It is useful in cases of persistent epithelial defects, corneal and
scleral melts, bullous keratopathy and limbal stem cell deficiency.
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
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
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 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.
We will look at amniotic membrane transplantation in conjunctival
- 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: firstname.lastname@example.org; website:
- Disclosure: No products or companies are mentioned that would
require financial disclosure.