Short-term outcomes of corneal epithelial reconstruction in patients with bilateral limbal stem cell deficiency using paralimbal oral mucosal epithelial transplantation

Isabekov R.S.; Gelyastanov A.M.; Malyugin B.E.; Borzenok S.A.; Ostrovskiy D.S.; Izmaylova S.B.

doi:https://doi.org/10.17116/oftalma202514105154

Isabekov R.S.

S.N. Fedorov National Medical Research Center “MINK “Eye Microsurgery”

ORCID: 0000-0001-9918-0459

Gelyastanov A.M.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”

ORCID: 0000-0003-4491-7331

Malyugin B.E.

Jules Stein Eye Institute — University of California at Los Angeles

ORCID: 0000-0001-5666-3493

Borzenok S.A.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”;
Russian University of Medicine

ORCID: 0000-0001-9160-6240

Ostrovskiy D.S.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”

ORCID: 0000-0002-2817-7102

Izmaylova S.B.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”

ORCID: 0000-0002-3516-1774

Short-term outcomes of corneal epithelial reconstruction in patients with bilateral limbal stem cell deficiency using paralimbal oral mucosal epithelial transplantation

Authors:

Isabekov R.S., Gelyastanov A.M., Malyugin B.E., Borzenok S.A., Ostrovskiy D.S., Izmaylova S.B.

More about the authors

Journal: Russian Annals of Ophthalmology. 2025;141(5): 54‑65

DOI: 10.17116/oftalma202514105154

Read: 966 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Isabekov RS, Gelyastanov AM, Malyugin BE, Borzenok SA, Ostrovskiy DS, Izmaylova SB. Short-term outcomes of corneal epithelial reconstruction in patients with bilateral limbal stem cell deficiency using paralimbal oral mucosal epithelial transplantation. Russian Annals of Ophthalmology. 2025;141(5):54‑65. (In Russ.)
https://doi.org/10.17116/oftalma202514105154

Подписка 2026 Вестник офтальмологии (Russian Annals of Ophthalmology)

Использование инфографики авторами научных работ

Close metadata

OBJECTIVE

This study analyzed the outcomes of corneal epithelium reconstruction using the method of paralimbal oral mucosal epithelial transplantation (PLOMET) in patients with bilateral limbal stem cell deficiency.

MATERIAL AND METHODS

PLOMET surgery was performed in 10 patients with bilateral limbal stem cell deficiency. Surgical outcomes were monitored for 12 months postoperatively. Impression cytology of the ocular surface with immunohistochemical (IHC) analysis for specific keratins (K3, K4, K7, K12) was performed before and after surgery in addition to standard and supplementary diagnostic methods.

RESULTS

Corneal re-epithelialization within 1—2 months was achieved in all patients. In the late postoperative period, 2 out of 10 patients experienced spontaneous epithelial erosions, associated with systemic comorbidities and certain environmental factors. At 12 months postoperatively, 9 out of 10 patients demonstrated slight improvement in visual acuity, and best-corrected visual acuity exceeded 0.1 in 2 out of 10 patients. Grading of corneal status by three independent experts demonstrated a reduction in conjunctivalization, decreased neovascularization, and improved corneal transparency in 8 out of 10 patients. IHC results showed positive staining for K4, characteristic of oral mucosal epithelial cells, in 7 out of 8 patients, whereas only one patient exhibited marked K12 expression characteristic of corneal epithelium.

CONCLUSION

Paralimbal oral mucosa epithelial transplantation (PLOMET) enables stable corneal re-epithelialization and partial improvement in visual acuity. The latter is limited by the degree of corneal stromal opacification, providing a rationale for optical keratoplasty as a second stage of visual rehabilitation in this patient population.

Keywords:

oral mucosal epithelial transplantation

limbal stem cell deficiency

corneal burn

bilateral limbal stem cell deficiency

Authors:

Isabekov R.S.

S.N. Fedorov National Medical Research Center “MINK “Eye Microsurgery”

ORCID: 0000-0001-9918-0459

Gelyastanov A.M.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”

ORCID: 0000-0003-4491-7331

Malyugin B.E.

