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Guideline Redefines Amniotic Membrane’s Role in Ocular Surface Disease

October 15, 2021 Douglas K. Devries, OD, Paul M. Karpecki, OD, FAAO, Seema Nanda, OD Optometry Times Journal, October digital edition 2021, Volume 13, Issue 10

Earlier and proactive use is suggested for a variety of corneal diseases Every day, patients are referred for treatment of corneal-involved ocular surface diseases such as persistent epithelial defect (PED), recurrent corneal erosion (RCE), and epithelial basement membrane dystrophy (EBMD), among others. Many patients have received prior palliative treatments that were initially effective but ultimately insufficient, resulting in a condition that returns worse than before. Fortunately, in many cases, we are able to use cryopreserved amniotic membrane (CAM) to provide permanent relief for these patients. Our use of CAM for reparative treatment in cases once relegated to palliative care has expanded. As its use becomes increasingly integral to our respective practices, we are in lockstep with ophthalmic corneal surgeons who are incorporating this therapy. Recognition of this expanded role was the impetus for a Consensus Guideline developed by Marguerite McDonald, MD; Neel Desai, MD; Mark Milner, MD; Clifford Salinger, MD; and John Sheppard, MD, MMSc; in conjunction with Bio-Tissue, Inc, manufacturer of CAMs Prokera, AmnioGuard, and AmnioGraft.1

Reexamining the role The Consensus Guideline reexamines the role of CAM in cornea-involved ocular surface disease (OSD) and notes that for many of these disease states, existing standards rely too heavily on palliative treatments and fail to recommend disease- modifying therapies early in the treatment algorithm.2-4 The guideline authors write that their collective experience with amniotic membrane (AM) for treatment of cornea-involved OSDs and for presurgical optimization of the ocular surface indicates that treatment protocols should include earlier, proactive use of AM.1 Our practice patterns with respect to CAM reflect this and other recommendations. For example, the authors of the guideline indicate that superficial keratectomy followed by application of CAM should be the standard of care for treatment of RCE—and we agree.1 The standards of care for many cornea-involved OSDs—including RCE—routinely recommend bandage contact lenses (BCLs) to passively aid in reepithelialization, but BCLs pose inherent risks, including infectious keratitis, dry eye disease (DED), inflammation, and corneal hypoxia and edema.5 Disease-modifying therapy Two types of AM are used for ophthalmic purposes: cryopreserved and dehydrated. The guideline authors explain that the cryopreservation process allows CAM to retain heavy chain (HC) peptide covalently conjugated with high molecular weight hyaluronic acid (HA), which is noncovalently complexed with pentraxin-3 (PTX3)—HC-HA/PTX3—and that this biologic matrix is responsible for CAM’s anti-inflammatory and regenerative healing properties.6-9 CAM is distinct from dehydrated AM because CAM provides regenerative healing, characterized by a limited inflammatory and fibrotic response that is maintained in cryopreservation.10 CAM suppresses inflammation by facilitating neutrophil apoptosis, polarizing M1 to M2 macrophages, and suppressing Th1 and Th17 lymphocyte activation; inhibits scarring by preventing myofi broblast differentiation and reprogramming into progenitor cells; and promotes regenerative healing by augmenting mesenchymal stem cell function and maintaining stem cell quiescence.6 Here, we share how we use CAM in our practices, discuss how our efforts reflect the Consensus Guideline, and make recommendations on how to effectively integrate CAM into clinical practice.

Nanda on PED, RCE, and EBMD Patients who have sustained trauma to the cornea and are at risk of developing persistent epitheliopathies are excellent candidates for CAM as first-line therapy. Every day I see people who have had unsuccessful palliative treatment for corneal wounds. The story is always the same: Other frustrated doctors refer these patients out of sheer desperation because they see corneal wounds that close and then reopen a month later. In cases of RCE, I debride the cornea if the edges are rough, then I apply CAM, and I see the patient back the next day. At that visit, I stain the cornea with fluorescein, with the CAM in place, which allows me to see the degree of improvement. I follow patients according to the amount of injury to their corneas. In milder cases, the cornea may heal quickly, so follow-up may be a week later. With more tissue damage, the cornea may take longer to mend and need another CAM to aid in wound healing. The key is to look for microcystic edema: If present, a second membrane may be warranted. Watch these corneas because erosions can still occur; however, with CAM, the likelihood can be decreased dramatically. I monitor patients every few months until they are healed. As the Consensus Guideline indicates, CAM provides anti-inflammatory and regenerative healing properties that a BCL does not. The application is just as easy, but the results are far superior. Why? The BCL will dehydrate the cornea, causing an increased propensity of infection because patients do not always adhere to the protocol of using antibiotic drops. Chronic conditions such as herpetic lesions, corneal keratitis, and even centrally located epithelial defects from traumatic injuries can be managed effectively and efficiently with CAM.

