Diagnosis and management of limbal stem cell deficiency, challenges, and future prospects

References

• Gonzalez G, Sasamoto Y, Ksander BR, et al. Limbal stem cells: identity, developmental origin and therapeutic potential. Wiley Interdiscip Rev Dev Biol. 2018;7(2). 10.1002/wdev.303
   PubMed Web of Science ®Google Scholar
• Sacchetti M, Rama P, Bruscolini A, et al. Limbal stem cell transplantation: clinical results, limits, and perspectives. Stem Cells Int. 2018;2018:8086269.
   PubMed Web of Science ®Google Scholar
• Blanpain C, Horsley V, Fuchs E. Epithelial stem cells: turning over new leaves. Cell. 2007;128(3):445–458.
   PubMed Web of Science ®Google Scholar
• Davanger M, Evensen A. Role of the pericorneal papillary structure in renewal of corneal epithelium. Nature. 1971;229(5286):560–561.
   PubMed Web of Science ®Google Scholar
• Deng SX, Borderie V, Chan CC, et al., Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea. 38(3): 364–375. 2019. .
   PubMed Web of Science ®Google Scholar
• Dua HS, Shanmuganathan VA, Powell-Richards AO, et al. Limbal epithelial crypts: a novel anatomical structure and a putative limbal stem cell niche. Br J Ophthalmol. 2005;89(5):529–532. .
   PubMed Web of Science ®Google Scholar
• Ahmad S. Concise review: limbal stem cell deficiency, dysfunction, and distress. Stem Cells Transl Med. 2012;1(2):110–115.
   PubMed Web of Science ®Google Scholar
• Sridhar MS. Anatomy of cornea and ocular surface. Indian J Ophthalmol. 2018;66(2):190–194.
   PubMed Web of Science ®Google Scholar
• Gouveia RM, Lepert G, Gupta S, et al. Assessment of corneal substrate biomechanics and its effect on epithelial stem cell maintenance and differentiation. Nat Commun. 2019;10(1):1–17.
   PubMed Web of Science ®Google Scholar
• Thoft R, Friend J, Jm E, et al. The X, Y, Z hypothesis of comeol epitheliol mointenonce to the editor : for the past few years, studies of corneal epithelial of corneal epithelial disease. Department of ophthalmology. Invest Ophthalmol Vis Sci. 1983;24:1442–1443.
   PubMed Web of Science ®Google Scholar
• Wagoner MD. Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol. 1997;41:275–313.
   PubMed Web of Science ®Google Scholar
• Yoon JJ, Ismail S, Sherwin T. Limbal stem cells: central concepts of corneal epithelial homeostasis. World J Stem Cells. 2014;6(4):391–403.
   PubMedGoogle Scholar
• Jawaheer L, Anijeet D, Ramaesh K. Diagnostic criteria for limbal stem cell deficiency - a systematic literature review. Surv Ophthalmol. 2016;62(4):522–532.
   PubMed Web of Science ®Google Scholar
• Kim KH, Mian SI. Diagnosis of corneal limbal stem cell deficiency. Curr Opin Ophthalmol. 2017;28(4):355–362.
   PubMed Web of Science ®Google Scholar
• Fernandez-Buenaga R, Aiello F, Zaher SS, et al. Twenty years of limbal epithelial therapy: an update on managing limbal stem cell deficiency. BMJ Open Opthalmology. 2018;3(1):e000164.
   PubMed Web of Science ®Google Scholar
• Dua HS, Azuara-blanco A. Limbal stem cells of the corneal epithelium. Surv Ophthalmol. 2000;44(5):415–425.
   PubMed Web of Science ®Google Scholar
• Le Q, Xu J, Deng SX. Review. The diagnosis of limbal stem cell deficiency. Ocul Surf. 2018;16(1):58–69.
   PubMed Web of Science ®Google Scholar
• Vazirani J, Nair D, Shanbhag S, et al. Limbal stem cell deficiency -demography and underlying causes. Am J Ophthalmol. 2018;188:99–103.
   PubMed Web of Science ®Google Scholar
• Mohammadpour M, Javadi MA, Karimian F. Limbal stem cell deficiency in the context of autoimmune polyendocrinopathy. Eur J Ophthalmol. 2006;16(6):870–872.
   PubMed Web of Science ®Google Scholar
• Di Iorio E, Kaye SB, Ponzin D, et al. Limbal stem cell deficiency and ocular phenotype in ectrodactyly-ectodermal dysplasia-clefting syndrome caused by p63 mutations. Ophthalmology. 2012;119(1):74–83.
