Skip to main content
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 8/2018

06.04.2018 | Review Article

Current perspectives on corneal collagen crosslinking (CXL)

verfasst von: Sandeepani K. Subasinghe, Kelechi C. Ogbuehi, George J. Dias

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 8/2018

Einloggen, um Zugang zu erhalten

Abstract

Corneal collagen crosslinking has revolutionized the treatment of keratoconus and post-refractive corneal ectasia in the past decade. Corneal crosslinking with riboflavin and ultraviolet A is proposed to halt the progression of keratectasia. In the original “Conventional Dresden Protocol” (C-CXL), the epithelium is removed prior to the crosslinking process to facilitate better absorption of riboflavin into the corneal stroma. Studies analyzing its short- and long-term outcomes revealed that although there are inconsistencies as to the effectiveness of this technique, the advantages prevail over the disadvantages. Therefore, corneal crosslinking (CXL) is widely used in current practice to treat keratoconus. In an attempt to improve the visual and topographical outcomes of C-CXL and to minimize time-related discomfort and endothelial-related side effects, various modifications such as accelerated crosslinking and transepithelial crosslinking methods have been introduced. The comparison of outcomes of these modified techniques with C-CXL has also returned contradictory results. Hence, it is difficult to clearly identify an optimal procedure that can overcome issues associated with the CXL. This review provides an up-to-date analysis on clinical and laboratory findings of these popular crosslinking protocols used in the treatment of keratoconus. It is evident from this review that in general, these modified techniques have succeeded in minimizing the immediate complications of the C-CXL technique. However, there were contradictory viewpoints regarding their effectiveness when compared with the conventional technique. Therefore, these modified techniques need to be further investigated to arrive at an optimal treatment option for keratoconus.
Literatur
4.
Zurück zum Zitat Boimer C, Lee K, Sharpen L, Mashour RS, Slomovic AR (2011) Evolving surgical techniques of and indications for corneal transplantation in Ontario from 2000 to 2009. Can J Ophthalmol 46(4):360–366PubMedCrossRef Boimer C, Lee K, Sharpen L, Mashour RS, Slomovic AR (2011) Evolving surgical techniques of and indications for corneal transplantation in Ontario from 2000 to 2009. Can J Ophthalmol 46(4):360–366PubMedCrossRef
6.
Zurück zum Zitat Sorkin N, Varssano D (2014) Corneal collagen crosslinking: a systematic review. Ophthalmologica 232(1):10–27PubMedCrossRef Sorkin N, Varssano D (2014) Corneal collagen crosslinking: a systematic review. Ophthalmologica 232(1):10–27PubMedCrossRef
12.
Zurück zum Zitat Tsugita A, Okada Y, Uehara K (1965) Photosensitized inactivation of ribonucleic acids in the presence of riboflavin. Biochim Biophys Acta 103(2):360–363PubMedCrossRef Tsugita A, Okada Y, Uehara K (1965) Photosensitized inactivation of ribonucleic acids in the presence of riboflavin. Biochim Biophys Acta 103(2):360–363PubMedCrossRef
24.
Zurück zum Zitat Golomb G, Schoen FJ, Smith MS, Linden J, Dixon M, Levy RJ (1987) The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses. Am J Pathol 127(1):122–130PubMedPubMedCentral Golomb G, Schoen FJ, Smith MS, Linden J, Dixon M, Levy RJ (1987) The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses. Am J Pathol 127(1):122–130PubMedPubMedCentral
26.
Zurück zum Zitat Daxer A, Misof K, Grabner B, Ettl A, Fratzl P (1998) Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci 39(3):644–648PubMed Daxer A, Misof K, Grabner B, Ettl A, Fratzl P (1998) Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci 39(3):644–648PubMed
