ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2021-3S-740-745ophthalmology-1652Research ArticleСтатьиЭпителиальные осложнения при различных протоколах кросслинкинга роговичного коллагенаEpithelial Complications in Various Corneal Collagen Crosslinking Protocolshttps://orcid.org/0000-0003-1721-9378БубноваИ. А.BubnovaI. A.

Бубнова Ирина Алексеевна, доктор медицинских наук, старший научный сотрудник отдела патологии оптических сред

ул. Россолимо, 11а, б, Москва, 119021

Bubnova Irina A., MD, senior science researcher of Optical media pathology department 

Rossolimo str., 11A, В, Moscow, 119021

bubnovai@mail.ruhttps://orcid.org/0000-0002-4406-3068СаркисоваК. Г.SarkisovaK. G.

Саркисова Кристина Гургеновна, аспирант отдела патологии оптических сред

ул. Россолимо, 11а, б, Москва, 119021

Sarkisova Kristina G., postgraduate of Optical media pathology department 

Rossolimo str., 11A, В, Moscow, 119021

ФГБНУ «Научно-исследовательский институт глазных болезней»РоссияResearch Institute of Eye DiseasesRussian Federation202122102021183S740745Copyright © Бубнова И.А., Саркисова К.Г., 20212021Бубнова И.А., Саркисова К.Г.Bubnova I.A., Sarkisova K.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/1652

В данном литературном обзоре описаны эпителиальные осложнения, которые возникают после проведения процедуры кросслинкинга роговичного коллагена. В настоящее время применяют стандартный, различные варианты трансэпителиального и ускоренного протоколов, а также их комбинацию. При этом отмечаются проблемы и осложнения, связанные с деэпителизацией или с воздействием на сохраненный эпителий как специальными веществами, разрушающими плотные связи между эпителиальными клетками, так и с эффектами УФ-излучения, которое подается с большей мощностью и в более короткие сроки. При этом разработка множества новых вариантов различных модификаций и протоколов проведения процедуры кросслинкинга роговичного коллагена с целью сохранения эпителия и тем самым обеспечения комфорта и безопасности пациента может привести к замкнутому кругу в виде эпителиальных осложнений и снижения эффекта от вмешательства. В связи с этим важно проводить более полные, стандартизированные исследования, направленные на комплексную оценку всех аспектов и параметров процедуры КРК.

This literature review describes epithelial complications that occur after corneal collagen crosslinking. Currently, the standard, different variants of the transepithelial and accelerated protocols, as well as their combination, are used. Moreover, in most cases, there are problems and complications associated with de-epithelialization or with impact to the preserved epithelium, both with special substances that destroy tight connections between epithelial cells, and with UV radiation, which supplied with increased illumination intensity and in a shorter time. At the same time, the development of many new options for various modifications and protocols for the corneal collagen crosslinking in order to preserve the epithelium and, thereby, provide the comfort and safety for the patient, can lead to a vicious circle in the form of epithelial complications and a decrease in the effect of the procedure. Therefore, it is important to conduct more complete, standardized studies aimed at a comprehensive assessment of all aspects and parameters of the corneal crosslinking procedure.

