Corneal stromal lenticule is a part of corneal stroma, which can be created by manual dissection, by femtosecond laser from the donor cornea, but chiefly it is a waste product of a refractive procedure ReLex SMILE (Small Incision Lenticule Extraction). Corneal lenticule has a huge potential in corneal surgery. In recent years, many studies have been published to show the possibility to use this tissue to treat corneal defects, as well as in refractive surgery. Thanks to the quantity of lenticules which arise every day during SMILE operations, this tissue is much more accessible than any other kind of corneal tissue. According to the experience with lenticule implantation in animal models, or even human patients, lenticule implantation is considered safe, reversible method, which is not associated with immune rejection or other severe complications. However, the crucial step before the process of lenticule implantation, is proper preservation of this tissue. Donor corneal tissue containing endothelium is usually preserved in hypothermia and then usable maximally for two weeks. Newer methods such as organ culture storage and use of a sterile cornea prolong the time of usability of the tissue. The possibilities for corneal lenticule storage are theoretically wider thanks to the fact, that we do not need to preserve fragile cellular structures. Besides the storage in hypothermia, other preserving methods such as cryopreservation and storage after decellularization have been tested. This review aimed to examine the current literature that describes possible methods of corneal lenticule preservation. A comprehensive search was created based on articles published in English on PubMed.gov, Cochranelibrary.com and Scopus.com using following keywords: corneal lenticule preservation, corneal lenticule storage, cold storage corneal lenticule, corneal lenticule cryopreservation till 2020.

Department of Ophthalmology University Hospital Kralovske Vinohrady and 3rd Medical Faculty Srobarova 1150 50 Prague 10 100 34 Prague Czech Republic

Zobrazit více v PubMed

Amano S, Shimomura N, Yokoo S, Araki-Sasaki K, Yamagami S (2008) Decellularizing corneal stroma using N2 gas. Mol vis 14:878–882 PubMed PMC

Armitage WJ (2011) Preservation of Human Cornea. Transfusion Medicine and Hemotherapy: Offizielles Organ Der Deutschen Gesellschaft Fur Transfusionsmedizin Und Immunhamatologie 38(2):143–147. https://doi.org/10.1159/000326632 DOI

Bandeira F, Yam GH-F, Liu Y-C, Devarajan K, Mehta JS (2019) Three-dimensional neurite characterization of small incision lenticule extraction derived Lenticules. Invest Ophthalmol vis Sci 60(13):4408–4415. https://doi.org/10.1167/iovs.19-27566 PubMed DOI

Bhandari V, Ganesh S, Brar S, Pandey R (2016) Application of the SMILE-derived glued Lenticule patch graft in Microperforations and partial-thickness corneal defects. Cornea 35(3):408–412. https://doi.org/10.1097/ICO.0000000000000741 PubMed DOI

Calhoun WR, Akpek EK, Weiblinger R, Ilev IK (2015) Evaluation of broadband spectral transmission characteristics of fresh and gamma-irradiated corneal tissues. Cornea 34(2):228–234. https://doi.org/10.1097/ICO.0000000000000323 PubMed DOI

Daoud YJ, Smith R, Smith T, Akpek EK, Ward DE, Stark WJ (2011) The intraoperative impression and postoperative outcomes of gamma-irradiated corneas in corneal and glaucoma patch surgery. Cornea 30(12):1387–1391. https://doi.org/10.1097/ICO.0b013e31821c9c09 PubMed DOI

El Zarif M, Alió JL, Alió Del Barrio JL, De Miguel MP, Abdul Jawad K, Makdissy N (2021) Corneal stromal regeneration: A review of human clinical studies in Keratoconus treatment. Front Med 8:650724. https://doi.org/10.3389/fmed.2021.650724 DOI

Fasolo A, Galzignato A, Pedrotti E, Chierego C, Cozzini T, Bonacci E, Marchini G (2021) Femtosecond laser-assisted implantation of corneal stroma lenticule for keratoconus. Int Ophthalmol. https://doi.org/10.1007/s10792-021-01739-8 PubMed DOI PMC