27.
Zurück zum Zitat Bailey AJ (1987) Structure, function and ageing of the collagens of the eye. Eye 1(2):175–183PubMedCrossRef Bailey AJ (1987) Structure, function and ageing of the collagens of the eye. Eye 1(2):175–183PubMedCrossRef
29.
Zurück zum Zitat Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 135(5):620–627PubMedCrossRef Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 135(5):620–627PubMedCrossRef
38.
Zurück zum Zitat Samaras K, Doutch J, Hayes S, Marshall J, Meek KM, O’Brart DP (2009) Effect of epithelial retention and removal on riboflavin absorption in porcine corneas. J Refract Surg 25(9):771–775PubMedCrossRef Samaras K, Doutch J, Hayes S, Marshall J, Meek KM, O’Brart DP (2009) Effect of epithelial retention and removal on riboflavin absorption in porcine corneas. J Refract Surg 25(9):771–775PubMedCrossRef
41.
Zurück zum Zitat Wollensak G, Wilsch M, Spoerl E, Seiler T (2004) Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/UVA. Cornea 23(5):503–507PubMedCrossRef Wollensak G, Wilsch M, Spoerl E, Seiler T (2004) Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/UVA. Cornea 23(5):503–507PubMedCrossRef
48.
Zurück zum Zitat Tabibian D, Kling S, Hammer A, Richoz O, Hafezi F (2017) Repeated cross-linking after a short time does not provide any additional biomechanical stiffness in the mouse cornea in vivo. J Refract Surg 33(1):56–60PubMedCrossRef Tabibian D, Kling S, Hammer A, Richoz O, Hafezi F (2017) Repeated cross-linking after a short time does not provide any additional biomechanical stiffness in the mouse cornea in vivo. J Refract Surg 33(1):56–60PubMedCrossRef
50.
Zurück zum Zitat Matteoli S, Virga A, Paladini I, Mencucci R, Corvi A (2016) Investigation into the elastic properties of ex vivo porcine corneas subjected to inflation test after cross-linking treatment. J Appl Biomater Funct Mater 14(2):e163–e170PubMed Matteoli S, Virga A, Paladini I, Mencucci R, Corvi A (2016) Investigation into the elastic properties of ex vivo porcine corneas subjected to inflation test after cross-linking treatment. J Appl Biomater Funct Mater 14(2):e163–e170PubMed
53.
Zurück zum Zitat Hayes S, Kamma-Lorger CS, Boote C, Young RD, Quantock AJ, Rost A, Khatib Y, Harris J, Yagi N, Terrill N (2013) The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma. PLoS One 8(1):e52860PubMedPubMedCentralCrossRef Hayes S, Kamma-Lorger CS, Boote C, Young RD, Quantock AJ, Rost A, Khatib Y, Harris J, Yagi N, Terrill N (2013) The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma. PLoS One 8(1):e52860PubMedPubMedCentralCrossRef
56.
Zurück zum Zitat Akhtar S, Almubrad T, Paladini I, Mencucci R (2013) Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking: ultrastructural studies. Mol Vis 19:1526–1537PubMedPubMedCentral Akhtar S, Almubrad T, Paladini I, Mencucci R (2013) Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking: ultrastructural studies. Mol Vis 19:1526–1537PubMedPubMedCentral
62.
Zurück zum Zitat Bottós K, Dreyfuss J, Regatieri C, Lima-Filho A, Schor P, Nader H, Chamon W (2008) Immunofluorescence confocal microscopy of porcine corneas following collagen cross-linking treatment with riboflavin and ultraviolet A. J Refract Surg 24(7):S715–S719PubMedCrossRef Bottós K, Dreyfuss J, Regatieri C, Lima-Filho A, Schor P, Nader H, Chamon W (2008) Immunofluorescence confocal microscopy of porcine corneas following collagen cross-linking treatment with riboflavin and ultraviolet A. J Refract Surg 24(7):S715–S719PubMedCrossRef
65.
Zurück zum Zitat Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE (2006) Biomechanical evidence of the distribution of cross-links in corneastreated with riboflavin and ultraviolet A light. J Cataract Refract Surg 32(2):279–283PubMedCrossRef Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE (2006) Biomechanical evidence of the distribution of cross-links in corneastreated with riboflavin and ultraviolet A light. J Cataract Refract Surg 32(2):279–283PubMedCrossRef
