Joana Berberan Santos Silva

Introduction

The amniotic membrane (AM) is the innermost layer of the placenta, comprising a thick basement membrane and an avascular stromal matrix. It has been used in ophthalmology since the early twentieth century, with renewed interest following the work of Kim and Tseng in the 1990s, who demonstrated its efficacy in ocular surface reconstruction (1). Its unique biological properties, including anti-inflammatory, anti-fibrotic, anti- angiogenic, and pro-epithelialisation effects, make it a versatile adjunct in the management of a wide range of ocular surface conditions (1,2). Amniotic membrane transplantation (AMT) is now an established surgical technique in corneal and anterior segment practice, and familiarity with its indications and applications is essential for ophthalmic trainees.

Biological Properties

The therapeutic effects of the amniotic membrane derive from its structural and biochemical composition. The basement membrane provides a substrate for epithelial cell migration and differentiation, whilst the stroma suppresses transforming growth factor-beta (TGF-β) signalling, thereby reducing myofibroblast differentiation and scar formation (2). The AM contains a range of growth factors, including epidermal growth factor (EGF), hepatocyte growth factor (HGF), and nerve growth factor (NGF), which promote epithelial healing and corneal nerve regeneration (3). Its avascular nature and immunomodulatory properties render it immunologically privileged, minimising the risk of rejection (1).

Amniotic membrane is available in two principal forms: cryopreserved and dehydrated. Cryopreserved AM retains viable cells and a fuller complement of growth factors, whilst dehydrated AM provides a durable, acellular scaffold. The choice between them depends on the clinical indication and surgical preference (2).

Indications

AMT has a broad range of ophthalmic indications, the most common of which include:

Persistent epithelial defects (PEDs): AMT is widely used in the management of PEDs that fail to heal with conventional lubricant therapy. It promotes re-epithelialisation by providing a stable basement membrane and suppressing stromal inflammation (3).

Acute ocular surface burns: In chemical or thermal injuries, AMT applied within the first two weeks reduces acute inflammation, limits limbal stem cell loss, and improves long-term visual outcomes. Early application is associated with significantly better prognosis (4).

Pterygium surgery: AMT is used as an alternative to conjunctival autograft following pterygium excision, particularly where donor conjunctiva is limited. It reduces recurrence rates compared with bare sclera excision alone (2).

Neurotrophic keratopathy: AMT supports corneal healing in the context of reduced corneal sensation, where conventional treatment has failed. It may be used alongside or following pharmacological neurotrophic agents (3).

Limbal stem cell deficiency (LSCD): AMT serves as a carrier substrate in cultivated limbal epithelial transplantation (CLET) and as an adjunct in ocular surface reconstruction in cases of partial or total LSCD (1).

Dry eye and ocular surface inflammation: The self-retained amniotic membrane contact lens (ProKera) is used in the outpatient setting for moderate-to-severe dry eye, recurrent corneal erosion, and filamentary keratitis (5).

Surgical Technique

AMT may be performed as a primary surgical procedure or as an adjunct to other ocular surface interventions. Two principal methods of fixation are used: suture-based and sutureless.

In the sutured technique, the AM is secured to the ocular surface using interrupted or running absorbable sutures (typically 8-0 or 10-0 Vicryl), with the basement membrane surface placed facing upward to facilitate epithelialisation. The membrane may be applied as a single layer (patch graft) or as multiple layers (sandwich technique) depending on the depth and extent of the defect (2,6).

Sutureless delivery is achieved using the ProKera system, in which a ring of amniotic membrane is self- retained on the ocular surface like a therapeutic contact lens. This approach is suitable for less severe indications and can be performed in the outpatient or emergency setting without the need for theatre (5).

Post-operative management includes topical antibiotic prophylaxis, preservative-free lubrication, and regular follow-up to assess membrane integration and epithelial healing. The AM is gradually absorbed or replaced by native epithelium over two to six weeks.

Investigations

Prior to AMT, assessment of the underlying condition and ocular surface status is essential. Slit-lamp examination with fluorescein and Rose Bengal or lissamine green staining quantifies epithelial defect size and identifies areas of devitalised tissue. Anterior segment optical coherence tomography (AS-OCT) can be used to assess stromal depth and integrity. In cases of PED or neurotrophic keratopathy, in vivo confocal microscopy (IVCM) allows evaluation of corneal nerve density and immune cell infiltration, which may guide prognosis and treatment response (3).

Systemic causes of ocular surface disease, including autoimmune conditions, Stevens-Johnson syndrome, and graft-versus-host disease, should be identified and optimally managed in collaboration with relevant specialties prior to surgical intervention.

Management Outcomes and Complications

AMT is generally well tolerated with a favourable safety profile. Reported complications include membrane displacement, secondary infection, subepithelial fibrosis, and, rarely, corneal perforation in the context of very thin or melting stroma (2). The risk of disease transmission from donor tissue is minimised by standardised screening protocols, though informed consent should address this theoretical risk.

Outcomes are best when AMT is performed early in the disease course. In acute chemical injuries, application within the first ten days is associated with significantly improved visual acuity and reduced limbal stem cell loss at one year (4). In PEDs, healing rates of 70–90% have been reported with cryopreserved AMT, with outcomes superior to lubricants alone (3).

Conclusion

Amniotic membrane transplantation is a safe and versatile technique with a well-established role in ophthalmic practice. Its anti-inflammatory, anti-scarring, and pro-epithelialisation properties make it applicable across a wide spectrum of anterior segment conditions, from acute chemical injuries to chronic neurotrophic keratopathy. Both sutured and sutureless delivery systems allow flexibility in application across surgical and outpatient settings. A sound understanding of the biological rationale, indications, and surgical principles of AMT is essential for all clinicians involved in the management of ocular surface disease.

References

1. Kim JC, Tseng SCG. Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea. 1995;14(5):473–484.

2. Dua HS, Gomes JAP, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51–77.

3. Sheha H, Liang L, Li J, Tseng SCG. Sutureless amniotic membrane transplantation for severe bacterial keratitis. Cornea. 2009;28(10):1118–1123.

4. Meller D, Pires RTF, Mack RJS, et al. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology. 2000;107(5):980–990.

5. Cheng AMS, Zhao D, Chen R, et al. Accelerated restoration of ocular surface health in dry eye disease by self- retained cryopreserved amniotic membrane. Ocul Surf. 2016;14(1):56–63.

6. Tseng SCG, Prabhasawat P, Barton K, Gray T, Meller D. Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol. 1998;116(4):431–441.