Skip to main content
SpringerLink
Log in

Systematic review and meta-analysis investigating autograft versus allograft cultivated limbal epithelial transplantation in limbal stem cell deficiency

  • Review
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Currently, regenerative medicine has attracted much attention among researchers investigating new methods to treat ocular surface diseases. Based on this new concept, cultivated limbal epithelial transplantation (CLET), whether in the form of autograft or allograft, has emerged as a promising surgical procedure for treating limbal stem cell deficiency (LSCD). Given that there is no updated comparison between autograft and allograft CLETs, the present review and meta-analysis aims to compare and determine the efficacy of two different CLET techniques, autologous versus allogeneic, based on a literature review of relevant studies.

Methods

A comprehensive search of electronic databases, including PubMed, Web of Science, Cochrane Library, Embase and Scopus, for related articles was performed in March 2018 to obtain relevant articles and to conduct a meta-analysis investigating the success rate of ocular surface regeneration and two-line improvement in best-corrected visual acuity (BCVA) using autograft versus allograft transplantations.

Results

A total of 30 studies, including 1306 eyes from 1288 patients with LSCD, with a sample size ranging from 6 to 200 and follow-up period of 0.6–156 months, were reviewed. Of 1306 eyes, 982 (75.2%) underwent autograft and 324 (24.8%) received allografts from living or deceased donors. Meta-analysis revealed that there was no significant difference between autograft and allograft CLETs in terms of success rate and two-line BCVA improvement. The prospective studies showed a zero difference between the two groups; only two retrospective studies included in the analysis pulled the autografts up to 1.82 and 1.2 times more than allografts in terms of success rate and two-line BCVA improvement, respectively [pooled OR 1.82 (95% CI 0.80–4.11); pooled OR 1.2 (95% CI 0.54–2.65)]. There was no statistically significant evidence of bias in the meta-analysis in terms of success rates and two-line BCVA improvement.

Conclusions

The present analysis revealed no significant differences in success rates or visual improvement between autograft and allograft surgical techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Pellegrini G, Golisano O, Paterna P et al (1999) Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J Cell Biol 145:769–782

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Lavker RM, Tseng SC, Sun T-T (2004) Corneal epithelial stem cells at the limbus: looking at some old problems from a new angle. Exp Eye Res 78:433–446

    CAS  PubMed  Google Scholar 

  3. Dua HS, Azuara-Blanco A (2000) Autologous limbal transplantation in patients with unilateral corneal stem cell deficiency. Br J Ophthalmol 84:273–278

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Espana EM, Di Pascuale MA, He H et al (2004) Characterization of corneal pannus removed from patients with total limbal stem cell deficiency. Invest Ophthalmol Vis Sci 45:2961–2966

    PubMed  Google Scholar 

  5. Santos MS, Gomes JA, Hofling-Lima AL et al (2005) Survival analysis of conjunctival limbal grafts and amniotic membrane transplantation in eyes with total limbal stem cell deficiency. Am J Ophthalmol 140:223–230

    PubMed  Google Scholar 

  6. Tseng SC (1996) Regulation and clinical implications of corneal epithelial stem cells. Mol Biol Rep 23:47–58

    CAS  PubMed  Google Scholar 

  7. Nishida K, Kinoshita S, Ohashi Y et al (1995) Ocular surface abnormalities in aniridia. Am J Ophthalmol 120:368–375

    CAS  PubMed  Google Scholar 

  8. Yin J, Jurkunas U (2018) Limbal stem cell transplantation and complications. Semin Ophthalmol 33:134–141

    PubMed  Google Scholar 

  9. Pellegrini G, Traverso CE, Franzi AT et al (1997) Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet 349:990–993

    CAS  PubMed  Google Scholar 

  10. Shortt AJ, Tuft SJ, Daniels JT (2011) Corneal stem cells in the eye clinic. Br Med J 100:209–225

    Google Scholar 

  11. Haagdorens M, Van Acker SI, Van Gerwen V et al (2016) Limbal stem cell deficiency: current treatment options and emerging therapies. Stem Cells Int. https://doi.org/10.1155/2016/9798374

    Article  PubMed  Google Scholar 

  12. Shimmura S, Tsubota K (2008) Surgical treatment of limbal stem cell deficiency: are we really transplanting stem cells? Am J Ophthalmol 146:154–155

    PubMed  Google Scholar 

  13. Dua HS, Gomes JA, King AJ, Maharajan VS (2004) The amniotic membrane in ophthalmology. Surv Ophthalmol 49:51–77

    PubMed  Google Scholar 

  14. Gomes JA, Romano A, Santos MS, Dua HS (2005) Amniotic membrane use in ophthalmology. Curr Opin Ophthalmol 16:233–240

    PubMed  Google Scholar 

  15. Kim JC, Tseng SC (1995) Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea 14:473–484

    CAS  PubMed  Google Scholar 

  16. Tsubota K, Satake Y, Ohyama M et al (1996) Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens–Johnson syndrome. Am J Ophthalmol 122:38–52