66.
Zurück zum Zitat Schilde T, Spoerl E, Kohlhaas M, Pillunat LE (2005) Depth dependence of stiffening on riboflavin/UVA treated corneas. Invest Ophth Vis Sci 46(13):4958–4958 Schilde T, Spoerl E, Kohlhaas M, Pillunat LE (2005) Depth dependence of stiffening on riboflavin/UVA treated corneas. Invest Ophth Vis Sci 46(13):4958–4958
67.
Zurück zum Zitat Wollensak G, Spoerl E, Seiler T (2003) Stress-strain measurements of human and porcine corneas after riboflavin–ultraviolet-A-induced cross-linking. J Cataract Refract Surg 29(9):1780–1785PubMedCrossRef Wollensak G, Spoerl E, Seiler T (2003) Stress-strain measurements of human and porcine corneas after riboflavin–ultraviolet-A-induced cross-linking. J Cataract Refract Surg 29(9):1780–1785PubMedCrossRef
69.
Zurück zum Zitat Tiveron MC Jr, Pena CRK, Hida RY, Moreira LB, Branco FRE, Kara-Junior N (2017) Topographic outcomes after corneal collagen crosslinking in progressive keratoconus: 1-year follow-up. Arq Bras Oftalmol 80(2):93–96PubMedCrossRef Tiveron MC Jr, Pena CRK, Hida RY, Moreira LB, Branco FRE, Kara-Junior N (2017) Topographic outcomes after corneal collagen crosslinking in progressive keratoconus: 1-year follow-up. Arq Bras Oftalmol 80(2):93–96PubMedCrossRef
76.
Zurück zum Zitat Pang X, Peng X, Fan Z, Jia H, Wu T (2016) Comparison of central corneal thickness using ultrasound pachymetry during corneal collagen cross-linking. Eye Sci 28(1):15–19 Pang X, Peng X, Fan Z, Jia H, Wu T (2016) Comparison of central corneal thickness using ultrasound pachymetry during corneal collagen cross-linking. Eye Sci 28(1):15–19
77.
Zurück zum Zitat Kim TG, Kim KY, Han JB, Jin KH (2016) The long-term clinical outcome after corneal collagen cross-linking in Korean patients with progressive keratoconus. Korean J Ophthalmol 30(5):326–334PubMedPubMedCentralCrossRef Kim TG, Kim KY, Han JB, Jin KH (2016) The long-term clinical outcome after corneal collagen cross-linking in Korean patients with progressive keratoconus. Korean J Ophthalmol 30(5):326–334PubMedPubMedCentralCrossRef
111.
Zurück zum Zitat Sinha R, Gupta N, Sharma N, Gupta R, Titiyal J (2010) Keratoconus: A review of presentation patterns. Indian J Ophthalmol 58 (3):263–268 Sinha R, Gupta N, Sharma N, Gupta R, Titiyal J (2010) Keratoconus: A review of presentation patterns. Indian J Ophthalmol 58 (3):263–268
113.
Zurück zum Zitat Wernli J, Schumacher S, Spoerl E, Mrochen M (2013) The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time corneal cross-linking efficacy. Invest Ophthalmol Vis Sci 54(2):1176–1180PubMedCrossRef Wernli J, Schumacher S, Spoerl E, Mrochen M (2013) The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time corneal cross-linking efficacy. Invest Ophthalmol Vis Sci 54(2):1176–1180PubMedCrossRef
115.
Zurück zum Zitat Søndergaard AP, Hjortdal J, Breitenbach T, Ivarsen A (2010) Corneal distribution of riboflavin prior to collagen cross-linking. Curr Eye Res 35(2):116–121PubMedCrossRef Søndergaard AP, Hjortdal J, Breitenbach T, Ivarsen A (2010) Corneal distribution of riboflavin prior to collagen cross-linking. Curr Eye Res 35(2):116–121PubMedCrossRef
119.
Zurück zum Zitat Schumacher S, Oeftiger L, Mrochen M (2011) Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation. Invest Ophthalmol Vis Sci 52(12):9048–9052PubMedCrossRef Schumacher S, Oeftiger L, Mrochen M (2011) Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation. Invest Ophthalmol Vis Sci 52(12):9048–9052PubMedCrossRef
121.
