellows, optometrists, coordinators, nurses, data management and statistical support teams, are CITI-certifi ed and GCP-trained. In most instances, a clinical trial conducted at the SERI Research Clinic will be assigned a team comprising of the following personnel: • Principal Investigator • Clinical Research Coordinator • Data management and statistical support • Project Manager • Research Optometrist expertise, as and when required. • Co- Investigators • Clinical Trial Coordinator

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www.seri.com.sg

Clinical Trials Capabilities SERI has the expertise and experience to conduct all forms of ophthalmic and vision research clinical trials/studies, involving both drug-related and/or medical devices, in all of the sub-specialties including:

• Corneal Diseases & Refractive Surgery • Cataract • Glaucoma • Ocular Infl ammation / Uveitis • Neuro-Ophthalmology • Oculoplastic • Pediatric-Ophthalmology • Retinal Diseases • Optometry • Health Service Research • Epidemiology studies • Dry Eyes

Participant Recruitment The SERI Research Clinic personnel are diligent and experienced in recruiting study participants, with emphasis on personalised attention, as well as strict adherence to the highest ethical standards. This has resulted in our studies enjoying a high and exemplary retention rate, as well as a cohort of happy and compliant study participants. The centralised location and the easy accessibility to the eye clinics at the Singapore National Eye Centre, as well as Singapore’s multi-ethnic (Chinese, Malay, Indian and Caucasian) population, makes the SERI Research Clinic one of the most ideal and conducive hub to conduct impactful and successful clinical trials and research studies. As the comfort, safety and well-being of our study participants are of paramount importance to us, we consistently solicit feedback from them, in the form of surveys and questionnaires, so as to continuously improve our services and concurrently ensure a safe and comfortable environment for all our study participants. The SERI Research Clinic remains steadfast in its unwavering commitment to address sight-threatening disorders within our society and across Asia. This is clearly refl ected in our concerted and sustained eff orts to conduct high quality and impactful clinical trials/ research studies, with the ultimate aim to tackle and combat the region’s most prevalent eye diseases. In this quest of ours, we are humbled and remain grateful to our study participants who have supported and participated in our studies, and remain the focus of our research.

Support Services by SERI Administration (in conjunction with research conducted at the SERI Research Clinic) • Sponsor liaison/contact point • Feasibility queries and negotiation of research-related legal contracts • Consultation on study costs/budget and pricing of research at SERI/SNEC, as well as assistance to formulate and formalize study budgets • Logistics, administrative and planning support for new studies, including the required due diligence in terms of ethical (IRB), legal and regulatory (HSA) requirements • Development of knowledge transfer, intellectual property management, technology exploitation and commercialization activities. • Advice and information on funding opportunities • Administration of peer-reviewed competitive grants, as well as intra-mural grants i.e. from initial point of submission to the disbursement of funds and concurrent claims to funding body

Head: Prof Aung Tin Director, Research Clinic: Dr Baskaran Mani Contact Us: Prof Aung Tin at [email protected], Dr Baskaran at [email protected]

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Technology Development and Commercialization Offi ce

Background

SERI researchers continuously produce world-class results that have received widespread international recognition. In addition to generating an impressive publication track record and a growing reputation, the outcomes of this research include multiple commercially promising technologies which we are looking to bring to market, either via licensing to industry or via spin- off s. The SERI Technology Development and Commercialization (TD&C) offi ce proactively pursues the translation of SERI’s research into tangible products - encompassing therapeutics, devices, diagnostics and software.

The TD&C offi ce serves as a one-stop support entity for all technology transfer and business development activities, working closely with academics, clinicians and industrial partners to bring potentially impactful ideas to market. We are involved in commercialization of technologies emanating from the entire breadth of our scope of research; often beginning the process with ideas are still in the infancy of development, reviewing inventions to explore potential applications, evaluating technical and commercially-related risks, establishing development and commercialization strategies (including locating development and strategic partners), and providing support on IP protection together with the SingHealth IP offi ce. Our entrepreneurial approach and diverse expertise enable us to drive the development of our promising technologies to create social and economic impact, always seeking to bring value to patients.

