Michael Duplessie MD.

6000 Executive Blvd, Suite 525

N. Bethesda MD 20852

301.493.6404

Sutureless Approach of Amniotic Membrane

Transplantation for Common Diseases

Disclosure and Acknowledgment

• Cryopreserved amniotic membrane (AmnioGraft®) is

obtained from Bio-Tissue.

• Amniotic membrane transplantation for ocular surface

reconstruction using AmnioGraft® is the ONLY one

approved by FDA in 2001, and by Medicare for hospitals

in Jan 2004 (CPT #65780) and for ASCs in July 2005.

• Development of ProKera®, a sutureless AmnioGraft®,

is supported by a SBIR grant from NIH, NEI, approved by

FDA as a type II Device in Dec 2003, and is launched by

Bio-Tissue in April 2005.

AMT Indications

Corneal Other Diseases,

262, 8%Conjunctivochalasis,

257, 8%

Bullous Keratopahty,

229, 7%

Conjunctival/Caruncle

Lesion, 208, 6%

Symblepharon, 132, 4%

Limbal Stem Cell

Deficiency, 100, 3%

Glaucoma/Bleb

Problems, 70, 2%

Socket Problems , 60,

2%

Lid Problems, 48, 1%

Implant Problems, 36, 1%

Scleral Diseases, 35, 1%

Limbal Lesion Removal,

30, 1%

With other Surgical

Procedures, 11, 0%

Corneal Defect and

Ulceration, 724, 22%

Pterygium &

Pseudoterygium, 1152,

34%

Pterygium & Pseudoterygium

Corneal Defect and Ulceration

Corneal Other Diseases

Conjunctivochalasis

Bullous Keratopahty

Conjunctival/Caruncle Lesion

Symblepharon

Limbal Stem Cell Deficiency

Glaucoma/Bleb Problems

Socket Problems

Lid Problems

Implant Problems

Scleral Diseases

Limbal Lesion Removal

With other Surgical Procedures

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

Papilloma of the conjunctiva

Keratoacanthoma of the

conjunctiva

Provide a New Basement

Membrane

Anti-inflammation

Anti-scarring

Anti-angiogenesis

Amniotic Membrane: A New Strategy for Tissue

Reconstruction and Engineering

The ONLY FDA-

approved AM graft

A

B

Stromal Surface

Sticky Side

C

D

Two Major Modes of AMT

AM either dissolves or

removed after healing

Time of AM dissolution

coincides with healing

If AM dissolves in one week,

suspect “exposure” problem

Suture (10-0 nylon) purse-

string running perilimbal

sclera

Prokera™ without sutures

IOP by Tonopen and

fluorescein staining without

removing Prokera™

As a Temporary Graft (bandage or patch)

AM does not dissolve but

integrates into the host tissue

(cornea or conjunctiva)

One or multiple layers to fill in

stromal defect as a filler for

any irregular shape (the

orientation matters only for the

top layer with sticky side

down)

Suture (10-0 nylon) interrupted

(bulbar) and 8-0 Vicryl over

fornix,

Fibrin Glue without sutures

As a Permanent Graft

To reduce acute inflammation Chemical and Thermal Burns (Acute Stage)

Stevens-Johnson Syndrome (Acute Stage)

To reduce chronic and recalcitrant

inflammation

Herpes Zoster, Herpes Simplex, Vernal Keratitis

To reduce acute inflammation

induced by surgery or excimer laser High-risk PKP (neurotrophic)

Excimer laser ablation (PRK/PTK) of the cornea

AM as a Temporary Graft to Deliver

Anti-inflammatory Action

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

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

Preop

POD# 1 POD# 1

Acute Chemical Burn

1 wk

2 wk 2 wk

1 wk

4 month

3 wk

5 wk

5 wk

7/2/86 9/3/86

9/3/86

Acute HZO in a

Patient with HIV Preop

8 day

Acute HSV-1

Sutureless ProKera®

04.24.05

Day 1

04.25.05

Chemical Burn

Day 3

04.27.05

OS Day 5

04.29.05

OS 04.24.05

06.06.05

09.23.05 10 Days after Chemical Burn

09.26.05 Day 3 after 1st ProKera

09.26.05

Day 3

09.28.05

Day 5

09.30.05

Day 7

10.03.05

Day 10

10.03.05

Day 10

10.05.05

Day 12

10.08.05

Day 15

10.10.05

Day 17

Switcht

to BCL

09.23.05 10 Days after Chemical Burn

10.10.05 27 Days after Chemical Burn

09.23.05

Day 0

09.26.05

Day 3

10.03.05

Day 10

10.05.05

Day 12

What Happened

in the

Conjunctiva

beyond

ProKera?

