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Translational Asian Age-related macular degeneration Programme (TAAP)

Overview

This programme is a multi-modal, multi-dimensional approach to understanding Age-related Macular Degeneration (AMD), through the integrated expertise of retinal specialists, clinician-scientists, and basic scientists from across major research institutes in Singapore, as well as other countries in Asia and beyond.

AMD is a major cause of vision loss, which leads to enormous socioeconomic and healthcare costs. The numbers affected is rising rapidly, due in part, to an ageing population. A subtype called polypoidal choroidal vasculopathy (PCV) makes up 50% of AMD in Asians, but current understanding of this subtype remains limited.

The Translational Asian Age-related macular degeneration Programme (TAAP) is an ambitious “bench-to-bedside-to-population” programme with 5-inter-linked themes which addresses key research questions aligned to clinical needs and strong industry interest:


  • Theme 1 (Population Health) will determine how common AMD/PCV is and the factors leading to increased risk of AMD/PCV in Asians to help plan future preventative interventions.

  • Theme 2 (Pathophysiology) will examine the underlying pathophysiological changes at the cellular/molecular/genetic level in AMD through cell-based and animal experiments.

  • Theme 3 (Novel Imaging Biomarkers) will exploit a multitude of novel imaging technologies in collaboration with industry partners to find ways in which imaging can help guide treatment to achieve better outcomes. 

  • Theme 4 (Therapy) will test and develop new therapeutic strategies through multi-centre clinical trials.

  • Theme 5 (Quality Of Life) will determine how AMD/PCV affects the quality of life among Asian patients, the cost of healthcare and also investigate the effect of new behavioral therapy to improve coping strategies among patients.


TAAP will build on the strong track record of the team of investigators and their ongoing international collaborative network and strong industry support. The broad-based research proposed has high potential for commercialisation and significant clinical and population outcomes that will lead to reduction of blindness reduction caused by AMD, by 20% within 10 years. TAAP is aligned to the Ministry of Health’s (MOH) priorities in “ageing” and “precision medicine”.


Our Vision

TAAP: targeted at addressing Unmet Needs

FOCUS: Broad-based, bench-to-bedside-to-population, addressing clinical gaps

TEAM: International, multi-disciplinary team of clinicians, clinician scientists and researchers across all healthcare institutions in Singapore, with leading Asian collaborators with a strong track record in Asian AMD research


Theme Title Unmet Needs Deliverables
Population HealthNo data on long-term epidemiology, disease burden and risk factors among Asians
  • Characterise disease burden and risk factors

  • Facilitate 'precision' public health strategies
PathophysiologyIncomplete understanding of complex mechanisms
  • Understand new disease pathways  and translate to clinical and commercialisation outcomes
Novel Imaging BiomarkersLack of biomarkers for Asian AMD detection and treatment response
  • Develop novel imaging technology for biomarkers
TherapyHigh retreatment burden, lack of long-term outcome data, purely driven by industry
  • Asian-specific clinical trials to test 'personalised medicine' and cost-effective strategies
Patient-Centered OutcomesFunctional, cognitive psychosocial impact remains unclear
  • Improve patient-centered outcomes
        

Clinical and Healthcare Significance

The objective of the proposed TAAP programme is to address the unmet clinical and population need through a broad-based inter-linked “bench to bedside to population” approach, which will enhance our understanding of not only the basic mechanisms of AMD and PCV, but also translate basic research into clinical studies and commercialisation outcomes, develop novel imaging diagnostics, improve therapeutic strategies as well as lay the foundation for future cell-based therapy and rehabilitation technologies. The improved health outcome for patients with AMD would significantly reduce the financial burden on both the individuals as well as the population at large. The proposed multi-disciplinary research project will improve coordination and collaboration of research efforts across Singapore and other Asian countries, and lead to the establishment of national infrastructure platforms and coordinated services for AMD, within the region.


Aims
The overall aim of Theme 1 is to determine the long-term incidence and progression of AMD in Asians, and characterise the unique environmental, dietary, and genetic risk profiles of AMD among Asian populations. The long-term goal is to facilitate ‘precision public health’, by providing the right intervention to the right population at the right time in the future. 

Hypothesis: Asians have unique AMD epidemiology and risk profiles (e.g., dietary and genetic factors) that differ from White populations. There is ethnic difference in AMD incidence and progression among Asian subgroups.

The overall aim of Theme 2 is to understand the pathophysiological mechanisms underlying metabolic dysfunction, polarised macrophages/monocytes and epigenetic changes in nAMD/PCV. 

