Cultivated Limbal Epithelial Transplant Versus Conjunctival Limbal Auto Transplant in Uniocular Limbal Stem Cell Deficiency: Long-Term Results

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Rajan Sharma Ashok Sharma, MS Verinder S Nirankari, MD


Purpose: To evaluate and compare long-term efficacy of cultivated limbal epithelial cell transplant (CLET) and conjunctival limbal autograft (CLAU) in uniocular limbal stem cell deficiency (LSCD) in chemically injured eyes.

Methods: This was a retrospective, interventional, comparative study, and comprised of sixty- one patients with unilateral severe LSCD who underwent CLET (10) and CLAU (51 patients).

Surgical Procedure: Surgical procedure in CLET included superficial keratectomy, excision of fibrovascular tissue, securing amniotic membrane supporting cultured limbal stem cells and placement of bandage contact lens. CLAU included superficial keratectomy, excision of fibrovascular tissue, securing limbal stem cells graft with / without amniotic membrane transplant (AMT).

Results: Following CLET ocular surface improved in all 10 patients and visual acuity improved significantly in three cases. CLAU was performed in 33 eyes and combined CLAU + AMT in 18 eyes. Visual acuity improved significantly in 26 (51%) eyes. Ocular surface and symblepharon grades improved in all patients during a mean 58.7±21.9 months follow up.

Conclusion: CLET and CLAU is safe and effective in rehabilitating the ocular surface before penetrating keratoplasty (PKP) in uniocular severe LSCD. CLET has the advantage of avoiding iatrogenic limbal stem cell deficiency. CLAU enabled us to repair symblepharon simultaneously by taking extra conjunctiva.

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SHARMA, Rajan; SHARMA, Ashok; NIRANKARI, Verinder S. Cultivated Limbal Epithelial Transplant Versus Conjunctival Limbal Auto Transplant in Uniocular Limbal Stem Cell Deficiency: Long-Term Results. Medical Research Archives, [S.l.], v. 10, n. 7, july 2022. ISSN 2375-1924. Available at: <>. Date accessed: 08 aug. 2022. doi:
Research Articles