10.10.05

Day 17

10.08.05

Day 15

10.03.05

Day 10

10.12.05

Day 19 Inject

Kenalog

To reduce acute inflammation Chemical and Thermal Burns (Acute Stage)

Stevens-Johnson Syndrome (Acute Stage)

To reduce chronic and recalcitrant

inflammation

Herpes Zoster, Herpes Simplex, Vernal Keratitis

To reduce acute inflammation

induced by surgery or excimer laser High-risk PKP (neurotrophic)

Excimer laser ablation (PRK/PTK) of the cornea

AM as a Temporary Graft to Deliver

Anti-inflammatory Action

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

Two Major Modes of AMT

AM either dissolves or

removed after healing

Time of AM dissolution

coincides with healing

If AM dissolves in one week,

suspect “exposure” problem

Suture (10-0 nylon) purse-

string running perilimbal

sclera

Prokera™ without sutures

IOP by Tonopen and

fluorescein staining without

removing Prokera™

As a Temporary Graft (bandage or patch)

AM does not dissolve but

integrates into the host tissue

(cornea or conjunctiva)

One or multiple layers to fill in

stromal defect as a filler for

any irregular shape (the

orientation matters only for the

top layer with sticky side

down)

Suture (10-0 nylon) interrupted

(bulbar) and 8-0 Vicryl over

fornix,

Fibrin Glue without sutures

As a Permanent Graft

To Restore Corneal Integrity

AM as a Permanent Graft

(one or multiple layers)

Persistent epithelial defect, ulcer,

descemetocele, and perforation

Painful bullous keratopathy

Band keratopathy

Recurrent corneal erosion

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

HSV-1 Deep Ulcer

Restore

stromal

thickness

CF

20/70

Preop 1 Week

2 Week 7 Month

20/70

Decemetocele following Pseudomonas

Infection and Glaucoma Drainage Implant

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

OD 06.14.05

Corneal Perforation

Follow-up 5 weeks

Corneal Perforation

Restore

stromal

thickness

Before

Band Keratopathy with PED

75 days 28 days

OS PRE-OP

Band and Bullous Keratopathy with PED

1ST POP WEEK

OS PRE-OP

Band and Bullous Keratopathy with PED

POP 2 MONTH

Reconstruct conjunctival surface without

conjunctival autograft during removal of large

lesions if the surrounding host tissue is healthy

AM as a Graft for Conjunctival

Surface Reconstruction

Tumor, CIN

Conjunctivochalasis/SLK

Scar or Symblepharon

LOGIC Syndrome

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

Differential Diagnosis

Symptoms

• Diurnal

Variation

• Worst Gaze

• Increased

Blinking

ATD Dry Eye

Worst in P.M.

Up Gaze

Improved

Exposure Zone

Improved

Chalasis Dry Eye

Same throughout

the day

Down Gaze

Worsened

Non-Exposure

Zone

Worsened

Di Pascuale et al Br J Ophthalmol, 2004

Rose Bengal

Punctal

Occlusion

Di Pascuale et al Br J Ophthalmol, 2004

CCh Detected by

Fluorescein

CCh Detected by

Roes Bengal

Anterior Migration of Mucocutaneous Junction

and Regional “Blepharitis”

Normal Mild CCh

Moderate

CCh

Severe

CCh

Increasing Conjunctival Redness

as if “Conjunctivitis”

Vigorous

Blinking

under Slit

Lamp

Finger

Compress

the Lids

against the

Globe

10.29.03

01.12.04

Conjunctivochalasis

After AMT

1/14/05

3/18/05

Conjunctivochalasis

Preop

1 wk 1.5 month

Tenon’s Capsule Reinforcement

and Replacement by AM

“Tenting” Effect Created by Forceps

under Topical Anesthesia

OS OD Superior Limbic

Keratoconjunctivitis

3/11/05

09/21/04

Reconstruct conjunctival surface with or without

conjunctival autograft and intraoperative

application of 0.04% MMC to fornix if the

surrounding host tissue is not healthy

AM as a Graft for Conjunctival

Surface Reconstruction

Tumor, CIN

Conjunctivochalasis

Scar or Symblepharon

LOGIC Syndrome

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

Primary Pterygium

Recurrent Pterygium

OD OS

PRE OP

4th POP WEEK

Multi-Recurrent Pterygium

with Motility Restriction

and Symblepharon

09.29.03

09.29.03

OS

10.29.03

10.29.03 11.12.03 11.12.03

OD

20/30

02.11.04

20/15

10.03.05

OD Chemical Burn

10.05.05

10.03.05

10.10.05 10.12.05

11.16.05

10.05.05

10.03.05

10.10.05 10.12.05

11.16.05

10.03.05 11.16.05

11.16.05

10.03.05

02.01.06

Ocular surface reconstruction can be augmented by AMT to restore

a stroma with an intact basement membrane and reduced

inflammation and scarring.

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.

AMNIOGRAFT® can be used in conjunction with intraoperative

application of MMC to restore conjunctival surface with abnormal

inflamed host tissue.

AMNIOGRAFT® can be used to restore stem cell stromal substrate or

“niche” and help promote epithelial stem cell expansion in vivo and

ex vivo.

Fibrin glue simplifies AMNIOGRAFT® use as a “sutureless”

permanent graft,

PROKERA™ simplifies AMNIOGRAFT® ’s use as a “sutureless”

temporary graft.

Conclusion