   PubMed Web of Science ®Google Scholar
• Cheung AY, Patel S, Kurji KH, et al. Ocular surface stem cell transplantation for treatment of keratitis – ichthyosis – deafness syndrome. Cornea. 2019;38(1):123–126.
   PubMed Web of Science ®Google Scholar
• Haagdorens M, Van ASI, Van GV, et al. Limbal stem cell deficiency: current treatment options and emerging therapies. Stem Cells Int. 2016;2016:9798374.
   PubMed Web of Science ®Google Scholar
• Vanden Oever MJ, Tolar J, Nusrat A. Advances in understanding and treating dystrophic epidermolysis bullosa. F1000 Prime Reports. 2014;6: 1–9.
   PubMedGoogle Scholar
• Fernandes M, Sangwan VS, Vemuganti GK. Limbal stem cell deficiency and xeroderma pigmentosum: a case report. Eye. 2004;18(7):741–743.
   PubMed Web of Science ®Google Scholar
• Fatima A, Iftekhar G, Sangwan VS, et al. 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. .
   PubMed Web of Science ®Google Scholar
• Choi SH, Kim MK, Oh JY. Corneal limbal stem cell deficiency in children with stevens-johnson syndrome. Am J Ophthalmol Internet]. 2019;199:1–8.
   PubMed Web of Science ®Google Scholar
• Sinha S, Singh RB, Dohlman TH, et al. Prevalence of persistent corneal epithelial defects in chronic ocular graft-versus-host disease. Am J Ophthalmol. 2020;218:296–303.
   PubMed Web of Science ®Google Scholar
• Samson CM, Nduaguba C, Baltatzis S, et al. Limbal Stem Cell Transplantation in Chronic Inflammatory Eye Disease. Ophthalmology. 2002;109(5):862–868. .
   PubMed Web of Science ®Google Scholar
• Sangwan VS, Jain V, Vemuganti GK, et al. Vernal Keratoconjunctivitis With Limbal Stem Cell Deficiency. Cornea. 2011;30(5):491–496. .
   PubMed Web of Science ®Google Scholar
• Uchino Y, Goto E, Takano Y, et al. Long-standing bullous keratopathy is associated with peripheral conjunctivalization and limbal deficiency. Ophthalmology. 2006;113(7):1098–1101. .
   PubMed Web of Science ®Google Scholar
• Secretariat MA. Limbal stem cell transplantation: an evidence-based analysis. Ont Health Technol Assess Ser. 2008;8:1–58.
   Google Scholar
• Kaliki S, Mohammad FALI, Tahiliani P, et al. Concomitant simple limbal epithelial transplantation after surgical excision of ocular surface squamous neoplasia. Am J Ophthalmol. 2017;174:68–75.
   PubMed Web of Science ®Google Scholar
• Mishra DK, Veena U, Kaliki S, et al. Differential expression of stem cell markers in ocular surface squamous neoplasia. PLoS One. 2016;11(9):1–13. .
   Web of Science ®Google Scholar
• Lichtinger A, Pe’er J, Frucht-Pery J, et al. Limbal stem cell deficiency after topical mitomycin c therapy for primary acquired melanosis with atypia. Ophthalmology. 2010;117(3):431–437.
   PubMed Web of Science ®Google Scholar
• Puangsricharern V, Tseng SCG. Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology. 1995;102(10):1476–1485.
   PubMed Web of Science ®Google Scholar
• Deng SX, Sejpal KD, Tang Q, et al. Characterization of limbal stem cell deficiency by in vivo laser scanning confocal microscopy: a microstructural approach. Arch Ophthalmol. 2012;130(4):440–445. .
   PubMedGoogle Scholar
• Tur VM, Almaazmi A, Alsaadi A, et al. Columnar keratopathy: an early manifestation of limbal stem cell de fi ciency. J EuCornea. 2019;3(3–5):1–4.
   Google Scholar
• Dua HS, Joseph A, Shanmuganathan VA, et al. Stem cell differentiation and the effects of deficiency. Eye. 2003;17(8):877–885. .
   PubMed Web of Science ®Google Scholar
• Solomon A, Ellies P, Anderson DF, et al. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency. Ophthalmology. 2002;109(6):1159–1166. .
   PubMed Web of Science ®Google Scholar
• Dua HS, Gomes JAP, Singh A. Corneal epithelial wound healing. Br J Ophthalmol. 1994;78(5):401–408.
