Amniotic Membrane Transplantation for Corneal Indications

Overview

Superficial corneal opacity after AMT

Superficial corneal opacity before AMT

Our strategy for corneal surface reconstruction includes amniotic membrane transplantation (AMT). There are two modes for clinical use of AMT; permanent graft or overlaid graft.

When used as a permanent graft, the aim of AMT is to fill in the corneal stromal defect.

When used as a overlaid graft, the aim of AMT is to reduce ocular surface inflammation to promote epithelial healing with minimal or no scarring.

Indications for AMT as a permanent graft

Non-healing Corneal Epithelial Defects/Ulcer/Descemetocele

Corneal defect caused by Acute HSV-I

Before AMT

After AMT

The main cause for non-healing epithelial defects is a “neurotrophic state” meaning there is reduced ocular sensitivity. Therefore, the first line management should start with punctal occlusion followed by autologous serum (if available) or insertion of a high DK bandage contact lens.

If the epithelial defect has no/minimal stromal loss, amniotic membrane transplantation (AMT) can be performed by either inserting PROKERA™ or suturing a single layer of amniotic membrane (AM) (AMNIOGRAFT® size 2.5 x 2.0 cm or 2.0 x 1.5 cm) to cover both the cornea and the perilimbal conjunctiva (as if a large bandage contact lens). 10-O nylon sutures should be placed in a purse-string running fashion about 3 mm from the limbus with about 6-8 scleral bites. Start the running suture in the inferior quadrant and after tying, the end can be left long – the knot does not need to be buried.

It is also a good idea to make a small sutured temporary tarsorrhaphy to narrow the lid fissure.

If the epithelial defect has notable stromal loss (up to descemetocele), the area with the stromal loss should be filled with one or multiple layers of AM. A piece of AM (AMNIOGRAFT® size 2.5 x 2.0 cm) should be cut into smaller pieces and placed into the defect. The orientation of the layers of AM filling the defect does not matter.

If fibrin glue is used, it is best to lay all layers of AM first in the ulcer crater and then apply one drop of fibrinogen and wait several seconds to allow it to percolate through the tissue before adding several drops of thrombin over it to secure the tissue.

If fibrin glue is not used, the AM can be secured using several interrupted 10-O nylon sutures.

After securing the AM filling the defect, a larger layer of AM with the stromal surface facing down is laid and sutured to the healthy stroma with 10-O nylon in either interrupted or running (either zig-zag or purse string) fashion to make sure the top layer of membrane, which will act as a permanent graft, is in close contact with the corneal surface. The knot does not need to be buried.

Lay the remaining AMNIOGRAFT® down to cover the entire cornea, limbus, and part of conjunctiva as if a bandage CL (orientation does not matter), and suture it in the same manner as described above under “the epithelial defect with no/minimal stromal loss”.

A sutured tarsorrhaphy is beneficial to narrow the lid fissure.

Diagnosis of Conjunctivochalasis

Corneal defect caused by Acute HSV-I

Layers of AM secured with fibrin glue to fill the defect

Layers of AM sutured to cover the defect

If the perforation site is less than 2 mm in diameter, first form the anterior chamber with air or one drop of Healon through the perforation site. Trim the Amniotic membrane (AM) (AMNIOGRAFT® size 2.5 x 2.0 cm) into small pieces and place them in multiple layers to fill the defect. Once the defect is filled the layers of AM can be secured with fibrin glue or sutures.

To secure these layers of AM with fibrin glue, apply one drop of fibrinogen over the layers of AM filling the defect. Wait for several seconds to allow the fibrinogen to percolate through the AM before adding several drops of thrombin over it. Alternately, AM can be secured to the corneal surface using 10-O nylon sutures.

Afterwards, a larger piece of AM is placed with the stromal surface facing the cornea is sutured to the healthy stroma with 10-O nylon in either interrupted or running fashion (zig-zag or purse string) to make sure the top membrane acting as a permanent graft is tightly flattened as a patch graft. The knot does not have to be buried.