Hypothesis: AMD/PCV susceptibility gene variants, metabolic dysfunction, abnormal immune activation and inflammatory response play key roles in the development and progression of AMD/PCV, therefore, are potential novel therapeutic targets. Progress in understanding molecular and cellular mechanisms of AMD/PCV will facilitate the establishment of disease models that recapitulate human AMD/PCV pathophysiology, for new drug screening and target validation. 

The overall aim of Theme 3 is to develop and validate novel imaging technology for evaluating different stages of AMD and PCV, including novel qualitative and quantitative software to identify imaging biomarkers to guide treatment and stratify patients. 

Hypothesis: Using novel imaging technologies, it is possible to further characterise AMD and PCV-related changes in the retina and choroid. This will improve understanding of the pathophysiological features of AMD/PCV, provide insights into the natural course of the disease, elucidate similarities with other neurodegenerative conditions such as Alzheimer’s disease (AD) and characterise risk factors for progression. 

The overall aim of Theme 4 is to develop, test and discover new therapeutic strategies to treat AMD/PCV, and to develop personalised medicine strategies to allow individual patients to receive the most appropriate treatment choice, minimise over or under-treatment and achieve improved long-term visual outcomes. 

Hypothesis: We hypothesise that response to therapy among PCV patients is variable and that detailed study of disease phenotypes, using clinical and imaging biomarkers can better guide therapy at an individual level. 

The overall aim of Theme 5 is to determine the psychometric, epidemiological, behavioural, clinical, neuroscience and health economics impact of AMD and PCV among Asians. We will develop and validate sophisticated instruments; implement studies to better understand and quantify the patient-centred and economic impact of AMD; and investigate the cost-effectiveness of a practical model for adults with AMD and its subtypes, for improving depressive symptoms, patient outcomes and other aspects of quality of life. 

Hypothesis: Our novel instruments and approaches will provide a better understanding of the patient-centred and economic impact of AMD/PCV; and our practical problem-solving therapy model will be effective in reducing depressive symptoms and improving other outcomes while being cost-effective as compared to the current mode of care.


Research Track Record and Expertise

SERI has a long track record in leading and coordinating major, multi-site translational programmes in eye diseases with translational clinical outcomes, industry collaboration and commercialisation outcomes. We have successfully managed two previous TCR-Flagship programmes which were focused on corneal diseases and glaucoma. Our current program will extend this experience and track record to address AMD. Furthermore, the team of investigators has a significant track record of collaborative programmes focusing on Asian AMD and PCV, which have resulted in major publications including major clinical trials and clinical guidelines, co-funded by industry partners, including pharmaceutical companies. 

The TAAP programme will leverage on the significant track record in AMD/PCV research by a diverse team of clinicians/scientists/investigators. The proposed projects will build on three valuable prospective clinical cohorts that have been cultivated over the past decade, including the Singapore Epidemiology of Eye Disease (SEED) population study cohort (since 2004), the Phenotyping Asian AMD cohort of patients presenting with treatment naïve AMD (since 2009) and the follow up cohorts of patients who participated in two prospective randomised controlled trials EVEREST-II and PLANET (since 2014), thus offering a unique opportunity to evaluate long-term outcomes and influence of various biomarkers.


Lead & Theme Principal Investigator

Theme Theme Title Theme Principal Investigators(s) and Institution
1 Population Health: Characterising disease burden, novel and genetic risk factors among Asians

Prof Cheng Ching-Yu, SERI/SNEC/Duke-NUS

Prof Wong Tien Yin, SNEC/SERI/Duke-NUS

2 Pathophysiology: Understanding new disease mechanisms and pathways

Assoc Prof Wang Xiaomeng, IMCB/NTU

3 Novel Imaging Biomarkers: New technology to understand disease progression to guide treatment

Prof Leopold Schmetterer, SERI/NTU

Assoc Prof Caroline Chee, NUHS/NUS

4 Therapy: Clinical trials to test novel strategies and therapies, guided by personalised medicine

Prof Gemmy Cheung, SNEC/SERI (Corresponding and Lead Principal Investigator)