Jules Stein Eye Institute — University of California at Los Angeles

ORCID: 0000-0001-5666-3493

Borzenok S.A.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”;
Russian University of Medicine

ORCID: 0000-0001-9160-6240

Ostrovskiy D.S.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”

ORCID: 0000-0002-2817-7102

Izmaylova S.B.

S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery”

ORCID: 0000-0002-3516-1774

Received:

02.05.2025

Accepted:

18.06.2025

Close metadata

References:

Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JAP, Pellegrini G, Shimmura S, Kruse FE; and The International Limbal Stem Cell Deficiency Working Group. Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea. 2019;38(3):364-375. https://doi.org/10.1097/ICO.0000000000001820
Ramos T, Scott D, Ahmad S. An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva. Stem Cells International. 2015;2015:1-7. https://doi.org/10.1155/2015/601731
Haagdorens M, Van Acker SI, Van Gerwen V, Ní Dhubhghaill S, Koppen C, Tassignon MJ, Zakaria N. Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies. Stem Cells International. 2016;2016(1): 9798374. https://doi.org/10.1155/2016/9798374
Jabbehdari S, Baradaran-Rafii A, Yazdanpanah G, Hamrah P, Holland EJ, Djalilian AR. Update on the Management of High-Risk Penetrating Keratoplasty. Current Ophthalmology Reports. 2017;5(1):38-48. https://doi.org/10.1007/s40135-017-0119-2
Basu S, Sureka SP, Shanbhag SS, Kethiri AR, Singh V, Sangwan VS. Simple Limbal Epithelial Transplantation: Long-Term Clinical Outcomes in 125 Cases of Unilateral Chronic Ocular Surface Burns. Ophthalmology. 2016; 123(5):1000-1010. https://doi.org/10.1016/j.ophtha.2015.12.042
Shanbhag SS, Nikpoor N, Rao Donthineni P, Singh V, Chodosh J, Basu S. Autologous limbal stem cell transplantation: a systematic review of clinical outcomes with different surgical techniques. British Journal of Ophthalmology. 2020;104(2):247-253. https://doi.org/10.1136/bjophthalmol-2019-314081
Malyugin BE, Gerasimov MY, Borzenok SA. Glueless Simple Limbal Epithelial Transplantation: The Report of the First 2 Cases. Cornea. 2020; 39(12):1588-1591. https://doi.org/10.1097/ICO.0000000000002467
Malyugin BE, Gerasimov MY, Borzenok SA, Golovin AV. Simple limbal epithelial transplantation. Fyodorov Journal of Ophthalmic Surgery. 2019;(1):77-86. (In Russ.). https://doi.org/10.25276/0235-4160-2019-1-77-86
Bykov VL. Gistologiya i embrional’noe razvitie organov polosti rta cheloveka. M.: GEOTAR-Media; 2014. (In Russ.).
Borzenok SA, Malyugin BE, Gerasimov MYu, Ostrovsky DS. Cultivated autologous oral mucosal epithelial transplantation. Russian Journal of Transplantology and Artificial Organs. 2021;23(1):171-177. (In Russ.). https://doi.org/10.15825/1995-1191-2021-1-171-177
Nanci A. Ten Cate’s Oral Histology. 2017. Accessed November 17, 2024. https://shop.elsevier.com/books/ten-cates-oral-histology/nanci/978-0-323-48524-1
Wong JW, Gallant-Behm C, Wiebe C, Mak K, Hart DA, Larjava H, Häkkinen L. Wound healing in oral mucosa results in reduced scar formation as compared with skin: evidence from the red Duroc pig model and humans. Wound Repair and Regeneration. 2009;17(5):717-729. https://doi.org/10.1111/j.1524-475X.2009.00531.x
Barrett AW, Morgan M, Nwaeze G, Kramer G, Berkovitz BKB. The differentiation profile of the epithelium of the human lip. Archives of Oral Biology. 2005;50(4):431-438. https://doi.org/10.1016/j.archoralbio.2004.09.012
Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. British Journal of Ophthalmology. 2004;88(10):1280-1284. https://doi.org/10.1136/bjo.2003.038497
Liu J, Sheha H, Fu Y, Giegengack M, Tseng SCG. Oral Mucosal Graft With Amniotic Membrane Transplantation for Total Limbal Stem Cell Deficiency. American Journal of Ophthalmology. 2011;152(5):739-747.e1. https://doi.org/10.1016/j.ajo.2011.03.037
Kara N, Dogan L. Simple Oral Mucosal Epithelial Transplantation in a Patient With Bilateral Limbal Stem Cell Deficiency. Eye and Contact Lens. 2021;47(1):65-67. https://doi.org/10.1097/ICL.0000000000000744
Malyugin B, Kalinnikova S, Isabekov R, Ostrovskiy D, Knyazer B, Gerasimov M. Diagnostic Algorithm for Surgical Management of Limbal Stem Cell Deficiency. Diagnostics. 2023;13(2):199. https://doi.org/10.3390/diagnostics13020199
Chentsova EV, Petrova AO, Egorova NS, Storozheva MV, Ponomarev IN, Borovkova NV. Use of a Bioconstruct with cultured buccal epithelial cells in the treatment of patients with corneal injuries. Sovremennye tekhnologii v oftal’mologii. 2020;4:46-47. (In Russ.). https://doi.org/10.25276/2312-4911-2020-4-46-47
Schulze-Bonsel K, Feltgen N, Burau H, Hansen L, Bach M. Visual acuities “hand motion” and “counting fingers” can be quantified with the freiburg visual acuity test. Investigative Ophthalmology & Visual Science. 2006;47(3): 1236-1240. https://doi.org/10.1167/iovs.05-0981
Saw VP, Minassian D, Dart JK, Ramsay A, Henderson H, Poniatowski S, Warwick RM, Cabral S; Amniotic Membrane Tissue User Group (AMTUG). Amniotic membrane transplantation for ocular disease: a review of the first 233 cases from the UK user group. British Journal of Ophthalmology. 2007; 91(8):1042-1047. https://doi.org/10.1136/bjo.2006.098525
Sirotkina KV, Chentsova EV. The possibilities of using the inhibitors of matrix metalloproteinases for keratoplasty. Transplantologiya. The Russian Journal of Transplantation. 2023;15(3):347-358. (In Russ.). https://doi.org/10.23873/2074-0506-2023-15-2-347-358
Trufanov SV, Malozhen SA, Polunina EG, Pivin EA, Tekeeva LYu. Recurrent corneal erosion syndrome (a review). Ophthalmology in Russia. 2015; 12(2):4-12. (In Russ.). https://doi.org/10.18008/1816-5095-2015-2-4-12
Vazirani J, Mariappan I, Ramamurthy S, Fatima S, Basu S, Sangwan VS. Surgical Management of Bilateral Limbal Stem Cell Deficiency. The Ocular Surface. 2016;14(3):350-364. https://doi.org/10.1016/j.jtos.2016.02.006
Denig R. Circumcorneal transplantation of buccal mucous membrane as a curative measure in diseases of the eye. Archives of ophthalmology. 1929; 1(3):351-357. https://doi.org/10.1001/archopht.1929.00810010367007
Ballen PH. Mucous Membrane Grafts in Chemical (Lye) Burns. American Journal of Ophthalmology. 1963;55(2):302-312. https://doi.org/10.1016/0002-9394(63)92687-4
Gipson IK, Geggel HS, Spurr-Michaud SJ. Transplant of Oral Mucosal Epithelium to Rabbit Ocular Surface Wounds In Vivo. Archives of ophthalmology. 1986;104(10):1529-1533. https://doi.org/10.1001/archopht.1986.01050220123039
Malyugin BE, Gerasimov MY. Clinical outcomes of autologous cultured oral mucosal epithelium transplantation for treatment of limbal stem cell deficiency. Fyodorov Journal of Ophthalmic Surgery. 2020;(4):77-85. (In Russ.). https://doi.org/10.25276/0235-4160-2020-4-77-85
Chen HC, Chen HL, Lai JY, Chen CC, Tsai YJ, Kuo MT, Chu PH, Sun CC, Chen JK, Ma DH. Persistence of transplanted oral mucosal epithelial cells in human cornea. Investigative Ophthalmology & Visual Science. 2009;50(10): 4660-4668. https://doi.org/10.1167/iovs.09-3377
Inatomi T, Nakamura T, Kojyo M, Koizumi N, Sotozono C, Kinoshita S. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. American Journal of Ophthalmology. 2006;142(5):757-764. https://doi.org/10.1016/j.ajo.2006.06.004
Choe HR, Yoon CH, Kim MK. Ocular Surface Reconstruction Using Circumferentially-trephined Autologous Oral Mucosal Graft Transplantation in Limbal Stem Cell Deficiency. Korean Journal of Ophthalmology. 2019; 33(1):16. https://doi.org/10.3341/kjo.2018.0111
Ngowyutagon P, Prabhasawat P, Chirapapaisan C, Jaru-Ampornpan P, Pornpanich K, Ekpo P, Sukon N, Matamnan S. Successful Ocular Surface Reconstruction in Complete Ankyloblepharon With the Simple Oral Mucosal Epithelial Transplantation Technique: A Case Report. Cornea. 2021;40(11): 1482-1486. https://doi.org/10.1097/ICO.0000000000002638
Zhu YF, Qiu WY, Xu YS, Yao YF. Clinical efficacy of a new surgical technique of oral mucosal epithelial transplantation for severe ocular surface disorders. BMC Ophthalmology. 2023;23(1):145. https://doi.org/10.1186/s12886-023-02879-4
Aravena C, Yu F, Aldave AJ. Long-Term Visual Outcomes, Complications, and Retention of the Boston Type I Keratoprosthesis. Cornea. 2018;37(1):3-10. https://doi.org/10.1097/ICO.0000000000001405
Baradaran-Rafii A, Delfazayebaher S, Aghdami N, Taghiabadi E, Bamdad S, Roshandel D. Midterm outcomes of penetrating keratoplasty after cultivated oral mucosal epithelial transplantation in chemical burn. The Ocular Surface. 2017;15(4):789-794. https://doi.org/10.1016/j.jtos.2017.08.006
Gerasimov MY, Ostrovskiy DS, Shatskikh AV, Borzenok SA, Malyugin BE. Labial mucosal epithelium grafting in an ex vivo human donor cornea model. Experimental Eye Research. 2022;216:108931. https://doi.org/10.1016/j.exer.2022.108931
Prabhasawat P, Chirapapaisan C, Jiravarnsirikul A, Ekpo P, Uiprasertkul M, Thamphithak R, Matamnan S, Boonwong C. Phenotypic Characterization of Corneal Epithelium in Long-Term Follow-Up of Patients Post-Autologous Cultivated Oral Mucosal Epithelial Transplantation. Cornea. 2021; 40(7):842-850. https://doi.org/10.1097/ICO.0000000000002498
Gaddipati S, Muralidhar R, Sangwan VS, Mariappan I, Vemuganti GK, Balasubramanian D. Oral epithelial cells transplanted on to corneal surface tend to adapt to the ocular phenotype. Indian Journal of Ophthalmology. 2014; 62(5):644-648. https://doi.org/10.4103/0301-4738.109517
Nakamura T, Inatomi T, Cooper LJ, Rigby H, Fullwood NJ, Kinoshita S. Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases. Ophthalmology. 2007;114(6):1080-1088. https://doi.org/10.1016/j.ophtha.2006.09.034
Malhotra C, Jain AK. Human amniotic membrane transplantation: Different modalities of its use in ophthalmology. World Journal of Transplantation. 2014;4(2):111-121. https://doi.org/10.5500/wjt.v4.i2.111
Fatima A, Iftekhar G, Sangwan VS, Vemuganti GK. Ocular surface changes in limbal stem cell deficiency caused by chemical injury: a histologic study of excised pannus from recipients of cultured corneal epithelium. Eye. 2008;22(9):1161-1167. https://doi.org/10.1038/sj.eye.6702895
Burkhardt A. Intraepithelial lymphocytes and Langerhans cells in the oral mucosa — dynamic aspects. Journal of the Dental Association of South Africa. 1992;47(5):200-203.