    CAS  PubMed  Google Scholar 

  17. Akle C, Welsh K, Adinolfi M et al (1981) Immunogenicity of human amniotic epithelial cells after transplantation into volunteers. Lancet 318:1003–1005

    Google Scholar 

  18. Zhao Y, Ma L (2015) Systematic review and meta-analysis on transplantation of ex vivo cultivated limbal epithelial stem cell on amniotic membrane in limbal stem cell deficiency. Cornea 34:592–600

    PubMed  Google Scholar 

  19. Cauchi PA, Ang GS, Azuara-Blanco A, Burr JM (2008) A systematic literature review of surgical interventions for limbal stem cell deficiency in humans. Am J Ophthalmol 46(251–259):e252

    Google Scholar 

  20. Prabhasawat P, Ekpo P, Uiprasertkul M et al (2012) Efficacy of cultivated corneal epithelial stem cells for ocular surface reconstruction. Clin Ophthalmol 6:1483–1492

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Baradaran-Rafii A, Ebrahimi M, Kanavi MR et al (2010) Midterm outcomes of autologous cultivated limbal stem cell transplantation with or without penetrating keratoplasty. Cornea 29:502–509

    PubMed  Google Scholar 

  22. Basu S, Ali H, Sangwan VS (2012) Clinical outcomes of repeat autologous cultivated limbal epithelial transplantation for ocular surface burns. Am J Ophthalmol 153:643–650

    PubMed  Google Scholar 

  23. Chen P, Zhou Q, Wang J et al (2016) Characterization of the corneal surface in limbal stem cell deficiency and after transplantation of cultured allogeneic limbal epithelial cells. Graefes Arch Clin Exp Ophthalmol 254:1765–1777

    CAS  PubMed  Google Scholar 

  24. Cheng J, Zhai H, Wang J et al (2017) Long-term outcome of allogeneic cultivated limbal epithelial transplantation for symblepharon caused by severe ocular burns. BMC Ophthalmol 17:8

    PubMed  PubMed Central  Google Scholar 

  25. Daya SM, Watson A, Sharpe JR et al (2005) Outcomes and DNA analysis of ex vivo expanded stem cell allograft for ocular surface reconstruction. Ophthalmol 112:470–477

    Google Scholar 

  26. Di Iorio E, Ferrari S, Fasolo A et al (2010) Techniques for culture and assessment of limbal stem cell grafts. Ocul Surf 8:146–153

    PubMed  Google Scholar 

  27. Fasolo A, Pedrotti E, Passilongo M et al (2016) Safety outcomes and long-term effectiveness of ex vivo autologous cultured limbal epithelial transplantation for limbal stem cell deficiency. Br J Ophthalmol 101:640–649

    PubMed  Google Scholar 

  28. Ganger A, Vanathi M, Mohanty S, Tandon R (2015) Long-term outcomes of cultivated limbal epithelial transplantation: evaluation and comparison of results in children and adults. Biomed Res Int. https://doi.org/10.1155/2015/480983

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gisoldi RAMC, Pocobelli A, Villani CM et al (2010) Evaluation of molecular markers in corneal regeneration by means of autologous cultures of limbal cells and keratoplasty. Cornea 29:715–722

    Google Scholar 

  30. Kawashima M, Kawakita T, Satake Y et al (2007) Phenotypic study after cultivated limbal epithelial transplantation for limbal stem cell deficiency. Arch Ophthalmol 125:1337–1344

    PubMed  Google Scholar 

  31. Koizumi N, Inatomi T, Suzuki T et al (2001) Cultivated corneal epithelial stem cell transplantation in ocular surface disorders. Ophthalmol 108:1569–1574

    CAS  Google Scholar 

  32. Kolli S, Ahmad S, Lako M, Figueiredo F (2010) Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells 28:597–610

    CAS  PubMed  Google Scholar 

  33. Nakamura T, Inatomi T, Sotozono C et al (2006) Transplantation of autologous serum-derived cultivated corneal epithelial equivalents for the treatment of severe ocular surface disease. Ophthalmology 113:1765–1772

    PubMed  Google Scholar 

  34. Parihar JKS, Parihar AS, Jain VK et al (2017) Allogenic cultivated limbal stem cell transplantation versus cadaveric keratolimbal allograft in ocular surface disorder: 1-year outcome. Int Ophthalmol 37:1323–1331

    PubMed  Google Scholar 

  35. Pathak M, Cholidis S, Haug K et al (2013) Clinical transplantation of ex vivo expanded autologous limbal epithelial cells using a culture medium with human serum as single supplement: a retrospective case series. Acta Ophthalmol 91:769–775

    PubMed  Google Scholar 

  36. Pauklin M, Fuchsluger TA, Westekemper H et al (2010) Midterm results of cultivated autologous and allogeneic limbal epithelial transplantation in limbal stem cell deficiency. Dev Ophthalmol 45:57–70

    PubMed  Google Scholar 

  37. Qi X, Xie L, Cheng J et al (2013) Characteristics of immune rejection after allogeneic cultivated limbal epithelial transplantation. Ophthalmology 120:931–936

