Amniotic Membrane Transplantation for Ocular Surface Reconstruction

Amniotic Membrane Transplantation for Ocular Surface Reconstruction AmnioGraft

Disclosure and Acknowledgment • Transplantation of cryopreserved amniotic membrane (AmnioGraft®) is obtained from Bio-Tissue, which licenses Dr. Tseng’s patents.

ProKera

• Dr. Tseng and his family owns more than 5% of TissueTech, Inc., which also owns Bio-Tissue, Inc.. • Development of ProKera®, a sutureless AmnioGraft®, is supported by SBIR grants R43 EY14768 and R44 EY14768 from NIH, NEI.

Scheffer C. G. Tseng M.D., Ph.D.

• Ex vivo expansion of limbal epithelial stem cells using AmnioGraft® as a Biologic is supported by grants RO1 EY06819 and RO1 EY15735 from NIH, NEI.

Ocular Surface Center Ocular Surface Research & Education Foundation TissueTech, Inc., Miami, FL [email protected] www.ocularsurface.com

Fetal Strategy for Scar-less Wound Healing & Regeneration by Cyropreserved Amniotic Membrane

Amniotic Membrane Uses in Ophthalmology

70 60

# of Papers

50 z Anti-inflammation

40

z Anti-scarring 30

z Anti-angiogenesis

AmnioGraft®

20

ProKera™

?

10

1940

1946

De Rotth 1947 Sorsby et al

1995

1996 1997 1998

1999

2000

2001

2002

2003

Kim & Tsubota et al Tseng

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

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Amniotic Membrane Transplantation for Ocular Surface Reconstruction

Quarterly Volume With other Surgical Procedures, 11, 0%

2000

Medicare ASC Reimbursement

1800

Implant Problems, 36, 1%

1400

Lid Problems, 48, 1%

FDA 510(k) approved ProKera as II Medical Device

1200 1000

FDA classified AG as Tissue

800

400

Pterygium & Pseudoterygium

Scleral Diseases, 35, 1%

1600

600

AMT Indications

Limbal Lesion Removal, 30, 1%

Socket Problems , 60, 2%

ProKera Launch

Medicare Hospital Reimbursement

0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Two Major Modes of AMT As a Biological Bandage ¾ AM either dissolves or removed after healing ¾ Time of AM dissolution coincides with healing ¾ Suture (10-0 nylon) purse-string running perilimbal sclera ¾ Prokera™ without sutures

As a Permanent Graft ¾ AM does not dissolve but integrates into the host tissue (cornea or conjunctiva) ¾ One or multiple layers to fill in stromal defect as a filler for any irregular shape ¾ Suture (10-0 nylon) interrupted (bulbar) and 8-0 Vicryl over fornix, ¾ Fibrin Glue without sutures

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

Corneal Other Diseases Conjunctivochalasis Bullous Keratopahty Conjunctival/Caruncle Lesion Symblepharon

Glaucoma/Bleb Problems, 70, 2%

AmnioGraft Launch

200

Corneal Defect and Ulceration

Pterygium & Pseudoterygium, 1152, 34%

Corneal Defect and Ulceration, 724, 22%

Glaucoma/Bleb Problems Socket Problems

Limbal Stem Cell Deficiency, 100, 3%

Lid Problems Implant Problems

Symblepharon, 132, 4%

Scleral Diseases Limbal Lesion Removal

Conjunctival/Caruncle Lesion, 208, 6% Bullous Keratopahty, 229, 7%

Limbal Stem Cell Deficiency

With other Surgical Procedures

Conjunctivochalasis, 257, 8%

Corneal Other Diseases, 262, 8%

N = 3,354 Data Source: Bio-Tissue, Inc. (2002)