Zurück zum Zitat Mazzotta C, Balestrazzi A, Traversi C, Baiocchi S, Caporossi T, Tommasi C, Caporossi A (2007) Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg retinal tomograph II in vivo confocal microscopy in humans. Cornea 26(4):390–397. https://doi.org/10.1097/ICO.0b013e318030df5a PubMedCrossRef Mazzotta C, Balestrazzi A, Traversi C, Baiocchi S, Caporossi T, Tommasi C, Caporossi A (2007) Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg retinal tomograph II in vivo confocal microscopy in humans. Cornea 26(4):390–397. https://​doi.​org/​10.​1097/​ICO.​0b013e318030df5a​ PubMedCrossRef
122.
Zurück zum Zitat Wollensak G, Spoerl E, Wilsch M, Seiler T (2004) Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA treatment. Cornea 23(1):43–49PubMedCrossRef Wollensak G, Spoerl E, Wilsch M, Seiler T (2004) Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA treatment. Cornea 23(1):43–49PubMedCrossRef
125.
Zurück zum Zitat Braun E, Kanellopoulos J, Pe L, Jankov M (2005) Riboflavin/ultraviolet A-induced collagen cross-linking in the management of keratoconus. Invest Ophth Vis Sci 46(13):4964–4964 Braun E, Kanellopoulos J, Pe L, Jankov M (2005) Riboflavin/ultraviolet A-induced collagen cross-linking in the management of keratoconus. Invest Ophth Vis Sci 46(13):4964–4964
128.
Zurück zum Zitat Tu K, Aslanides I (2009) Orbscan II anterior elevation changes following corneal collagen cross-linking treatment for keratoconus. J Refract Surg 25(8):715–722PubMedCrossRef Tu K, Aslanides I (2009) Orbscan II anterior elevation changes following corneal collagen cross-linking treatment for keratoconus. J Refract Surg 25(8):715–722PubMedCrossRef
133.
136.
Zurück zum Zitat Iseli HP, Popp M, Seiler T, Spoerl E, Mrochen M (2011) Laboratory measurement of the absorption coefficient of riboflavin for ultraviolet light (365 nm). J Refract Surg 27(3):195–201PubMed Iseli HP, Popp M, Seiler T, Spoerl E, Mrochen M (2011) Laboratory measurement of the absorption coefficient of riboflavin for ultraviolet light (365 nm). J Refract Surg 27(3):195–201PubMed
138.
Zurück zum Zitat Baiocchi S, Mazzotta C, Cerretani D, Caporossi T, Caporossi A (2009) Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium. J Cataract Refract Surg 35(5):893–899PubMedCrossRef Baiocchi S, Mazzotta C, Cerretani D, Caporossi T, Caporossi A (2009) Corneal crosslinking: riboflavin concentration in corneal stroma exposed with and without epithelium. J Cataract Refract Surg 35(5):893–899PubMedCrossRef
141.
Zurück zum Zitat Sharma N, Maharana P, Singh G, Titiyal JS (2010) Pseudomonas keratitis after collagen crosslinking for keratoconus: case report and review of literature. J Cataract Refract Surg 36(3):517–520PubMedCrossRef Sharma N, Maharana P, Singh G, Titiyal JS (2010) Pseudomonas keratitis after collagen crosslinking for keratoconus: case report and review of literature. J Cataract Refract Surg 36(3):517–520PubMedCrossRef
142.
Zurück zum Zitat Zamora KV, Males JJ (2009) Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea 28(4):474–476PubMedCrossRef Zamora KV, Males JJ (2009) Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea 28(4):474–476PubMedCrossRef
150.
Zurück zum Zitat Hammer A, Richoz O, Mosquera SA, Tabibian D, Hoogewoud F, Hafezi F (2014) Corneal biomechanical properties at different corneal cross-linking (CXL) irradiancescorneal biomechanics at higher UV-A irradiances. Invest Ophthalmol Vis Sci 55(5):2881–2884PubMedCrossRef Hammer A, Richoz O, Mosquera SA, Tabibian D, Hoogewoud F, Hafezi F (2014) Corneal biomechanical properties at different corneal cross-linking (CXL) irradiancescorneal biomechanics at higher UV-A irradiances. Invest Ophthalmol Vis Sci 55(5):2881–2884PubMedCrossRef
145.
Zurück zum Zitat Dai J, Chu R, Zhou X, Chen C, Qu X, Wang X (2006) One-year outcomes of epi-LASIK for myopia. J Refract Surg 22(6):589–595PubMedCrossRef Dai J, Chu R, Zhou X, Chen C, Qu X, Wang X (2006) One-year outcomes of epi-LASIK for myopia. J Refract Surg 22(6):589–595PubMedCrossRef
