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Long-term results of accelerated corneal collagen crosslinking in paediatric patients with progressive keratoconus: 10-year follow-up

Eye volume 38, pages 2522–2529 (2024)Cite this article

Subjects

Abstract

Objectives

To evaluate the 10-year visual, refractive, and tomographic outcomes of epithelium-off accelerated corneal collagen cross-linking (ACCL) in paediatric patients with progressive keratoconus (KC) and to compare the stages in terms of re-progression.

Methods

Patients under 18 years of age with progressive KC who underwent ACCL between 2010 and 2012 and completed at least 10 years of follow-up were included in this retrospective study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, and corneal tomography parameters were evaluated preoperatively and at 1, 5, and 10 years postoperatively. The effect of stage and age on re-progression was analysed.

Results

The study included 175 eyes of 97 patients (mean age: 14.46 ± 2.17 years). Improvement in UDVA and CDVA was observed in all postoperative periods compared to the preoperative period (each p-value < 0.05). The increase in spherical equivalent (SE), flattening of keratometry values, and decrease in thinnest corneal thickness (TCT) were statistically significant in the tenth year compared to preoperatively (each p-value < 0.05). Re-progression was observed in 16 eyes (9.14%). Haze was observed in 13 eyes (7.43%), 4 of which were permanent. Deep anterior lamellar keratoplasty was performed in 3 eyes (1.7%) and a second ACCL in 3 eyes (1.7%).

Conclusions

ACCL is an effective and safe long-term strategy to prevent progression of KC in paediatric patients. In the light of this study with a 10-year follow-up re-progression rate of 9.14%, long-term follow-up of patients after ACCL for possible re-progression and the need for re-CCL or keratoplasty may be recommended.

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Fig. 1: Changes in visual parameters over time.
Fig. 2

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Data availability

All data generated or analysed during this study are included in this published article.

References

  1. Arne JL, Fournié P. Keratoconus, the most common corneal dystrophy. Can keratoplasty be avoided?. Bull Acad Natl Med. 2011;195:113–29.

    PubMed  Google Scholar 

  2. Amsler M. Some data on the problem of keratoconus. Bull Soc Belg Ophtalmol. 1961;129:331–54.

    CAS  Google Scholar 

  3. Ertan A, Muftuoglu O. Keratoconus clinical findings according to different age and gender groups. Cornea. 2008;27:1109–13. https://doi.org/10.1097/ICO.0b013e31817f815a.

    Article  PubMed  Google Scholar 

  4. Sharma R, Titiyal JS, Prakash G, Sharma N, Tandon R, Vajpayee RB. Clinical profile and risk factors for keratoplasty and development of hydrops in north Indian patients with keratoconus. Cornea. 2009;28:367–70. https://doi.org/10.1097/ICO.0b013e31818cd077.

    Article  PubMed  Google Scholar 

  5. Imbornoni LM, McGhee CNJ, Belin MW. Evolution of Keratoconus: From Diagnosis to Therapeutics. Klin Monbl Augenheilkd. 2018;235:680–8. https://doi.org/10.1055/s-0044-100617.

    Article  PubMed  Google Scholar 

  6. Seitz B, Daas L, Hamon L, Xanthopoulou K, Goebels S, Spira-Eppig C, et al. Stage-appropriate treatment of keratoconus. Ophthalmologe. 2021;118:1069–88. https://doi.org/10.1007/s00347-021-01410-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–7. https://doi.org/10.1016/s0002-9394(02)02220-1.

    Article  PubMed  CAS  Google Scholar 

  8. Sorkin N, Varssano D. Corneal collagen crosslinking: a systematic review. Ophthalmologica. 2014;232:10–27. https://doi.org/10.1159/000357979.

    Article  PubMed  CAS  Google Scholar 

  9. Henriquez MA, Rodríguez AM, Izquierdo L Jr. Accelerated Epi-On Versus Standard Epi-Off Corneal Collagen Cross-Linking for Progressive Keratoconus in Pediatric Patients. Cornea. 2017;36:1503–8. https://doi.org/10.1097/ico.0000000000001366.

    Article  PubMed  Google Scholar 

  10. Henriquez MA, Villegas S, Rincon M, Maldonado C, Izquierdo L Jr. Long-term efficacy and safety after corneal collagen crosslinking in pediatric patients: Three-year follow-up. Eur J Ophthalmol. 2018;28:415–8. https://doi.org/10.1177/1120672118760149.

    Article  PubMed  Google Scholar 

  11. Henriquez MA, Hernandez-Sahagun G, Camargo J, Izquierdo L Jr. Accelerated Epi-On Versus Standard Epi-Off Corneal Collagen Cross-Linking for Progressive Keratoconus in Pediatric Patients: Five Years of Follow-Up. Cornea. 2020;39:1493–8. https://doi.org/10.1097/ico.0000000000002463.