    PubMed  Google Scholar 

  38. Rama P, Matuska S, Paganoni G et al (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363:147–155

    CAS  PubMed  Google Scholar 

  39. Ramírez BE, Sánchez A, Herreras JM et al (2015) Stem cell therapy for corneal epithelium regeneration following good manufacturing and clinical procedures. Biomed Res Int. https://doi.org/10.1155/2015/408495

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sangwan VS, Basu S, Vemuganti GK et al (2011) Clinical outcomes of xeno-free autologous cultivated limbal epithelial transplantation: a 10-year study. Br J Ophthalmol 95:1525–1529

    PubMed  Google Scholar 

  41. Schwab IR, Reyes M, Isseroff RR (2000) Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease. Cornea 19:421–426

    CAS  PubMed  Google Scholar 

  42. Sejpal K, Ali MH, Maddileti S et al (2013) Cultivated limbal epithelial transplantation in children with ocular surface burns. JAMA Ophthalmol 131:731–736

    PubMed  Google Scholar 

  43. Sharma S, Tandon R, Mohanty S et al (2011) Culture of corneal limbal epithelial stem cells: experience from benchtop to bedside in a tertiary care hospital in India. Cornea 30:1223–1232

    PubMed  Google Scholar 

  44. Shimazaki J, Higa K, Morito F et al (2007) Factors influencing outcomes in cultivated limbal epithelial transplantation for chronic cicatricial ocular surface disorders. Am J Ophthalmol 143:945–953

    PubMed  Google Scholar 

  45. Shortt AJ, Secker GA, Rajan MS et al (2008) Ex vivo expansion and transplantation of limbal epithelial stem cells. Ophthalmology 115:1989–1997

    PubMed  Google Scholar 

  46. Shortt AJ, Bunce C, Levis HJ et al (2014) Three-year outcomes of cultured limbal epithelial allografts in aniridia and Stevens–Johnson syndrome evaluated using the clinical outcome assessment in surgical trials assessment tool. Stem Cells Transl Med 3:265–275

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Tsai RJ-F, Li L-M, Chen J-K (2000) Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med 343:86–93

    CAS  PubMed  Google Scholar 

  48. Vazirani J, Basu S, Kenia H et al (2014) Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation. Am J Ophthalmol 157(584–590):e582

    Google Scholar 

  49. Zakaria N, Possemiers T, Dhubhghaill SN et al (2014) Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated limbal stem cell transplantation. J Transl Med 12:58

    PubMed  PubMed Central  Google Scholar 

  50. Shortt AJ, Secker GA, Notara MD et al (2007) Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol 52:483–502

    PubMed  Google Scholar 

  51. Baylis O, Figueiredo F, Henein C et al (2011) 13 years of cultured limbal epithelial cell therapy: a review of the outcomes. J Cell Biochem 112:993–1002

    CAS  PubMed  Google Scholar 

  52. Sangwan VS, Matalia HP, Vemuganti GK et al (2006) Clinical outcome of autologous cultivated limbal epithelium transplantation. Indian J Ophthalmol 54:29–34

    PubMed  Google Scholar 

  53. DeSousa JL, Daya S, Malhotra R (2009) Adnexal surgery in patients undergoing ocular surface stem cell transplantation. Ophthalmology 116:235–242

    PubMed  Google Scholar 

  54. Bakhtiari P, Djalilian A (2010) Update on limbal stem cell transplantation. Middle East Afr J Ophthalmol 17:9–14

    PubMed  PubMed Central  Google Scholar 

  55. Behaegel J, Ní Dhubhghaill S, Koppen C, Zakaria N (2017) Safety of cultivated limbal epithelial stem cell transplantation for human corneal regeneration. Stem cells Int. https://doi.org/10.1155/2017/6978253

    Article  PubMed  PubMed Central  Google Scholar 

  56. Lim M, Umapathy T, Baharuddin P, Zubaidah Z (2011) Characterization and safety assessment of bioengineered limbal epithelium. Med J Malaysia 66:335–341

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, No 23, Paydarfard-9th Boostan St., Pasdaran Ave, Tehran, 1666673111, Iran

    Mohammad Amir Mishan, Alireza Baradaran-Rafii & Mozhgan Rezaei Kanavi

  2. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Amir Mishan

  3. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Yaseri

  4. Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Alireza Baradaran-Rafii

Authors
  1. Mohammad Amir Mishan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mehdi Yaseri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alireza Baradaran-Rafii
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mozhgan Rezaei Kanavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mozhgan Rezaei Kanavi.

Ethics declarations

Conflicts of interest

The authors have no commercial or proprietary interest in any concept or product described in this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mishan, M.A., Yaseri, M., Baradaran-Rafii, A. et al. Systematic review and meta-analysis investigating autograft versus allograft cultivated limbal epithelial transplantation in limbal stem cell deficiency. Int Ophthalmol 39, 2685–2696 (2019). https://doi.org/10.1007/s10792-019-01092-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-019-01092-x

Keywords

Search

Navigation