кератоконускросслинкинг роговичного коллагенароговицадемаркационная линиярибофлавинkeratconuscorneal crosslinkingcorneademarcation lineriboflavinReferencesWollensak G., Spoerl E., Seiler T. Riboflavin/ultraviolet-A–induced collagen crosslinking for the treatment of keratoconus. American journal of ophthalmology. 2003;135(5):620–627. DOI: 10.1016/s0002-9394(02)02220-1Wollensak G., Spoerl E., Seiler T. Riboflavin/ultraviolet-A–induced collagen crosslinking for the treatment of keratoconus. American journal of ophthalmology. 2003;135(5):620–627. DOI: 10.1016/s0002-9394(02)02220-1Mazzotta C., Balestrazzi A., Baiocchi S., Traversi C., Caporossi A. Stromal haze after combined riboflavin‐UVA corneal collagen cross‐linking in keratoconus: in vivo confocal microscopic evaluation. Clinical experimental ophthalmology. 2007;35(6):580–582. DOI: 10.1111/j.1442-9071.2007.01536.xMazzotta C., Balestrazzi A., Baiocchi S., Traversi C., Caporossi A. Stromal haze after combined riboflavin‐UVA corneal collagen cross‐linking in keratoconus: in vivo confocal microscopic evaluation. Clinical experimental ophthalmology. 2007;35(6):580–582. DOI: 10.1111/j.1442-9071.2007.01536.xZamora K.V., Males J.J. Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea. 2009;28(4):474–476. DOI: 10.1097/ICO.0b013e31818d381aZamora K.V., Males J.J. Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea. 2009;28(4):474–476. DOI: 10.1097/ICO.0b013e31818d381aБубнова И., Сурнина З., Аверич В., Саркисова К. Влияние кросслинкинга роговичного коллагена на структуру роговицы при кератоконусе. Вестник офтальмологии. 2020;136(5):268–276. DOI: 10.17116/oftalma2020136052268Bubnova I., Surnina Z., Averich V., Sarkisova K. Effect of corneal collagen crosslinking on the corneal structure in keratoconus. Annals of Ophthalmology = Vestnik oftal’mologii. 2020;136(5):268–276 (In Russ.). DOI: 10.17116/oftalma2020136052268Шелудченко В.М., Воронин Г.В., Осипян Г. А., Джалили Р. Методы хирургического лечения кератэктазии и анализ послеоперационного качества зрения. Вестник офтальмологии. 2020;136(5-2):308–316. DOI: 10.17116/oftalma2020136052308Sheludchenko V.M., Voronin G.V., Osipyan G.A., Jalili R. Methods of surgical treatment of keratectasia and analysis of the postoperative quality of vision. Annals of Ophthalmology = Vestnik oftal’mologii. 2020;136(5-2):308–316 (In Russ.). DOI: 10.17116/oftalma2020136052308Wachler B.S.B., Pinelli R., Ertan A., Chan C.C.K. Safety and efficacy of transepithelial crosslinking (C3-R/CXL). Journal of Cataract Refractive Surgery. 2010;36(1):186– 188. DOI: 10.1016/j.jcrs.2009.08.019Wachler B.S.B., Pinelli R., Ertan A., Chan C.C.K. Safety and efficacy of transepithelial crosslinking (C3-R/CXL). Journal of Cataract Refractive Surgery. 2010;36(1):186– 188. DOI: 10.1016/j.jcrs.2009.08.019Soeters N., Wisse R.P., Godefrooij D.A., Imhof S.M., Tahzib N.G. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. American journal of ophthalmology. 2015;159(5):821–828.e823. DOI: 10.1016/j.ajo.2015.02.005Soeters N., Wisse R.P., Godefrooij D.A., Imhof S.M., Tahzib N.G. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. American journal of ophthalmology. 2015;159(5):821–828.e823. DOI: 10.1016/j.ajo.2015.02.005Koppen C., Wouters K., Mathysen D., Rozema J., Tassignon M.-J. Refractive and topographic results of benzalkonium chloride–assisted transepithelial crosslinking. Journal of Cataract Refractive Surgery. 2012;38(6):1000–1005. DOI: 10.1016/j.jcrs.2012.01.024Koppen C., Wouters K., Mathysen D., Rozema J., Tassignon M.