    Article  PubMed  Google Scholar 

  12. Polido J, Araújo M, Wakamatsu TH, Alexander JG, Cabral T, Ambrósio R Jr., et al. Long-term Safety and Efficacy of Corneal Collagen Crosslinking in a Pediatric Group With Progressive Keratoconus: A 7-year Follow-up. Am J Ophthalmol. 2023;250:59–69. https://doi.org/10.1016/j.ajo.2023.01.012.

    Article  PubMed  CAS  Google Scholar 

  13. Vinciguerra R, Bordignon N, Ferraro V, Mazzotta C, Rosetta P, Vinciguerra P. Corneal Collagen Cross Linking for Progressive Keratoconus in Paediatric Patients: up to 14 years of follow up. Am J Ophthalmol. 2023 https://doi.org/10.1016/j.ajo.2023.07.017.

  14. Kamiya K, Ishii R, Shimizu K, Igarashi A. Evaluation of corneal elevation, pachymetry and keratometry in keratoconic eyes with respect to the stage of Amsler-Krumeich classification. Br J Ophthalmol. 2014;98:459–63. https://doi.org/10.1136/bjophthalmol-2013-304132.

    Article  PubMed  Google Scholar 

  15. Yıldırım Y, Olcucu O, Gunaydin ZK, Ağca A, Ozgurhan EB, Alagoz C, et al. Comparison of Accelerated Corneal Collagen Cross-linking Types for Treating Keratoconus. Curr Eye Res. 2017;42:971–5. https://doi.org/10.1080/02713683.2017.1284241.

    Article  PubMed  Google Scholar 

  16. Anitha V, Vanathi M, Raghavan A, Rajaraman R, Ravindran M, Tandon R. Pediatric keratoconus - Current perspectives and clinical challenges. Indian J Ophthalmol. 2021;69:214–25. https://doi.org/10.4103/ijo.IJO_1263_20.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chatzis N, Hafezi F. Progression of keratoconus and efficacy of pediatric [corrected] corneal collagen cross-linking in children and adolescents. J Refract Surg. 2012;28:753–8. https://doi.org/10.3928/1081597x-20121011-01.

    Article  PubMed  Google Scholar 

  18. Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio R Jr, Guell JL, et al. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34:359–69. https://doi.org/10.1097/ico.0000000000000408.

    Article  PubMed  Google Scholar 

  19. Eissa SA, Yassin A. Prospective, randomized contralateral eye study of accelerated and conventional corneal cross-linking in pediatric keratoconus. Int Ophthalmol. 2019;39:971–9. https://doi.org/10.1007/s10792-018-0898-y.

    Article  PubMed  Google Scholar 

  20. Marty AS, Jurkiewicz T, Febvay C, Mouchel R, Burillon C. Safety and efficiency of epithelium-off accelerated corneal cross-linking for progressive keratoconus in pediatric patients. J Fr Ophtalmol. 2021;44:828–34. https://doi.org/10.1016/j.jfo.2020.11.012.

  21. Nicula CA, Rednik AM, Bulboacă AE, Nicula D. Comparative Results Between “Epi-Off” Conventional and Accelerated Corneal Collagen Crosslinking for Progressive Keratoconus in Pediatric Patients. Ther Clin Risk Manag. 2019;15:1483–90. https://doi.org/10.2147/tcrm.S224533.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Cinar Y, Han CC, Sahin A, Syed ZA. Long term results of accelerated corneal collagen cross-linking in pediatric keratoconus. Eur J Ophthalmol. 2021;31:3494–9. https://doi.org/10.1177/11206721211018362.

    Article  PubMed  Google Scholar 

  23. Li Y, Lu Y, Du K, Yin Y, Hu T, Fu Y, et al. Comparison of Efficacy and Safety Between Standard, Accelerated Epithelium-Off and Transepithelial Corneal Collagen Crosslinking in Pediatric Keratoconus: A Meta-Analysis. Front Med. 2022;9:787167 https://doi.org/10.3389/fmed.2022.787167.

    Article  Google Scholar 

  24. Amer I, Elaskary A, Mostafa A, Hazem HA, Omar A, Abdou A. Long-Term Visual, Refractive and Topographic Outcomes of “Epi-off” Corneal Collagen Cross-Linking in Pediatric Keratoconus: Standard versus Accelerated Protocol. Clin Ophthalmol. 2020;14:3747–54. https://doi.org/10.2147/opth.S275797.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Salman A, Darwish T, Ghabra M, Kailani O, Khalil H, Shaaban R. Clinical Outcomes of Accelerated Corneal Cross-Linking for Pediatric Keratoconus. J Ophthalmol. 2021;2021:1851883 https://doi.org/10.1155/2021/1851883.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Sarac O, Caglayan M, Uysal BS, Uzel AGT, Tanriverdi B, Cagil N. Accelerated versus standard corneal collagen cross-linking in pediatric keratoconus patients: 24 months follow-up results. Cont Lens Anterior Eye. 2018;41:442–7. https://doi.org/10.1016/j.clae.2018.06.001.

