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Amniotic membrane extract eye drops for ocular surface diseases: use and clinical outcome in real-world practice

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Abstract

Purpose

To study the indications and clinical outcomes, in a real-word setting, of amniotic membrane extract eye drops (AMEED) use for ocular surface disease (OSD).

Methods

A retrospective study of patients treated with topical AMEED between January 2018 and January 2020 was conducted. Patients were classified in two groups according to specific OSD—dry eye disease (DED) and wound healing delay (WHD) groups. Demographics, comorbidities, treatment duration and clinical outcomes were analysed.

Results

A total of 50 eyes of 36 patients with or without previous treatments were included. Patients in the DED group presented more systemic comorbidities (83 vs 22%; p < 0.001) and spent more mean time under AMEED treatment (10 vs 7.2 months average) than the WHD group (p = 0.0104). In four patients, long-term treatment (more than 24 months) was reported. Global similar symptomatic improvement was reported for both groups (DED 88.9% vs WHD 100%; p = 0.486), with the WHD group especially consisting in general relief (78%) and the DED group reporting more pain improvement (44%) (p = 0.011). Regarding patients with autologous serum as a previous treatment, no statistical differences were found in subjective or objective improvement. An overall success was achieved in 94.4% of the cases and no adverse events were found.

Conclusion

AMEED administration is a promising mean to treat OSD such as dry eye, persistent epithelial defect and corneal ulcers. Although AMEED may be effective in the treatment of severe DED and persistent epithelial defect or corneal ulcers, conclusions are limited owing to the absence of controlled clinical trials.

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References

  1. Jones L, Downie LE, Korb D et al (2017) TFOS DEWS II management and therapy report. Ocul Surf 15:575–628. https://doi.org/10.1016/j.jtos.2017.05.006

    Article  PubMed  Google Scholar 

  2. Soni NG, Jeng BH (2016) Blood-derived topical therapy for ocular surface diseases. Br J Ophthalmol 100:22–27. https://doi.org/10.1136/bjophthalmol-2015-306842

    Article  PubMed  Google Scholar 

  3. Murri MS, Moshirfar M, Birdsong OC et al (2018) Amniotic membrane extract and eye drops: A review of literature and clinical application. Clin Ophthalmol 12:1105–1112. https://doi.org/10.2147/OPTH.S165553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Malhotra C, Jain AK (2014) Human amniotic membrane transplantation: Different modalities of its use in ophthalmology. World J Transp 4:111–21. https://doi.org/10.5500/wjt.v4.i2.111

    Article  Google Scholar 

  5. Jirsova K, Jones GLA (2017) Amniotic membrane in ophthalmology: properties, preparation, storage and indications for grafting—a review. Cell Tissue Bank 18:193–204. https://doi.org/10.1007/s10561-017-9618-5

    Article  CAS  PubMed  Google Scholar 

  6. Li J, Koike-Soko C, Sugimoto J et al (2015) Human amnion-derived Stem Cells have immunosuppressive properties on NK Cells and Monocytes. Cell Transp 24:2065–2076. https://doi.org/10.3727/096368914X685230

    Article  Google Scholar 

  7. Baradaran-Rafii A, Asl NS, Ebrahimi M et al (2018) The role of amniotic membrane extract eye drop (AMEED) in in vivo cultivation of limbal stem cells. Ocul Surf 16:146–153. https://doi.org/10.1016/j.jtos.2017.11.001

    Article  PubMed  Google Scholar 

  8. Tighe S, Mead OG, Lee A, Tseng SC (2020) Basic science review of birth tissue uses in ophthalmology. Taiwan J Ophthalmol 10:3–12. https://doi.org/10.4103/tjo.tjo_4_20

    Article  PubMed  PubMed Central  Google Scholar 

  9. McDonald MB, Sheha H, Tighe S et al (2018) Treatment outcomes in the DRy eye amniotic membrane (DREAM) study. Clin Ophthalmol 12:677–681. https://doi.org/10.2147/OPTH.S162203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tighe S, Moein HR, Chua L et al (2017) Topical cryopreserved amniotic membrane and umbilical cord eye drops promote re-epithelialization in a murine corneal abrasion model. Investig Ophthalmol Vis Sci 58:1586–1593. https://doi.org/10.1167/iovs.16-20834

    Article  CAS  Google Scholar 

  11. Shahriari HA, Famil Tokhmehchi MR, Hashemi NF (2008) Comparison of the effect of amniotic membrane suspension and autologous serum on alkaline corneal epithelial wound healing in the rabbit model. Cornea 27:1148–1150. https://doi.org/10.1097/ICO.0b013e318173138a