-J. Refractive and topographic results of benzalkonium chloride–assisted transepithelial crosslinking. Journal of Cataract Refractive Surgery. 2012;38(6):1000–1005. DOI: 10.1016/j.jcrs.2012.01.024Filippello M., Stagni E., O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. Journal of Cataract Refractive Surgery. 2012;38(2):283–291. DOI: 10.1016/j.jcrs.2011.08.030Filippello M., Stagni E., O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. Journal of Cataract Refractive Surgery. 2012;38(2):283–291. DOI: 10.1016/j.jcrs.2011.08.030Touboul D., Efron N., Smadja D., Praud D., Malet F., Colin J. Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus. Journal of refractive surgery. 2012;28(11):769–776. DOI: 10.3928/1081597X-20121016-01Touboul D., Efron N., Smadja D., Praud D., Malet F., Colin J. Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus. Journal of refractive surgery. 2012;28(11):769–776. DOI: 10.3928/1081597X-20121016-01Wollensak G., Iomdina E. Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement. Journal of Cataract Refractive Surgery. 2009;35(3):540–546. DOI: 10.1016/j.jcrs.2008.11.036Wollensak G., Iomdina E. Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement. Journal of Cataract Refractive Surgery. 2009;35(3):540–546. DOI: 10.1016/j.jcrs.2008.11.036Spoerl E., Mrochen M., Sliney D., Trokel S., Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007;26(4):385–389. DOI: 10.1097/ICO.0b013e3180334f78Spoerl E., Mrochen M., Sliney D., Trokel S., Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007;26(4):385–389. DOI: 10.1097/ICO.0b013e3180334f78Leccisotti A., Islam T. Transepithelial corneal collagen cross-linking in keratoconus. Journal of Refractive Surgery. 2010;26(12):942–948. DOI: 10.3928/1081597X20100212-09Leccisotti A., Islam T. Transepithelial corneal collagen cross-linking in keratoconus. Journal of Refractive Surgery. 2010;26(12):942–948. DOI: 10.3928/1081597X20100212-09Малюгин Б.Э., Измайлова С.Б., Мерзлов Д.Е., Пронкина С.А., Поручикова Е.П., Семыкин А.Ю. Отдаленные результаты использования различных технологий УФ-кросслинкинга у пациентов с прогрессирующим кератоконусом. Офтальмохирургия. 2015;4:42–49.Malyugin B.E., Izmailova S.B., Merzlov D.E., Pronkina S.A., Poruchikova E.P., Semykin A.Yu. Long-term results of using various UV-crosslinking technologies in patients with progressive keratoconus. Fyodorov Journal of Ophthalmic Surgery = Oftal’mokhirurgiya. 2014;4:42– 49 (In Russ.).Taneri S., Oehler S., Lytle G., Dick H.B. Evaluation of epithelial integrity with various transepithelial corneal cross-linking protocols for treatment of keratoconus. Journal of ophthalmology. 2014;2014:614380. DOI: 10.1155/2014/614380Taneri S., Oehler S., Lytle G., Dick H.B. Evaluation of epithelial integrity with various transepithelial corneal cross-linking protocols for treatment of keratoconus. Journal of ophthalmology. 2014;2014:614380. DOI: 10.1155/2014/614380Stojanovic A., Zhou W., Utheim T.P. Corneal collagen cross-linking with and without epithelial removal: a contralateral study with 0.5 % hypotonic riboflavin solution. BioMed research international. 2014;2014:619398. DOI: 10.1155/2014/619398Stojanovic A., Zhou W., Utheim T.P. Corneal collagen cross-linking with and without epithelial removal: a contralateral study with 0.5 % hypotonic riboflavin solution. BioMed research international. 