We believe fi nding the right industrial partner is key to taking an invention to marketplace. As such, the team forms a channel through which inquiries regarding potential external collaborations fl ow in and reach SERI research staff , as well as being central to facilitating, formalizing and developing these research activities from a commercial point of view. It is also involved in external communications towards key stakeholders with regard to commercialization, aiming to attract further industry and academic partners to form collaborations with SERI.

The TD&C team further oversees the operation of the SNEC ophthalmic technologies incubator. This framework is intended to facilitate the close, focused, fl exible and rapid nurturing and development of a series of technologies which will later form a string of medical technology companies. Building on the continuously growing SERI IP portfolio, these technologies arise from diverse domains, including devices, therapeutics, software and diagnostics, giving SERI a unique portfolio which has market attractiveness in a wide range of fi elds. Incubator and other SERI and SingHealth staff provide administrative, fi nance, market research, business planning, legal and IP support as well as links to potential industry and funding partners.

Contact Us: The SERI TD&C offi ce seeks to engage any party, industrial or academic, which has an interest in collaborating with SERI on commercially-oriented ophthalmology research projects. We can provide information regarding SERI’s research interests, licensable IP, the commercializable research currently underway, our common models of collaboration, as well as arrange for more in-depth contacts with SERI researchers and clinicians from the Singapore National Eye Centre. If you have an interest in working with SERI to bring promising ophthalmic technology to the market, we welcome your inquiry and look forward to hearing from you! Danny BELKIN XiaoQin FANG Cassandra LIM Director, TD&C Senior Manager, TD&C / SNEC Administrative Executive, TD&C Email: [email protected] Incubator Email: Email: [email protected] Tel: +65 6576 7214 [email protected] Tel.: +65 6576 7253 Tel: +65 6576 7252 Tarun Kumar MAHESHWARI Alvin KOK Senior Manager, TD&C Senior Manager, TD&C Email: [email protected] Email: [email protected] Tel.: +65 6576 7254 Tel.: +65 6576 7257

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www.seri.com.sg Administration, Research Aff airs & Support Services Platform

An integrated part of SERI, this platform works in partnership with the SERI faculty to provide a multi-spectrum and comprehensive administrative support to facilitate world-class research and knowledge transfer.

In this context, the Administrative core serves as “enablers” i.e. to enable SERI to effi ciently fulfi ll its purpose in accordance with its pre-determined strategies in key areas of research. In line with this role, the administrative core provides comprehensive support (encompassing fi nance, human resource, corporate aff airs, research administration, as well as philanthropy and development), to meet the research needs of SERI so as to ensure its continued success and sustainability. This support is multi-prong as not only does this platform provide core administrative, operations and systems support, it further facilitates in the nurturing process of research talents and the cultivation of a robust research culture through concerted communications initiatives and stakeholder engagement. In essence, this core remains integral in supporting the entire length and breadth of SERI’s research and its potentially impactful outcomes.

An overview of this platform’s scope of responsibilities include the following: • Remit encompasses the entire Administrative, Human Resource, Finance, Operations, Research Aff airs and Philanthropy Development portfolios. • Responsible for the tabulation and monitoring of SERI’s research outcomes and key performance indicators on a regular basis, so as to ensure that the stipulated parameters are met, in line with SERI research aspirations. • Assists with the implementation and monitoring of the Institute’s SOPs, strategies, as well as short and long-term plans, so as to ensure the effi cient and smooth operations of the Institute. • Renders support for all Finance and Accounting functions, as well as the monitoring and tabulation of SERI’s CAPEX, manpower as well as the annual operating budget. • Extends support for the overall provision of Human Resources services (including recruitment and retention), policies, and promotes talent development programs that have high value-add and are knowledge-based. • Supports the diverse aspects of research administrative functions for SERI, including ethics/regulatory and legal governance; SOPs and compliance, research fi nance and trial budgeting, intellectual property and commercialization, quality assurance, organization of research-specifi c events, conferences and meetings. • Provides comprehensive support for SERI’s fundraising and development activities via the execution of a purposeful development plan, and managing all fund-raising initiatives and related charitable or development projects for the Institution. • Acts as the point of contact and key liaison between diff erent collaborators across Singapore, as well as funding bodies such as NMRC, BMRC, NRF, A*STAR and other external agencies. • Performs grant administration and management duties, and reports grant outcomes to funding bodies. This includes monitoring and tracking the budget of each project and acting as pre-emptive prompter for under-utilized budgets, or over-spending of budgets, and so on. • Responsible for all corporate, communication and branding eff orts, including the conceptualization of branding collaterals for professional meetings, seminars and conferences.

