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Ocular Surface Surgeries
Dr. Tseng was the first pioneering Transplantation of Autologous and Allogeneic Limbal Epithelial Stem Cells to treat Limbal Stem Cell Deficiency.

Dr. Tseng was the first pioneering Amniotic Membrane Transplantation for ocular surface reconstruction.

General Strategies of Ocular Surface Reconstruction

Fig. 20 (click to enlarge)
Fig. 21 (click to enlarge)

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]

Relevant Literature

  • 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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Transplantation of Autologous Limbal Epithelial Stem Cells

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.

Location of Ocular Surface Epithelial Stem Cells

Fig. 22 (click to enlarge)

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.

A typical clinical example

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).

Fig. 23 (click to enlarge)
Fig. 25 (click to enlarge)
Fig. 24 (click to enlarge)

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Transplantation of Allogeneic Limbal Epithelial Stem Cells

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.

A typical clinical example

Fig. 26 (click to enlarge)

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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Amniotic Membrane Transplantation

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.

Patent Granted

Fig. 27 (click to enlarge)

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]

 

What is Amniotic Membrane?

Fig. 28 (click to enlarge)

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.

How does Amniotic Membrane work?

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.

To Learn more about Amniotic Membrane Transplantation

[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).
Fig. 29 (click to enlarge)
Fig. 31 (click to enlarge)
Fig. 49 (click to enlarge)
Fig. 30 (click to enlarge)
Fig. 48 (click to enlarge)

Relevant Literature

  • 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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Transplantation of Ex Vivo Expanded Limbal Epithelial Stem Cells

Patients

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.

Physicians

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.

Pre-clinical Rabbit Study

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).

Fig. 38 (click to enlarge)
Fig. 40 (click to enlarge)
Fig. 39 (click to enlarge)
Fig. 41 (click to enlarge)

 

Relevant Literature

  • 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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