   PubMed Web of Science ®Google Scholar
• Zheng T, Xu J. Age-related changes of human limbus on in vivo confocal microscopy. Cornea. 2008;27(7):782–786.
   PubMed Web of Science ®Google Scholar
• Chan EH, Chen L, Yu FEI, et al. Epithelial thinning in limbal stem cell deficiency. Am J Ophthalmol. 2015;160(669–677.e4):669–677.e4. .
   Google Scholar
• Tseng SCG. Concept and application of limbal stem cells. Eye. 1989;3(2):141–157.
   PubMed Web of Science ®Google Scholar
• Nubile M, Lanzini M, Miri A, et al. In vivo confocal microscopy in diagnosis of limbal stem cell deficiency. Am J Ophthalmol. 2013;155(2):220–232.
   PubMed Web of Science ®Google Scholar
• Tsubota K, Kajiwara K, Ugajin S, et al. Conjunctival brush cytology. Acta Cytol. 1990;34(2):233–235.
   PubMed Web of Science ®Google Scholar
• Prabhasawat P, Luangaram A, Ekpo P, et al. Epithelial analysis of simple limbal epithelial transplantation in limbal stem cell deficiency by in vivo confocal microscopy and impression cytology. Cell Tissue Bank. 2019;20(1):95–108.
   PubMed Web of Science ®Google Scholar
• Ohji M, Ohmi G, Kiritoshi SK A. Goblet cell density in thermal and chemical injuries. Arch Ophthalmol. 1987;105(12):1686–1688.
   PubMedGoogle Scholar
• Garcia I, Etxebarria J, Boto-de-los-bueis A, et al. Comparative study of limbal stem cell deficiency diagnosis methods : detection of MUC5AC mRNA and goblet cells in corneal epithelium. Ophthalmology. 2012;119(5):923–929.
   PubMed Web of Science ®Google Scholar
• Shimmura S, Tsubota K. Surgical treatment of limbal stem cell deficiency: are we really transplanting stem cells? Am J Ophthalmol. 2008;146(2):154–155.
   PubMed Web of Science ®Google Scholar
• Haagdorens M, Behaegel J, Rozema J, et al. A method for quantifying limbal stem cell niches using OCT imaging. Br J Ophthalmol. 2017;101(9):1250–1255.
   PubMed Web of Science ®Google Scholar
• Lathrop KL, Gupta D, Kagemann L, et al. Optical coherence tomography as a rapid, accurate, noncontact method of visualizing the palisades of vogt. Investig Ophthalmol Vis Sci. 2012;53(3):1381–1387.
   PubMed Web of Science ®Google Scholar
• Banayan N, Georgeon C, Grieve K, et al. Spectral-domain Optical Coherence Tomography in Limbal Stem Cell Deficiency. A Case-Control Study. Am J Ophthalmol. 2018;190:179–190.
   PubMed Web of Science ®Google Scholar
• Mehtani A, Agarwal MC, Sharma S, et al. Diagnosis of limbal stem cell deficiency based on corneal epithelial thickness measured on anterior segment optical coherence tomography. Indian J Ophthalmol. 2017;65:1120–1126.
   PubMed Web of Science ®Google Scholar
• Schlereth SL, Hos D, Matthaei M, et al. New technologies in clinical trials in corneal diseases and limbal stem cell deficiency: review from the European vision institute special interest focus group meeting. Ophthalmic Res. 2021;64(2):145–167.
   PubMed Web of Science ®Google Scholar
• Ramírez BE, Victoria DA, Murillo GM, et al. 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.
   PubMed Web of Science ®Google Scholar
• Aravena C, Bozkurt K, Chuephanich P, et al. Classification of limbal stem cell deficiency using clinical and confocal grading. Cornea. 2019;38(1):1–7.
   PubMed Web of Science ®Google Scholar
• Deng SX, Kruse F, Gomes JAP, et al., Global consensus on the management of limbal stem cell deficiency. Cornea. 39(10): 1291–1302. 2020.
   PubMed Web of Science ®Google Scholar
• Iyer G, Srinivasan B, Agarwal S, et al., Surgical management of limbal stem cell deficiency. Asia-Pacific J Ophthalmol. 9(6): 512–523. 2020.
   PubMed Web of Science ®Google Scholar
• Rossen J, Amram A, Milani B, et al. Contact lens-induced limbal stem cell deficiency. Ocul Surf. 2016;14(4):419–434.