    Article  CAS  PubMed  Google Scholar 

  12. Liang L, Li W, Ling S et al (2009) Amniotic membrane extraction solution for ocular chemical burns. Clin Exp Ophthalmol 37:855–863. https://doi.org/10.1111/j.1442-9071.2009.02159.x

    Article  PubMed  Google Scholar 

  13. Bonci P, Bonci P, Lia A (2005) Suspension made with amniotic membrane: clinical trial. Eur J Ophthalmol 15:441–445

    Article  Google Scholar 

  14. Yeu E, Goldberg DF, Mah FS et al (2019) Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease. Clin Ophthalmol 13:887–894. https://doi.org/10.2147/OPTH.S203510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bron AJ, Evans VE, Smith JA (2003) Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 22:640–650. https://doi.org/10.1097/00003226-200310000-00008

    Article  PubMed  Google Scholar 

  16. Tsubota K, Goto E, Shimmura S, Shimazaki J (1999) Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology 106:1984–1989. https://doi.org/10.1016/S0161-6420(99)90412-8

    Article  CAS  PubMed  Google Scholar 

  17. Dua HS, Said DG, Messmer EM et al (2018) Neurotrophic keratopathy. Prog Retin Eye Res 66:107–131. https://doi.org/10.1016/j.preteyeres.2018.04.003

    Article  PubMed  Google Scholar 

  18. Giannaccare G, Carnevali A, Senni C et al (2020) Umbilical Cord blood and serum for the treatment of ocular diseases: a comprehensive review. Ophthalmol Ther 9:235–248. https://doi.org/10.1007/s40123-020-00239-9

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wei Y, Asbell PA (2014) The core mechanism of dry eye disease is inflammation. Eye Contact Lens 40:248–256. https://doi.org/10.1097/ICL.0000000000000042

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bourgeois M, Loisel F, Obert L et al (2019) Can the amniotic membrane be used to treat peripheral nerve defects? a review of literature. Hand Surg Rehabil 38:223–232. https://doi.org/10.1016/j.hansur.2019.05.006

    Article  CAS  PubMed  Google Scholar 

  21. Sacchetti M, Lambiase A (2017) Neurotrophic factors and corneal nerve regeneration. Neural Regen Res 12:1220–1224. https://doi.org/10.4103/1673-5374.213534

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bischoff M, Stachon T, Seitz B et al (2017) Growth factor and interleukin concentrations in amniotic membrane-conditioned medium. Curr Eye Res 42:174–180. https://doi.org/10.3109/02713683.2016.1164189

    Article  CAS  PubMed  Google Scholar 

  23. Sabater-Cruz N, Figueras-Roca M, González Ventosa A et al (2020) Current clinical application of sclera and amniotic membrane for ocular tissue bio-replacement. Cell Tissue Bank 21:597–603. https://doi.org/10.1007/s10561-020-09848-x

    Article  PubMed  Google Scholar 

  24. Harloff S, Hartwig D, Kasper K et al (2008) Epitheliotrophic capacity of serum eye drops from healthy donors versus serum from immunosuppressed patients with rheumatoid arthritis Epitheliotrophe Kapazität von Serum-Augentropfen gesunder versus immunsupprimierter Patienten mit rheumatoider Arthritis. Klin Monbl Augenheilkd 225:200–206. https://doi.org/10.1055/s-2008-1027199

    Article  CAS  PubMed  Google Scholar 

  25. Stenwall PA, Bergström M, Seiron P et al (2015) Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmol 93:654–657. https://doi.org/10.1111/aos.12801

    Article  CAS  PubMed  Google Scholar 

  26. Giannaccare G, Versura P, Buzzi M et al (2017) Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci 56:595–604. https://doi.org/10.1016/j.transci.2017.07.023

    Article  PubMed  Google Scholar 

  27. Wang L, Cao K, Wei Z et al (2020) Autologous serum eye drops versus artificial tear drops for dry eye disease: a systematic review and meta-analysis of randomized controlled trials. Ophthalmic Res 63:443–451. https://doi.org/10.1159/000505630

    Article  PubMed  Google Scholar 

  28. Yilmaz U, Küçük E, Koç Ç, Gökler E (2017) Comparison of autologous serum versus preservative free artificial tear in patients with dry eyes due to systemic isotretinoin therapy. Curr Eye Res 42:827–831. https://doi.org/10.1080/02713683.2016.1255758

    Article  CAS  PubMed  Google Scholar 

  29. Shtein RM, Shen JF, Kuo AN et al (2020) Autologous serum-based eye drops for treatment of ocular surface disease: a report by the American academy of ophthalmology. Ophthalmology 127:128–133. https://doi.org/10.1016/j.ophtha.2019.08.018