Ganesh S, Brar S, Rao PA (2014) Cryopreservation of extracted corneal lenticules after small incision lenticule extraction for potential use in human subjects. Cornea 33(12):1355–1362. https://doi.org/10.1097/ICO.0000000000000276 PubMed DOI PMC

Hashimoto Y, Funamoto S, Sasaki S, Honda T, Hattori S, Nam K, Kimura T, Mochizuki M, Fujisato T, Kobayashi H, Kishida A (2010) Preparation and characterization of decellularized cornea using high-hydrostatic pressurization for corneal tissue engineering. Biomaterials 31(14):3941–3948. https://doi.org/10.1016/j.biomaterials.2010.01.122 PubMed DOI

He M, Jin H, He H, Ding H, Wang W, Liu L, Zhang C, Zhong X (2018) Femtosecond laser-assisted small incision endokeratophakia using a xenogeneic lenticule in rhesus monkeys. Cornea 37(3):354–361. https://doi.org/10.1097/ICO.0000000000001470 PubMed DOI

Chae JJ, Choi JS, Lee JD, Lu Q, Stark WJ, Kuo IC, Elisseeff JH (2015) Physical and biological characterization of the gamma-irradiated human cornea. Cornea 34(10):1287–1294. https://doi.org/10.1097/ICO.0000000000000555 PubMed DOI

Chaurasia S, Das S, Roy A (2020) A review of long-term corneal preservation techniques: relevance and renewed interests in the COVID-19 era. Indian J Ophthalmol 68(7):1357–1363. https://doi.org/10.4103/ijo.IJO_1505_20 PubMed DOI PMC

Isidan A, Liu S, Li P, Lashmet M, Smith LJ, Hara H, Cooper DKC, Ekser B (2019) Decellularization methods for developing porcine corneal xenografts and future perspectives. Xenotransplantation 26(6):e12564. https://doi.org/10.1111/xen.12564 PubMed DOI PMC

Islam MM, Sharifi R, Mamodaly S, Islam R, Nahra D, Abusamra DB, Hui PC, Adibnia Y, Goulamaly M, Paschalis EI, Cruzat A, Kong J, Nilsson PH, Argüeso P, Mollnes TE, Chodosh J, Dohlman CH, Gonzalez-Andrades M (2019) Effects of gamma radiation sterilization on the structural and biological properties of decellularized corneal xenografts. Acta Biomater 96:330–344. https://doi.org/10.1016/j.actbio.2019.07.002 PubMed DOI PMC

Jhanji V, Sharma N, Vajpayee RB (2010) Intraoperative perforation of Descemet’s membrane during „big bubble" deep anterior lamellar keratoplasty. Int Ophthalmol 30(3):291–295. https://doi.org/10.1007/s10792-009-9334-7 PubMed DOI

Jin H, He M, Liu H, Zhong X, Wu J, Liu L, Ding H, Zhang C, Zhong X (2019) Small-incision femtosecond laser-assisted intracorneal concave lenticule implantation in patients with keratoconus. Cornea 38(4):446–453. https://doi.org/10.1097/ICO.0000000000001877 PubMed DOI PMC

Jin H, Liu L, Ding H, He M, Zhang C, Zhong X (2018) Small incision femtosecond laser-assisted X-ray-irradiated corneal intrastromal xenotransplantation in rhesus monkeys: a preliminary study. Curr Mol Med 18(9):612–621. https://doi.org/10.2174/1566524019666190129123935 PubMed DOI PMC

Li J, Shi S, Zhang X, Ni S, Wang Y, Curcio CA, Chen W (2012) Comparison of different methods of glycerol preservation for deep anterior lamellar keratoplasty eligible corneas. Invest Ophthalmol vis Sci 53(9):5675–5685. https://doi.org/10.1167/iovs.12-9936 PubMed DOI

Li M, Wei R, Yang W, Shang J, Fu D, Xia F, Choi J, Zhou X (2020) Femtosecond laser-assisted allogenic lenticule implantation for corneal Ectasia After LASIK: A 3-Year in vivo confocal microscopic investigation. J Refractive Surg (thorofare, n. J.: 1995) 36(11):714–722. https://doi.org/10.3928/1081597X-20200826-02 DOI