2014;2014:619398. DOI: 10.1155/2014/619398Anisimov S., Anisimova S.Y., Mistryukov A., Anisimova N.J. Technology of the Local Cross-linking (Part 1): Keratotensotopography and Vacuum-compression Topographic Test—New Diagnostic Possibilities for Studying the Local Biomechanical Properties of Cornea. Int J Kerat Ect Cor Dis 2017;6(1):14–16.Anisimov S., Anisimova S.Y., Mistryukov A., Anisimova N.J. Technology of the Local Cross-linking (Part 1): Keratotensotopography and Vacuum-compression Topographic Test—New Diagnostic Possibilities for Studying the Local Biomechanical Properties of Cornea. Int J Kerat Ect Cor Dis 2017;6(1):14–16.Koppen C., Gobin L., Tassignon M.-J. The absorption characteristics of the human cornea in ultraviolet-a crosslinking. Eye contact lens. 2010;36(2):77–80. DOI: 10.1097/ICL.0b013e3181d0b74bKoppen C., Gobin L., Tassignon M.-J. The absorption characteristics of the human cornea in ultraviolet-a crosslinking. Eye contact lens. 2010;36(2):77–80. DOI: 10.1097/ICL.0b013e3181d0b74bPodskochy A. Protective role of corneal epithelium against ultraviolet radiation damage. Acta Ophthalmologica Scandinavica. 2004;82(6):714–717. DOI: 10.1111/j.1600-0420.2004.00369.xPodskochy A. Protective role of corneal epithelium against ultraviolet radiation damage. Acta Ophthalmologica Scandinavica. 2004;82(6):714–717. DOI: 10.1111/j.1600-0420.2004.00369.xKolozsvári L., Nógrádi A., Hopp B.l., Bor Z. UV absorbance of the human cornea in the 240-to 400-nm range. Investigative ophthalmology visual science. 2002;43(7):2165–2168.Kolozsvári L., Nógrádi A., Hopp B.l., Bor Z. UV absorbance of the human cornea in the 240-to 400-nm range. Investigative ophthalmology visual science. 2002;43(7):2165–2168.Wu M.-F., Stachon T., Wang J., Song X., Colanesi S., Seitz B., et al. Effect of keratocyte supernatant on epithelial cell migration and proliferation after corneal crosslinking (CXL). Current eye research. 2016;41(4):466–473. DOI: 10.3109/02713683.2015.1050739Wu M.-F., Stachon T., Wang J., Song X., Colanesi S., Seitz B., et al. Effect of keratocyte supernatant on epithelial cell migration and proliferation after corneal crosslinking (CXL). Current eye research. 2016;41(4):466–473. DOI: 10.3109/02713683.2015.1050739Caporossi A., Mazzotta C., Baiocchi S., Caporossi T., Paradiso A.L. Transepithelial corneal collagen crosslinking for keratoconus: qualitative investigation by in vivo HRT II confocal analysis. European journal of ophthalmology. 2012;22(7_suppl):81–88. DOI: 10.5301/ejo.5000125Caporossi A., Mazzotta C., Baiocchi S., Caporossi T., Paradiso A.L. Transepithelial corneal collagen crosslinking for keratoconus: qualitative investigation by in vivo HRT II confocal analysis. European journal of ophthalmology. 2012;22(7_suppl):81–88. DOI: 10.5301/ejo.5000125Buzzonetti L., Petrocelli G. Transepithelial corneal cross-linking in pediatric patients: early results. Journal of Refractive Surgery. 2012;28(11):763–767. DOI: 10.3928/1081597X-20121011-03Buzzonetti L., Petrocelli G. Transepithelial corneal cross-linking in pediatric patients: early results. Journal of Refractive Surgery. 2012;28(11):763–767. DOI: 10.3928/1081597X-20121011-03Magli A., Forte R., Tortori A., Capasso L., Marsico G., Piozzi E. Epithelium-off corneal collagen cross-linking versus transepithelial cross-linking for pediatric keratoconus. Cornea. 2013;32(5):597–601. DOI: 10.1097/ICO.0b013e31826cf32dMagli A., Forte R., Tortori A., Capasso L., Marsico G., Piozzi E. Epithelium-off corneal collagen cross-linking versus transepithelial cross-linking for pediatric keratoconus. Cornea. 2013;32(5):597–601. DOI: 10.1097/ICO.0b013e31826cf32dYuksel E., Novruzlu S., Ozmen M.C., Bilgihan K. A study comparing standard and transepithelial collagen cross-linking riboflavin solutions: epithelial findings and pain scores. Journal of Ocular Pharmacology Therapeutics. 2015;31(5):296–302. DOI: 10.1089/jop.2014.0090Yuksel E., Novruzlu S., Ozmen M.C., Bilgihan K. A study comparing standard and transepithelial collagen cross-linking riboflavin solutions: epithelial findings and pain scores. Journal of Ocular Pharmacology Therapeutics. 2015;31(5):296–302. DOI: 10.1089/jop.2014.0090Yuksel E., Cubuk M.O., Yalcin N.G. Accelerated epithelium-on or accelerated epithelium-off corneal collagen cross-linking: Contralateral comparison study. Taiwan journal of ophthalmology. 2020;10(1):37. DOI: 10.4103/tjo.tjo_11_19Yuksel E., Cubuk M.O., Yalcin N.G. Accelerated epithelium-on or accelerated epithelium-off corneal collagen cross-linking: Contralateral comparison study. Taiwan journal of ophthalmology. 2020;10(1):37. DOI: 10.4103/tjo.tjo_11_19Ghanem V.C., Ghanem R.C., De Oliveira R. Postoperative pain after corneal collagen cross-linking. Cornea. 2013;32(1):20–24. DOI: 10.1097/ICO.0b013e31824d6fe3Ghanem V.C., Ghanem R.C., De Oliveira R. Postoperative pain after corneal collagen cross-linking. Cornea. 2013;32(1):20–24. DOI: 10.1097/ICO.0b013e31824d6fe3Al-Aqaba M., Calienno R., Fares U., Otri A.M., Mastropasqua L., Nubile M. The effect of standard and transepithelial ultraviolet collagen cross-linking on human corneal nerves: an ex vivo study. American journal of ophthalmology. 2012;153(2):258–266.e252. DOI: 10.1016/j.ajo.2011.07.006Al-Aqaba M., Calienno R., Fares U., Otri A.M., Mastropasqua L., Nubile M. The effect of standard and transepithelial ultraviolet collagen cross-linking on human corneal nerves: an ex vivo study. American journal of ophthalmology. 2012;153(2):258–266.e252. DOI: 10.1016/j.ajo.2011.07.006Rubinfeld R.S., Caruso C., Ostacolo C. Corneal cross-linking: the science beyond the myths and misconceptions. Cornea. 2019;38(6):780–790. DOI: 10.1097/ICO.0000000000001912Rubinfeld R.S., Caruso C., Ostacolo C. Corneal cross-linking: the science beyond the myths and misconceptions. Cornea. 2019;38(6):780–790. DOI: 10.1097/ICO.0000000000001912Bao F., Zheng Y., Liu C., Zheng X., Zhao Y., Wang Y. Changes in corneal biomechanical properties with different corneal cross-linking irradiances. Journal of Refractive Surgery. 2018;34(1):51–58. DOI: 10.3928/1081597X-20171025-01Bao F., Zheng Y., Liu C., Zheng X., Zhao Y., Wang Y. Changes in corneal biomechanical properties with different corneal cross-linking irradiances. Journal of Refractive Surgery. 2018;34(1):51–58. DOI: 10.3928/1081597X-20171025-01Li H., Liu T., Mu B., Zhao X., Xue C., Shen M. Biomechanical effect of ultravioletA-riboflavin cross-linking on simulated human corneal stroma model and its correlation with changes in corneal stromal microstructure. Experimental eye research. 2020;197:108109. DOI: 10.1016/j.exer.2020.108109Li H., Liu T., Mu B., Zhao X., Xue C., Shen M. Biomechanical effect of ultravioletA-riboflavin cross-linking on simulated human corneal stroma model and its correlation with changes in corneal stromal microstructure. Experimental eye research. 2020;197:108109. DOI: 10.1016/j.exer.2020.108109Hashemian H., Jabbarvand M., Khodaparast M., Ameli K. Evaluation of corneal changes after conventional versus accelerated corneal cross-linking: a randomized controlled trial. Journal of Refractive Surgery. 2014;30(12):837–842. DOI: 10.3928/1081597X-20141117-02Hashemian H., Jabbarvand M., Khodaparast M., Ameli K. Evaluation of corneal changes after conventional versus accelerated corneal cross-linking: a randomized controlled trial. Journal of Refractive Surgery. 