When I trained as an optometrist 30 years ago, amniotic membranes were reserved for the worst possible cases of ocular surface disease (OSD). Since then, cryopreserved amniotic membrane (CAM) has become a mainstay of treatment for dry eye disease (DED) and other OSDs. In fact, a recent, retrospective cohort study of fee-for-service Medicare patients found that dry eye accounted for 44.2% of all sutureless amniotic membrane diagnosis claims in 2020.¹

This dramatic increase in utilization has come hand-in-hand with our growing understanding of the science behind DED; what we once considered a simple disorder we now know is an incredibly complex and multifactorial disease driven by neurosensory abnormalities and inflammation, among other factors.²

Understanding the Role of Corneal Nerves in DED

One of the most significant changes in recent years has been our growing understanding of the relationship between corneal nerve damage and DED, which has significantly altered the treatment paradigm. When a patient has chronic dry eye, the corneal nerves become inflamed, which, over time, can lead to desensitization and the development of neurotrophic keratitis (NK).³

I work in a tertiary dry eye center, and I often take referrals of “dry eye patients” who, when I check corneal sensitivity, demonstrate early-stage NK. These patients absolutely still have dry eye—they may have decreased tear production or meibomian gland dysfunction, for example—but it is important to remember the corneal nerves are also a contributing factor to their DED because the corneal nerves are responsible for tear production, blink rate, and corneal wound healing. Studies have shown that corneal nerves were significantly depleted in dry eye, even suggesting that nerve density could be used to gauge the severity of DED.³

Building on these findings, a landmark study in 2017 demonstrated that participants with DED who were treated with a self-retained CAM (Prokera; BioTissue, Inc.) had significantly improved signs and symptoms of DED, increased corneal nerve density, and better corneal sensitivity.⁴ Moreover, the timing of acceptable CAM use in NK has shifted earlier: In one retrospective study, patients with early-stage NK who failed prior conservative therapies and were treated with shelf-stable CAM (CAM360 AG; BioTissue, Inc.) and a 24-hour collagen shield had improved corneal epithelial integrity, visual acuity, and corneal sensitivity.⁵ Thus, we have moved toward earlier intervention with CAM in these patients because it can restore the corneal nerves before more substantial damage occurs.

Assessing Possible Candidates for CAM

Working in a tertiary care center, I often see patients after they have tried all the typical options: artificial tears, punctal plugs, lid scrubs, warm compresses, cyclosporine, lifitegrast; the list goes on. If a patient has been referred to me for a dry eye workup, I usually start with these conservative therapies, as well as intense pulsed light therapy or a low-dose corticosteroid. However, if the patient returns and I have documented that these therapies are not working, it is time to consider a CAM. This is also when insurance coverage and prior authorizations become part of the discussion. With Medicare patients, I proceed directly to CAM when the clinical indication and treatment history support it. With many commercial insurance plans, however, a prior authorization is often needed, so documenting their previous treatment failures is vital.

A patient’s corneal sensitivity level also influences the clinical decision. If testing reveals a neurotrophic component, it changes my typical treatment algorithm and accelerates my decision to place a CAM. In some patients with early-stage NK, for example, I may use a membrane as a temporary step while waiting for the approval of cenegermin.

Using the CAM Portfolio

Although I use several types of amniotic membranes in my practice, I mostly use CAM as opposed to dehydrated membranes, because the cryopreservation process helps retain the growth factors that provide the anti-inflammatory, antiscarring, and antiangiogenic properties⁶; however, my exact choice depends on the particular patient.

I usually begin with CAM360 AG, which is a shelf-stable, ringless CAM option. Because it is ringless, it is a relatively comfortable, patient-friendly option. However, it does have to be placed with a collagen shield, and you have to patch the patient. Therefore, an elderly patient who drove to the appointment and only has 20/40 vision in their other eye, for instance, may not be the best candidate for CAM360 AG—a dehydrated membrane and bandage contact lens may be more appropriate for them.

Glaucoma is another factor that needs to be considered when thinking about using CAM. Many of my dry eye patients also have end-stage glaucoma, and though I have seen good results with multilayer membranes like BioVance 3L (Celularity Inc), these kinds of membranes require a pressure patch. Not only does this render the patient monocular, but they would also not be able to use drops to treat their glaucoma for 24 to 48 hours in the patched eye.

Though cost is another factor that needs to be considered, I would caution other optometrists not to choose a membrane solely based on cost concerns. Read the research supporting the use of membranes and pay attention to how the membranes were used and who specifically they were efficacious for; a little background information can ensure that you choose the membrane that will give your patients the most possible benefit.

Conclusion

From my perspective, the dramatic increase in CAM use just shows how much we have improved our identification of patients who could benefit and our growing understanding of DED as a disease where multiple risk factors can interact with and exacerbate each other. Precisely because of its highly varied causes and presentations, it is paramount that we assess our DED patients as individuals and take the time to consider what they have tried, if they have a neurotrophic component, and what other comorbid conditions may be at play in causing their DED.

As I have seen in my 30 years of practice, the use of amniotic membranes in dry eye is increasing for a reason. I expect CAM use in dry eye to continue to grow as both the technology around it and our understanding of DED itself continue to improve. More clinicians and large organizations will be introduced to this technology, and having it in more hands will give us an even greater understanding of what dry eye etiologies and patient characteristics allow for its most efficacious use.

References

1. Vail DG, Nudleman E, Abdeljaber L, Haque ME, Pershing S. Utilization patterns and costs of ocular amniotic membrane grafts in the Medicare population. Ophthalmology. 2026;133(1):51-59. doi:10.1016/j.ophtha.2025.08.023

2. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276-283. doi:10.1016/j.jtos.2017.05.008

3. Vereertbrugghen A, Galletti JG. Corneal nerves and their role in dry eye pathophysiology. Exp Eye Res. 2022;222:109191. doi:10.1016/j.exer.2022.109191

4. John T, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. 2017;2017:6404918. doi:10.1155/2017/6404918

5. Bauza AM. Management of stage 1 neurotrophic keratopathy with shelf-stable, cryopreserved amniotic membrane: a retrospective study. Clin Ophthalmol. 2026;20:591419. doi:10.2147/OPTH.S591419

6. Zhang Y, Helman A, Mead OG, Tighe S, Zhu Y, Tseng SCG. Processing methods affect biological properties of amniotic membrane sheet products. Cornea. 2025;44(6):671-678. doi:10.1097/ICO.0000000000003849.

Lauren McLoughlin, OD is a practicing optometrist, director of the residency program, and director of the Ocular Surface Wellness Center at Eyesight Ophthalmic Services in Portsmouth, New Hampshire. She reports affiliations with Dompe, Biotissue, Sight Sciences, Alcon, Bausch + Lomb, Lenz Therapeutics, Brill, Ocubio, and Harrow Health.