    Article  PubMed  Google Scholar 

  30. Thanathanee O, Phanphruk W, Anutarapongpan O et al (2013) Contamination risk of 100% autologous serum eye drops in management of ocular surface diseases. Cornea 32:1116–1119. https://doi.org/10.1097/ICO.0b013e3182910036

    Article  PubMed  Google Scholar 

  31. Russo A, Bonci P, Bonci P (2012) The effects of different preservation processes on the total protein and growth factor content in a new biological product developed from human amniotic membrane. Cell Tissue Bank 13:353–361. https://doi.org/10.1007/s10561-011-9261-5

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Researchers are members of AMEED Research Group and considered co-authors of the present study. They contributed to patient recruitment and follow-up: Miriam Ferrán-Fuertes, Diana Mora Ramírez, Carlos Luis Moser and Mónica Lecumberri López: Hospital General de L’Hospitalet (Hospitalet de Llobregat, Spain); Oscar Gris Castellón and Miriam Barbany Rodríguez: Instituto de Microcirugía Ocular (Barcelona, Spain); Sara Martín Nalda and Laia Bisbe López: Hospital Universitari de la Vall d'Hebron (Barcelona, Spain); Noelia Sabater-Cruz, Maite Sáinz de la Maza, Ramon Quintana, Josep Torras Sanvicens, Marc Figueras-Roca and Ricardo P Casaroli-Marano: Hospital Clínic de Barcelona (Barcelona, Spain); Núria Planas: Hospital Sant Joan de Deu Esplugues (Esplugues de Llobregat, Spain); Rafael Iturralde: Hospital Universitario Pamplona (Pamplona, Spain); Miquel Domingo Vinyals: Instituto Oftalmológico Castanera (Barcelona Spain); Jeisibel Malave: Institut Català de la Retina (Barcelona, Spain); Jorge Pradas Chacón, Suhel Elnayef: Consorci Sanitari Terrassa (Terrassa, Spain); Daniela Ortiz: Hospital Joan XXIII Tarragona (Tarragona, Spain); Silvia Bover: Hospital Josep Trueta (Girona, Spain); Noemí Barnils: Hospital Universitari de Bellvitge (Hospitalet de Llobregat, Spain); Pablo Infiesta Madurga: Fundació Althaia (Manresa, Spain).

Funding

None.

Author information

Authors and Affiliations

  1. Hospital Clinic de Barcelona, Institut Clinic D’Oftalmologia (ICOF), Sabino de Arana s/n, 08028, Barcelona, Spain

    Noelia Sabater-Cruz, Marc Figueras-Roca & Ricardo P. Casaroli-Marano

  2. Admiravisión, Institut Oftalmològic Integral, Barcelona, Spain

    Noelia Sabater-Cruz

  3. Hospital de la Creu Roja d’Hospitalet – Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain

    Miriam Ferrán-Fuertes

  4. Barcelona Tissue Bank – Banc de Sang i Teixits (BTB), Barcelona, Spain

    Elba Agustí, Eva M. Martínez-Conesa, María Luisa Pérez-Rodríguez, Anna Vilarrodona & Ricardo P. Casaroli-Marano

  5. Department of Surgery, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

    Ricardo P. Casaroli-Marano

Authors
  1. Noelia Sabater-Cruz
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  2. Marc Figueras-Roca
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  3. Miriam Ferrán-Fuertes
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  4. Elba Agustí
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  5. Eva M. Martínez-Conesa
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  8. Ricardo P. Casaroli-Marano
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Consortia

AMEED Study Group

  • Diana Mora Ramírez
  • , Carlos Luis Moser
  • , Mónica Lecumberri López
  • , Oscar Gris Castellón
  • , Miriam Barbany Rodríguez
  • , Sara Martín Nalda
  • , Laia Bisbe López
  • , Maite Sáinz de la Maza
  • , Ramon Quintana
  • , Josep Torras Sanvicens
  • , Núria Planas
  • , Rafael Iturralde
  • , Miquel Domingo Vinyals
  • , Jeisibel Malave
  • , Jorge Pradas Chacón
  • , Suhel Elnayef
  • , Daniela Ortiz
  • , Silvia Bover
  • , Noemí Barnils
  •  & Pablo Infiesta Madurga

Corresponding author

Correspondence to Noelia Sabater-Cruz.

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The authors declare no conflicts of interest.

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CEIm Hospital Clinic de Barcelona; HCB/2015/0985.

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Consent requirement was waived by the IRB.

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Sabater-Cruz, N., Figueras-Roca, M., Ferrán-Fuertes, M. et al. Amniotic membrane extract eye drops for ocular surface diseases: use and clinical outcome in real-world practice. Int Ophthalmol 41, 2973–2979 (2021). https://doi.org/10.1007/s10792-021-01856-4

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  • DOI: https://doi.org/10.1007/s10792-021-01856-4

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