The remaining AM can be laid down to cover the cornea, limbus, and part of conjunctiva like a therapeutic bandage contact lens (orientation does not matter), and suture it in the same manner as described above. Alternatively, PROKERA™ can be inserted as an overlaid graft.

A sutured tarsorrhaphy is beneficial especially for eyes with a neurotrophic state.

If the perforation site is more than 2 mm in diameter, a tectonic graft will be needed to fill the defect.

AMT for Bullous and Band Keratopathy

Corneal defect caused by Acute HSV-I

Band & Bullous Before AMT

Band & Bullous After AMT

One of two methods of amniotic membrane transplantation (AMT) can be used depending on the amount of stromal loss following the debridement of loose epithelium using a dry Weckcel or by blunt scraping.

If the defect includes no/minimal stromal loss, suture a layer of amniotic membrane (AM) (AMNIOGRAFT® size 2.0 x 1.5 cm) with the stromal surface facing down toward the healthy stroma using 10-O nylon in either interrupted or running (either zig-zag or purse string). Alternatively, PROKERA™ can be inserted as an overlaid graft. Epithelial healing will take place underneath the layer of AM.

If the epithelial defect includes notable stromal loss, a surgical technique similar to “epikeratophakia” is appropriate. After removal of the band keratopathy or bullous epithelium prepare a lamellar pocket to allow insertion of the membrane to ensure that epithelialization will take place on the top, but not underneath the membrane.

First, a superficial trephination (a quarter turn) up to 8 or 9 mm in diameter is performed on the corneal surface. Then a lamellar pocket 2-mm deep is created 360° toward the limbus using a crescent blade. After the lamellar pocket is created, the AM will be secured to the corneal surface using either fibrin glue or 10-O nylon sutures.

If fibrin glue is used to secure the AM, the membrane should be placed on the eye surface outside of the defect area with stromal side up. Apply the thrombin component of the fibrin glue to the defect area and apply the fibrinogen component of the glue to the stromal surface of the AM and flip the membrane to cover the defect with stromal surface down. Use a muscle hook is used to stretch the membrane over the defect and tuck it in the lamellar pocket.

Alternately, AM can be secured to the corneal surface using 10-O nylon sutures.

Indications for AMT as a overlaid graft

AMT After Superficial Keratectomy

If there was no significant stromal loss and the remaining stroma is smooth, AMT can be performed as an overlaid graft by either inserting PROKERA™ or suturing amniotic membrane (AMNIOGRAFT® size 1.5 x 1.0 cm or 2.0 x 1.5 cm) as a single layer to cover both corneal and perilimbal conjunctiva (as if a large bandage contact lens). Starting in the inferior quadrant, suture the amniotic membrane with a 10-O nylon suture in a purse-string running fashion about 3 mm from the limbus with 6 to 8 scleral bites. After tying, the end can be left long and the knot does not need to be buried.

If there was significant stromal loss and the remaining stroma is irregular, before an overlaid graft can be placed as described above, the defect is first filled in with additional layer(s) of amniotic membrane (AMNIOGRAFT® size 1.5 x 1.0 cm or 2.0 x 1.5 cm) using fibrin glue or 10-O nylon sutures.

Trim the membrane to the size of the defect. If fibrin glue is used to secure this bottom layer, the membrane should be placed on the eye surface outside of the defect area with stromal side up. Apply the thrombin component of the fibrin glue to the defect area and apply the fibrinogen component of the glue to the stromal surface of the AM, the membrane is flipped back to cover the defect with stromal surface down and a muscle hook is used to stretch the membrane over the defect. After the glue has set, trim the excess membrane from around the defect.

Alternately, AM can be secured to the corneal surface using 10-O nylon sutures.

AMT for Controlling Inflammation and Promoting Healing

For acute chemical burns, acute Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis

SJS before AMT

SJS after AMT

To cover both corneal and conjunctival surfaces, secure a large piece of amniotic membrane (AM) (AMNIOGRAFT® size 3.5 x 3.5 cm) to the skin surface of the upper lid margin using a 10-O nylon suture in an interrupted or running manner. Push the AM up into the upper fornix with a muscle hook and use a double-armed 4-O black silk suture in a mattress fashion to secure the AM to the skin surface with a bolster made of butterfly tubing. The remaining AM is spread to cover the upper bulbar conjunctiva and a part of the upper corneal surface.

