Some corneal diseases can be treated with amniotic membrane transplantation

It is useful in cases of persistent epithelial defects, corneal and scleral melts, bullous keratopathy and limbal stem cell deficiency.

Amar Agarwal

Amniotic membrane has the great advantage of being easily obtainable. When used for ophthalmological purposes, it is taken from placentas obtained via elective Cesarian section and handled in utmost sterile conditions.

Persistent epithelial defects

Amniotic membrane has been used in the treatment of persistent epithelial defects secondary to neurotrophic corneas, autoimmune disorders or limbal stem cell deficiency. In these cases, amniotic membrane may act by inhibiting collagenases while at the same time providing collagen and a basement membrane for epithelial cells to grow on. The amniotic membrane also provides growth factors, all of which provide a conducive atmosphere for epithelial cells to grow.

Corneal and scleral melts

Amniotic membrane is used as a patch-graft or an inlay-onlay graft in the case of corneal or scleral melt. It is used to fill the defect and replace stromal matrix loss caused by the melt. This is done by using multilayered amniotic membrane.

The amniotic membrane is repeatedly folded on itself using fibrin glue to stick the multiple layers to each other. Once this inlay is prepared, the base and edges of the defect are scraped, and all necrotic tissues as well as loose epithelium are removed. The inlay is then used to fill the defect and is stuck into place using glue as well as anchoring sutures. An amniotic membrane patch or an onlay graft is then used to cover the inlay graft in such a manner as to extend beyond the denuded epithelium. This onlay provides anti-inflammatory effects and promotes wound healing.

Confocal microscopy of the transplanted amniotic membrane filler shows its contraction, remodeling with new collagen formation and its population by corneal stroma-derived cells by about 3 months, implying the integration of the filler inlay graft into the corneal matrix. Re-epithelialization of the amniotic membrane is essential for integration of the graft into the stroma. While in the sclera, integration into scleral stroma usually halts the disease process; in the cornea, the graft persists as a scar in the stroma. Nevertheless, it still makes the cornea amenable to a future transplant in a quiet eye.

Certain studies have also used this technique in very deep ulcers and descemetoceles. Amniotic membrane use alone is insufficient in cases of corneal ulcer with active infection, and this should be avoided. It may also not be enough by itself to provide tectonic support in cases of large areas of scleral melt with staphyloma formation or in large corneal ulcers in which tissue with greater tectonic support, such as a corneal or scleral tectonic graft, should be used. In cases with ongoing scleral melt and necrosis, additional medical management directed at the disease pathology would also be required.

Bullous keratopathy

Bullous keratopathy secondary to surgery or Fuchs’ dystrophy in an eye with no potential for vision can be treated with amniotic membrane grafting. The amniotic membrane may be used as isolated treatment after removing the unhealthy epithelium or in conjunction with anterior stromal puncture or phototherapeutic keratectomy. The membrane is spread out under tension and sutured onto the cornea with the stromal side facing down. It acts as a good alternative to conjunctival hooding in these cases and also provides better cosmetic results to the patient than the conjunctival flap. It also does not decrease the chances of survival of a future keratoplasty if required, unlike conjunctival flaps.

Limbal stem cell deficiency

The limbal stem cells are responsible for continuous replenishment of the corneal epithelial cells, and this is proposed to occur via the X, Y, Z hypothesis of Thoft and Friend.

Partial limbal stem cell deficiency

Amniotic membrane can be used in partial limbal stem cell deficiency as an isolated treatment modality. It is spread over the corneal and conjunctival surface and anchored in place using sutures with or without fibrin glue. This may be attributed to its unique property that has been identified in laboratory studies of prolonging the life span of corneal and conjunctival progenitor cells and of maintaining slow-cycling label-retaining cells. It can thus be used to expand the surviving limbal stem cells and the transient amplifying cells of the cornea.

Figure 1. Conjunctival limbal autograft (A) being taken from contralateral eye. Conjunctival limbal autograft (B) after harvesting. Two such grafts are harvested. Unhealthy epithelium and pannus (C) being resected off the affected eye in preparation for limbal stem cell transplantation. The inferior conjunctival limbal autograft (D) being sutured in place. The recipient eye after both grafts (E) have been sutured in place. An amniotic membrane (F) is used to cover the entire ocular surface. Images: Agarwal A

Total limbal stem cell deficiency

In a patient with total limbal stem cell deficiency, stem cell transplantation restores the normal phenotypic corneal epithelium. It also acts as a barrier to conjunctivalization. Amniotic membrane is used in conjunction with limbal stem cell autograft (Figures 1a to 1f) or allograft. In all these cases, it has multiple beneficiary effects. It gives a protective cover over the transplanted stem cells and protects it from external trauma or lid movements until the stem cells have taken. Its anti-inflammatory properties as well as inhibition of angiogenesis help in suppressing graft rejection to an extent. It decreases corneal scar formation after pannus excision. It also promotes epithelial differentiation, adhesion and migration from the newly transplanted limbal stem cells.

The limbal stem cells are harvested as an autograft from the other eye of the same patient or taken as an allograft. An allograft can be from either a living related donor or a cadaveric eye. The advantages of a cadaveric eye include the ability to transplant a much greater number of limbal stem cells, which is not possible in either autograft or living related donor because of the risk of inducing iatrogenic limbal stem cell deficiency. It is also used in those cases in which the patient or the relative is not willing to be a donor.

Once the host cornea is cleared of scar tissue and pannus, the limbal stem cell donor tissue is sutured onto the host limbus. The entire graft and sometimes also the entire donor cornea, depending on the amount of corneal dissection, are covered with the amniotic membrane. A small central hole may be cut with scissors over the pupillary area to enable the patient to see in case only one eye is functional. The amniotic membrane, because of its unique properties, helps in making the perilimbal microenvironment conducive to the limbal stem cell transplantation.

Next month

We will look at amniotic membrane transplantation in conjunctival diseases.

Reference:

• Thoft RA, Friend J. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci. 1983;24(10):1442-1443.

• Amar Agarwal, MS, FRCS, FRCOphth, is director of Dr. Agarwal’s Eye Hospital and Eye Research Centre. Prof. Agarwal is the 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; email: dragarwal@vsnl.com; website: www.dragarwal.com.
• Disclosure: No products or companies are mentioned that would require financial disclosure.