154.
Zurück zum Zitat Çınar Y, Cingü AK, Türkcü FM, Çınar T, Yüksel H, Özkurt ZG, Çaça I (2014) Comparison of accelerated and conventional corneal collagen cross-linking for progressive keratoconus. Cutan Ocul Toxicol 33(3):218–222PubMedCrossRef Çınar Y, Cingü AK, Türkcü FM, Çınar T, Yüksel H, Özkurt ZG, Çaça I (2014) Comparison of accelerated and conventional corneal collagen cross-linking for progressive keratoconus. Cutan Ocul Toxicol 33(3):218–222PubMedCrossRef
155.
Zurück zum Zitat Sadoughi MM, Einollahi B, Baradaran-Rafii A, Roshandel D, Hasani H, Nazeri M (2016) Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study. Int Ophthalmol:1–8. https://doi.org/10.1007/s10792-016-0423-0 Sadoughi MM, Einollahi B, Baradaran-Rafii A, Roshandel D, Hasani H, Nazeri M (2016) Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study. Int Ophthalmol:1–8. https://​doi.​org/​10.​1007/​s10792-016-0423-0
156.
Zurück zum Zitat Tomita M, Mita M, Huseynova T (2014) Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg 40(6):1013–1020CrossRefPubMed Tomita M, Mita M, Huseynova T (2014) Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg 40(6):1013–1020CrossRefPubMed
158.
Zurück zum Zitat Brittingham S, Tappeiner C, Frueh BE (2014) Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes standard versus rapid cross-linking treatment. Invest Ophthalmol Vis Sci 55(12):8371–8376PubMedCrossRef Brittingham S, Tappeiner C, Frueh BE (2014) Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes standard versus rapid cross-linking treatment. Invest Ophthalmol Vis Sci 55(12):8371–8376PubMedCrossRef
164.
Zurück zum Zitat Kymionis GD, Tsoulnaras KI, Liakopoulos DA, Skatharoudi CA, Grentzelos MA, Tsakalis NG (2016) Corneal stromal demarcation line depth following standard and a modified high intensity corneal cross-linking protocol. J Refract Surg 32(4):218–222PubMedCrossRef Kymionis GD, Tsoulnaras KI, Liakopoulos DA, Skatharoudi CA, Grentzelos MA, Tsakalis NG (2016) Corneal stromal demarcation line depth following standard and a modified high intensity corneal cross-linking protocol. J Refract Surg 32(4):218–222PubMedCrossRef
167.
Zurück zum Zitat Mencucci R, Mazzotta C, Corvi A, Terracciano L, Rechichi M, Matteoli S (2015) In vivo thermographic analysis of the corneal surface in keratoconic patients undergoing riboflavin–UV-A accelerated cross-linking. Cornea 34(3):323–327PubMedCrossRef Mencucci R, Mazzotta C, Corvi A, Terracciano L, Rechichi M, Matteoli S (2015) In vivo thermographic analysis of the corneal surface in keratoconic patients undergoing riboflavin–UV-A accelerated cross-linking. Cornea 34(3):323–327PubMedCrossRef
168.
Zurück zum Zitat Kurt T, Ozgurhan EB, Yildirim Y, Akcay BIS, Cosar MG, Bozkurt E, Taskapili M (2016) Accelerated (18 mW/cm2) corneal cross-linking for progressive keratoconus: 18-month results. J Ocul Pharmacol Ther 32(4):186–191PubMedCrossRef Kurt T, Ozgurhan EB, Yildirim Y, Akcay BIS, Cosar MG, Bozkurt E, Taskapili M (2016) Accelerated (18 mW/cm2) corneal cross-linking for progressive keratoconus: 18-month results. J Ocul Pharmacol Ther 32(4):186–191PubMedCrossRef
169.
Zurück zum Zitat Pahuja N, Kumar NR, Francis M, Shanbagh S, Shetty R, Ghosh A, Roy AS (2016) Correlation of clinical and biomechanical outcomes of accelerated crosslinking (9 mW/cm2 in 10 minutes) in keratoconus with molecular expression of ectasia-related genes. Curr Eye Res 41(11):1419–1423PubMedCrossRef Pahuja N, Kumar NR, Francis M, Shanbagh S, Shetty R, Ghosh A, Roy AS (2016) Correlation of clinical and biomechanical outcomes of accelerated crosslinking (9 mW/cm2 in 10 minutes) in keratoconus with molecular expression of ectasia-related genes. Curr Eye Res 41(11):1419–1423PubMedCrossRef
