Download fulltext HTML
1.
Sanal Dogan A, Gurda C, Caliskan S, Onder E, Kaymaz F, Bilgic E. Effects of Topical Ozone Application on Outcomes after Accelerated Corneal Collagen Cross-linking: An Experimental Study. JOVR [Internet]. 2020Jul.29 [cited 2024Apr.23];15(3):289–298. Available from: https://knepublishing.com/index.php/JOVR/article/view/7447

https://doi.org/10.18502/jovr.v15i3.7447

statistics

  • 1003 Abstract Views
  • 466 PDF Views
  • 0 HTML Views

authors

  • Aysun Sanal Dogan

    Aysun Sanal Dogan

    Department of Ophthalmology, Saglik Bilimleri University, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
    https://orcid.org/0000-0002-7401-8903
  • Canan Gurda

    Canan Gurda

    Department of Ophthalmology, Saglik Bilimleri University, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
  • Sinan Caliskan

    Sinan Caliskan

    Department of Ophthalmology, Saglik Bilimleri University, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
  • Evrim Onder

    Evrim Onder

    Department of Pathology, Saglik Bilimleri University, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
  • Figen Kaymaz

    Figen Kaymaz

    Department of Histology and Embryology, Hacettepe University, School of Medicine, Ankara, Turkey
  • Elif Bilgic

    Elif Bilgic

    Department of Histology and Embryology, Hacettepe University, School of Medicine, Ankara, Turkey

Published Date

  • Jul 29, 2020
This journal is publishing all the articles under Creative Commons Attribution License CC BY 4.0.

Effects of Topical Ozone Application on Outcomes after Accelerated Corneal Collagen Cross-linking: An Experimental Study

Journal of Ophthalmic and Vision Research (JOVR) / July–September 2020, Volume 15, Issue 3 / Pages 289–298

Abstract

Purpose: Ozone is a trioxygen molecule that spontaneously degrades into oxygen and oxygen free radicals. This study was designed to assess the effects of topical ozone application on outcomes after corneal collagen cross-linking (CXL).


Methods: Enucleated fresh cadaver yearling sheep eyes (n = 28) were divided into five groups: control (C, n = 6), sham (S, n = 6), ozone only (Z, n = 6), CXL only (X, n = 5), and Ozone + CXL (ZX, n = 5). In all groups, except C, the epithelial layer was removed. In group Z, 20 μg/mL liquid ozone was topically applied. In group X, CXL was performed in the accelerated pulse mode. In group ZX, both CXL and ozone were applied. Post-interventional oxygen levels were determined and corneal confocal microscopy and optical coherence tomography were performed. Corneas were evaluated using light and electron microscopy.


Results: Pre-interventional central corneal thickness (CCT) was highest in the control group and considerably similar in the remaining groups (P = 0.006). Pre- and post-interventional CCT were significantly different in the ozonated groups (Z and ZX) (P = 0.028; P = 0.043). Demarcation line depths were similar in groups Z, X, and ZX (P = 0.343). Increased stromal tissue reflectivity was observed in groups Z, X, and ZX. Oxygen levels were higher in the ozonated groups (Z and ZX) (P = 0.006), and caspase activity was higher in the CXL groups (X and ZX) (P = 0.028) as compared to the other groups. Group ZX showed tighter, more regular, and parallel fibrils.


Conclusion: Ozone increases corneal stromal oxygenation which can probably augment the effect of CXL. Future studies should investigate the safety and feasibility of ozone application during CXL.

Keywords:

Ozone, Corneal Collagen Cross-linking, Corneal Confocal Microscopy, Corneal Oxygen, Experimental

References
1. Chen S, Mienaltowski MJ, Birk DE. Regulation of corneal stroma extracellular matrix assembly. Exp Eye Res 2015;133:69–80.

2. Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio R Jr, Guell JL, et al. Group of panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea 2015;34:359–369.

3. Meek KM, Tuft SJ, Huang YF, Gill PS, Hayes S, Newton RH, Bron AJ. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci 2005;46:1948–1956.

4. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003;135:620–627.

5. Wollensak G, Wilsch M, Spoerl E, Seiler T. Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/UVA. Cornea 2004;23:503–507.