2014;30(12):837–842. DOI: 10.3928/1081597X-20141117-02Анисимова Н., Анисимов С., Шилова Н., Земская А., Гаврилова Н., Анисимова С. Ультрафиолетовый кросслинкинг в лечении кератоконуса при существенном уменьшении толщины роговицы. Вестник офтальмологии 2020;136(2):99–106. DOI: 10.17116/oftalma202013602199Anisimova N., Anisimov S., Shilova N., Zemskaya A., Gavrilova N., Anisimova S. Ultraviolet crosslinking in the treatment of keratoconus with a significant reduction in corneal thickness. Annals of Ophthalmology = Vestnik oftal’mologii. 2020;136(2):99–106 (In Russ.). DOI: 10.17116/oftalma202013602199Kymionis G.D., Grentzelos M.A., Plaka A.D., Stojanovic N., Tsoulnaras K.I., Mikropoulos D.G. Evaluation of the corneal collagen cross-linking demarcation line profile using anterior segment optical coherence tomography. Cornea. 2013;32(7):907–910. DOI: 10.1097/ICO.0b013e31828733eaKymionis G.D., Grentzelos M.A., Plaka A.D., Stojanovic N., Tsoulnaras K.I., Mikropoulos D.G. Evaluation of the corneal collagen cross-linking demarcation line profile using anterior segment optical coherence tomography. Cornea. 2013;32(7):907–910. DOI: 10.1097/ICO.0b013e31828733eaSeiler T., Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea. 2006;25(9):1057–1059. DOI: 10.1097/01.ico.0000225720.38748.58Seiler T., Hafezi F. Corneal cross-linking-induced stromal demarcation line. Cornea. 2006;25(9):1057–1059. DOI: 10.1097/01.ico.0000225720.38748.58Kymionis G.D., Tsoulnaras K.I., Grentzelos M.A., Liakopoulos D.A., Tsakalis N.G., Blazaki S.V. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. American journal of ophthalmology. 2014;158(4):671–675.e671. DOI: 10.1016/j.ajo.2014.07.005Kymionis G.D., Tsoulnaras K.I., Grentzelos M.A., Liakopoulos D.A., Tsakalis N.G., Blazaki S.V. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. American journal of ophthalmology. 2014;158(4):671–675.e671. DOI: 10.1016/j.ajo.2014.07.005Ozgurhan E.B., Sezgin Akcay B.I., Yildirim Y., Karatas G., Kurt T., Demirok A. Evaluation of corneal stromal demarcation line after two different protocols of accelerated corneal collagen cross-linking procedures using anterior segment optical coherence tomography and confocal microscopy. Journal of ophthalmology. 2014;2014:981893. DOI: 10.1155/2014/981893Ozgurhan E.B., Sezgin Akcay B.I., Yildirim Y., Karatas G., Kurt T., Demirok A. Evaluation of corneal stromal demarcation line after two different protocols of accelerated corneal collagen cross-linking procedures using anterior segment optical coherence tomography and confocal microscopy. Journal of ophthalmology. 2014;2014:981893. DOI: 10.1155/2014/981893Yam J.C., Chan C.W., Cheng A.C. Corneal collagen cross-linking demarcation line depth assessed by Visante OCT after CXL for keratoconus and corneal ectasia. Journal of Refractive Surgery. 2012;28(7):475–481. DOI: 10.3928/1081597X-20120615-03Yam J.C., Chan C.W., Cheng A.C. Corneal collagen cross-linking demarcation line depth assessed by Visante OCT after CXL for keratoconus and corneal ectasia. Journal of Refractive Surgery. 2012;28(7):475–481. DOI: 10.3928/1081597X-20120615-03Filippello M., Stagni E., Buccoliero D., Bonfiglio V., Avitabile T. Transepithelial cross-linking in keratoconus patients: confocal analysis. Optometry Vision Science. 2012;89(10):e1–e7. DOI: 10.1097/OPX.0b013e318269c8e5Filippello M., Stagni E., Buccoliero D., Bonfiglio V., Avitabile T. Transepithelial cross-linking in keratoconus patients: confocal analysis. Optometry Vision Science. 