171.
Zurück zum Zitat Filippello M, Stagni E, O’Brart D (2012) Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg 38(2):283–291PubMedCrossRef Filippello M, Stagni E, O’Brart D (2012) Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg 38(2):283–291PubMedCrossRef
173.
179.
Zurück zum Zitat Mannermaa E, Vellonen K-S, Urtti A (2006) Drug transport in corneal epithelium and blood–retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 58(11):1136–1163PubMedCrossRef Mannermaa E, Vellonen K-S, Urtti A (2006) Drug transport in corneal epithelium and blood–retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 58(11):1136–1163PubMedCrossRef
182.
Zurück zum Zitat Mastropasqua L, Lanzini M, Curcio C, Calienno R, Mastropasqua R, Colasante M, Mastropasqua A, Nubile M (2014) Structural modifications and tissue response after standard epi-off and iontophoretic corneal crosslinking with different irradiation procedures. Invest Ophthalmol Vis Sci 55(4):2526–2533. https://doi.org/10.1167/iovs.13-13363 PubMedCrossRef Mastropasqua L, Lanzini M, Curcio C, Calienno R, Mastropasqua R, Colasante M, Mastropasqua A, Nubile M (2014) Structural modifications and tissue response after standard epi-off and iontophoretic corneal crosslinking with different irradiation procedures. Invest Ophthalmol Vis Sci 55(4):2526–2533. https://​doi.​org/​10.​1167/​iovs.​13-13363 PubMedCrossRef
183.
Zurück zum Zitat Lafond M, Aptel F, Mestas J-L, Lafon C (2017) Ultrasound-mediated ocular delivery of therapeutic agents: a review. Expert Opin Drug Deliv 14(4):539–550PubMedCrossRef Lafond M, Aptel F, Mestas J-L, Lafon C (2017) Ultrasound-mediated ocular delivery of therapeutic agents: a review. Expert Opin Drug Deliv 14(4):539–550PubMedCrossRef
184.
Zurück zum Zitat Kanellopoulos AJ (2009) Collagen cross-linking in early keratoconus with riboflavin in a femtosecond laser-created pocket: initial clinical results. J Refract Surg 25(11):1034–1037PubMedCrossRef Kanellopoulos AJ (2009) Collagen cross-linking in early keratoconus with riboflavin in a femtosecond laser-created pocket: initial clinical results. J Refract Surg 25(11):1034–1037PubMedCrossRef
192.
Zurück zum Zitat Gatzioufas Z, Raiskup F, O’Brart D, Spoerl E, Panos GD, Hafezi F (2016) Transepithelial corneal cross-linking using an enhanced riboflavin solution. J Refract Surg 32(6):372–377PubMedCrossRef Gatzioufas Z, Raiskup F, O’Brart D, Spoerl E, Panos GD, Hafezi F (2016) Transepithelial corneal cross-linking using an enhanced riboflavin solution. J Refract Surg 32(6):372–377PubMedCrossRef
195.
Zurück zum Zitat Uematsu M, Kumagami T, Kusano M, Yamada K, Mishima K, Fujimura K, Sasaki H, Kitaoka T (2007) Acute corneal epithelial change after instillation of benzalkonium chloride evaluated using a newly developed in vivo corneal transepithelial electric resistance measurement method. Ophthalmic Res 39(6):308–314PubMedCrossRef Uematsu M, Kumagami T, Kusano M, Yamada K, Mishima K, Fujimura K, Sasaki H, Kitaoka T (2007) Acute corneal epithelial change after instillation of benzalkonium chloride evaluated using a newly developed in vivo corneal transepithelial electric resistance measurement method. Ophthalmic Res 39(6):308–314PubMedCrossRef
196.
Zurück zum Zitat Saettone MF, Chetoni P, Cerbai R, Mazzanti G, Braghiroli L (1996) Evaluation of ocular permeation enhancers: in vitro effects on corneal transport of four β-blockers, and in vitro/in vivo toxic activity. Int J Pharm 142(1):103–113CrossRef Saettone MF, Chetoni P, Cerbai R, Mazzanti G, Braghiroli L (1996) Evaluation of ocular permeation enhancers: in vitro effects on corneal transport of four β-blockers, and in vitro/in vivo toxic activity. Int J Pharm 142(1):103–113CrossRef