AM as a Biological Bandage to Deliver Anti-inflammatory Action z To reduce acute inflammation z Chemical and Thermal Burns (Acute Stage) z Stevens-Johnson Syndrome (Acute Stage)

z To reduce chronic and recalcitrant inflammation z Herpes Zoster, Herpes Simplex, Vernal Keratitis

z To reduce acute inflammation induced by surgery or excimer laser z High-risk PKP (neurotrophic) z Excimer laser ablation (PRK/PTK) of the cornea Kim et al, 1998; Meller et al, 2000; Sridhar et al, 2000; Choi et al, 1998; Park & Tseng, 2000; Wang et al, 2001; Heiligenhaus et al, 2001; Kenyon et al, 2003

2

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

7/2/86

9/3/86

Grade 1

Grade 2

Grade 3

9/3/86

Di Pascuale et al Ophthalmology, 2005

 AMT for Acute Chemical Burns & Acute SJS/TENS

Kim et al, EER 70:329, 1998 Meller et al, Ophthalmology 107:980, 2000 John et al, Ophthalmology 109:351, 2002

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

A CASE EXAMPLE

Pre-OP

1st POP Day

2nd POP Week

3rd POP Week

1st POP Week

4th POP Month

3

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

Stevens Johnson Syndrome

08/17/02

08/17/02

11/14/02

AM as a Biological Bandage to Deliver Anti-inflammatory Action z To reduce acute inflammation z Chemical and Thermal Burns (Acute Stage) z Stevens-Johnson Syndrome (Acute Stage)

z To reduce chronic and recalcitrant inflammation z Herpes Zoster, Herpes Simplex, Vernal Keratitis

z To reduce acute inflammation induced by surgery or excimer laser z High-risk PKP (neurotrophic) z Excimer laser ablation (PRK/PTK) of the cornea Kim et al, 1998; Meller et al, 2000; Sridhar et al, 2000; Choi et al, 1998; Park & Tseng, 2000; Wang et al, 2001; Heiligenhaus et al, 2001; Kenyon et al, 2003

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

4

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

Acute HZO in a Patient with HIV

Preop

8 day

Acute HSV-1

Sutureless ProKera®

09.23.05 8 Days after Chemical Burn

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

5

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

09.26.05 Day 3

09.28.05 Day 5

1

09.26.05 Day 3 after 1st ProKera 2

1

09.30.05 Day 7

09.23.05 8 Days after Chemical Burn

2

10.03.05 Day 10 3

10.08.05 Day 15

10.03.05 Day 10

10.05.05 Day 12 Switched to BCL

10.10.05

6.01.06

10.10.05 Day 17

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

6

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

09.23.05 Day 0

10.03.05 Day 10

09.26.05 Day 3

1

What Happened in the Conjunctiva beyond ProKera?

10.03.05 Day 10

10.08.05 Day 15

2

10.05.05 Day 12

2

10.10.05 Day 17

Inject Kenalog

3

10.12.05 Day 19

3

Two Major Modes of AMT As a Biological Bandage ¾ AM either dissolves or removed after healing ¾ Time of AM dissolution coincides with healing ¾ Suture (10-0 nylon) purse-string running perilimbal sclera ¾ Prokera™ without sutures

As a Permanent Graft ¾ AM does not dissolve but integrates into the host tissue (cornea or conjunctiva) ¾ One or multiple layers to fill in stromal defect as a filler for any irregular shape ¾ Suture (10-0 nylon) interrupted (bulbar) and 8-0 Vicryl over fornix, ¾ Fibrin Glue without sutures

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

AM as a Permanent Graft (one or multiple layers) To Restore Corneal Integrity z Persistent epithelial defect, ulcer, descemetocele, and perforation z Painful bullous keratopathy z Band keratopathy z Recurrent corneal erosion z Superficial keratectomy Lee et al, 1997; Kruse et al, 1999; Azuara-Blanco et al, 1999; Chen et al; 2000; Hanada et al, 2001; Letko et al, 2001; Su & Lin, 2000; Pires et al, 1999; Anderson et al, 2001; Kenyon et al, 2003

7

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

HSV-1 Deep Ulcer

Preop

CF

1 Week

Decemetocele following Pseudomonas Infection and Glaucoma Drainage Implant

2 Week

7 Month

Restore stromal thickness

20/70

Solomon et al, Ophthalmology 109:694-703, 2002

20/70

AM as a Graft for Conjunctival Surface Reconstruction Reconstruct conjunctival surface without conjunctival autograft during removal of large lesions if the surrounding host tissue is healthy z z z z