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Administration, Research Aff airs & Support Services: Our Capabilities

Feasibility/NDA Contract Negotiation/ RCA/Patents Legal Issues

Ethics/Regulatory/ Finance Research Database/ Insurance Management Outcome Tracking

Corporate Study/Budget/ Grant Management Communication/ Cost Tabulation Events Management

Director, Administration, Research Affairs & Support Services: Dr Vandana Ramachandran Contact Us: [email protected]

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Overview SIPRAD is Singapore’s strategic response to the unmet medical needs of the global population suff ering vision loss due to retinal angiogenic diseases (RAD). Retinal angiogenic diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR) and diabetic macular edema (DME) represent the leading causes of vision impairment in developed countries.

Our Vision To develop an industry standard platform in retinal angiogenic diseases that leverages SERI & IMCB’s complementary expertise in clinical and pre-clinical science, with an aim to identify and validate novel biomarkers and targets, and evaluate potential anti-angiogenic therapeutics in partnership with the pharmaceutical industry.

Age-Related Macular Degeneration Diabetic Retinopathy

SIPRAD – An Integrated Entity

Aims • To conduct clinical studies in order to identify new biomarkers and targets underlying RAD • To investigate a portfolio of 10-20 previously identifi ed targets, and to validate their roles in RAD; to establish new relevant RAD animal models based on the most promising new targets • To collaborate with industry in drug repurposing for RAD

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SIPRAD Capabilities Overview

Pre-Clinical Clinical Industrial Alignment & Business Development

In Vitro Cell-Based Assays Large, well characterized cohorts -Human Retinal Microvascular of AMD and DR subjects with Leverage and align SERI & IMCB Endothelial Cell Proliferation biosamples available expertise to create a unique “Target Assay to Clinic” platform -Vascular Cell Migration Assay Ability to rapidly execute clinical recruitment and trials with an established & experienced clinical Aligns its operations with industry Ex Vivo Organotypic Culture standards (timelines, communication, research team -Choroid Sprouting Assay and deliverables) -Metatarsal Assay Extensive relationship with local & overseas institutions enabling Focus on communication, culture Rodent Models of RAD including multi-centre eff orts of urgency and hires with industrial Transgenic Mouse Model experience (Akimba, Akita, Kimba)

Clinical, imaging and blood biomarkers can be used to identify New Rabbit RAD Models Adopt Dual Business Model (CRO and potential diagnostic, prognostic and Discovery Business Models) to increase therapeutic targets potential Return on Investment (ROI) Non-human Primate Laser- Induced CNV GAMA (Genetics of AMD in Asians) consortium with 6300 AMD cases and 16,000 controls from around Proteomics and Bioinformatics Asia

Choroid Sprouting Assay Akimba Mice Vascular Leakage Rabbit Retinal Neovascularization

SIPRAD Team SERI IMCB Prof Wong Tien Yin (PI) Prof Hong Wanjin (Co-PI) Assoc Prof Gemmy Cheung Prof Walter Hunziker Dr Gavin Tan Asst Prof Wang Xiaomeng Prof Cheng Ching-Yu Dr Wang Haishan Dr Veluchamy Amutha Barathi Dr Jayantha Gunaratne Dr Assoc Prof Yasuo Yanagi Vladimir Korzh Dr Zhou Lei Dr Tom Carney Dr Vinay Tergaonkar Asst Contact us: Prof Choi Hyungwon Senior Manager Dr Srivani Sistla [email protected]

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