Skip to main content

Advertisement

Log in

The efficiency and safety of oxygen-supplemented accelerated transepithelial corneal cross-linking

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the impact of oxygen delivery on the clinical outcomes of accelerated transepithelial corneal cross-linking (A-TE CXL).

Methods

Fifty-seven eyes of 44 progressive keratoconus (KCN) patients were randomly separated into two age–sex-matched groups. Twenty-nine eyes of 23 KCN patients that underwent oxygen-supplemented A-TE CXL formed the study group and 28 eyes of 21 patients treated with the same procedure but under room air conditions formed the control group. All patients were examined preoperatively, one, six and twelve months after the procedure. The logMAR spectacle-corrected distance visual acuity (CDVA), maximum keratometry (Kmax), mean keratometry, apical posterior keratometry, cylindrical power, minimum central corneal thickness, keratoconus vertex front and back, ocular aberrations, endothelial cell density (ECD), demarcation line depth (DLD) and proportion measures were recorded for statistical analysis.

Results

The preoperative, 1st, 6th and 12th months mean Kmax values of the study group were 55.14 ± 3.99D, 54.85 ± 3.82D, 54.37 ± 3.84D and 54.40 ± 3.86, respectively, and 54.47 ± 3.17D, 54.52 ± 2.97D, 54.25 ± 2.95D and 54.20 ± 2.97 in the control group. The mean Kmax value was decreased significantly more in the oxygen-supplemented group after 12 months compared to the control group (p = 0.019). The mean DLD was also significantly deeper in the study group (320 ± 17 µm) compared to the control group (269 ± 19 µm). There was no significant difference between the two groups in terms of ECD alterations at any of the time intervals (p > 0.05).

Conclusion

Keratoconus progression was significantly halted in both groups 12 months after the treatment. In addition, oxygen supplementation during A-TE CXL further significantly increased clinical outcomes compared to room air conditions without any significant change in ECD measures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Romero-Jiménez M, Santodomingo-Rubido J, Wolffsohn JS (2010) Keratoconus: a review. Contact Lens Anterior Eye 33:157–166

    Article  Google Scholar 

  2. Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ (2014) The pathogenesis of keratoconus. Eye 28:189–195. https://doi.org/10.1038/eye.2013.278

    Article  CAS  PubMed  Google Scholar 

  3. Jouve L, Borderie V, Sandali O et al (2017) Conventional and iontophoresis corneal cross-linking for keratoconus: efficacy and assessment by optical coherence tomography and confocal microscopy. Cornea 36:153–162. https://doi.org/10.1097/ICO.0000000000001062

    Article  PubMed  Google Scholar 

  4. Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 135:620–627. https://doi.org/10.1016/S0002-9394(02)02220-1

    Article  CAS  PubMed  Google Scholar 

  5. Cifariello F, Minicucci M, Di Renzo F et al (2018) Epi-off versus epi-on corneal collagen cross-linking in keratoconus patients: a comparative study through 2-year follow-up. J Ophthalmol. https://doi.org/10.1155/2018/4947983

    Article  PubMed  PubMed Central  Google Scholar 

  6. Subasinghe SK, Ogbuehi KC, Dias GJ (2018) Current perspectives on corneal collagen crosslinking (CXL). Graefe’s Arch Clin Exp Ophthalmol 256:1363–1384. https://doi.org/10.1007/s00417-018-3966-0

    Article  CAS  Google Scholar 

  7. Rossi S, Santamaria C, Boccia R et al (2018) Standard, transepithelial and iontophoresis corneal cross-linking: clinical analysis of three surgical techniques. Int Ophthalmol 38:2585–2592. https://doi.org/10.1007/s10792-017-0772-3

    Article  PubMed  Google Scholar 

  8. Rubinfeld RS, Caruso C, Ostacolo C (2019) Corneal cross-linking: the science beyond the myths and misconceptions. Cornea 38:780–790. https://doi.org/10.1097/ICO.0000000000001912

    Article  PubMed  Google Scholar 

  9. Morrison PWJ, Khutoryanskiy VV (2014) Enhancement in corneal permeability of riboflavin using calcium sequestering compounds. Int J Pharm 472:56–64. https://doi.org/10.1016/j.ijpharm.2014.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kissner A, Spoerl E, Jung R et al (2010) Pharmacological modification of the epithelial permeability by benzalkonium chloride in UVA/Riboflavin corneal collagen cross-linking. Curr Eye Res 35:715–721. https://doi.org/10.3109/02713683.2010.481068

    Article  CAS  PubMed  Google Scholar 

  11. 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. Investig Ophthalmol Vis Sci 54:1176–1180. https://doi.org/10.1167/iovs.12-11409

