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Like growing a flowering plant in the garden,
successful ocular surface reconstruction requires knowledge
and skills to 1) restore normal ocular
surface defense (neuroanatomic integration) so that a
stable tear film can be achieved (providing rain), 2) restore
epithelial stem cells (providing seeds), and 3) restore stem
cell stromal niche (providing soil) [see Fig.
20]
- Grueterich M, Espana EM, Romano
A, Touhami A, Tseng SCG. Surgical approaches for limbal
stem cell deficiency. Comtemporary Ophthalmol 1:1-7, 2002.
- Ex
vivo expansion of limbal epithelial stem cells: Amniotic
membrane serving as a stem cell niche. Surv Ophthalmol
48:631-646, 2003.
- Espana EM, Di Pascuale M, Grueterich
M, Solomon A, Tseng SCG. Keratolimbal allograft for corneal
surface reconstruction. Eye 18:406-417, 2004.
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If Limbal Stem Cell Deficiency involves one
eye, transplantation of limbal epithelial stem cells using
the procedure termed Conjunctival Limbal Autograft (CLAU)
from the normal healthy eye can be considered.
Epithelial stem cells are the ultimate source
of regeneration and wound healing. Corneal epithelial stem
cells are located exclusively at the limbus (between the
cornea and the conjunctiva), and conjunctival epithelial
stem cells are enriched at the fornix (deep sac) [See Fig.
22].
Drs. Kenyon and Tseng were the first reporting
clinical efficacy of CLAU
Kenyon KR, Tseng SCG. Limbal autograft transplantation
for ocular surface disorders. Ophthalmology 96:709-723,
1989.
Other related publications
Tsai RJF, Sun T-T, Tseng SCG. Comparison
of limbal and conjunctival autograft transplantation for
corneal surface reconstruction in rabbits. Ophthalmology
97:446-455, 1990
Tsai RJF, Tseng SCG. Effect of stromal
inflammation on the outcome of limbal transplantation for
corneal surface reconstruction. Cornea 14:439-449, 1995
If you would like to receive a reprint
of the article in pdf file listed above, please contact
Dr. Tseng at stseng@ocularsurface.com
by stating which Article or simply copy the entire citation.
This patient suffered from chemical burn to
the left eye resulting in a persistent corneal epithelial
defect (Fig. 23, upper
left) and total LSCD for 7 months. The epithelial healing
started immediately following CLAU taken from the right
eye (Fig. 23, the rest).
During the surgery, the conjunctivalized pannus tissue was
removed from the left eye (Fig.
24, upper panel), and two strips (each spanning from
6 to 8 mm limbal arc length) were removed from the right
eye (Fig. 24, lower panel).
Several weeks after CLAU, the deep stromal vascularization
regressed (Fig. 25, upper
panel). The resultant corneal surface was normal, smooth,
and non-inflamed with improved vision lasting for several
years, while the donor eye also maintained healthy surface
after limbal removal (Fig.
25, lower panel).
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If Limbal Stem Cell Deficiency involves both
eyes, transplantation of limbal epithelial stem cells from
a cadaveric donor using the procedure termed Keratolimbal
Allograft (KLAL) or from a living-related donor using the
procedure termed Conjunctival Limbal Allograft (lr-CLAL)
can be considered.
Systemic immunosuppression for a prolonged,
if not indefinite, will have to
be administered to prevent allograft rejection.
Dr. Tseng and Dr. Tsai were the
first reporting clinical efficacy of KLAL
Tsai RJF, Tseng SCG. Human allograft limbal
transplantation for corneal surface reconstruction. Cornea
13:389-400, 1994
Tseng SCG, Prabhasawat P, Barton K, Gray T,
Meller D. Amniotic membrane transplantation with or without
limbal allografts for corneal surface reconstruction in
patients with limbal stem cell deficiency. Arch Ophthalmol
116:431-441, 1998.
Solomon A, Ellies P, Anderson DF, Touhami
A, Grueterich M, Espana E, Ti S-E, Goto E, Feuer WJ, Tseng
SCG. Long-term outcome of kerarolimbal allograft with or
without penetrating keratoplasty for total limbal stem cell
deficiency. Ophthalmology 109:1159-1166, 2002.
If you would like to receive a reprint of
the article in pdf file listed above, please contact Dr.
Tseng at stseng@ocularsurface.com
by stating which Article or simply copy the entire citation.