   PubMed Web of Science ®Google Scholar
• Ghosh S, Salvador-culla B, Kotagiri A, et al. Acute chemical eye injury and limbal stem cell deficiency — a prospective study in the United Kingdom. Cornea. 2019;38(1):8–12.
   PubMed Web of Science ®Google Scholar
• Ueno H, Ferrari G, Hattori T, et al. Dependence of Corneal Stem/Progenitor Cells on Ocular Surface Innervation. Investig Ophthalmol Vis Sci. 2012;53(2):867–872.
   PubMed Web of Science ®Google Scholar
• Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571–579.
   PubMedGoogle Scholar
• Wang AL, Weinlander E, Metcalf BM, et al. The use of topical insulin to treat refractory neurotrophic corneal ulcers. Cornea. 2017;36(11):1426–1428.
   PubMed Web of Science ®Google Scholar
• Tong CM, Iovieno A, Yeung SN. Topical insulin for neurotrophic corneal ulcers. Can J Ophthalmol Can d’ophtalmologie 2020;55:e170–e172.
   PubMed Web of Science ®Google Scholar
• Amescua G, Akpek EK, Farid M, et al. Blepharitis preferred practice pattern ®. Ophthalmology. 2019;126(1):56–93. .
   Web of Science ®Google Scholar
• Iovieno A, Lambiase A, Micera A, et al. In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis. Eur J Ophthalmol. 2009;19(5):708–716. .
   PubMed Web of Science ®Google Scholar
• Espana EM, Shah S, Santhiago MR, et al. Graft versus host disease: clinical evaluation, diagnosis and management. Graefe’s Arch Clin Exp Ophthalmol. 2013;251(5):1257–1266.
   PubMed Web of Science ®Google Scholar
• Buonavoglia A, Leone P, Dammacco R, et al. Pemphigus and mucous membrane pemphigoid: an update from diagnosis to therapy. Autoimmun Rev. 2019;18(4):349–358.
   PubMed Web of Science ®Google Scholar
• Atallah MR, Palioura S, Perez VL, et al. Limbal stem cell transplantation: current perspectives. Clin Ophthalmol. 2016;1:593–602.
   Google Scholar
• Sivaraman KR, Jivrajka RV, Soin K, et al. Superior limbic keratoconjunctivitis-like inflammation in patients with chronic graft-versus-host disease. Ocul Surf. 2016;14(3):393–400.
   PubMed Web of Science ®Google Scholar
• Yeh S, Chu T, Cheng H, et al. The use of autologous serum to reverse severe contact lens-induced limbal stem cell deficiency. Cornea. 2020;39(6):736–741.
   PubMed Web of Science ®Google Scholar
• Schornack MM. Limbal stem cell disease: management with scleral lenses. Clin Exp Optom. 2011;94(6):592–594.
   PubMed Web of Science ®Google Scholar
• Chahal HS, Estrada M, Sindt CW, et al. Scleral contact lenses in an academic oculoplastics clinic: epidemiology and emerging considerations. Ophthalmic Plast Reconstr Surg. 2018;34(3):231–236.
   PubMed Web of Science ®Google Scholar
• Dua HS, Miri A, Elalfy MS, et al. Amnion-assisted conjunctival epithelial redirection in limbal stem cell grafting. Br J Ophthalmol. 2017;101(7):913–919.
   PubMed Web of Science ®Google Scholar
• Sippel KC, Ma JJK, Foster CS. Amniotic membrane surgery. Curr Opin Ophthalmol. 2001;12(4):363–369.
   PubMed Web of Science ®Google Scholar
• Sabater AL, Perez VL. Amniotic membrane use for management of corneal limbal stem cell deficiency. Curr Opin Ophthalmol. 2017;28(4):363–369.
   PubMed Web of Science ®Google Scholar
• Kolomeyer AM, Do BK, Chu DS. Placement of prokera in the management of ocular manifestations of acute stevens-johnson syndrome in an outpatient. Eye Contact Lens. 2013;39(3):e7–11.
   PubMed Web of Science ®Google Scholar
• Herbort CP, Zografos L, Zwingli M, et al. Topical retinoic acid in dysplastic and metaplastic keratinization of corneoconjunctival epithelium. Graefe’s Arch Clin Exp Ophthalmol. 1988;226(1):22–26.