    Article  Google Scholar 

  12. Kamaev P, Friedman MD, Sherr E, Muller D (2012) Photochemical kinetics of corneal cross-linking with riboflavin. Investig Ophthalmol Vis Sci 53:2360–2367. https://doi.org/10.1167/iovs.11-9385

    Article  Google Scholar 

  13. Hill J, Liu C, Deardorff P et al (2020) Optimization of oxygen dynamics, UV-A Delivery, and drug formulation for accelerated epi-on corneal crosslinking. Curr Eye Res 45:450–458. https://doi.org/10.1080/02713683.2019.1669663

    Article  CAS  PubMed  Google Scholar 

  14. Scott McCall A, Kraft S, Edelhauser HF et al (2010) Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA). Investig Ophthalmol Vis Sci 51:129–138. https://doi.org/10.1167/iovs.09-3738

    Article  Google Scholar 

  15. Richoz O, Hammer A, Tabibian D et al (2013) The biomechanical effect of corneal collagen cross-linking (CXL) with riboflavin and UV-A is oxygen dependent. Transl Vis Sci Technol 2:6. https://doi.org/10.1167/tvst.2.7.6

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang J, Wang L, Li Z et al (2020) Corneal biomechanical evaluation after conventional corneal crosslinking with oxygen enrichment. Eye Contact Lens 46:306–309. https://doi.org/10.1097/ICL.0000000000000645

    Article  PubMed  Google Scholar 

  17. Mazzotta C, Sgheri A, Bagaglia SA et al (2020) Customized corneal crosslinking for treatment of progressive keratoconus: clinical and OCT outcomes using a transepithelial approach with supplemental oxygen. J Cataract Refract Surg 46:1582–1587. https://doi.org/10.1097/j.jcrs.0000000000000347

    Article  PubMed  Google Scholar 

  18. Kamiya K, Kanayama S, Takahashi M, Shoji N (2020) Visual and topographic improvement with epithelium-on, oxygen-supplemented, customized corneal cross-linking for progressive keratoconus. J Clin Med 9:3222. https://doi.org/10.3390/jcm9103222

    Article  PubMed Central  Google Scholar 

  19. Seiler T, Hafezi F (2006) Corneal cross-linking-induced stromal demarcation line. Cornea 25:1057–1059. https://doi.org/10.1097/01.ico.0000225720.38748.58

    Article  PubMed  Google Scholar 

  20. Gomes JAP, Tan D, Rapuano CJ et al (2015) Global consensus on keratoconus and ectatic diseases. Cornea 34:359–369. https://doi.org/10.1097/ICO.0000000000000408

    Article  PubMed  Google Scholar 

  21. Arslan AK, Yaşar Ş, Çolak C, Yoloğlu S (2018) WSSPAS: an interactive web application for sample size and power analysis with R using shiny. Turk Klin J Biostat 10:224–246. https://doi.org/10.5336/biostatic.2018-62787

    Article  Google Scholar 

  22. Meek KM, Hayes S (2013) Corneal cross-linking—a review. Ophthalmic Physiol Opt 33:78–93. https://doi.org/10.1111/opo.12032

    Article  PubMed  Google Scholar 

  23. Mastropasqua L (2015) Collagen cross-linking: when and how? A review of the state of the art of the technique and new perspectives. Eye Vis 2:1–10. https://doi.org/10.1186/s40662-015-0030-6

    Article  Google Scholar 

  24. Vinciguerra P, Randleman JB, Romano V et al (2014) Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg 31:746–753. https://doi.org/10.3928/1081597X-20141021-06

    Article  Google Scholar 

  25. Kirgiz A, Eliacik M, Yildirim Y (2019) Different accelerated corneal collagen cross-linking treatment modalities in progressive keratoconus. Eye Vis 6:1–9. https://doi.org/10.1186/s40662-019-0141-6

    Article  Google Scholar 

  26. Malhotra C, Jain AK, Gupta A et al (2017) Demarcation line depth after contact lens–assisted corneal crosslinking for progressive keratoconus: comparison of dextran-based and hydroxypropyl methylcellulose–based riboflavin solutions. J Cataract Refract Surg 43:1263–1270. https://doi.org/10.1016/j.jcrs.2017.07.032

    Article  PubMed  Google Scholar 

  27. Jacob S, Kumar DA, Agarwal A et al (2014) Contact lens-assisted collagen cross-linking (CACXL): a new technique for cross-linking thin corneas. J Refract Surg 30:366–372. https://doi.org/10.3928/1081597X-20140523-01

    Article  PubMed  Google Scholar 

  28. O’Brart DPS (2017) Corneal collagen crosslinking for corneal ectasias: a review. Eur J Ophthalmol 27:253–269. https://doi.org/10.5301/ejo.5000916

    Article  PubMed  Google Scholar 

  29. Eraslan M, Toker E, Cerman E, Ozarslan D (2017) Efficacy of epithelium-off and epithelium-on corneal collagen cross-linking in pediatric keratoconus. Eye Contact Lens 43:155–161. https://doi.org/10.1097/ICL.0000000000000255

