In my practice, I see many patients who require complex ocular surface reconstruction, such as those with Stevens-Johnson syndrome, ocular cicatricial pemphigoid, or significant scar tissue resulting from chemical injuries or prior surgeries. In these cases, the structures and systems that help keep the epithelium from drying out have often been impaired, delaying and impeding healing.¹ 

Limbal stem cell deficiency is also common in these patients, further slowing healing in areas where scar tissue has been removed from the cornea.² There may also be extensive adhesions associated with the scar tissue, which may be attached to the sclera, to the extraocular muscles, or even to the eyelids. The presence of these adhesions further complicates what may already be a difficult ocular surface reconstruction; they can be challenging to free up during surgery, and there may be significant bleeding from the many blood vessels in the tissue. Additionally, great care must be used when dissecting scar tissue away from the extraocular muscles.

For ocular reconstructions that are complicated by these factors, cryopreserved amniotic membranes (CAMs) can be a versatile, vital tool in the surgeon’s armamentarium. Capable of being used either as a temporary biologic bandage or as a longer-term tissue substrate, CAM promotes epithelial healing, reduces inflammation, and limits scar formation, all of which are key factors for successfully managing complex ocular surface disease.³

Using Amniotic Membranes in Complex Ocular Surface Reconstruction

Two main strategies can help surgeons performing amniotic membrane transplantation for ocular surface repair. The first is to use the amniotic membrane as a temporary biologic bandage. In this role, it functions almost like a scab, covering and protecting the area and providing its anti-scarring and anti-inflammatory effects to help promote healing of the epithelium underneath it. Eventually, an intact epithelium grows under it, and the membrane can either be removed or become dislodged. Amniotic membranes can be used this way in patients with Stevens-Johnson syndrome to suppress inflammation in the acute phase of the disease, particularly in the first 1 to 2 weeks. It is also useful in selected pterygium cases; if a pterygium is covering a large section of the cornea, surgeons can place a conjunctival autograft over the scleral bed, but may also suture a sheet of amniotic membrane over the entire cornea to help speed epithelial healing.⁴

The second approach is to use the amniotic membrane as a tissue substrate. In this method, the epithelium grows over top of the membrane, which permanently remains in place. This approach can help to minimize inflammation at a conjunctival autograft donor site; the technique involves gluing the amniotic membrane down and tucking its edges under the surrounding conjunctiva to facilitate epithelial growth. It can also be layered in areas of corneal or scleral thinning to provide additional thickness in areas where tissue has been lost.⁴ Surgeons should remember that amniotic membrane does not contain any living epithelial cells, so there should be some normal epithelium surrounding the area of placement. If there is no normal surrounding epithelium or if the eye is heavily scarred, a very light dose of mitomycin C can be useful. In my practice, I typically use a low concentration (0.2 mg/mL) and apply it with a sponge to the undersurface of elevated conjunctiva for 20 to 30 seconds. The goal is to decrease the activity of fibroblasts, the cells responsible for producing scar tissue, without shutting down healing completely. Fibroblasts play important roles in tissue health, so overuse of mitomycin C can increase the risk of long-term complications, such as scleral or corneal melting, which sometimes may not occur until many years later.⁵

Minimizing inflammation and scarring while protecting the limbal architecture is critical for any successful ocular surface reconstruction.⁴ As such, in larger pterygium cases it can be useful to suture a sheet of amniotic membrane over the cornea and then apply a large-diameter soft contact lens for 1 to 2 weeks. This helps stabilize the membrane, increases its duration of activity, and improves comfort by covering sutures. Postoperatively, surgeons can treat the eye with topical steroids for 2 to 3 months and also can consider placing a depot of triamcinolone in the inferior fornix.⁶ 

Considerations and Techniques When Using Amniotic Membrane Products

Amniotic membrane products are available in freeze-dried and cryopreserved forms. Both forms are available as sheets that can be fastened to the tissue with fibrin glue or sutures. Freeze-dried sheets can also be placed under a contact lens to prevent movement and facilitate healing of a persistent epithelial defect; these have the advantages of longer shelf life and do not require specialized freezers for storage, which can be advantageous in private practice settings.⁷ Compared to the cryopreserved versions, however, there is less literature supporting the effectiveness of freeze-dried formulations.

Cryopreserved membranes are also available as a sutureless device that can be placed on the eye like a contact lens.⁴ Some patients find these devices uncomfortable, but anecdotally I have found that most patients tolerate them reasonably well. I have also noticed that the duration the membrane remains on the eye can vary depending on the level of inflammation and blinking, which is an important factor to consider when utilizing CAM. A therapeutic soft contact lens or a temporary suture tarsorrhaphy may be utilized to prolong the lifespan of the membrane on the eye.⁸

Proper handling of the membrane is also critical to the success of the procedure. With cryopreserved sheets, technique includes measuring the area to be covered with calipers, using the built-in 1-mm grid on the membrane packaging for sizing, and cutting the membrane accordingly. I mark the edges and center of the membrane piece I am using with a surgical pen before transferring it to the eye; this step is especially helpful in a bloody field where visualization is limited. To make the markings adhere, I lightly dry the membrane first, place my marks, and then rehydrate it with balanced salt solution for easier handling before placement. When orienting the membrane, the stromal side (the side against the paper) should be placed against the ocular surface. If the membrane flips or rolls up and the orientation is unclear, a Weck-Cel sponge can be used as a test: the stromal side will stick to the sponge, while the basement membrane side will not.

Although amniotic membranes are an extremely useful tool, they have specific use cases. Because the membranes do not provide viable tissue, I use conjunctival autografts to cover defects when possible. I may also harvest an autograft from the fellow eye, if it is unaffected, or use buccal mucosal grafts from the lip or cheek. Amniotic membrane can be useful, however, when other graft options are not feasible or when additional anti-inflammatory support is needed.

Conclusion

For ocular surface cases, it is important to remember that inflammation is the enemy. The body’s natural tendency is to close defects as quickly as possible, often with thick scar tissue.⁹ The challenge is to remove existing scar tissue while preventing the formation of even more scarring. When applied appropriately, as part of a broader surgical strategy, the use of amniotic membranes can significantly improve healing and help minimize the cycle of inflammation and scarring that defines complex ocular surface disease.

Darren Gregory, MD, is an ophthalmologist practicing at the University of Colorado Sue Anschutz-Rodgers Eye Center who specializes in the treatment of diseases of the cornea and ocular surface. Dr. Gregory reports no industry affiliations/relevant disclosures.

 References

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