Tumor, CIN Conjunctivochalasis/SLK Scar or Symblepharon LOGIC Syndrome

z z z z

Pterygium Glaucoma bleb revision Scleromalacia Scleral melt

Tseng et al, 1997; Prabhasawat & Tseng, 1997; Azuara-Blanco et al, 1999; Meller et al, 2000; Gabric et al, 1999; Mejia et al, 2000; Honavar et al, 2000; Paridaens et al, 2001; Prabhasawat et al, 1997; Solomon et al, 2001; Ma et al; 2000; Shimazaki et al, 1998; Budenz et al, 2000; Rodriquez-Ares et al, 1999

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

Courtesy of F. Fantes,MD

8

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

10.29.03

How to Apply Fibrin Glue using Amniotic Membrane on Conjunctival Indications 1

2

3

4

5

6

Conjunctivochalasis

01.12.04

After AMT

09.29.03

10.29.03

OS

PRE OP

20/30

4th POP WEEK 09.29.03 11.12.03

02.11.04 11.12.03 10.29.03 OD

20/15

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

9

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

Ocular Cicatricial Pemphigoid

AM as a Graft for Conjunctival Surface Reconstruction

AM

Pre-op

2 M Post-op

1. Swap with conjunctival autograft and Cover the defect created by removing conjunctival autograft 2. In conjunction with preserved sclera or pericardium to cover the exposed implant/explant z z z z

7 M Post-op4 months Post-op

11 M Post-op

Chemical Burn

Pre-op (12/4/02)

Tumor, CIN Conjunctivochalasis Scar or Symblepharon LOGIC Syndrome

z z z z

Pterygium Glaucoma bleb revision Scleral melt Exposed implants

Tseng et al, 1997; Prabhasawat & Tseng, 1997; Azuara-Blanco et al, 1999; Meller et al, 2000; Gabric et al, 1999; Mejia et al, 2000; Honavar et al, 2000; Paridaens et al, 2001; Prabhasawat et al, 1997; Solomon et al, 2001; Ma et al; 2000; Shimazaki et al, 1998; Budenz et al, 2000; Rodriquez-Ares et al, 1999

Scleral Melt after Scleral Buckle Extrusion and Infection

MMG

\\

3 Months PO (3/6/03)

CA

AMT

MMG

Tseng et al, Ophthalmology, in press, 2005

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

10

Amniotic Membrane Transplantation for Ocular Surface Reconstruction

Scleral Melt after Pterygium Surgery 05.11.05

Ex Vivo Expansion of Limbal Epithelial Stem Cells z Encouraging human results Autologous

Pellegrini et al, 1997 Tsai et al, 2000 Schwab et al, 2000

Allogeneic Koizumi et al, 2001

05.17.05- Surgery

z Encouraging rabbit results Short-term Long-term

08.10.05

Koizumi et al, 2000 Ti et al, 2002, IOVS

Dr. Tseng has obtained FDA’s Approval of IND No. 10313 for Phase I clinical trial, supported by NIH, NEI

Conclusion z Ocular surface reconstruction and tissue engineering can be augmented by AMT to restore a stroma with an intact basement membrane and reduced inflammation and scarring. z AMNIOGRAFT® can be used as a permanent graft to restore the corneal and conjunctival integrity if the surrounding host cells (including stem cells) are normal. z AMNIOGRAFT® can be used to restore stem cell stromal substrate or “niche” and help promote epithelial stem cell expansion in vivo and ex vivo. z Fibrin glue simplifies AMNIOGRAFT® use as a “sutureless” permanent graft, z PROKERA™ simplifies AMNIOGRAFT® ’s use as a “sutureless” biological bandage.

Presented by Scheffer C.G. Tseng, MD, PhD 6th Annual Somatic Cell Therapy Symposium 2006

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