   PubMed Web of Science ®Google Scholar
• Mammo DA, Kanakamedala P, Hou JH. Severe corneal and conjunctival keratinization with rapid response to topical Vitamin A ointment. Ophthalmology. 2019;126(10):1408.
   PubMed Web of Science ®Google Scholar
• Holland EJ. Management of limbal stem cell deficiency: a historical perspective, past, present, and future. Cornea. 2015;34(Supplement 10):S9–15.
   PubMed Web of Science ®Google Scholar
• Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709–722.
   PubMed Web of Science ®Google Scholar
• Shanbhag SS, Nikpoor N, Donthineni PR, et al. Autologous limbal stem cell transplantation: a systematic review of clinical outcomes with different surgical techniques. Br J Ophthalmol. 2020;104(2):247–253.
   PubMed Web of Science ®Google Scholar
• Kheirkhah A, Raju VK, Tseng SC. Minimal conjunctival limbal autograft for total limbal stem cell deficiency. Cornea. 2008;27(6):730–733.
   PubMed Web of Science ®Google Scholar
• Pellegrini G, Traverso CE, Franzi AT, et al. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet. 1997;349(9057):990–993.
   PubMed Web of Science ®Google Scholar
• Bobba S, Chow S, Watson S, et al. Clinical outcomes of xeno-free expansion and transplantation of autologous ocular surface epithelial stem cells via contact lens delivery: a prospective case series. Stem Cell Res Ther. 2015;6(1):1–14.
   PubMed Web of Science ®Google Scholar
• Figueiredo GS, Bojic S, Rooney P, et al. Gamma-irradiated human amniotic membrane decellularised with sodium dodecyl sulfate is a more efficient substrate for the ex vivo expansion of limbal stem cells. Acta Biomater. 2017;1:124–133.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Rama P, Matuska S, Paganoni G, et al. Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010;363(2):147–155.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Systematic Review ML. Meta-analysis on transplantation of ex vivo cultivated limbal epithelial stem cell on amniotic membrane in limbal stem cell deficiency. Cornea. 2015;34(5):592–600.
   PubMed Web of Science ®Google Scholar
• Ghareeb AE, Lako M, Figueiredo FC. Recent advances in stem cell therapy for limbal stem cell deficiency: a narrative review. Ophthalmol Ther. 2020;9(4):809–831.
   PubMed Web of Science ®Google Scholar
• Bedford P, Jy J, Collins L, et al. Considering cell therapy product “good manufacturing practice” status. Front Med. 2018;5:1–4.
   Web of Science ®Google Scholar
• Shukla V, Seoane-Vazquez E, Fawaz S, et al. The landscape of cellular and gene therapy products: authorization, discontinuations, and cost. Hum Gene Ther Clin Dev. 2019;30(3):102–113. .
   PubMed Web of Science ®Google Scholar
• Sangwan VS, Basu S, Macneil S, et al. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol. 2012;96(7):931–934.
   PubMed Web of Science ®Google Scholar
• Thokala P, Singh A, Singh VK, et al. Economic, clinical and social impact of simple limbal epithelial transplantation for limbal stem cell deficiency. Br J Ophthalmol. 2021;105(1):1–6. .
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Jackson CJ, Myklebust IT, Håkon E, et al. Simple limbal epithelial transplantation: current status and future perspectives. Stem Cells Transl Med. 2020;9(3):316–327.
   PubMed Web of Science ®Google Scholar
• Yin J, Jurkunas U. Limbal stem cell transplantation and complications. Semin Ophthalmol. 2018;33(1):134–141.
   PubMed Web of Science ®Google Scholar
• Daya SM, Bell RWD, Habib NE, et al. Clinical and pathologic findings in human keratolimbal allograft rejection. Cornea. 2000;19(4):443–450.
   PubMed Web of Science ®Google Scholar
• Bhalekar S, Basu S, Sangwan VS. Successful management of immunological rejection following allogeneic simple limbal epithelial transplantation (SLET) for bilateral ocular burns. BMJ Case Rep. 2013;2013:bcr2013009051.
   Google Scholar
• Vazirani J, Basu S, Sangwan VS, Allograft rejection after living-related simple limbal epithelial transplantation. Indian J Ophthalmol. Internet]. 2021;69:433–435.
   PubMed Web of Science ®Google Scholar
• Rama P, Ferrari G, Pellegrini G. Cultivated limbal epithelial transplantation. Curr Opin Ophthalmol. 2017;28(4):387–389.
