Femtosecond laser crosslinking of the cornea for non-invasive vision correction

Abstract

The prevalence of myopia has increased worldwide over the last 50 years. Its incidence in the United States and Europe is now almost twice that 50 years ago, and it is even more prevalent in East Asia. Spectacles and contact lenses remain the most common means of vision correction, but the permanent correction of refractive errors, by refractive surgery, has emerged as an attractive alternative. However, such surgery is an invasive procedure that may compromise corneal structure, and post-surgical complications have been reported. We propose a novel, non-invasive approach to permanent vision correction based on a different mode of laser–cornea interaction. Our approach induces the formation of a low-density plasma that produces reactive oxygen species, which react with the surrounding proteins, forming crosslinks and triggering spatially resolved changes in mechanical properties. We show that the proposed method changes the refractive power of the eye, and confirm its safety and stability.

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Fig. 1: Step-by-step illustration of the use of the proposed laser-assisted process for the non-invasive correction of refractive errors
Fig. 2: Laser-induced changes of the refractive power.
Fig. 3: Differences in structure between control and laser-treated pig eyes.
Fig. 4: Time course of treatment-induced changes in the corneal ERP of live rabbits.
Fig. 5: Histological sections of H&E-stained rabbit corneas.
Fig. 6: Mechanism of curvature adjustment.

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Acknowledgements

This research was partly funded by the Wallace H. Coulter Foundation. The authors thank S. Trokel for helpful discussions and comments on the manuscript, D. Paik for allowing us to use the equipment in his laboratory, J. Yu, F. Ji, C. Diao and J. Fan for assisting with laser treatment, the experimental set-up and figure preparation, D. Bian for performing the refractive index measurements, and W.D.A.M. De Boer and W. Yang for running TPF experiments. The authors also thank S. Jockusch for help with running EPR spectroscopy experiments. The authors acknowledge Fundação para a Ciência e Tecnologia (FCT) projects PTDC/SAU-ENB/122128/2010 and PEST-C/SAU/UI3282/2013 and COMPETE programmes FCOMP-01-0124-FEDER-021163 and FCOMP-01-0124-FEDER-037299 for support for the multiphoton microscopy equipment. The authors thank JenLab GmbH for providing the required equipment and A. Kaiser for transporting the pig eyes.

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C.W. and S.V. designed the ex vivo and in vivo treatments, as well as tissue culturing studies. C.W. performed these experiments. M.F., G.M. and M.Z. assisted C.W. with the characterization. M.F. and S.V. designed the ROS trapping experiment, tyrosine crosslinking and SHG analysis of treated corneal tissue. M.F. performed the experiments, and C.W. assisted. M.Z. performed the in vivo CLSM measurements, and C.W. analysed them. C.W. and G.M. built the experimental set-up. S.V. initiated, designed and supervised the project. C.W., M.F. and S.V. wrote the manuscript.

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Correspondence to Chao Wang or Sinisa Vukelic.

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Supplementary discussion; Supplementary data; Supplementary Figures 1–12; Supplementary References 1–12.

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Wang, C., Fomovsky, M., Miao, G. et al. Femtosecond laser crosslinking of the cornea for non-invasive vision correction. Nature Photon 12, 416–422 (2018). https://doi.org/10.1038/s41566-018-0174-8

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