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Keynote Address, GAEBA Scientific Meeting, San Diego, 14 April 2015 Developing Global Conversations in Banking

Corneal Transplantation and Eye Banking: (The Good, the Bad, and the Worst…)

Donald Tan MBBS FRCSE FRCSG FRCOphth FAMS

Arthur Lim Professor in Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School Dept of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore Senior Advisor, Singapore National Eye Centre President, Asia Society President, Association of Eye Banks of Asia Past President, Cornea Society Chairman, Asia Cornea Foundation (and… Heather Machin)

Chia-Li Pang BSC MA

Senior Manager, Singapore Executive Director, Asia Cornea Society Treasurer, Asia Cornea Foundation Financial Disclosure

I have the following financial interests or relationships to disclose:

– Carl Zeiss Meditec – Santen, Inc. – Eye-Lens Pte Ltd – Network Medical Products – – This is the Future of Corneal

PK

The “Good”… pd DALK

d DALK

Review article commissioned by The Lancet Journal

DSAEK

DMEK

DALK DSAEK DMEK

Tan DT, Dart JK, Holland EJ, Kinoshita S. . Lancet 2012 May 5:379 (9827):1749-61 Shifting the Paradigm to Selective Lamellar Keratoplasty

PK

• Much less rejection • Better vision • Stronger eye ALK EK • Less rejection • Donor advantage • Stronger eye • Better survival • Graft survival? • Good visual results • Endothelial cell loss?

• Poor visual results • Learning curve • Difficult surgery • Donor cutting • Longer surgical time • Cost

General trend globally to adopt these lamellar procedures wherever possible, but clearly major differences and trends occurring around the world, with variable adoption rates and approaches Deep Anterior Lamellar Keratoplasty (DALK)

21 yr old with RE LE Bilateral DALKs performed

RE

6/6 6/6

Stromal Rejection LE

6/6 6/6 Advantage of EK over PK: Fuchs’ Dystrophy

RE LE

DMEK PK

Bilateral blunt ocular trauma

20/20 CF Changing Trends in Keratoplasty: SNEC 1991 – 2014 The Singapore Corneal Transplant Study (SCTS)

2014: PK: 14% 400 DALK: 30% DSEK: 51% 350 DMEK DMEK: 4% DSAEK DALK 300 PK

250

200

150

100

50

0

'91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 12 '13 '14 Who’s Doing What? Corneal Transplantation Around the World

Methodology • Peer Reviewed Literature Search • Major Eye Banking Associations (EBAA, EEBA, etc) • Data from Transplant Registries (ACGR, NHSBT etc) • Corneal Societies/members (SITraC, ACS, etc) • Individual (National) Eye Banks • Individual Ophthalmology Institutions

Challenges • Lack of data in many continents, countries (e.g. Eastern Europe, Africa, Asia) • Cornea transplant/eye bank registries: variable response rates from surgeons • Published studies: data sets differ in time periods, many institution-specific studies • Lack of uniformity in definitions for disease Indications (e.g.””; “”: scar or active keratitis?; Corneal Transplantation Around the World

National Registries/Associations Eye Banks/Ophthalmic Institutions

Eye Bank Association of America (EBAA) Beijing Tongren Eye Bank, China Association of Eye Banks of Asia (AEBA) Shandong Eye Institute, China European Eye Banks Association (EEBA) Ramayamma International Eye Bank of LVPEI, India UK NHS Blood and Transplant (NHSBT) Cornea Centre and Eye Bank, Tokyo Dental College, Japan Australian Corneal Graft Registry (ACGR) Kyoto Prefectural University of Medicine, Japan Eye Bank Association Australia New Zealand Seoul St Mary’s Eye , South Korea Latin American Transplantation Report (ABTO) Santa Lucia International Eye Bank of the Philippines Society Italiana Trapianto di Cornea (SITraC) King Khaled Eye Hospital, Saudi Arabia German Ophthalmological Society Singapore Eye Bank, Singapore Eye Bank Association of India (EBAI) Pretoria Eye Institute, South Africa Hospital Authority Lions Eye Bank, Hong Kong National Eye Bank of Sri Lanka, Sri Lanka Korean Network for Organ Sharing (KONOS) National Taiwan University Hospital, Taiwan Thai Red Cross Eye Bank, Thailand Singapore Cornea Transplant Study (SCTS) Jakarta Eye Center, Indonesia Individuals SightLife, USA

Keryn Williams, Australia Shigeru Kinoshita, Japan John Armitage, UK Graeme Pollock, Australia Naoshi Shinozaki, Japan Mark Jones, UK Jose Alvero Pereira Gomes, Brazil Veera Ramani, Malaysia Kevin Corcoran, USA Zhiqiang Pan, China Tin Win, Myanmar David Korroch, USA Lixin Xie, China Ma Dominga Padilla, Philippines Jeremy Shuman, USA Iva Dekaris, Croatia Ali Alrajhi, Saudi Arabia Berthold Seitz, Germany Usha Gopinathan, India Ed Sevenster, South Afrina David Touboul, France Johan Hutauruk, Indonesia Yu-Chih Hou, Taiwan Marcus Ang, Singapore Made Susiyanti, Indonesia Lalida Pariyakanok, Thailand Howard Cajucom-Uy, Singapore Aldo Caparossi, Italy Pham Ngoc Dong, Vietnam Chia-Li Pang, Singapore Choun-Ki Joo, South Korea