   PubMed Web of Science ®Google Scholar
• Dong Y, Peng H, Lavker RM. Emerging therapeutic strategies for limbal stem cell deficiency. J Ophthalmol. 2018;2018:7894647.
   PubMed Web of Science ®Google Scholar
• Tomasello L, Musso R, Cillino G, et al. Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells. Stem Cell Res Ther. 2016;7:1–14.
   PubMed Web of Science ®Google Scholar
• Tomasello L, Coppola A, Pitrone M, et al. PFN1 and integrin-β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells. J Cell Mol Med. 2019;23(11):7210–7221.
   PubMed Web of Science ®Google Scholar
• Fiorica C, Tomasello L, Palumbo FS, et al. Production of a double-layer scaffold for the “on-demand” release of fibroblast-like limbal stem cells. ACS Appl Mater Interfaces. 2019;11(25):22206–22217.
   PubMed Web of Science ®Google Scholar
• Le Q, Chauhan T, Yung M, et al. Outcomes of limbal stem cell transplant: a meta-analysis. JAMA Ophthalmol. 2020;138(6):660–670.
   PubMed Web of Science ®Google Scholar
• Serna-Ojeda JC, Basu S, Vazirani J, et al. Systemic immunosuppression for limbal allograft and allogenic limbal epithelial cell transplantation. Med Hypothesis, Discov Innov Ophthalmol. 2020;9:23–32.
   PubMedGoogle Scholar
• Lee WB, Shtein RM, Kaufman SC, et al. Boston Keratoprosthesis: outcomes and complications, a report by the American academy of ophthalmology. Ophthalmology. 2015;122(7):1504–1511.
   PubMed Web of Science ®Google Scholar
• Shanbhag SS, Senthil S, Mohamed A, et al. Outcomes of the Boston type 1 and the Aurolab keratoprosthesis in eyes with limbal stem cell deficiency. Br J Ophthalmol. 2021;105(4):473-478.
   Web of Science ®Google Scholar
• Calonge M, Pérez I, Galindo S, et al. A proof-of-concept clinical trial using mesenchymal stem cells for the treatment of corneal epithelial stem cell deficiency. Transl Res. 2019;206:18–40.
   PubMed Web of Science ®Google Scholar
• Patil S, D’Souza C, Patil P, et al. Culture and characterization of human dental pulp-derived stem cells as limbal stem cells for corneal damage repair. Mol Med Rep. 2019;20(5):4688–4694.
   PubMed Web of Science ®Google Scholar
• Mikhailova A, Ilmarinen T, Uusitalo H, et al. Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells. Stem Cell Reports. 2014;2(2):219–231.
   PubMed Web of Science ®Google Scholar
• Theerakittayakorn K, Nguyen HT, Musika J, et al. Differentiation induction of human stem cells for corneal epithelial regeneration. Int J Mol Sci. 2020;21(21):7834.
   PubMed Web of Science ®Google Scholar
• Inamochi A, Tomioka A, Kitamoto K, et al. Simple oral mucosal epithelial transplantation in a rabbit model. Sci Rep. 2019;9(1):18088.
   PubMed Web of Science ®Google Scholar
• Kara N, Dogan L. Simple oral mucosal epithelial transplantation in a patient with bilateral limbal stem cell deficiency. Eye Contact Lens. 2021;47(1):65–67.
   PubMed Web of Science ®Google Scholar
• Hongisto H, Vattulainen M, Ilmarinen T, et al. Efficient and scalable directed differentiation of clinically compatible corneal limbal epithelial stem cells from human pluripotent stem cells. J Vis Exp. 2018;140:1–9.
   Google Scholar
• Figueiredo FC, Glanville JM, Arber M, et al. The Ocular Surface A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes. Ocul Surf. 2021;20:48–61.
   PubMed Web of Science ®Google Scholar
• National Library of Medicine (U.S.). (2020, July). First in Human (FIH) study to assess safety and efficacy of the CorNeat KPro for the treatment of corneal blindness. Identifier NCT04485858. Available from: https://clinicaltrials.gov/ct2/show/NCT04485858?term=corneat&draw=2&rank=1
   Google Scholar
• McTiernan CD, Simpson FC, Haagdorens M, et al. LiQD Cornea: pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation. Sci Adv. 2020;6(25):1–12.
   Web of Science ®Google Scholar
• Isaacson A, Swioklo S, Connon CJ. 3D bioprinting of a corneal stroma equivalent. Exp Eye Res. 2018;173:188–193.
   PubMed Web of Science ®Google Scholar