    Article  PubMed  Google Scholar 

  27. Alipour F, Ansari S, Dadman N, Hafezi F. Accelerated Corneal Collagen Cross-Linking in Pediatric Keratoconus. J Curr Ophthalmol. 2021;33:285–90. https://doi.org/10.4103/joco.joco_163_20.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hed S, Matlov Kormas R, Shashar S, Malyugin BE, Boyko M, Knyazer B. Corneal Cross-Linking as Treatment in Pediatric Keratoconus: Comparison of Two Protocols. J Ophthalmol. 2021;2021:2659828 https://doi.org/10.1155/2021/2659828.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Ozer MD, Batur M, Mesen S, Tekın S, Seven E, Yasar T. Comparison of the efficacy of accelerated corneal cross-linking therapy in different pediatric age groups having progressive keratoconus. Int Ophthalmol. 2020;40:2651–8. https://doi.org/10.1007/s10792-020-01446-w.

    Article  PubMed  Google Scholar 

  30. Taşçı YY, Taşlıpınar G, Eyidoğan D, Saraç Ö, Çağıl N. Five-Year Long-Term Results of Standard Collagen Cross-Linking Therapy in Patients with Keratoconus. Turk J Ophthalmol. 2020;50:200–5. https://doi.org/10.4274/tjo.galenos.2020.53810.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35:1358–62. https://doi.org/10.1016/j.jcrs.2009.03.035.

    Article  PubMed  Google Scholar 

  32. Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34:796–801. https://doi.org/10.1016/j.jcrs.2007.12.039.

    Article  PubMed  Google Scholar 

  33. Kocak I, Aydin A, Kaya F, Koc H. Comparison of transepithelial corneal collagen crosslinking with epithelium-off crosslinking in progressive keratoconus. J Fr Ophtalmol. 2014;37:371–6. https://doi.org/10.1016/j.jfo.2013.11.012.

    Article  PubMed  CAS  Google Scholar 

  34. Ivarsen A, Hjortdal J. Collagen cross-linking for advanced progressive keratoconus. Cornea. 2013;32:903–6. https://doi.org/10.1097/ICO.0b013e31828321dd.

    Article  PubMed  Google Scholar 

  35. Wu H, Luo S, Fang X, Shang X, Xie Z, Xiao X, et al. Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis. Graefes Arch Clin Exp Ophthalmol. 2021;259:239–46. https://doi.org/10.1007/s00417-020-04861-y.

    Article  PubMed  Google Scholar 

  36. Saad S, Saad R, Goemaere I, Cuyaubere R, Borderie M, Borderie V et al. Efficacy, Safety, and Outcomes following Accelerated and Iontophoresis Corneal Crosslinking in Progressive Keratoconus. J Clin Med. 2023;12 https://doi.org/10.3390/jcm12082931.

  37. Kuechler SJ, Tappeiner C, Epstein D, Frueh BE. Keratoconus Progression After Corneal Cross-Linking in Eyes With Preoperative Maximum Keratometry Values of 58 Diopters and Steeper. Cornea. 2018;37:1444–8. https://doi.org/10.1097/ico.0000000000001736.

    Article  PubMed  Google Scholar 

  38. Iqbal M, Elmassry A, Saad H, Am Gad A, Ibrahim O, Hamed N, et al. Standard cross-linking protocol versus accelerated and transepithelial cross-linking protocols for treatment of paediatric keratoconus: a 2-year comparative study. Acta Ophthalmol. 2020;98:e352–e62. https://doi.org/10.1111/aos.14275.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Havva Kanbak for her contribution to obtaining corneal tomography images.

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Authors and Affiliations

  1. University of Health Sciences, Beyoglu Eye Training and Research Hospital, Department of Ophthalmology, Istanbul, Turkey

    Sibel Ahmet, Gizem Yayla Akincilar, Ahmet Kirgiz, Nilay Kandemir Besek, Burcu Kemer Atik, Husna Topcu & Gunes Gumus Kasapoglu

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Contributions

SA and BKA wrote the main text of the article. AK and HT led several revisions. HT reviewed and revised the manuscript, and GY and GG collected data and prepared figures. NKB served as the primary senior editor. All authors reviewed the manuscript.

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Correspondence to Sibel Ahmet.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the ‘U.H.S. Istanbul Training and Research Hospital Clinical Research Ethics Committee with reference number 211/2023. Informed consent was obtained from all the study participants and from the parents or legal guardians of each patient involved in the study. The study was conducted in accordance with the Declaration of Helsinki.

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Ahmet, S., Yayla Akincilar, G., Kirgiz, A. et al. Long-term results of accelerated corneal collagen crosslinking in paediatric patients with progressive keratoconus: 10-year follow-up. Eye 38, 2522–2529 (2024). https://doi.org/10.1038/s41433-024-03064-7

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