Assoc Prof Colin Tan, TTSH/NTU

5 Quality Of Life: Improving patient-centered outcomes in AMD and PCV. Prof Ecosse Lamoureux, SERI/Duke-NUS Prof Dan Milea, SNEC/SERI
Contact Person Email
1 Prof Gemmy Cheung
Lead Principal Investigator and
Theme Principal Investigator 3 & 4

gemmy.cheung.c.m@singhealth.com.sg

2 Prof Cheng Ching-Yu
Theme Principal Investigator 1

cheng.ching.yu@seri.com.sg

3 Prof Wong Tien Yin
Theme Principal Investigator 1

wong.tien.yin@singhealth.com.sg

4 Assoc Prof Wang Xiaomeng
Theme Principal Investigator 2

WangXiaomeng@ntu.edu.sg

​5 ​Prof Leopold Schmetterer
Theme Principal Investigator 3
leopold.schmetterer@seri.com.sg
​6Assoc Prof Caroline Chee
Theme Principal Investigator 3
ophv5@nus.edu.sg
​7 ​Assoc Prof Colin Tan
Theme Principal Investigator 4
Colin_Tan_SH@ttsh.com.sg
​8Prof Ecosse Lamoureux
Theme Principal Investigator 5
ecosse.lamoureux@seri.com.sg
​9 ​Prof Dan Milea
Theme Principal Investigator 5
dan.milea@snec.com.sg
                 

Co-Investigators

Singapore Eye Research Institute (SERI)
Assoc Prof Charumathi Sabanayagam, Senior Clinician Scientist

Singapore National Eye Centre (SNEC)
Dr Ning Cheung Danny, Consultant 
Dr Anna Tan, Consultant
Dr Kelvin Teo, Consultant

Duke-NUS Medical School
Prof Jie Jin Wang, Academic Medicine Research Institute
Prof Eric Finkelestein, Health Services and Systems Research Program 
Dr Sharon Cohan Sung, Clinical Sciences 
Dr Eva Fenwick, Clinical Sciences

Tan Tock Seng Hospital (TTSH)
Adj Assoc Prof Augustinus Laude, Senior Consultant, Ophthalmology 

A*STAR
Prof Walter Hunziker, Institute of Molecular and Cell Biology
Dr Roshni Singaraja, Translational Laboratories in Genetic Medicine

National University of Singapore (NUS)
Assoc Prof Christopher Chen, Pharmacology

Oversea Collaborators
University of Sydney, Australia
University of Melbourne, Australia 
Flinders University, Australia 
Beijing Tongren Hospital, China 
The Chinese University of Hong Kong, Hong Kong 
Hong Kong Eye Hospital, Hong Kong 
Taipei Veterans General Hospital, Taiwan 
Huazhong University of Science and Technology
Osaka University, Japan 
Kyoto University, Japan 
Topcon Corporation, Japan 
Nihon University Hospital, Japan 
Seoul National University Bundang Hospital, Korea 
The Catholic University of Korea, Korea 
Nanyang Technological University, Singapore
Queen’s University Belfast, UK 
Ruprecht-Karls-University Heidelberg, Germany 
Washington University School of Medicine, USA 
Duke University Eye Centre, USA 

Partners
Singapore National Eye Centre (SNEC)
Singapore Eye Research Institute (SERI)
National University Hospital System (NUHS)
Tan Tock Seng Hospital (TTSH)
Duke-NUS Medical School (Duke-NUS)
Agency for Science, Technology and Research (A-STAR)
Nanyang Technological University (NTU) 


TAAP Governance Structure



Patient and Public Engagement

This study will be of major clinical and health care interest. Our ongoing clinical studies, supported by the experienced research coordinators from SERI, have been actively engaging patients. All new patients referred for AMD and PCV are approached by our research team, who will educate patients on the disease, common treatment and expectations. This information forms part of the patient counselling and encourages patients to participate in clinical studies to help improve current understanding and treatment outcome of this potentially blinding condition. Results from our previous studies, such as smoking as a risk factor of AMD and PCV, are actively disseminated to patients and thus form an ongoing loop of understanding how translation of research to patient care occurs. 


Industry Interest

The platforms in the TAPP programme provide a rare and unique opportunity to allow clinicians and basic scientists to come together with industry players in addressing crucial medical research questions, in a multi-faceted manner. 

We have a strong, long-standing collaborative partnership with global companies with an interest in AMD and PCV. We have specific projects developed in partnership with significant industry interest including: 

  • Epidemiological and risk factor data (Theme 1) 

  • Novel candidate targets (Theme 2) 

  • Development of novel amyloid imaging technology (Theme 3) 

  • Development of novel imaging biomarkers (Theme 3)

  • Long term follow up of clinical trials (Theme 4, collaborations with pharmaceutical companies and imaging companies) 


We are keen to discuss and develop new partnerships and seek out Research and Development collaborations. 
We look forward to hearing from you. 

For TAAP scientific-related matters: 
Principal Investigator

For TAAP administrative-related matters: