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Офтальмохирургия. 2020; : 77-85

Клинические результаты трансплантации аутологичного культивированного эпителия полости рта при дисфункции стволовых клеток лимба роговицы

Малюгин Б. Э., Борзенок С. А., Герасимов М. Ю.

https://doi.org/10.25276/0235-4160-2020-4-77-85

Аннотация

В обзоре представлен анализ результатов клинических исследований трансплантации аутологичного культивированного эпителия полости рта у пациентов с синдромом лимбальной недостаточности (СЛН) роговицы за последние 15 лет. Приведены подробная характеристика и оценка клинических исходов, динамики остроты зрения и частоты осложнений. Полученные в ходе анализа результаты подтверждают состоятельность концепции реэпителизации роговицы с помощью данной технологии. Трансплантация аутологичного культивированного эпителия полости рта способствует образованию стойкого эпителиального покрова в 81,5% случаев и увеличению остроты зрения в 78,8% у пациентов с СЛН. Технология не требует системной иммуносупрессивной терапии, а в сравнении с кератопротезированием сопровождается меньшим числом и тяжестью осложнений. У порядка 15% пациентов регистрируется развитие поверхностной периферической неоваскуляризации роговицы, спонтанно регрессирующей к 12 мес. наблюдений. Опираясь на результаты клинических исследований, тактика ведения пациентов с двусторонним СЛН требует дальнейшей оптимизации с учетом патогенеза основного заболевания. Таким образом, трансплантация аутологичного культивированного эпителия полости рта представляется перспективным научно-практическим направлением офтальмотрансплантологии, требующим дальнейшего углубленного изучения и широкого внедрения в клиническую практику.

Список литературы

1. Deng SX, Borderie V, Chan CC, et al. Global Consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea. 2019;38(3):364–375. doi: 10.1097/ICO.0000000000001820

2. 2Yin J, Jurkunas U. Limbal stem cell transplantation and complications. Semin Ophthalmol. 2018;33(1):134–141. doi: 10.1080/08820538.2017.1353834

3. Tsai RJF, Tseng SCG. Human allograft limbal transplantation for corneal surface reconstruction. Cornea. 1994;13: 389–400. doi: 10.1097/00003226-199409000-00003

4. Kwitko S, Marinho D, Barcaro S, et al. Allograft conjunctival transplantation for bilateral ocular surface disorders. Ophthalmology. 1995;102(7): 1020–1025. doi: 10.1016/s0161-6420(95)30918-9

5. Basu S, Fernandez MM, Das S, et al. Clinical outcomes of xeno-free allogeneic cultivated limbal epithelial transplantation for bilateral limbal stem cell deficiency. Br J Ophthalmol. 2012;96: 1504–1509. doi: 10.1136/bjophthalmol-2012-301869

6. Holland EJ, Mogilishetty G, Skeens HM, et al. Systemic immunosuppression in ocular surface stem cell transplantation: results of a 10-year experience. Cornea. 2012;31(6): 655–661. doi: 10.1097/ICO.0b013e31823f8b0c

7. Krakauer M, Welder JD, Pandya HK, Nassiri N, Djalilian AR. Adverse effects of systemic immunosuppression in keratolimbal allograft. J Ophthalmol. 2012;2012: 576712. doi: 10.1155/2012/576712

8. Bachmann B, Taylor RS, Cursiefen C. Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based metaanalysis. Ophthalmology. 2010;117(7): 1300-1305.e7. doi: 10.1016/j.ophtha.2010.01.039

9. Basu S, Sureka SP, Shanbhag SS, et al. Simple limbal epithelial transplantation: long-term clinical outcomes in 125 cases of unilateral chronic ocular surface burns. Ophthalmology. 2016;123(5): 1000–1010. doi: 10.1016/j.ophtha.2015.12.042

10. Figueiredo GS, Salvador-Culla B, Baylis OJ, et al. Outcomes of penetrating keratoplasty following autologous cultivated limbal epithelial stem cell transplantation. Stem Cells. 2018;36(6): 925–931. doi: 10.1002/stem.2803

11. Мороз З.И., Власова В.А., Ковшун Е.В. История кератопротезирования в МНТК «Микрохирургия глаза» имени академика С.Н. Фёдорова. Офтальмохирургия. 2013;4: 50–55. [Moroz ZI, Vlasova VA, Kovshun EV. The history of keratoprosthetics in the S. Fyodorov Eye Microsurgery Federal State Institution. Fyodorov Journal of Ophthalmic Surgery. 2013;4: 50–55. (In Russ.)]

12. Фёдоров С.Н., Мороз З.И., Ковшун Е.В. и др. Новый способ кератопротезирования истонченных сосудистых бельм. Офтальмохирургия. 1995;2: 50–53. [Fyodorov SN, Moroz ZI, Kovshun EV, et al. Novyi sposob keratoprotezirovaniya istonchennykh sosudistykh bel’m. Fyodorov Journal of Ophthalmic Surgery. 1995;2: 50–53. (In Russ.)]

13. Малюгин Б.Э., Борзенок С.А., Ковшун Е.В., Головин А.В., Шацких А.В., Энкина А.В., Островский Д.С., Белодедова А.В., Джонс М.М. Морфологические изменения роговицы кролика при имплантации новой модели опорной пластинки кератопротеза. Вестник офтальмологии. 2020;136: 77–86. doi: 10.17116/oftalma202013605177 [Malyugin BE, Borzenok SA, Kovshun EV, et al. Evaluation of morphological changes in the rabbit cornea during implantation of a new keratoprosthesis. The Russian Annals of Ophthalmology. 2020;136: 77–86. (In Russ.)]

14. Aravena CYF, Aldave AJ. Long-term visual outcomes, complications, and retention of the Boston type I keratoprosthesis. Cornea. 2018;37(1): 3–10. doi: 10.1097/ICO.0000000000001405

15. Priddy J, Bardan AS, Tawfik HS, Liu C. Systematic review and meta-analysis of the medium- and longterm outcomes of the Boston type 1 keratoprosthesis. Cornea. 2019;38(11): 1465–1473. doi: 10.1097/ICO.0000000000002098

16. Nakamura T, Endo K, Cooper LJ, et al. The successful culture and autologous transplantation of rabbit oral mucosal epithelial cells on amniotic membrane. Invest Ophthalmol Vis Sci. 2003;44(1): 106–116. doi: 10.1167/iovs.02-0195

17. Squier С, Brogden KA. Human oral mucosa: Development, structure and function. John Wiley & Sons, Inc.; 2011: 23.

18. Nakamura T, Inatomi T, Sotozono C, et al. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004;88: 1280–1284. doi: 10.1136/bjo.2003.038497

19. Nishida K, Yamato M, Hayashida Y, et al. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. New Engl J Med. 2004;351: 1187–1196. doi: 10.1056/NEJMoa040455

20. Ang LP, Nakamura T, Inatomi T, et al. Autologous serum-derived cultivated oral epithelial transplants for severe ocular surface disease. Arch Ophthalmol. 2006;124: 1543–1551. doi: 10.1001/archopht.124.11.1543

21. Inatomi T, Nakamura T, Koizumi N, et al. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006;141: 267–275. doi: 10.1016/j.ajo.2005.09.003

22. Inatomi T, Nakamura T, Kojyo M, et al. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol. 2006;142:757–764. doi: 10.1016/j.ajo.2006.06.004

23. Nakamura T, Inatomi T, Cooper LJ, et al. Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases. Ophthalmology. 2007;114: 1080–1088. doi: 10.1016/j.ophtha.2006.09.034

24. Satake Y, Dogru M, Yamane GY, et al. Barrier function and cytologic features of the ocular surface epithelium after autologous cultivated oral mucosal epithelial transplantation. Arch Ophthalmol. 2008;126:23–28. doi: 10.1001/archopht.126.1.23

25. Chen HC, Chen HL, Lai JY, et al. Persistence of transplanted oral mucosal epithelial cells in human cornea. Investig Ophthalmol Vis Sci. 2009;50: 4660–4668. doi: 10.1167/iovs.09-3377

26. Ma DH, Kuo MT, Tsai YJ, et al. Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye. 2009;23: 1442–1450. doi: 10.1038/eye.2009.60

27. Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011;95: 942–946. doi: 10.1136/bjo.2010.188714

28. Satake Y, Higa K, Tsubota K, Shimazaki J. Longterm outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011;118: 1524–1530. doi: 10.1016/j.ophtha.2011.01.039

29. Priya CG, Arpitha P, Vaishali S, et al. Adult human buccal epithelial stem cells: Identification, ex vivo expansion, and transplantation for corneal surface reconstruction. Eye. 2011;25: 1641–1649. doi: 10.1038/eye.2011.230

30. Takeda K, Nakamura T, Inatomi T, et al. Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease. Am J Ophthalmol. 2011;152: 195–201. doi: 10.1016/j.ajo.2011.01.046

31. Burillon C, Huot L, Justin V, et al. Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) transplantation for the treatment of corneal limbal epithelial stem cell deficiency. Investig Ophthalmol Vis Sci. 2012;53: 1325–1331. doi: 10.1167/iovs.11-7744

32. Chen HC, Yeh LK, Tsai YJ, et al. Expression of angiogenesis-related factors in human corneas after cultivated oral mucosal epithelial transplantation. Investig Ophthalmol Vis Sci. 2012;53: 5615–5623. doi: 10.1167/iovs.11-9293

33. Hirayama M, Satake Y, Higa K, Yamaguchi T, Shimazaki J. Transplantation of cultivated oral mucosal epithelium prepared in fibrin-coated culture dishes. Investig Ophthalmol Vis Sci. 2012;53: 1602–1609. doi: 10.1167/iovs.11-7847

34. Sotozono C, Inatomi T, Nakamura T, et al. Visual improvement after cultivated oral mucosal epithelial transplantation. Ophthalmology. 2013;120: 193–200. doi: 10.1016/j.ophtha.2012.07.053

35. Gaddipati S, Muralidhar R, Sangwan VS, et al. Oral epithelial cells transplanted on to corneal surface tend to adapt to the ocular phenotype. Indian J Ophthalmol. 2014;62: 644–648. doi: 10.4103/0301-4738.109517

36. Sotozono C, Inatomi T, Nakamura T, et al. Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity. Acta Ophthalmol. 2014;92: e447–e453. doi: 10.1111/aos.12397

37. Kolli S, Ahmad S, Mudhar HS, et al. Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. Stem Cells. 2014;32: 2135–2146. doi: 10.1002/stem.1694

38. Dobrowolski D, Orzechowska-Wylegala B, Wowra B, et al. Cultivated oral mucosa epithelium in ocular surface reconstruction in aniridia patients. Biomed Res Int. 2015;2015: 281870. doi: 10.1155/2015/281870

39. Prabhasawat P, Ekpo P, Uiprasertkul M, et al. Long-term result of autologous cultivated oral mucosal epithelial transplantation for severe ocular surface disease. Cell Tissue Bank. 2016;17(3): 491–503. doi: 10.1007/s10561-016-9575-4

40. Baradaran-Rafii A, Delfazayebaher S, Aghdami N, et al. Midterm outcomes of penetrating keratoplasty after cultivated oral mucosal epithelial transplantation in chemical burn. Ocul Surf. 2017;15(4): 789–794. doi: 10.1016/j.jtos.2017.08.006

41. Kim YJ, Lee HJ, Ryu JS, et al. Prospective clinical trial of corneal reconstruction with biomaterial-free cultured oral mucosal epithelial cell sheets. Cornea. 2018;37(1): 76–83. doi: 10.1097/ICO.0000000000001409

42. Gopakumar V, Agarwal S, Srinivasan B, et al. Clinical outcome of autologous cultivated oral mucosal epithelial transplantation in ocular surface reconstruction. Cornea. 2019;38(10): 1273–1279. doi: 10.1097/ICO.0000000000002082

43. Всемирная организация здравоохранения. Нарушения зрения и слепота. Доступно по: https://www.who.int/ru/news-room/fact-sheets/detail/blindness-and-visual-impairment [Ссылка активна на 14.06.2020]. [World Health Organization. Blindness and vision impairment. Available from: https://www.who.int/news-room/fact-sheets/detail/blindness-and-visualimpairment [Accessed 14 June 2020].

44. Liu CY, Kao WW. Corneal epithelial wound healing. Prog Mol Biol Transl Sci. 2015;134: 61–71. doi: 10.1016/bs.pmbts.2015.05.002

Fyodorov Journal of Ophthalmic Surgery. 2020; : 77-85

Clinical outcomes of autologous cultured oral mucosal epithelium transplantation for treatment of limbal stem cell deficiency

Malyugin B. E., Borzenok S. A., Gerasimov M. Y.

https://doi.org/10.25276/0235-4160-2020-4-77-85

Abstract

The review presents an analysis of clinical trials results for autologous cultured oral mucosal epithelium transplantation (COMET) in patients with bilateral corneal limbal stem cell deficiency (LSCD) over the past 15 years. Detailed characteristics and evaluation are given for anatomical outcomes, visual acuity changes, and complication rates. The results obtained during the analysis confirm the consistency of the concept of corneal re-epithelization by means of COMET. COMET promoted persistent corneal re-epithelization in 81.5% of cases, and visual acuity improvement in 78.8% of patients with LSCD. COMET does not require systemic immunosuppression, and it is accompanied by much smaller numbers and significantly lower grades of complications compared with keratoprosthesis. About 15% of patients experienced developing superficial peripheral corneal neovascularization regressed spontaneously by 12 months of observation. Based on the COMET clinical trials results, the management of patients with bilateral LSCD is under optimization by reference to the pathogenesis of the underlying disease. Thus, autologous cultured oral mucosal epithelium transplantation seems promising for further studies and introduction into routine clinical practice.

References

1. Deng SX, Borderie V, Chan CC, et al. Global Consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea. 2019;38(3):364–375. doi: 10.1097/ICO.0000000000001820

2. 2Yin J, Jurkunas U. Limbal stem cell transplantation and complications. Semin Ophthalmol. 2018;33(1):134–141. doi: 10.1080/08820538.2017.1353834

3. Tsai RJF, Tseng SCG. Human allograft limbal transplantation for corneal surface reconstruction. Cornea. 1994;13: 389–400. doi: 10.1097/00003226-199409000-00003

4. Kwitko S, Marinho D, Barcaro S, et al. Allograft conjunctival transplantation for bilateral ocular surface disorders. Ophthalmology. 1995;102(7): 1020–1025. doi: 10.1016/s0161-6420(95)30918-9

5. Basu S, Fernandez MM, Das S, et al. Clinical outcomes of xeno-free allogeneic cultivated limbal epithelial transplantation for bilateral limbal stem cell deficiency. Br J Ophthalmol. 2012;96: 1504–1509. doi: 10.1136/bjophthalmol-2012-301869

6. Holland EJ, Mogilishetty G, Skeens HM, et al. Systemic immunosuppression in ocular surface stem cell transplantation: results of a 10-year experience. Cornea. 2012;31(6): 655–661. doi: 10.1097/ICO.0b013e31823f8b0c

7. Krakauer M, Welder JD, Pandya HK, Nassiri N, Djalilian AR. Adverse effects of systemic immunosuppression in keratolimbal allograft. J Ophthalmol. 2012;2012: 576712. doi: 10.1155/2012/576712

8. Bachmann B, Taylor RS, Cursiefen C. Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based metaanalysis. Ophthalmology. 2010;117(7): 1300-1305.e7. doi: 10.1016/j.ophtha.2010.01.039

9. Basu S, Sureka SP, Shanbhag SS, et al. Simple limbal epithelial transplantation: long-term clinical outcomes in 125 cases of unilateral chronic ocular surface burns. Ophthalmology. 2016;123(5): 1000–1010. doi: 10.1016/j.ophtha.2015.12.042

10. Figueiredo GS, Salvador-Culla B, Baylis OJ, et al. Outcomes of penetrating keratoplasty following autologous cultivated limbal epithelial stem cell transplantation. Stem Cells. 2018;36(6): 925–931. doi: 10.1002/stem.2803

11. Moroz Z.I., Vlasova V.A., Kovshun E.V. Istoriya keratoprotezirovaniya v MNTK «Mikrokhirurgiya glaza» imeni akademika S.N. Fedorova. Oftal'mokhirurgiya. 2013;4: 50–55. [Moroz ZI, Vlasova VA, Kovshun EV. The history of keratoprosthetics in the S. Fyodorov Eye Microsurgery Federal State Institution. Fyodorov Journal of Ophthalmic Surgery. 2013;4: 50–55. (In Russ.)]

12. Fedorov S.N., Moroz Z.I., Kovshun E.V. i dr. Novyi sposob keratoprotezirovaniya istonchennykh sosudistykh bel'm. Oftal'mokhirurgiya. 1995;2: 50–53. [Fyodorov SN, Moroz ZI, Kovshun EV, et al. Novyi sposob keratoprotezirovaniya istonchennykh sosudistykh bel’m. Fyodorov Journal of Ophthalmic Surgery. 1995;2: 50–53. (In Russ.)]

13. Malyugin B.E., Borzenok S.A., Kovshun E.V., Golovin A.V., Shatskikh A.V., Enkina A.V., Ostrovskii D.S., Belodedova A.V., Dzhons M.M. Morfologicheskie izmeneniya rogovitsy krolika pri implantatsii novoi modeli opornoi plastinki keratoproteza. Vestnik oftal'mologii. 2020;136: 77–86. doi: 10.17116/oftalma202013605177 [Malyugin BE, Borzenok SA, Kovshun EV, et al. Evaluation of morphological changes in the rabbit cornea during implantation of a new keratoprosthesis. The Russian Annals of Ophthalmology. 2020;136: 77–86. (In Russ.)]

14. Aravena CYF, Aldave AJ. Long-term visual outcomes, complications, and retention of the Boston type I keratoprosthesis. Cornea. 2018;37(1): 3–10. doi: 10.1097/ICO.0000000000001405

15. Priddy J, Bardan AS, Tawfik HS, Liu C. Systematic review and meta-analysis of the medium- and longterm outcomes of the Boston type 1 keratoprosthesis. Cornea. 2019;38(11): 1465–1473. doi: 10.1097/ICO.0000000000002098

16. Nakamura T, Endo K, Cooper LJ, et al. The successful culture and autologous transplantation of rabbit oral mucosal epithelial cells on amniotic membrane. Invest Ophthalmol Vis Sci. 2003;44(1): 106–116. doi: 10.1167/iovs.02-0195

17. Squier S, Brogden KA. Human oral mucosa: Development, structure and function. John Wiley & Sons, Inc.; 2011: 23.

18. Nakamura T, Inatomi T, Sotozono C, et al. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004;88: 1280–1284. doi: 10.1136/bjo.2003.038497

19. Nishida K, Yamato M, Hayashida Y, et al. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. New Engl J Med. 2004;351: 1187–1196. doi: 10.1056/NEJMoa040455

20. Ang LP, Nakamura T, Inatomi T, et al. Autologous serum-derived cultivated oral epithelial transplants for severe ocular surface disease. Arch Ophthalmol. 2006;124: 1543–1551. doi: 10.1001/archopht.124.11.1543

21. Inatomi T, Nakamura T, Koizumi N, et al. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006;141: 267–275. doi: 10.1016/j.ajo.2005.09.003

22. Inatomi T, Nakamura T, Kojyo M, et al. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol. 2006;142:757–764. doi: 10.1016/j.ajo.2006.06.004

23. Nakamura T, Inatomi T, Cooper LJ, et al. Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases. Ophthalmology. 2007;114: 1080–1088. doi: 10.1016/j.ophtha.2006.09.034

24. Satake Y, Dogru M, Yamane GY, et al. Barrier function and cytologic features of the ocular surface epithelium after autologous cultivated oral mucosal epithelial transplantation. Arch Ophthalmol. 2008;126:23–28. doi: 10.1001/archopht.126.1.23

25. Chen HC, Chen HL, Lai JY, et al. Persistence of transplanted oral mucosal epithelial cells in human cornea. Investig Ophthalmol Vis Sci. 2009;50: 4660–4668. doi: 10.1167/iovs.09-3377

26. Ma DH, Kuo MT, Tsai YJ, et al. Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye. 2009;23: 1442–1450. doi: 10.1038/eye.2009.60

27. Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011;95: 942–946. doi: 10.1136/bjo.2010.188714

28. Satake Y, Higa K, Tsubota K, Shimazaki J. Longterm outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011;118: 1524–1530. doi: 10.1016/j.ophtha.2011.01.039