This patient suffering from Stevens Johnson
syndrome complained of reduced vision (20/400) and had total
LSCD in both eyes with vascularization and scarring on the
cornea (Fig. 26, left
upper). The patient first received punctal occlusion, autologous
serum eye drops, lid margin eversion, scleral contact lens
and topical retinoid acid ointment to augment ocular surface
defense for 7 months. Subsequently, the patient was placed
on systemic immunosuppression using oral Prednisone, CellCept
and Prograf, and received KLAL, amniotic membrane transplantation
as a graft and a bandage, and tarsorrhaphy (Fig.
26, left lower). The patient then received cataract
extraction and lens implantation to restore a vision of
20/25 (Fig. 26, right
lower).
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Drs. Kim and Tseng were the first reintroducing
amniotic membrane transplantation for ocular surface reconstruction.
Kim JC, Tseng SCG. Transplantation of preserved
human amniotic membrane for surface reconstruction in severely
damaged rabbit corneas. Cornea 14:473-484, 1995.
If you would like to receive a reprint of
the article in pdf file listed above, please contact Dr.
Tseng at stseng@ocularsurface.com
by stating which Article or simply copy the entire citation.
Dr. Tseng has obtained US Patents (No. 6,152,142
and 6,326,019) for the proprietary method of preserving
human amniotic membrane and its clinical uses.
Due to this new method of preserving amniotic
membrane, there has been a surge of interests in ophthalmic
uses in ocular surface research and reconstruction [see
Fig. 27]
Amniotic membrane is the innermost layer of
the placenta, and consists of a thick basement membrane
and an avascular stroma (See Fig.
28, left lower). Amniotic membrane enwraps the fetus
during pregnanacy, and may play a role in endowing "scarless
fetal wound healing", a phenomenon observed when fetal
surgeries are performed (Fig.
28, right lower). A number of clinical studies have
shown that amniotic membrane transplantation results in
rapid healing with reduced inflammation, scarring and unwanted
blood vessel formation.
A number of studies performed by us and
others have revealed some of the mechanisms explaining
how amniotic membrane works regarding its anti-inflammatory,
anti-scarring and anti-angiogenic actions. These findings
are summarized in our recent review.
- Tseng SCG, Espana EM, Kawakita T, Di Pascuale MA, Li W, He
H, Liu T-S, Cho T-H, Gao Y-Y, Liu L-K, Liu C-Y. How does
amniotic membrane work? Ocular Surface J. 2:177-187, 2004.
[Click
here to download Summary of Clinical Uses, pdf file ]
News Release -- Channel 7 News aired
on October 23, 2002 in Health Cast an interview of the following
three patients who received amniotic membrane transplantation
for different indications. [Click
here to view the video]
- Amniotic membrane used as a bandage
has resulted in rapid healing and saved the sight of a
patient suffering from Acute attack of Stevens Johnson
syndrome (Fig. 29).
- Amniotic membrane used as a graft
has resulted in total resolution of "Dry Eye Complaints"
of the left eye by correcting "Conjunctivochalasis",
which was found to be worse in the left eye and aggravated
aqueous tear deficiency noted in both eyes. (Fig.
30)
- Amniotic membrane was used together
with KLAL in the only seeing eye of this patient suffering
from chronic chemical burns to improve the ocular surface
before corneal transplantation and cataract extraction
and lens implantation, which resulted in a vision of 20/25.
(Fig. 31)
- Amniotic membrane
can be used to restore the surface integrity of the
donor where the conjunctival limbal autograft (CLAU)
is removed to avoid potential damage, and to help in
vivo expansion of CLAU in the recipient eye (Fig.
48).
- Amniotic membrane can help restore
the deep fornix during symblepharon lysis, especially
in conjunction with intraoperative application of 0.04%
mitomycin C to the fornix, in severe cicatricial ocular
surface diseases (Fig.
49).
- Meallet MA, Espana EM, Grueterich M, Ti S-E, Goto
E, Tseng SCG. Amniotic membrane transplantation
with conjunctival limbal autograft for total limbal stem
cell deficiency. Ophthalmology 110:1585-1592, 2003.
- Solomon A, Espana E, Tseng SCG.
Amniotic membrane transplantation for reconstruction
of conjunctival fornices. Ophthalmology 110:93-100, 2003.
- Tseng
SCG, Di Pascuale MA, Liu DT-Z, Gao Y-Y, Baradaran-Rafii,
A. Intraoperative mitomycin C and amniotic membrane transplantation
for fornix reconstruction in severe cicatricial ocular
surface diseases. Ophthalmology, submitted, 2004.
