Amniotic membrane tissue (AMT) is a powerful tool for managing ocular surface disease due to its anti-inflammatory, anti-angiogenic, and regenerative properties. The clinical use of AMT in ophthalmology began in the 1940s, when it was used as a conjunctival substitute after removal of fibrotic tissue. While the limited access to fresh amniotic tissue during this period constrained its utility, contemporary technological innovations in our ability to preserve, store, and distribute AMT have greatly expanded its availability and led to new applications. Currently, AMT is used across many different fields of medicine for purposes such as healing chronic wounds and burns, as well as in plastic surgery, oral medicine, and gynecology (1, 2). Even so, our understanding of its full potential in ophthalmology – and its application in clinical medicine more broadly – is only just beginning to emerge.
Understanding the biological utility of AMT
The most important component of AMT is the high molecular weight hyaluronic acid species, including the heavy chain-hyaluronan/pentraxin 3 complex (HC-HA/PTX3). HC-HA/PTX3 enables AMT to support limbal stem cells, facilitating the support and growth of the corneal epithelium (3). AMT reduces inflammation by facilitating neutrophil apoptosis, polarizing macrophages to facilitate anti-inflammatory processes, and suppressing specific lymphocyte activation. Its ability to act as a bandage treatment enables the anti-scarring function of AMT, as it protects the epithelium from damage caused by constant blinking and allows healing (4, 5). The regenerative properties of AMT have been demonstrated by an increase in sub-basal corneal nerve density and corneal sensitivity after a single treatment, with resolution in corneal punctate staining and improved tear film stability also being observed (6).
These biological components and their resultant biological efficacy are affected differently by the various methods used for the preservation of AMT; the main preparations used in ophthalmology are dehydrated amniotic membrane and cryopreserved amniotic membrane (CAM). Though dehydration methods preserve the structure of the tissue, enabling it to be used as a scaffold for cellular growth, it does not maintain the HC-HA/PTX3 complex (2).
Current uses of CAM
I typically employ the healing properties of CAM in conditions in which the corneal epithelium is affected, such as moderate to severe dry eye disease (DED), corneal ulcers like those due to herpetic infections, and bacterial keratitis that may result from contact lens overwear (1, 7). The ability of CAM to improve the health of the corneal epithelium has been demonstrated clinically in studies of DED, as CAM reduced corneal and conjunctival staining, as well as improved visual acuity, after five days of treatment with self-retained CAM (1). In one study, improvement in signs and symptoms were observed after only two days, with benefits lasting up to three months (8).
The speed with which CAM can improve the ocular surface is critical for patients facing scheduled cataract surgery, and thus this is another area where I frequently use CAM. Before cataract surgery is undertaken, obtaining precise biometry and keratometry is critical to ensure optimal visual outcomes. The quality of these preoperative measurements for intraocular lens selection depends on the health of the ocular surface (9). If the ocular surface needs improvement ahead of surgery – and especially if the patient is affected by an acute condition – I utilize CAM to heal the epithelium quickly, enabling the surgery to be safely performed to achieve optimal postoperative visual outcomes.
CAM also has the capability of improving corneal sensitivity and promoting corneal nerve regeneration, marking it as a mainstay treatment for patients with DED, neurotrophic keratopathy (NK), and possibly even corneal neuropathic pain. One study of DED patients showed that patients who used CAM had improvement in both the signs and symptoms of DED, as well as in corneal nerve density, corneal sensitivity, and corneal topography. This is thought to be due to the presence of neurotrophic factors, especially nerve growth factors, which promote corneal nerve regeneration (6,
Potential future applications
With the increasing accessibility of CAM, new applications of this technology continue to be developed. One area in which I would be interested to see more data is its ability to restore and regenerate corneal nerve anatomy, function, and integrity, such as in corneal neuropathic pain and NK. The more we learn about ocular surface disease, the more we understand that symptoms do not always correlate with clinical findings (11), and I think the role of corneal nerves could be critical in understanding this disconnect. Thus, I would love to see more data on what happens to the structure and function of corneal nerves when they are underactive in NK, and when they are overactive in corneal neuropathic pain after application of CAM.
Another area that deserves more investigation is the efficacy of CAM when it is layered with other treatments for nerve dysfunction, known as the “sandwich method.” In my own practice, I have found that this method of combining treatments is highly effective for Stage 1 and Stage 2 NK. In this approach, I place a CAM for one or two days to try to stabilize epithelium, after which I prescribe an eight-week course of recombinant human nerve growth factor (cenegermin 0.002%). After the treatment, I place another CAM due to the regenerated epithelium being so fragile, especially in patients with severe NK. Layering the treatments supports both corneal epithelial regeneration and corneal nerve regeneration. With so many treatment options available for ocular surface disease, it can be tricky to elucidate how to combine and layer treatments, but more often than not, complex cases require a combination of treatments. The availability of clinical data, or even case studies, assessing this combination of treatments would be helpful for clinicians when they are creating customized treatment plans for patients.
While the use of CAM is already well established for the treatment of many conditions affecting the ocular surface, I look forward to further research that will unlock even more of its numerous applications.
References
- A Walkden, “Amniotic membrane transplantation in ophthalmology: an updated perspective,” Clin Ophthalmol., 14, 2057 (2020). PMID: 32801614.
- N Hofmann et al., “Preparation of human amniotic membrane for transplantation in different application areas,” Front Transplant [Online ahead of print] (2023). PMID: 38993896.
- SC Tseng, “HC-HA/PTX3 purified from amniotic membrane as novel regenerative matrix: insight into relationship between inflammation and regeneration,” Invest Ophthalmol Vis Sci., 57, 5 (2016). PMID: 27116665.
- U Vaidyanathan et al., “Persistent corneal epithelial defects: a review article,” Med Hypothesis Discov Innov Ophthalmol., 8, 163 (2019). PMID: 31598519.
- GR Vera-Duarte et al., “Neurotrophic keratopathy: general features and new therapies,” Surv Ophthalmol., 69, 789 (2024). PMID: 38679146.
- T John et al., “Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease,” J Ophthalmol. [Online ahead of print] (2017). PMID: 28894606.
- B Gurnani, K Kaur, Bacterial Keratitis, StatPearls Publishing: 2025.
- M McDonald et al., “Association of treatment duration and clinical outcomes in dry eye treatment with sutureless cryopreserved amniotic membrane,” Clin Ophthalmol., 17, 2697 (2023). PMID: 37720008.
- N Venkateswaran et al., “Ocular surface optimization before cataract surgery,” Saudi J Ophthalmol., 36, 142 (2022). PMID: 36211316.
- OG Mead et al., “Amniotic membrane transplantation for managing dry eye and neurotrophic keratitis,” Taiwan J Ophthalmol., 10, 13 (2020). PMID: 32309119.
- R Hua et al., “Discrepancy between subjectively reported symptoms and objectively measured clinical findings in dry eye: a population-based analysis,” BMJ Open [Online ahead of print] (2014). PMID: 25168038.