197.
Zurück zum Zitat Nakamura T, Yamada M, Teshima M, Nakashima M, To H, Ichikawa N, Sasaki H (2007) Electrophysiological characterization of tight junctional pathway of rabbit cornea treated with ophthalmic ingredients. Biol Pharm Bull 30(12):2360–2364PubMedCrossRef Nakamura T, Yamada M, Teshima M, Nakashima M, To H, Ichikawa N, Sasaki H (2007) Electrophysiological characterization of tight junctional pathway of rabbit cornea treated with ophthalmic ingredients. Biol Pharm Bull 30(12):2360–2364PubMedCrossRef
202.
Zurück zum Zitat Pinelli R, El-Shawaf H (2009) Transepithelial tensioactive mediated CXL. J Cataract Refract Surg 4(37):67–70 Pinelli R, El-Shawaf H (2009) Transepithelial tensioactive mediated CXL. J Cataract Refract Surg 4(37):67–70
205.
Zurück zum Zitat Prasad R, Koul V (2012) Transdermal delivery of methotrexate: past, present and future prospects. Ther Deliv 3(3):315–325PubMedCrossRef Prasad R, Koul V (2012) Transdermal delivery of methotrexate: past, present and future prospects. Ther Deliv 3(3):315–325PubMedCrossRef
213.
Zurück zum Zitat Cassagne M, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, Soler V, Fournié P, Malecaze F (2016) Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Invest Ophthalmol Vis Sci 57(2):594. https://doi.org/10.1167/iovs.13-12595 PubMedCrossRef Cassagne M, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, Soler V, Fournié P, Malecaze F (2016) Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Invest Ophthalmol Vis Sci 57(2):594. https://​doi.​org/​10.​1167/​iovs.​13-12595 PubMedCrossRef
214.
Zurück zum Zitat Bouheraoua N, Jouve L, El Sanharawi M, Sandali O, Temstet C, Loriaut P, Basli E, Borderie V, Laroche L (2014) Optical coherence tomography and confocal microscopy following three different protocols of corneal collagen-crosslinking in keratoconus. Invest Ophthalmol Vis Sci 55(11):7601–7609. https://doi.org/10.1167/iovs.14-15662 PubMedCrossRef Bouheraoua N, Jouve L, El Sanharawi M, Sandali O, Temstet C, Loriaut P, Basli E, Borderie V, Laroche L (2014) Optical coherence tomography and confocal microscopy following three different protocols of corneal collagen-crosslinking in keratoconus. Invest Ophthalmol Vis Sci 55(11):7601–7609. https://​doi.​org/​10.​1167/​iovs.​14-15662 PubMedCrossRef
215.
Zurück zum Zitat Vinciguerra R, Spoerl E, Romano MR, Rosetta P, Vinciguerra P (2012) Comparative stress strain measurements of human corneas after transepithelial UV-A induced cross-linking: impregnation with iontophoresis, different riboflavin solutions and irradiance power. Invest Ophthalmol Vis Sci 53(14):1518 Vinciguerra R, Spoerl E, Romano MR, Rosetta P, Vinciguerra P (2012) Comparative stress strain measurements of human corneas after transepithelial UV-A induced cross-linking: impregnation with iontophoresis, different riboflavin solutions and irradiance power. Invest Ophthalmol Vis Sci 53(14):1518
211.
Zurück zum Zitat Vinciguerra P, Romano V, Rosetta P, Legrottaglie EF, Piscopo R, Fabiani C, Azzolini C, Vinciguerra R (2016) Transepithelial iontophoresis versus standard corneal collagen cross-linking: 1-year results of a prospective clinical study. J Refract Surg 32(10):672–678PubMedCrossRef Vinciguerra P, Romano V, Rosetta P, Legrottaglie EF, Piscopo R, Fabiani C, Azzolini C, Vinciguerra R (2016) Transepithelial iontophoresis versus standard corneal collagen cross-linking: 1-year results of a prospective clinical study. J Refract Surg 32(10):672–678PubMedCrossRef
Metadaten
Titel
Current perspectives on corneal collagen crosslinking (CXL)
verfasst von
Sandeepani K. Subasinghe
Kelechi C. Ogbuehi
George J. Dias
Publikationsdatum
06.04.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 8/2018
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-018-3966-0

