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Transplantation can replenish ocular surface epithelium in eye with limbal stem cell deficiency
Surgeons explain methods for allograft, autograft transplantations and the postoperatie course.
Stem cells are the ultimate source of the rapidly self-renewing corneal epithelium and are located in the basal layer of the limbal epithelium. They are present in the crypts of Vogt or the palisades of Vogt, which are principally located at the sclerocorneal limbus. These cells, like all stem cells, are poorly differentiated and have a low mitotic rate and asymmetrical DNA segregation. They are essential for the maintenance of a healthy corneal surface.
Limbal stem cells evolve into transiently amplifying cells. Both of these undergo cell division and remain in the poorly differentiated stage. They are both located in the limbal region, with the stem cells in the basal epithelium and transiently amplifying cells in the basal and suprabasal levels, extending up to the superficial layers.
Limbal stem cell deficiency
 Amar Agarwal |
Loss of limbal stem cells, or corneal stem cell deficiency, can be partial or total, unilateral or bilateral. The absence or malfunction of corneal stem cells, either primary (aniridia, congenital erythrokeratoderma, etc.) or secondary (chemical burns, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, etc.), results in loss of the regenerative capacity of the corneal epithelium.
Keratoplasty, lamellar or penetrating, is generally not successful in these patients, as the host’s corneal epithelium is only temporarily replaced and the limbal function continues to remain poor. Limbal stem cell transplantation is a surgical modality, described by Kenyon and Tseng, to replenish or repopulate the ocular surface epithelium when there is limbal stem cell deficiency.
Several techniques for limbal transplantation have been reported. All these procedures remove the host’s altered corneal epithelium and pannus and provide a new source of epithelium for a diseased ocular surface. From the donor tissue, transient amplifying cells are generated, which migrate onto the denuded corneal surface of the host. The donor tissue can be obtained from the other eye (limbal autograft) in cases of unilateral disease, from a cadaveric whole globe in cases of bilateral disease, or the corneoscleral rim of a living relative (limbal allograft) can be used.
Limbal allograft technique
From a cadaver eye: As success depends on transplantation of healthy limbal stem cells, fresh donor eyes are preferred. In cases with a cadaver eye, the whole globe is preferred, as it provides better stability while dissecting the donor tissue. Several variations of limbal autografts and allografts have been reported. Dua and Azuara-Blanco have described a modified procedure for limbal allograft.
The eye is first made tense by injecting air into the vitreous cavity through the optic nerve using a 26-gauge needle, and the nerve is clamped. The eye is held in a Tudor Thomas stand. A trephine 3 mm smaller than the corneal diameter is used to make a well-centered, superficial, partial thickness cut in the donor tissue (approximately 150 µm in depth). The cornea peripheral to the cut is then dissected using a bevel up dissector. The dissection is carried all the way through the limbus into a small peripheral rim of sclera, approximately 1 mm, with any conjunctiva present being retained. This corneoscleral rim is then cut free from the cadaver globe.
The recipient bed is prepared by doing a 360º peritomy and removing the conjuctivalized epithelium and underlying scar tissue off the cornea by blunt dissection. The donor graft is then placed at the host limbus and sutured in place using 10-0 nylon. Any gap is filled with a “spacer” made from donor corneal stroma or a piece of donor limbal tissue from the other eye of the same donor. The host conjunctiva is reapproximated to the limbus using interrupted sutures. If required, a tarsorrhaphy can be done.
The advantage of a cadaver eye is that a 360º limbal graft can be taken, thus providing more limbal stem cells. The larger graft also acts as a barrier for migration of conjunctivally derived epithelium over the cornea. The disadvantage is that there is a greater chance of rejection of the graft, and the patient may even require immunosuppressive therapy for his lifetime.
From a live related donor: Here, the procedure followed is the same as limbal autograft (explained below) except that the donor tissue is taken from a live, related donor (Figure 2), preferably after HLA typing and matching. This is done in case of bilateral limbal stem cell deficiency. Even though this theoretically decreases the chances of rejection as compared with a cadaver graft, postoperative systemic immunosuppressive therapy may be required.
Recipient eye: The recipient bed is prepared by doing a peritomy in the involved area and removing the conjuctivalized epithelium and underlying scar tissue off the cornea by blunt dissection. A bed is prepared for the graft by excising a rim of corneolimbal tissue corresponding in size to the donor. A thin rim of conjunctiva is also excised. The donor graft is then kept in place and sutured in place using 10-0 nylon (Figure 3). The host conjunctiva is approximated to the donor conjunctiva using interrupted sutures. If required, a tarsorrhaphy can be done. At the end, if necessary, an amniotic membrane transplantation can also be done (Figure 4).
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Images: Agarwal A |
Limbal autograft technique
In this procedure, the donor tissue is taken from the same or the opposite eye. Hence, it can be performed only in conditions with limited or unilateral limbal stem cell deficiency. The advantage is that the risk of graft rejection is low. The number of grafts taken depends on the severity and extent of involvement of the diseased eye. A maximum of up to 180º of limbal tissue may be excised from the donor eye without inducing iatrogenic limbal stem cell deficiency.
In case of both allografts and autografts, if a penetrating keratoplasty is also planned for the same sitting, it is done after the limbal grafts are sutured in place. The corneal graft generally has to be kept to within 7 mm in size to avoid encroaching onto the limbal graft.
Postoperative course
Generally, the epithelium starts growing from the graft within 2 to 3 days and becomes complete within 2 weeks. If at any stage, conjunctival epithelium is seen to grow over the limbus or cornea again, it is scraped off to allow the epithelialization to occur from the graft. The signs that are indicative of graft rejection include graft edema, graft neovascularization, vascularization over the graft onto the cornea, focal conjunctival injection or focal corneal epithelial defect in the sector of rejection.
For More Information:
- Amar Agarwal, MS, FRCS, FRCOphth is director of Dr. Agarwal’s Group of Eye Hospitals. Prof. Agarwal is author of several books published by SLACK, Incorporated, publisher of Ocular Surgery News, including Phaco Nightmares: Conquering Cataract Catastrophes, Bimanual Phaco: Mastering the Phakonit/MICS Technique, Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery, and Presbyopia: A Surgical Textbook. He can be reached at 19 Cathedral Road, Chennai 600 086, India; fax: 91-44-28115871; e-mail: dragarwal@vsnl.com; Web site: www.dragarwal.com.
References:
- Agarwal A. Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery. Thorofare, NJ: SLACK Incorporated; 2006.
- Agarwal A. Handbook of Ophthalmology. Thorofare, NJ: SLACK Incorporated; 2005.
- Agarwal A, Agarwal A, Agarwal S. Four Volume Textbook of Ophthalmology. New Delhi, India: Jaypee Brothers; 2000.
- Dua HS, Azuara-Blanco A. Autologous limbal transplantation in patients with unilateral corneal stem cell deficiency. Br J Ophthalmol. 2000;84(3):273-278.
- Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709-722.