6. Richoz 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. Transl Vis Sci Technol 2013;2:6.

7. Filippello M, Stagni E, O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg 2012;38:283–291.

8. Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol 2014;92:e30–e34.

9. Gu SF, Fan ZS, Wang LH, Tao XC, Zhang Y, Wang CQ, et al. A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas. Int J Ophthalmol 2015;8:94–97.

10. Wernli J, Schumacher S, Spoerl E, Mrochen M. The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time. Invest Ophthalmol Vis Sci 2013;54:1176–1180.

11. Mazzotta C, Traversi C, Caragiuli S, Rechichi M. Pulsed vs continuous light accelerated corneal collagen crosslinking: in vivo qualitative investigation by confocal microscopy and corneal OCT. Eye 2014;28:1179–1183.

12. Kamaev P, Friedman MD, Sherr E, Muller D. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci 2012;53:2360–2367.

13. Takemoto LJ, Hansen JS. Covalent and noncovalent interactions of membrane proteins from the chick lens. Exp Eye Res 1981;33:267–276.

14. Goosey JD, Zigler JS Jr, Kinoshita JH. Cross-linking of lens crystallins in a photodynamic system: a process mediated by singlet oxygen. Science 1980;208:1278–1280.

15. Fujimori E. Crosslinking and photoreaction of ozoneoxidized calf-lens alpha-crystallin. Invest Ophthalmol Vis Sci 1982;22:402–405.

16. Jernigan HM Jr. Role of hydrogen peroxide in riboflavinsensitized photodynamic damage to cultured rat lenses. Exp Eye Res 1985;41:121–129.

17. Pryor WA, Squadrito GL, Friedman M. The cascade mechanism to explain ozone toxicity: the role of lipid ozonation products. Free Radic Biol Med 1995;19:935–941.

18. Sanhueza PA, Reed GD, Davis WT, Miller TL. An environmental decision-making tool for evaluating ground-level ozone-related health effects. J Air Waste Manag Assoc 2003;53:1448–1459.

19. Hoigne J. Chemistry of aqueous ozone and transformation of pollutants by ozonation and advanced oxidation processes. In: Hutzinger O, editor. Quality and treatment of drinking water 2. The handbook of environmental chemistry. Volume 5 Water Pollution. Berlin: Springer- Verlag; 1998:83–143.

20. Von Gunten U. Ozonation of drinking water: part I. Oxidation kinetics and product formation. Water Res 2003;37:1443–1467.

21. Lee H, Kim EK, Kang SW, Kim JH, Hwang HJ, Kim TI. Effects of ozone exposure on the ocular surface. Free Radic Biol Med 2013;63:78–89.

22. Wu J, Doan H, Cuenca MA. Investigation of gaseous ozone as an anti-fungal fumigant for stored wheat. J Chem Technol Biotechnol 2006;81:1288–1293.

23. Vounotrypidis E, Athanasiou A, Kortüm K, Kook D, Shajari M, Priglinger S, et al. Long-term database analysis of conventional and accelerated crosslinked keratoconic mid-European eyes. Graefes Arch Clin Exp Ophthalmol 2018;256:1165–1172.

24. Zhu AY, Vianna LM, Borkenstein EM, Elisseeff J, Jun AS. Assessment of a novel corneal-shaping device with simultaneous corneal collagen cross-linking using a porcine eye model. Cornea 2016;35:114–121.

25. Messmer EM, Meyer P, Herwig MC, Loeffler KU, Schirra F, Seitz B, Thiel M, et al. Morphological and immunohistochemical changes after corneal cross-linking. Cornea 2013;32:111–117.

26. Akhtar S, Almubrad T, Paladini I, Mencucci R. Keratoconus corneal architecture after riboflavin/ultraviolet A crosslinking: ultrastructural studies. Mol Vis 2013;19:1526–1537.

27. Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci 1998;39:644–648.

28. Malik NS, Moss SJ, Ahmed N, Furth AJ, Wall RS, Meek KM. Ageing of the human corneal stroma: structural and biochemical changes. Biochim Biophys Acta 1992;1138:222–228.

29. Quantock AJ, Winkler M, Parfitt GJ, Young RD, Brown DJ, Boote C, et al. From nano to macro: studying the hierarchical structure of the corneal extracellular matrix. Exp Eye Res 2015;133:81–99.