1. Ramírez BE, Victoria DA, Murillo GM, Herreras JM, Calonge M. In vivo confocal microscopy assessment of the corneoscleral limbal stem cell niche before and after biopsy for cultivated limbal epithelial transplantation to restore corneal epithelium. Histol Histopathol. 2015;30(2):183-192.
2. Massie I, Dziasko M, Kureshi A, et al. Advanced imaging and tissue engineering of the human limbal epithelial stem cell niche. Methods Mol Biol. 2015;1235:179-202.
3. Thoft RA, Friend J. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci. 1983;24(10):1442-1443.
4. Bath C, Muttuvelu D, Emmersen J, Vorum H, Hjortdal J, Zachar V. Transcriptional dissection of human limbal niche compartments by massive parallel sequencing [published correction appears in PLoS One. 2013;8(11).
5. Chen JJ, Tseng SC. Abnormal corneal epithelial wound healing in partial-thickness removal of limbal epithelium. Invest Ophthalmol Vis Sci. 1991;32(8):2219-2233.
6. Daya SM, Chan CC, Holland EJ; Members of The Cornea Society Ocular Surface Procedures Nomenclature Committee. Cornea Society nomenclature for ocular surface rehabilitative procedures. Cornea. 2011;30(10):1115-1119.
7. Kruse FE, Chen JJ, Tsai RJ, Tseng SC. Conjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium. Invest Ophthalmol Vis Sci. 1990;31(9):1903-1913.
8. Sangwan VS. Limbal stem cells in health and disease. Biosci Rep. 2001;21(4):385-405.
9. Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709-723.
10. Pellegrini G, Traverso CE, Franzi AT, Zingirian M, Cancedda R, De Luca M. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet. 1997;349(9057):990-993.
11. Schwab IR. Cultured corneal epithelia for ocular surface disease. Trans Am Ophthalmol Soc. 1999;97:891-986.
12. Le Q, Chauhan T, Yung M, Tseng CH, Deng SX. Outcomes of Limbal Stem Cell Transplant: A Meta-analysis. JAMA Ophthalmol. 2020;138(6):660-670.
13. Pellegrini G, Dellambra E, Golisano O, et al. p63 identifies keratinocyte stem cells. Proc Natl Acad Sci U S A. 2001;98(6):3156-3161.
14. Kim JC, Tseng SC. Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea. 1995;14(5):473-484.
15. Sharma A, Pandey S, Sharma R, Mohan K, Gupta A. Cyanoacrylate tissue adhesive augmented tenoplasty: a new surgical procedure for bilateral severe chemical eye burns. Cornea. 1999;18(3):366-369.
16. Anderson DF, Ellies P, Pires RT, Tseng SC. Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol. 2001;85(5):567-575.
17. Sharma A, Sharma R. Limbal stem cell transplants and amniotic membrane grafts in ocular surface disease: current perspectives. J Clin Ophthalmol. 2018;2:70-79.
18. Cheung AY, Sarnicola E, Holland EJ. Long-Term Ocular Surface Stability in Conjunctival Limbal Autograft Donor Eyes. Cornea. 2017;36(9):1031-1035.
19. Ramachandran C, Basu S, Sangwan VS, Balasubramanian D. Concise review: the coming of age of stem cell treatment for corneal surface damage. Stem Cells Transl Med. 2014;3(10):1160-1168.
20. Borderie VM, Ghoubay D, Georgeon C, et al. Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency. Stem Cells Transl Med. 2019;8(12):1230-1241.
21. Sangwan VS, Basu S, Vemuganti GK, et al. Clinical outcomes of xeno-free autologous cultivated limbal epithelial transplantation: a 10-year study. Br J Ophthalmol. 2011;95(11):1525-1529.
22. Shortt AJ, Secker GA, Notara MD, et al. Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol. 2007;52(5):483-502.
23. Tsai RJ, Tsai RY. Ex vivo expansion of corneal stem cells on amniotic membrane and their outcome. Eye Contact Lens. 2010;36(5):305-309.
24. Haagdorens M, Van Acker SI, Van Gerwen V, et al. Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies. Stem Cells Int. 2016;2016:9798374.
25. Baradaran-Rafii A, Ebrahimi M, Kanavi MR, et al. Midterm outcomes of autologous cultivated limbal stem cell transplantation with or without penetrating keratoplasty. Cornea. 2010;29(5):502-509.
26. Basu S, Ali H, Sangwan VS. Clinical outcomes of repeat autologous cultivated limbal epithelial transplantation for ocular surface burns. Am J Ophthalmol. 2012;153(4):643-650.e6502.
27. Kolli S, Ahmad S, Lako M, Figueiredo F. Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells. 2010;28(3):597-610.
28. Pathak M, Cholidis S, Haug K, et al. 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. 2013;91(8):769-775.
