Long-term effects of epithelium-off corneal cross-linking in keratoconus therapy Case report
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Published:
Dec 31, 2024
Keywords:
keratoconus, corneal cross-linking, CXL, epithelium-off corneal cross-linking, epi-off CXL, corneal flattening
Main Article Content
Abstract
Background: We report a well-documented cases of progressive corneal flattening and visual improvement after epithelium-off corneal cross-linking (epioff CXL) for keratoconus with long-term follow-up.
Case report: Two young men reported with deterioration of vision and diagnosed keratoconus few months earlier. Corneal tomography confirmed the previous diagnosis. Considering the age of the patients it was decided to perform epi-off CXL in both eyes. Based on several years of observation, no progression of the disease has been observed. In both cases, good visual acuity is maintained, what is unexpected the reduction in the maximum keratometry reading is still flattening also corneal thickness is reduced.
Conclusion: Continuous long-term flattening and corneal thinning after corneal cross-linking seems to be unpredictability in some cases. Our report highlights the importance of long-term evaluation of crosslinking techniques.
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1.
Maleszka-Kurpiel M, Jackowiak A, Robak M. Long-term effects of epithelium-off corneal cross-linking in keratoconus therapy. Ophthatherapy [Internet]. 2024Dec.31 [cited 2025Apr.24];11(4):353-9. Available from: https://journalsmededu.pl/index.php/ophthatherapy/article/view/3235
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Conservative treatment
Copyright: © Medical Education sp. z o.o. License allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
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2. Li X, Rabinowitz YS, Rasheed K et al. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology. 2004; 111: 440-6.
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4. Loukovitis E, Sfakianakis K, Syrmakesi P et al. Genetic aspects of keratoconus: a literature review exploring potential genetic contributionsand possible genetic relationships with comorbidities. Ophthalmol Ther. 2018; 7: 263-92.
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6. Zadnik K, Barr JT, Edrington TB et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci. 1998; 39: 2537-46.
7. Balasubramanian SA, Pye DC, Willcox MD. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus. Clin Exp Optom. 2013; 96: 214-8.
8. Jaskiewicz K, Maleszka-Kurpiel M, Michalski A et al. Non-allergic eye rubbing is a major behavioral risk factor for keratoconus. PLoS One. 2023; 18(4): e0284454. http://doi.org/10.1371/journal.pone.0284454.
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11. Kanclerz P, Przewłócka K, Toprak I et al. The prevalence of keratoconus in northern Poland: A cross-sectional study of patients from a primary healthcare practice. Cont Lens Anterior Eye. 2023; 46(4): 101846. http://doi.org/10.1016/j.clae.2023.101846.
12. Alghamdi A, Khan MS, Dakhil TA. Understanding Corneal Epithelial Thickness Mapping. Middle East Afr J Ophthalmol. 2023; 29(3): 147-55. http://doi.org/10.4103/meajo.meajo_207_22.
13. Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009; 25: 604-10.
14. Maleszka-Kurpiel M, Michalski A, Robak M et al. Inter-eye asymmetry in manifest refraction, keratometry and pachymetry in eyes with keratoconus. Klinika oczna. 2020; 122: 112-6.
15.Sarma P, Kaur H, Hafezi F et al. Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials. Taiwan J Ophthalmol. 2023; 13(2): 191-202. http://doi.org/10.4103/2211-5056.361974.
16. Meiri Z, Keren S, Rosenblatt A et al. Efficacy of Corneal Collagen Cross-Linking for the Treatment of Keratoconus: A Systematic Review and Meta-Analysis. Cornea. 2016; 35(3): 417-28. http://doi.org/10.1097/ICO.0000000000000723.
17. Maleszka-Kurpiel M, Michalski A, Robak M et al. Influence of corneal cross-linking on visual acuity and topometric indices in keratoconus. Klinika Oczna/Acta Ophthalmologica Polonica. 2020; 122(4): 165-70. http://doi.org/10.5114/ko.2020.101652.
18. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009; 35: 1358-62.
19. Wen D, Li Q, Song B et al. Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: a metaanalysis. Invest Ophthalmol Vis Sci. 2018; 59: 3920-31.
20. Hwang B, Pecsok M, Cheng BT et al. Rates of Failure of Corneal Crosslinking for Keratoconus in the United States. Invest Ophthalmol Vis Sci. 2024; 65(7): 4569.
21. Nicula C, Pop R, Rednik A et al. 10-Year Results of Standard Cross-Linking in Patients with Progressive Keratoconus in Romania. J Ophthalmol. 2019; 2019: 8285649. http://doi.org/10.1155/2019/8285649.
22. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003; 135: 620-7.
23. Brittingham S, Tappeiner C, Frueh BE. Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes. Invest Ophthalmol Vis Sci. 2014; 55: 8371-6.
24. Godefrooij DA, Gans R, Imhof SM et al. Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking Acta Ophthalmol. 2016; 94: 675-8.
25. Koller T, Pajic B, Vinciguerra P et al. Flattening of the cornea after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2011; 37(8): 1488-92. http://doi.org/10.1016/j.jcrs.2011.03.041.
26. Kymionis GD, Tsoulnaras KI, Liakopoulos DA et al. Excessive Corneal Flattening and Thinning After Corneal Cross-linking: Single-Case Report With 5-Year Follow-up. Cornea. 2015; 34(6): 704-6.
27. Santhiago MR, Giacomin NT, Medeiros CS et al. Intense early flattening after corneal collagen cross-linking. J Refract Surg. 2015; 31(6): 419-22.
28. Seifert FK, Theuersbacher J, Schwabe D et al. Long-Term Outcome of Corneal Collagen Crosslinking with Riboflavin and UV-A Irradiation for Keratoconus. Curr Eye Res. 2022; 47(11): 1472-8. http://doi.org/10.1080/02713683.2022.2117383.
29. Caporossi A, Mazzotta C, Baiocchi S et al. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol. 2010; 149(4): 585-93. http://doi.org/10.1016/j.ajo.2009.10.021.
30. Wittig-Silva C, Chan E, Islam FM et al. A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results. Ophthalmology. 2014; 121: 812-21.
31. Wu W, Wang Y, Xu L. Meta-analysis of Pentacam vs. ultrasound pachymetry in central corneal thickness measurement in normal, post- LASIK or PRK, and keratoconic or keratoconus-suspect eyes. Graefes Arch Clin Exp Ophthalmol. 2014; 252: 91-9.
32. Rocha KM, Perez-Straziota CE, Stulting RD et al. Epithelial and stromal remodeling after corneal collagen cross-linking evaluated by spectral-domain OCT. J Refract Surg. 2014; 30: 122-7.
33. Reinstein DZ, Gobbe M, Archer TJ et al. Epithelial thickness profile as a method to evaluate the effectiveness of collagen cross-linking treatment after corneal ectasia. J Refract Surg. 2011; 27: 356-63.
2. Li X, Rabinowitz YS, Rasheed K et al. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology. 2004; 111: 440-6.
3. Wagner H, Barr JT, Zadnik K. Collaborative longitudinal evaluation of keratoconus (CLEK) Study: methods and findings to date. Contact Lens Anterior Eye. 2007; 30: 223-32.
4. Loukovitis E, Sfakianakis K, Syrmakesi P et al. Genetic aspects of keratoconus: a literature review exploring potential genetic contributionsand possible genetic relationships with comorbidities. Ophthalmol Ther. 2018; 7: 263-92.
5. Kabza M, Karolak JA, Rydzanicz M et al. Multiple differentially methylated regions specific to keratoconus explain known keratoconuslinkage loci. Invest Ophthalmol Vis Sci. 2019; 60: 1501-9.
6. Zadnik K, Barr JT, Edrington TB et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci. 1998; 39: 2537-46.
7. Balasubramanian SA, Pye DC, Willcox MD. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus. Clin Exp Optom. 2013; 96: 214-8.
8. Jaskiewicz K, Maleszka-Kurpiel M, Michalski A et al. Non-allergic eye rubbing is a major behavioral risk factor for keratoconus. PLoS One. 2023; 18(4): e0284454. http://doi.org/10.1371/journal.pone.0284454.
9. Harthan JS, Gelles JD, Block SS et al. Prevalence of Keratoconus Based on Scheimpflug Corneal Tomography Metrics in a Pediatric Population From a Chicago-Based School Age Vision Clinic. Eye Contact Lens. 2024; 50(3): 121-5. http://doi.org/10.1097/ICL.0000000000001072.
10. Kanellopoulos AJ, Kanellopoulos AJ. Topographic Keratoconus Incidence in Greece Diagnosed in Routine Consecutive Cataract Procedures: A Consecutive Case Series of 1250 Cases over 5 Years. J Clin Med. 2024; 13(8): 2378. http://doi.org/10.3390/jcm13082378.