A second large piece of AM (AMNIOGRAFT® size 3.5 x 3.5 cm) is secured to the lower lid with 10-O nylon sutures in the same manner to cover the lower fornix. The second piece of AM will overlap the first piece of AM on the corneal surface.

A temporary tarsorrhaphy is added to minimize the lid fissure if there is an exposure concern due to large scleral show or infrequent blinking as a result of a neurotrophic state (see Figure- Schematic Drawing/Video).

To cover only the corneal surface, AM (AMNIOGRAFT® 2.5 x 2.0 cm size) is secured using a 10-0 nylon suture at 2 to 3 mm from the limbus in a purse-string running fashion for a total of 8 to10 episcleral bites. The AM will cover the corneal surface like a biological bandage lens. Alternatively, PROKERA™ can be inserted following topical anesthetic eye drops and insertion of a lid speculum (see video for insertion and removal).

AMT following High-Risk Corneal Transplantation

AMT following High-Risk Corneal Transplantation

AMT for Corneal Degeneration

Salzmann’s Nodular Degeneration

Salzmann’s Nodular Degeneration Before AMT

Salzmann’s Nodular Degeneration ProKera Inserted

Salzmann’s Nodular Degeneration After AMT

Persistent Epithelial Defects

Corneal ulcers are serious and urgent clinical problems that can be complicated by microbial infections and threaten patient’s vision. Corneal ulcers can be caused by various insults (e.g., exogenously from chemical burns, infection, radiation, or surgeries, while endogenously from aging, diabetes mellitus, viral (herpes) infection, and autoimmune disorders) which have the common denominator – neurotrophic keratopathy. When all medical treatments fail and the ulceration persists, conventional surgical treatments include lamellar or full-thickness corneal transplantation (patch graft), tarsorrhaphy or conjunctival flap.

AMT offers the following advantages over corneal tissue use in the treatment of persistent epithelial defects:

avoidance of potential allograft rejection
postoperative astigmatism of tectonic corneal grafts
ease and convenience of use
feasibility in the event of corneal tissue shortage
preservation of a better aesthetic appearance
Even if corneal transplantation is needed, its success is promoted if performed in an eye that received AMT to reduce inflammation

Descemetocele and Perforation

For deeper stromal ulcers down to descemetocele, multiple layers of amniotic membrane (AM) can be used to restore the normal corneal thickness. When there is frank perforation even up to 3 mm in diameter, AMT may be used to seal the ulcer with or without additional tissue adhesive.

Infectious Keratitis and Scleritis

Corneal ulcers due to bacterial, fungal or viral causes can be managed by AMT after controlling the infection with proper antimicrobial treatment. This procedure results in decreased melting and inflammation at the lesion site with re-epithelialization within 2-3 weeks. Also it decreases the recurrence of infection.

Bullous Keratopathy

Bullous keratopathy is a disorder caused by corneal endothelial decomposition due to degeneration (Fuch’s endothelial dystrophy), surgical trauma, intractable glaucoma, or previous corneal graft failure. For those who do not have a visual potential, relief of pain and recurrent erosion will rely on several surgical treatments including cauterization, anterior stromal puncture, excimer laser photoablation, and conjunctival flap. After epithelial debridement, AMT provides pain relief and healing in addition to creating a smooth corneal epithelial surface 1 month after the procedure, and no recurrent bullae formation.

Band Keratopathy

Band keratopathy occurs in a number of corneal diseases characterized bchronic inflammation. Conventional treatments include chelation by EDTA and superficial keratectomy to remove superficial calcium deposit and corneal stromal tissue. AMT after this procedure has achieved a success rate of more than 90% in relieving patient’s pain, establishing a stable corneal epithelium, and in some eyes improved vision.