29. Priya CG, Arpitha P, Vaishali S, et al. Adult human buccal epithelial stem cells: Identification, ex vivo expansion, and transplantation for corneal surface reconstruction. Eye. 2011;25: 1641–1649. doi: 10.1038/eye.2011.230

30. Takeda K, Nakamura T, Inatomi T, et al. Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease. Am J Ophthalmol. 2011;152: 195–201. doi: 10.1016/j.ajo.2011.01.046

31. Burillon C, Huot L, Justin V, et al. Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) transplantation for the treatment of corneal limbal epithelial stem cell deficiency. Investig Ophthalmol Vis Sci. 2012;53: 1325–1331. doi: 10.1167/iovs.11-7744

32. Chen HC, Yeh LK, Tsai YJ, et al. Expression of angiogenesis-related factors in human corneas after cultivated oral mucosal epithelial transplantation. Investig Ophthalmol Vis Sci. 2012;53: 5615–5623. doi: 10.1167/iovs.11-9293

33. Hirayama M, Satake Y, Higa K, Yamaguchi T, Shimazaki J. Transplantation of cultivated oral mucosal epithelium prepared in fibrin-coated culture dishes. Investig Ophthalmol Vis Sci. 2012;53: 1602–1609. doi: 10.1167/iovs.11-7847

34. Sotozono C, Inatomi T, Nakamura T, et al. Visual improvement after cultivated oral mucosal epithelial transplantation. Ophthalmology. 2013;120: 193–200. doi: 10.1016/j.ophtha.2012.07.053

35. Gaddipati S, Muralidhar R, Sangwan VS, et al. Oral epithelial cells transplanted on to corneal surface tend to adapt to the ocular phenotype. Indian J Ophthalmol. 2014;62: 644–648. doi: 10.4103/0301-4738.109517

36. Sotozono C, Inatomi T, Nakamura T, et al. Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity. Acta Ophthalmol. 2014;92: e447–e453. doi: 10.1111/aos.12397

37. Kolli S, Ahmad S, Mudhar HS, et al. Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. Stem Cells. 2014;32: 2135–2146. doi: 10.1002/stem.1694

38. Dobrowolski D, Orzechowska-Wylegala B, Wowra B, et al. Cultivated oral mucosa epithelium in ocular surface reconstruction in aniridia patients. Biomed Res Int. 2015;2015: 281870. doi: 10.1155/2015/281870

39. Prabhasawat P, Ekpo P, Uiprasertkul M, et al. Long-term result of autologous cultivated oral mucosal epithelial transplantation for severe ocular surface disease. Cell Tissue Bank. 2016;17(3): 491–503. doi: 10.1007/s10561-016-9575-4

40. Baradaran-Rafii A, Delfazayebaher S, Aghdami N, et al. Midterm outcomes of penetrating keratoplasty after cultivated oral mucosal epithelial transplantation in chemical burn. Ocul Surf. 2017;15(4): 789–794. doi: 10.1016/j.jtos.2017.08.006

41. Kim YJ, Lee HJ, Ryu JS, et al. Prospective clinical trial of corneal reconstruction with biomaterial-free cultured oral mucosal epithelial cell sheets. Cornea. 2018;37(1): 76–83. doi: 10.1097/ICO.0000000000001409

42. Gopakumar V, Agarwal S, Srinivasan B, et al. Clinical outcome of autologous cultivated oral mucosal epithelial transplantation in ocular surface reconstruction. Cornea. 2019;38(10): 1273–1279. doi: 10.1097/ICO.0000000000002082

43. Vsemirnaya organizatsiya zdravookhraneniya. Narusheniya zreniya i slepota. Dostupno po: https://www.who.int/ru/news-room/fact-sheets/detail/blindness-and-visual-impairment [Ssylka aktivna na 14.06.2020]. [World Health Organization. Blindness and vision impairment. Available from: https://www.who.int/news-room/fact-sheets/detail/blindness-and-visualimpairment [Accessed 14 June 2020].

44. Liu CY, Kao WW. Corneal epithelial wound healing. Prog Mol Biol Transl Sci. 2015;134: 61–71. doi: 10.1016/bs.pmbts.2015.05.002