    Article  PubMed  Google Scholar 

  30. Diakonis VF, Likht NY, Yesilirmak N et al (2016) Corneal elasticity after oxygen enriched high intensity corneal cross linking assessed using atomic force microscopy. Exp Eye Res 153:51–55. https://doi.org/10.1016/j.exer.2016.10.008

    Article  CAS  PubMed  Google Scholar 

  31. Fredriksson A, Näslund S, Behndig A (2020) A prospective evaluation of photorefractive intrastromal cross-linking for the treatment of low-grade myopia. Acta Ophthalmol 98:201–206. https://doi.org/10.1111/aos.14190

    Article  PubMed  Google Scholar 

  32. Doughty MJ (1995) Evaluation of the effects of saline versus bicarbonate-containing mixed salts solutions on rabbit corneal epithelium in vitro. Ophthalmic Physiol Opt 15:585–599. https://doi.org/10.1016/0275-5408(95)00007-Z

    Article  CAS  PubMed  Google Scholar 

  33. Rechichi M, Daya S, Scorcia V et al (2013) Epithelial-disruption collagen crosslinking for keratoconus: one-year results. J Cataract Refract Surg 39:1171–1178. https://doi.org/10.1016/j.jcrs.2013.05.022

    Article  PubMed  Google Scholar 

  34. Stulting RD, Trattler WB, Woolfson JM, Rubinfeld RS (2018) Corneal crosslinking without epithelial removal. J Cataract Refract Surg 44:1363–1370. https://doi.org/10.1016/j.jcrs.2018.07.029

    Article  PubMed  Google Scholar 

  35. Hatami-Marbini H, Rahimi A (2015) Stiffening effects of riboflavin/UVA corneal collagen cross-linkingis hydration dependent. J Biomech 48:1052–1057. https://doi.org/10.1016/j.jbiomech.2015.01.038

    Article  CAS  PubMed  Google Scholar 

  36. Hatami-Marbini H, Rahimi A (2016) Interrelation of hydration, collagen cross-linking treatment, and biomechanical properties of the cornea. Curr Eye Res 41:616–622. https://doi.org/10.3109/02713683.2015.1042546

    Article  CAS  PubMed  Google Scholar 

  37. Lombardo M, Serrao S, Raffa P et al (2016) Novel technique of transepithelial corneal cross-linking using iontophoresis in progressive keratoconus. J Ophthalmol 2016:7472542. https://doi.org/10.1155/2016/7472542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kobashi H, Rong SS, Ciolino JB (2018) Transepithelial versus epithelium-off corneal crosslinking for corneal ectasia. J Cataract Refract Surg 44:1507–1516. https://doi.org/10.1016/j.jcrs.2018.08.021

    Article  PubMed  Google Scholar 

  39. Haberman ID, Lang PZ, Broncano AF et al (2018) Epithelial remodeling after corneal crosslinking using higher fluence and accelerated treatment time. J Cataract Refract Surg 44:306–312. https://doi.org/10.1016/j.jcrs.2017.12.021

    Article  PubMed  Google Scholar 

  40. Godefrooij DA, El Kandoussi M, Soeters N, Wisse RPL (2017) Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus. Clin Ophthalmol 11:1931–1936. https://doi.org/10.2147/OPTH.S139358

    Article  PubMed  PubMed Central  Google Scholar 

  41. 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. Investig Ophthalmol Vis Sci 55:8371–8376. https://doi.org/10.1167/iovs.14-15444

    Article  Google Scholar 

  42. Kymionis GD, Tsoulnaras KI, Grentzelos MA et al (2014) Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol 158:671-675.e1. https://doi.org/10.1016/j.ajo.2014.07.005

    Article  PubMed  Google Scholar 

  43. Spadea L, Di Genova L, Tonti E (2018) Corneal stromal demarcation line after 4 protocols of corneal crosslinking in keratoconus determined with anterior segment optical coherence tomography. J Cataract Refract Surg 44:596–602. https://doi.org/10.1016/j.jcrs.2018.02.017

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Neeran Narainswami from Pietermaritzburg Greys Hospital for his precious efforts to improve the language of this paper.

Funding

No financial support was received for this submission.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehmet Gökhan Aslan.

Ethics declarations

Conflict of interest

Emre Aydın declares that he has no conflict of interest. Mehmet Gökhan Aslan declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants and/or their parents included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aydın, E., Aslan, M.G. The efficiency and safety of oxygen-supplemented accelerated transepithelial corneal cross-linking. Int Ophthalmol 41, 2993–3005 (2021). https://doi.org/10.1007/s10792-021-01859-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-021-01859-1

Keywords

Navigation