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You may be eligible for an FDA approved clinical
research study (under IND #10313) if you have: (1) total
limbal stem cell deficiency (LSCD) and suffer from a severe
loss of vision and/or (2) if you have annoying ocular discomfort,
including light sensitivity and conventional treatments
have not worked to relieve them. The study is centered
around Bio-engineered Corneal Surface Tissue transplantation
where a limbal biopsy, 4-5 times smaller than the conventional
method is taken and used to grow stem cells in culture
on amniotic membrane. For more information and to see if
you are eligible, contact Dr. Scheffer Tseng at (305) 274-1299.
A Phase I, FDA approved Clinical Trial (under
IND #10313) is underway to test the safety and efficacy
of Bio-engineered Corneal Surface Tissue to treat ocular
surface diseases characterized by total limbal stem cell
deficiency (LSCD). Unilateral LSCD will be treated using
autologous tissue from the unaffected eye. Bilateral LSCD
will be treated using allogeneic tissue from a living-related
donor. The limbal biopsy will be approximately 2mm in size
compared to the conventional size of 8-10 mm and the limbal
epithelial stem cells will be expanded ex vivo in culture
on a cryopreserved amniotic membrane. This bio-engineered
corneal tissue will be used as a surgical graft to restore
the normal corneal epithelial phenotype lost due to LSCD.
For more information and to see if your patient is eligible,
contact Dr. Scheffer Tseng at (305) 274-1299.
Unilateral total limbal stem cell deficiency
was created in rabbits (Fig.
38). The control group received rabbit amniotic membrane
transplantation without ex vivo expansion of limbal epithelial
stem cells. The corneal surface was not improved in the
control group (Fig. 39).
Nevertheless, the experimental group (IV), in which ex vivo
expanded limbal epithelial stem cells were transplanted
with rabbit amniotic membrane, and the transplanted tissue
was further covered by an additional layer of human amniotic
membrane (to protect the newly expanded and transplanted
epithelial cells), there was an overwhelming success of
restoring the normal corneal surface (Fig.
40). This difference was observed and lasted for more
than one year (Fig. 41).
- Ti S-E, Anderson DF, Touhami A, Kim C, Tseng SCG. Factors
affecting outcome following transplantation of ex
vivo expanded limbal epithelium on amniotic membrane
for total limbal deficiency in rabbits. Invest Ophthalmol
Vis Sci 43:2584-2592, 2002.
- Espana EM, Ti S-E, Grueterich
M, Touhami A, Tseng SCG. Corneal stromal changes following
reconstruction by ex vivo expanded limbal epithelial
cells in rabbits with total limbal stem cell deficiency.
Br J Ophthalmol 87:1509-1514, 2003.
- Ti SE, Grueterich
M, Espana EM, Touhami A, Anderson DF, Tseng SCG. Correlation
of long-term phenotypic and clinical outcomes following
limbal epithelial transplantation cultivated on amniotic
membrane in rabbits. Br J Ophthalmol 88:422-427, 2004.
- Schwab
IR. Cultured corneal epithelia for ocular surface disease.
Trans Am Ophthalmol Soc 1999;97:891-986.
- Tsai RJF, Li
L-M, Chen J-K. Reconstruction of damaged corneas by
transplantation of autologous limbal epithelial cells.
N Eng J Med 2000;343:86-93.
- Schwab IR, Reyes M, Isseroff
RR. Successful transplantation of bioengineered tissue
replacements in patients with ocular surface disease.
Cornea 2000;19:421-6.
- Koizumi N, Inatomi T, Suzuki
T, et al. Cultivated corneal epithelial transplantation
for ocular surface reconstruction in acute phase of
Stevens-Johnson syndrome. Arch Ophthalmol 2001;119:298-300.
- Koizumi
N, Inatomi T, Suzuki T, et al. Cultivated corneal epithelial
stem cell transplantation in ocular surface disorders.
Ophthalmology 2001;108:1569-74.
- Grueterich M, Espana
EM, Touhami A, Ti SE, Tseng SCG. Phenotypic study of
a case with successful transplantation of ex vivo expanded
human limbal epithelium for unilateral total limbal
stem cell deficiency. Ophthalmology 109: 1547-1552, 2002.
- Grueterich M, Espana EM, Tseng
SCG. Ex vivo expansion of limbal epithelial stem cells:
Amniotic membrane serving as a stem cell niche. Surv
Ophthalmol 48:631-646, 2003.
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