29. Sangwan VS, Matalia HP, Vemuganti GK, et al. Clinical outcome of autologous cultivated limbal epithelium transplantation. Indian J Ophthalmol. 2006;54(1):29-34.
30. Sangwan VS, Basu S, Vemuganti GK, et al. Clinical outcomes of xeno-free autologous cultivated limbal epithelial transplantation: a 10-year study. Br J Ophthalmol. 2011;95(11):1525-1529.
31. Sejpal K, Ali MH, Maddileti S, et al. Cultivated limbal epithelial transplantation in children with ocular surface burns. JAMA Ophthalmol. 2013;131(6):731-736.
32. Subramaniam SV, Sejpal K, Fatima A, Gaddipati S, Vemuganti GK, Sangwan VS. Coculture of autologous limbal and conjunctival epithelial cells to treat severe ocular surface disorders: long-term survival analysis. Indian J Ophthalmol. 2013;61(5):202-207.
33. Vazirani J, Basu S, Kenia H, et al. Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation. Am J Ophthalmol. 2014;157(3):584-90.
34. Ganger A, Singh A, Kalaivani M, et al. Outcomes of surgical interventions for the treatment of limbal stem cell deficiency. Indian J Med Res. 2021;154(1):51-61.
35. Gomes JA, dos Santos MS, Cunha MC, Mascaro VL, Barros Jde N, de Sousa LB. Amniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical burn. Ophthalmology. 2003;110(3):466-473.
36. Santos MS, Gomes JA, Hofling-Lima AL, Rizzo LV, Romano AC, Belfort R Jr. Survival analysis of conjunctival limbal grafts and amniotic membrane transplantation in eyes with total limbal stem cell deficiency. Am J Ophthalmol. 2005;140(2):223-230.
37. Wylegala E, Dobrowolski D, Tarnawska D, et al. Limbal stem cells transplantation in the reconstruction of the ocular surface: 6 years experience. Eur J Ophthalmol. 2008;18(6):886-890.
38. Miri A, Al-Deiri B, Dua HS. Long-term outcomes of autolimbal and allolimbal transplants. Ophthalmology. 2010;117(6):1207-1213.
39. Javadi MA, Jafarinasab MR, Feizi S, Karimian F, Negahban K. Management of mustard gas-induced limbal stem cell deficiency and keratitis. Ophthalmology. 2011;118(7):1272-1281.
40. Eslani M, Cheung AY, Kurji K, Pierson K, Sarnicola E, Holland EJ. Long-term outcomes of conjunctival limbal autograft in patients with unilateral total limbal stem cell deficiency. Ocul Surf. 2019;17(4):670-674.
41. Ozer MD, Altınkurt E, Yilmaz YC, Gedik AC, Alparslan N. The Surgical Outcomes of Limbal Allograft Transplantation in Eyes Having Limbal Stem Cell Deficiency. J Curr Ophthalmol. 2020;32(2):132-141.
42. Nubile M, Curcio C, Dua HS, et al. Pathological changes of the anatomical structure and markers of the limbal stem cell niche due to inflammation. Mol Vis. 2013;19:516-525.
43. Cavallini GM, Pellegrini G, Volante V, et al. Chemical injury treated with autologous limbal epithelial stem cell transplantation and subconjunctival bevacizumab. Clin Ophthalmol. 2014;8:1671-1673. Published 2014 Aug 30.
44. El-Hofi AH, Helaly HA. Evaluation of limbal transplantation in eyes with bilateral severe ocular surface damage secondary to chemical injury. Clin Ophthalmol. 2019;13:383-390. Published 2019 Feb 18.
45. Saini JS, Sharma A. Ocular chemical burns--clinical and demographic profile. Burns. 1993;19(1):67-69.
46. "Sparklers Can Burn at 2,000 Degrees Fahrenheit" (PDF). United States Consumer Product Safety Commission. Retrieved 11 August 2014.
47. Tseng SC. Concept and application of limbal stem cells. Eye (Lond). 1989;3 ( Pt 2):141-157.
48. Basu S, Mohamed A, Chaurasia S, Sejpal K, Vemuganti GK, Sangwan VS. Clinical outcomes of penetrating keratoplasty after autologous cultivated limbal epithelial transplantation for ocular surface burns. Am J Ophthalmol. 2011;152(6):917-924.e1.
49. Qi X, Xie L, Cheng J, Zhai H, Zhou Q. Characteristics of immune rejection after allogeneic cultivated limbal epithelial transplantation. Ophthalmology. 2013;120(5):931-936.
50. Titiyal JS, Sharma N, Agarwal AK, Prakash G, Tandon R, Vajpayee R. Live Related versus Cadaveric Limbal Allograft in Limbal Stem Cell Deficiency. Ocul Immunol Inflamm. 2015;23(3):232-239.
51. Djalilian AR, Mahesh SP, Koch CA, et al. Survival of donor epithelial cells after limbal stem cell transplantation. Invest Ophthalmol Vis Sci. 2005;46(3):803-807.
52. Schlötzer-Schrehardt U, Freudenberg U, Kruse FE. Zukunftstechnologie Tissue-Engineering : Fokus auf die Stammzellnische [The emerging technology of tissue engineering : Focus on stem cell niche]. Ophthalmologe. 2017;114(4):327-340.