Here are pearls for use of CAM to treat PED, RCE, and EBMD: » Any patient with PED is a candidate for CAM. » CAM should be used first-line for an acute epithelial defect, proximal to the point of initial injury, when the risk of persistency is high. » CAM should be considered early for epithelial defects that present a high risk for delayed healing and scarring. » For patients with RCE and a sloughing epithelium (whether EBMD- or trauma-based) debridement and treatment with CAM should be considered early in the disease process. » CAM can be used without debridement in RCE without a sloughing epithelium, but with moderate topographic abnormalities and DED. » If RCE presents alongside an active infection, use CAM as soon as possible after identifying the etiology or antimicrobial sensitivities and controlling the infectious process. » CAM should be used in any patient with visually or topographically significant EBMD. » Patients whose EBMD appears to be turning into RCE should be treated with CAM. Conclusion CAM helps to treat corneal-involved OSD, as well as the sequelae of moderate to severe DED, earlier in the disease process. The Consensus Guideline reexamines the role of CAM in the treatment of corneal-involved OSD and suggests that treatment protocols include more proactive use of AM at earlier stages, with an emphasis on the benefits of such use of CAM because of its anti-scarring, anti-inflammatory, and antiangiogenic properties. The guideline provides an educational tool for eye care providers interested in introducing CAM to their own patients.

References 1. McDonald M, Desai N, Salinger C, Milner M, Sheppard J. Redefining the standar

d of care: a consensus guideline. The place of cryopreserved amniotic membrane in treatment protocols for cornea-involved ocular surface disease and before refractive cataract surgery. Bio-Tissue. April 2020. Accessed September 30, 2021. consensus-guide/ 2. Gupta S, Gupta P, Sayegh R. Healing a persistent corneal epithelial defect. EyeNet. August 2014. Accessed June 14, 2021. https://www.aao. org/eyenet/article/ healing-persistent-corneal-epithelial-defect 3. Weiner G. Confronting corneal ulcers. EyeNet. July 2012. Accessed June 14, 2021. confronting-cornealulcers 4. Thakrar R, Hemmati HD. Treatment of recurrent corneal erosions. EyeNet. March 2013. Accessed June 14, 2021. eyenet/article/ treatment-of-recurrent-corneal-erosions 5. Pathak AK, Rubins D, Feldman BH, et al. Bandage contact lenses after refractive surgery. EyeWiki. Updated September 13, 2021. Accessed September 26, 2021. Lenses_ After_Refractive_Surgery 6. Tseng SC. HC-HA/PTX3 purified from amniotic membrane as novel regenerative matrix: insight into relationship between inflammation and regeneration. Invest Ophthalmol Vis Sci. 2016;57(5):ORSFh11-8. doi:10.1167/iovs.15-17637 7. Jirsova K, Jones GLA. Amniotic membrane in ophthalmology: properties, preparation, storage and indications for grafting-a review. Cell Tissue Bank. 2017;18(2):193-204. doi:10.1007/s10561-017-9618-5 8. Rö ck T, Bartz-Schmidt KU, Landenberger J, Bramkamp M, Röck D. Amniotic membrane transplantation in reconstructive and regenerative ophthalmology. Ann Transplant. 2018;23:160-65. doi:10.12659/ AOT.906856 9. Watson CT, Breden F. The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease. Genes Immun. 2012;13(5):363-373. doi:10.1038/gene.2012.12 10. Cooke M, Tan EK, Mandrycky C, He H, O’Connell J, Tseng SC. Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/chorion tissue. J Wound Care. 2014;23(10):465-474, 476. doi:10.12968/jowc.2014.23.10.465 11. Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II report executive summary. Ocul Surf. 2017;15(4):802-812. doi:10.1016/j.jtos.2017.08.003

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