2012;89(10):e1–e7. DOI: 10.1097/OPX.0b013e318269c8e5Mastropasqua L., Nubile M., Lanzini M., Calienno R., Mastropasqua R., Agnifili L Morphological modification of the cornea after standard and transepithelial corneal cross-linking as imaged by anterior segment optical coherence tomography and laser scanning in vivo confocal microscopy. Cornea. 2013;32(6):855–861. DOI: 10.1097/ICO.0b013e3182844c60Mastropasqua L., Nubile M., Lanzini M., Calienno R., Mastropasqua R., Agnifili L Morphological modification of the cornea after standard and transepithelial corneal cross-linking as imaged by anterior segment optical coherence tomography and laser scanning in vivo confocal microscopy. Cornea. 2013;32(6):855–861. DOI: 10.1097/ICO.0b013e3182844c60Randleman J.B., Dawson D.G., Grossniklaus H.E., McCarey B.E., Edelhauser H.F. Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery. Journal of refractive surgery. 2008;24(1):S85. DOI: 10.3928/1081597X-20080101-15Randleman J.B., Dawson D.G., Grossniklaus H.E., McCarey B.E., Edelhauser H.F. Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery. Journal of refractive surgery. 2008;24(1):S85. DOI: 10.3928/1081597X-20080101-15Mazzotta C., Hafezi F., Kymionis G., Caragiuli S., Jacob S., Traversi C. In vivo confocal microscopy after corneal collagen crosslinking. The ocular surface. 2015;13(4):298–314. DOI: 10.1016/j.jtos.2015.04.007Mazzotta C., Hafezi F., Kymionis G., Caragiuli S., Jacob S., Traversi C. In vivo confocal microscopy after corneal collagen crosslinking. The ocular surface. 2015;13(4):298–314. DOI: 10.1016/j.jtos.2015.04.007Ng A.L.K., Chan T.C.Y., Lai J.S.M., Cheng A.C.K. Comparison of the central and peripheral corneal stromal demarcation line depth in conventional versus accelerated collagen cross-linking. Cornea. 2015;34(11):1432–1436. DOI: 10.1097/ICO.0000000000000626Ng A.L.K., Chan T.C.Y., Lai J.S.M., Cheng A.C.K. Comparison of the central and peripheral corneal stromal demarcation line depth in conventional versus accelerated collagen cross-linking. Cornea. 2015;34(11):1432–1436. DOI: 10.1097/ICO.0000000000000626Richoz O., Hammer A., Tabibian D., Gatzioufas Z., Hafezi F. The biomechanical effect of corneal collagen cross-linking (CXL) with riboflavin and UV-A is oxygen dependent. Translational vision science technology. 2013;2(7):6. DOI: 10.1167/tvst.2.7.6Richoz O., Hammer A., Tabibian D., Gatzioufas Z., Hafezi F. The biomechanical effect of corneal collagen cross-linking (CXL) with riboflavin and UV-A is oxygen dependent. Translational vision science technology. 2013;2(7):6. DOI: 10.1167/tvst.2.7.6Gatzioufas Z., Raiskup F., O’Brart D., Spoerl E., Panos G.D., Hafezi F. Transepithelial corneal cross-linking using an enhanced riboflavin solution. Journal of Refractive Surgery.2016;32(6):372–377.Gatzioufas Z., Raiskup F., O’Brart D., Spoerl E., Panos G.D., Hafezi F. Transepithelial corneal cross-linking using an enhanced riboflavin solution. Journal of Refractive Surgery.2016;32(6):372–377.Chow S.S.W., Chan T.C.Y., Wong I.Y.H., Fan M.C.Y., Lai J.S.M., Ng A.L.K. Early epithelial complications of accelerated trans-epithelial corneal crosslinking in treatment of keratoconus: a case series. International ophthalmology. 2018;38(6):2635–2638. DOI: 10.1007/s10792-017-0734-9Chow S.S.W., Chan T.C.Y., Wong I.Y.H., Fan M.C.Y., Lai J.S.M., Ng A.L.K. Early epithelial complications of accelerated trans-epithelial corneal crosslinking in treatment of keratoconus: a case series. International ophthalmology. 2018;38(6):2635–2638. DOI: 10.1007/s10792-017-0734-9

The authors declare that there are no conflicts of interest present.