Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Aug 6;15(3):289-298.
doi: 10.18502/jovr.v15i3.7447. eCollection 2020 Jul-Sep.

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

Aysun Sanal Dogan  1 , Canan Gurda  1 , Sinan Caliskan  1 , Evrim Onder  2 , Figen Kaymaz  3 , Elif Bilgic  3
Affiliations
Review

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

Aysun Sanal Dogan et al. J Ophthalmic Vis Res. .

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: Corneal Collagen Cross-linking; Corneal Confocal Microscopy; Corneal Oxygen; Experimental; Ozone.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Optical Coherence Tomography corneal images of the groups control (a), sham (b), ozone (c), cross-linking (d), ozone-cross-linking (e), respectively. Hyperreflectivity is increased in anterior stroma in groups X and Z, but generalized in ZX.
Figure 2
Figure 2
Corneal confocal images of groups sham (a), ozone (b), cross-linking (c), ozone-cross-linking (d), respectively. The keratocytes in stromal level shows straight extensions, which are signs of activity in all groups except control, which are exaggerated in ZX group.
Figure 3
Figure 3
(a) A section of cornea from control group (HE X 400). (b) Positively stained nuclei in a section from ZX group (Caspase X 400).
Figure 4
Figure 4
Images taken from transmissional electron microscopy of the corneas from groups (x100K); control (a), ozone (b), cross-linking (c), ozone-cross-linking (d), respectively. Collagen fibers and interlamellar spaces were examined by electron microscopy.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Chen S, Mienaltowski MJ, Birk DE. Regulation of corneal stroma extracellular matrix assembly. Exp Eye Res 2015;133:69–80. - PMC - PubMed
    1. 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. - PubMed
    1. 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. - PubMed
    1. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003;135:620–627. - PubMed
    1. 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. - PubMed

LinkOut - more resources