Weitere Artikel der Ausgabe 8/2018

Graefe's Archive for Clinical and Experimental Ophthalmology 8/2018 Zur Ausgabe

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Die Verwendung von Ophthalmika in der Schwangerschaft und Stillzeit stellt immer eine Off-label-Anwendung dar. Ein Einsatz von Arzneimitteln muss daher besonders sorgfältig auf sein Risiko-Nutzen-Verhältnis bewertet werden. In der vorliegenden …

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Vitrektomie Originalie

Die endogene Endophthalmitis ist eine hämatogen fortgeleitete, bakterielle oder fungale Infektion, die über choroidale oder retinale Gefäße in den Augapfel eingeschwemmt wird [ 1 – 3 ]. Von dort infiltrieren die Keime in die Netzhaut, den …

Bakterielle endogene Endophthalmitis

Vitrektomie Leitthema

Eine endogene Endophthalmitis stellt einen ophthalmologischen Notfall dar, der umgehender Diagnostik und Therapie bedarf. Es sollte mit geeigneten Methoden, wie beispielsweise dem Freiburger Endophthalmitis-Set, ein Keimnachweis erfolgen. Bei der …

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Die bestmögliche Wundheilung der Kornea, insbesondere ohne die Ausbildung von lichtstreuenden Narben, ist oberstes Gebot, um einer dauerhaften Schädigung der Hornhaut frühzeitig entgegenzuwirken und die Funktion des Auges zu erhalten.   

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.