Adoption of Endothelial Keratoplasty by Country (2011-12)

Sweden 52% SCTR 2012

USA 50.7% EBAA 2012

Singapore 44.38% SCTS 2012

UK 45.27% NHSBT 2011

Australia 36% ACGR 2011

Germany 24.8% German Ophth Soc 2011

Italy 23% SITraC 2011

Hong Kong 21.3% Hong Kong Lions Eye Bank 2012

Sri Lanka 11% NEBSL 2012

Brazil 7.19% ABTOl 2012 Transplant registries, national or regional Eye India 2.8% EBAI 2012 Bank statistics

Philippines 1.02% SLIEB 2011

Thailand 0.76% Thai Red Cross Eye Bank 2012

0% 10% 20% 30% 40% 50% 60% Adoption of DSAEK in US and developed countries

5 Stages in the Adoption of Medical Innovations Adoption of new innovations depends on:

• Confidence in superiority ✓ EK: 56.1% • Ease in adoption in 2014 • Short learning curve ✓ • Access to new technology ✓ • Economics ✓

Microkeratome Eye Bank-prepared

Donor Preparation pre-cut tissue Wilson CB. BMJ 2006;332:112-4 Rogers EM. Diffusion of Innovations. 4th Ed. New York: Free Press, 1995 Adoption of DSAEK in Developing Countries

5 Stages in the Adoption of Medical Innovations Adoption of new innovations depends on:

• Confidence in superiority • Ease in adoption • Short learning curve • Access to new technology✗ • Economics ✗

Microkeratome Eye Bank-prepared

Donor Preparation pre-cut tissue Wilson CB. BMJ 2006;332:112-4 Rogers EM. Diffusion of Innovations. 4th Ed. New York: Free Press, 1995 Adoption of Anterior Lamellar Keratoplasty by Country (2011-12)

28.2% SCTS 2012 Singapore

Brazil 27.2% ABTO 2012

26.1% SITraC 2011 Italy

Sri Lanka 20% NEBSL 2012

UK 13.36% NHSBT 2011

13.04% ACGR 2011 Australia

Hong Kong 12.5% Hong Kong Lions Eye Bank 2012 ALK: 1.98 % in India 7.5% EBAI 2012 2014 5.93% German Ophth Soc 2011 Germany Transplant registries, 4.77% Thai Red Cross Eye Bank 2012 national or regional Eye Thailand Bank statistics

USA 1.95% EBAA 2012

Philippines 1.02% SLIEB 2011

0% 5% 10% 15% 20% 25% 30% Adoption of Innovations in Medicine (Deep Anterior Lamellar Keratoplasty)

5 Stages in the Adoption of Medical Innovations Adoption of new innovations depends on:

• Confidence in superiority“ ✓ ” • Ease in adoption • Short learning curve✗ • Access to new technology✗ • Economics✗

Automated Lamellar Femtolaser – poor lamellar cut profile Therapeutic Wilson CB. BMJ 2006;332:112-4 Keratoplasty (ALTK) in the deep stroma Rogers EM. Diffusion of Innovations. 4th Ed. New York: Free Press, 1995 NOT FOR DALK Ophthalmology, March 2014 Australian Cornea Graft Registry: Real world results of Selective Lamellar Keratoplasty?

Surgeons who have performed >100 grafts Low volume surgeons had poorer outcomes

Surgeons who have performed less grafts

Surgeons who have In the “real world”, there performed 20+ EKs may be a very Surgeons who have performed True learning significant learning less EKs curve effect when curve of EK adopting new surgical procedures… Singapore Cornea Transplant Study (SCTS): 12 year comparison of PK v ALK v EK (2000-2011)

• 2,330 corneal transplants between 2000 to 2011 DALK • First grafts analyzed only: 1,242 grafts DSAEK • 8 corneal surgeons (+ 17 corneal fellows in training) P=0.02 p<0.001 • Same clinical training/protocols for PK, DALK and EK

PK DALK DSAEK PK SCTS Data No. of Survival No.of Survival No. of Survival cases Rate cases Rate cases Rate

Months 1st year 596 94.3% 296 96.3% 350 96.7%

2nd year 466 84.8% 200 95.8% 261 93.4%

3rd year 315 79.1% 114 94.8% 130 87.4%

4th year 236 75.4% 76 93.1% 76 83.8%

5th year 185 70.7% 36 93.1% 35 77.3% DALK is much better than PK…. in the Singapore Corneal Transplant Study at least …

DALK

p<0.001 PK

Singapore Corneal Transplant Study DALK: Stromal Rejection Fully recovery with steroids

DALK Major Advantage of DALK in DALK Developing Countries:

PK • Better graft survival in adverse

PK follow-up conditions, and high risk vascularized p=0.013 P=0.024 • Manual surgery – low cost

Anterior Stromal Dystrophies HSV Keratitis/Scarring • Lamellar grade tissue – better 10 year comparison 5 year comparison utilization Singapore National Eye Centre Advanced Corneal Transplantation Courses

>100 surgeons trained from 19 countries