11. Kanclerz P, Przewłócka K, Toprak I et al. The prevalence of keratoconus in northern Poland: A cross-sectional study of patients from a primary healthcare practice. Cont Lens Anterior Eye. 2023; 46(4): 101846. http://doi.org/10.1016/j.clae.2023.101846.
12. Alghamdi A, Khan MS, Dakhil TA. Understanding Corneal Epithelial Thickness Mapping. Middle East Afr J Ophthalmol. 2023; 29(3): 147-55. http://doi.org/10.4103/meajo.meajo_207_22.
13. Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009; 25: 604-10.
14. Maleszka-Kurpiel M, Michalski A, Robak M et al. Inter-eye asymmetry in manifest refraction, keratometry and pachymetry in eyes with keratoconus. Klinika oczna. 2020; 122: 112-6.
15.Sarma P, Kaur H, Hafezi F et al. Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials. Taiwan J Ophthalmol. 2023; 13(2): 191-202. http://doi.org/10.4103/2211-5056.361974.
16. Meiri Z, Keren S, Rosenblatt A et al. Efficacy of Corneal Collagen Cross-Linking for the Treatment of Keratoconus: A Systematic Review and Meta-Analysis. Cornea. 2016; 35(3): 417-28. http://doi.org/10.1097/ICO.0000000000000723.
17. Maleszka-Kurpiel M, Michalski A, Robak M et al. Influence of corneal cross-linking on visual acuity and topometric indices in keratoconus. Klinika Oczna/Acta Ophthalmologica Polonica. 2020; 122(4): 165-70. http://doi.org/10.5114/ko.2020.101652.
18. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009; 35: 1358-62.
19. Wen D, Li Q, Song B et al. Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: a metaanalysis. Invest Ophthalmol Vis Sci. 2018; 59: 3920-31.
20. Hwang B, Pecsok M, Cheng BT et al. Rates of Failure of Corneal Crosslinking for Keratoconus in the United States. Invest Ophthalmol Vis Sci. 2024; 65(7): 4569.
21. Nicula C, Pop R, Rednik A et al. 10-Year Results of Standard Cross-Linking in Patients with Progressive Keratoconus in Romania. J Ophthalmol. 2019; 2019: 8285649. http://doi.org/10.1155/2019/8285649.
22. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003; 135: 620-7.
23. Brittingham S, Tappeiner C, Frueh BE. Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes. Invest Ophthalmol Vis Sci. 2014; 55: 8371-6.
24. Godefrooij DA, Gans R, Imhof SM et al. Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking Acta Ophthalmol. 2016; 94: 675-8.
25. Koller T, Pajic B, Vinciguerra P et al. Flattening of the cornea after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2011; 37(8): 1488-92. http://doi.org/10.1016/j.jcrs.2011.03.041.
26. Kymionis GD, Tsoulnaras KI, Liakopoulos DA et al. Excessive Corneal Flattening and Thinning After Corneal Cross-linking: Single-Case Report With 5-Year Follow-up. Cornea. 2015; 34(6): 704-6.
27. Santhiago MR, Giacomin NT, Medeiros CS et al. Intense early flattening after corneal collagen cross-linking. J Refract Surg. 2015; 31(6): 419-22.
28. Seifert FK, Theuersbacher J, Schwabe D et al. Long-Term Outcome of Corneal Collagen Crosslinking with Riboflavin and UV-A Irradiation for Keratoconus. Curr Eye Res. 2022; 47(11): 1472-8. http://doi.org/10.1080/02713683.2022.2117383.
29. Caporossi A, Mazzotta C, Baiocchi S et al. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol. 2010; 149(4): 585-93. http://doi.org/10.1016/j.ajo.2009.10.021.
30. Wittig-Silva C, Chan E, Islam FM et al. A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results. Ophthalmology. 2014; 121: 812-21.
31. Wu W, Wang Y, Xu L. Meta-analysis of Pentacam vs. ultrasound pachymetry in central corneal thickness measurement in normal, post- LASIK or PRK, and keratoconic or keratoconus-suspect eyes. Graefes Arch Clin Exp Ophthalmol. 2014; 252: 91-9.
32. Rocha KM, Perez-Straziota CE, Stulting RD et al. Epithelial and stromal remodeling after corneal collagen cross-linking evaluated by spectral-domain OCT. J Refract Surg. 2014; 30: 122-7.
33. Reinstein DZ, Gobbe M, Archer TJ et al. Epithelial thickness profile as a method to evaluate the effectiveness of collagen cross-linking treatment after corneal ectasia. J Refract Surg. 2011; 27: 356-63.