Li Q, Wang H, Dai Z, Cao Y, Jin C (2017) Preparation and biomechanical properties of an Acellular porcine corneal stroma. Cornea 36(11):1343–1351. https://doi.org/10.1097/ICO.0000000000001319 PubMed DOI

Liang G, Wang L, Pan Z, Zhang F (2019) Comparison of the different preservative methods for refractive lenticules following SMILE. Curr Eye Res 44(8):832–839. https://doi.org/10.1080/02713683.2019.1597890 PubMed DOI

Lindstrom RL, Kaufman HE, Skelnik DL, Laing RA, Lass JH, Musch DC, Trousdale MD, Reinhart WJ, Burris TE, Sugar A (1992) Optisol corneal storage medium. Am J Ophthalmol 114(3):345–356. https://doi.org/10.1016/s0002-9394(14)71803-3 PubMed DOI

Liu Y-C, Williams GP, George BL, Soh YQ, Seah XY, Peh GSL, Yam GHF, Mehta JS (2017) Corneal lenticule storage before reimplantation. Mol vis 23:753–764 PubMed PMC

Mastropasqua L, Nubile M, Salgari N, Mastropasqua R (2018) Femtosecond laser-assisted stromal lenticule addition keratoplasty for the treatment of advanced keratoconus: a preliminary study. J Refractive Surg (thorofare, N.J. 1995) 34(1):36–44. https://doi.org/10.3928/1081597X-20171004-04 DOI

Mohamed-Noriega K, Toh K-P, Poh R, Balehosur D, Riau A, Htoon HM, Peh GSL, Chaurasia SS, Tan DT, Mehta JS (2011) Cornea lenticule viability and structural integrity after refractive lenticule extraction (ReLEx) and cryopreservation. Mol vis 17:3437–3449 PubMed PMC

Oh JY, Kim MK, Lee HJ, Ko JH, Wee WR, Lee JH (2009) Comparative observation of freeze-thaw-induced damage in pig, rabbit, and human corneal stroma. Veterinary Ophthalmol 12(Suppl 1):50–56. https://doi.org/10.1111/j.1463-5224.2009.00723.x DOI

Pradhan KR, Reinstein DZ, Carp GI, Archer TJ, Gobbe M, Gurung R (2013) Femtosecond laser-assisted keyhole endokeratophakia: Correction of hyperopia by implantation of an allogeneic lenticule obtained by SMILE from a myopic donor. J Refractive Surg (thorofare, N.J.: 1995) 29(11):777–782. https://doi.org/10.3928/1081597X-20131021-07 DOI

Raeder S, Utheim TP, Utheim OA, Nicolaissen B, Roald B, Cai Y, Haug K, Kvalheim A, Messelt EB, Drolsum L, Reed JC, Lyberg T (2007) Effects of organ culture and Optisol-GS storage on structural integrity, phenotypes, and apoptosis in cultured corneal epithelium. Invest Ophthalmol vis Sci 48(12):5484–5493. https://doi.org/10.1167/iovs.07-0494 PubMed DOI

Riau AK, Angunawela RI, Chaurasia SS, Lee WS, Tan DT, Mehta JS (2013) Reversible femtosecond laser-assisted myopia correction: A non-human primate study of lenticule re-implantation after refractive lenticule extraction. PLoS ONE 8(6):e67058. https://doi.org/10.1371/journal.pone.0067058 PubMed DOI PMC

Riau AK, Liu Y-C, Yam GHF, Mehta JS (2020) Stromal keratophakia: corneal inlay implantation. Prog Retin Eye Res 75:100780. https://doi.org/10.1016/j.preteyeres.2019.100780 PubMed DOI

Sachdev MS, Gupta D, Sachdev G, Sachdev R (2015) Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea. J Cataract Refract Surg 41(5):918–923. https://doi.org/10.1016/j.jcrs.2015.04.007 PubMed DOI

Shang Y, Li Y, Wang Z, Sun X, Zhang F (2021) Risk Evaluation of human corneal stromal lenticules from SMILE for reuse. J Refractive Surg (thorofare, N.J.: 1995) 37(1):32–40. https://doi.org/10.3928/1081597X-20201030-03 DOI

Stevenson W, Cheng S-F, Emami-Naeini P, Hua J, Paschalis EI, Dana R, Saban DR (2012) Gamma-irradiation reduces the allogenicity of donor corneas. Invest Ophthalmol vis Sci 53(11):7151–7158. https://doi.org/10.1167/iovs.12-9609 PubMed DOI PMC

Sun L, Yao P, Li M, Shen Y, Zhao J, Zhou X (2015) The Safety and predictability of implanting autologous Lenticule obtained by SMILE for hyperopia. J Refractive Surg (thorofare, n. j: 1995) 31(6):374–379. https://doi.org/10.3928/1081597X-20150521-03 DOI

Sun Y, Zhang T, Zhou Y, Liu M, Zhou Y, Yang X, Weng S, To C-H, Liu Q (2016) Reversible femtosecond laser-assisted endokeratophakia using cryopreserved allogeneic corneal lenticule. J Refractive Surg (thorofare, n. j: 1995) 32(8):569–576. https://doi.org/10.3928/1081597X-20160523-02 DOI

Trias E, Gallon P, Ferrari S, Piteira AR, Tabera J, Casaroli-Marano RP, Parekh M, Ruzza A, Franch A, Ponzin D (2020) Banking of corneal stromal lenticules: a risk-analysis assessment with the EuroGTP II interactive tool. Cell Tissue Bank 21(2):189–204. https://doi.org/10.1007/s10561-020-09813-8 PubMed DOI

Tripathi H, Mehdi MU, Gupta D, Sen S, Kashyap S, Nag TC, Purwar M, Jassal M, Agrawal AK, Mohanty S, Tandon R (2016) Long-term preservation of donor corneas in glycerol for keratoplasty: Exploring new protocols. Br J Ophthalmol 100(2):284–290. https://doi.org/10.1136/bjophthalmol-2015-306944 PubMed DOI

Wu F, Jin X, Xu Y, Yang Y (2015) Treatment of corneal perforation with lenticules from small incision lenticule extraction surgery: a preliminary study of 6 patients. Cornea 34(6):658–663. https://doi.org/10.1097/ICO.0000000000000397 PubMed DOI

Xia F, Zhao J, Fu D, Xu Y, Yao P, Li M, Aruma A, Zhou X (2020) Optical transmittance and ultrastructure of SMILE-derived lenticules subjected to three different preservative methods. Exp Eye Res 201:108357. https://doi.org/10.1016/j.exer.2020.108357 PubMed DOI

Yam GH-F, Yusoff NZBM, Goh T-W, Setiawan M, Lee X-W, Liu Y-C, Mehta JS (2016) Decellularization of human stromal refractive lenticules for corneal tissue engineering. Sci Rep 6:26339. https://doi.org/10.1038/srep26339 PubMed DOI PMC

Yang H, Zhou Y, Zhao H, Xue J, Jiang Q (2020) Application of the SMILE-derived lenticule in therapeutic keratoplasty. Int Ophthalmol 40(3):689–695. https://doi.org/10.1007/s10792-019-01229-y PubMed DOI

Yoeruek E, Bayyoud T, Maurus C, Hofmann J, Spitzer MS, Bartz-Schmidt K-U, Szurman P (2012) Reconstruction of corneal stroma with decellularized porcine xenografts in a rabbit model. Acta Ophthalmol 90(3):e206-210. https://doi.org/10.1111/j.1755-3768.2011.02300.x PubMed DOI

Yoshida J, Heflin T, Zambrano A, Pan Q, Meng H, Wang J, Stark WJ, Daoud YJ (2015) Gamma-irradiated sterile cornea for use in corneal transplants in a rabbit model. Middle East Afr J Ophthalmol 22(3):346–351. https://doi.org/10.4103/0974-9233.159760 PubMed DOI PMC

Zheng X, Zhang D, Li S, Zhang J, Zheng J, Du L, Gao J (2018) An experimental study of femto-laser in assisting xenograft acellular cornea matrix lens transplantation. Med Sci Monitor: Int Med J Exp Clin Res 24:5208–5215 DOI