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Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition

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Abstract

Background

Scleral cross-linking (SXL) by riboflavin and light application has been introduced as a possible treatment to increase scleral tissue stiffness and to inhibit excessive axial elongation of highly myopic eyes. We evaluated an ocular tissue damage threshold for blue light irradiation, and used SXL treatment to induce eye growth inhibition.

Methods

The sclera of 3-week-old rabbits (39 pigmented and 15 albino rabbits) were treated with different blue light intensities (450 ± 50 nm) and riboflavin. Alterations and a damage threshold were detected in ocular tissues by means of light microscopy and immunohistochemistry. The influence of SXL on the eye growth was examined in 21 young rabbits and was measured by using A-scan ultrasonography, micrometer caliper, and for selected eyes additionally by MR imaging.

Results

Light microscopic examinations demonstrated degenerative changes in ocular tissue after irradiation with blue light intensities above 400 mW/cm2 (with and without riboflavin application). Therefore, that light intensity was defined as the damage threshold. Tissue alteration in retina, choroid, and sclera and activation of retinal microglia cells and Müller cells could be earlier observed at blue light intensities of 150 and 200 mW/cm2. Albino rabbits were less sensitive to this SXL treatment. A significant reduction of the eye growth could be detected by SXL treatment with the minimal efficient blue light intensity of 15 mW/cm2 and maintained stable for 24 weeks.

Conclusions

SXL with riboflavin and blue light intensities below a defined damage threshold can induce a long lasting growth inhibitory effect on young rabbit eyes. Therefore, SXL might be a realistic approach to inhibit eye elongation in highly myopic eyes.

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Acknowledgments

The work presented in this publication was kindly supported by funding from the German Federal Ministry of Education and Research (BMBF 1315883 to CK, NK, AK, MF), from the Deutsche Forschungsgemeinschaft (GRK 1097/1 and 1097/2 to AR; RE849/17-1 to AR and FR1825/1-1 to MF). Furthermore, the work was supported from the Medical Faculty of the University of Leipzig (Project No. 984000-176, Admin. No. 78621956 to AK) and from the Government of Saxony, Germany: the Ministry for Science and Art and the Sächsische Aufbau-Bank to MF (SAB Project No. 100 175 031, University Leipzig Project No. 5081-7008). The study was also supported in part by the Deutsche Forschungsgemeinschaft (Transregio: TRR 67-A6 to AP and DH).

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    Authors and Affiliations

    1. Limmat Eye Center, Hardtturnstraße 133, 8005, Zürich, Switzerland

      Hans Peter Iseli

    2. Department of Ophthalmology, Leipzig University Hospital, Liebigstraße 10-14, 04103, Leipzig, Germany

      Hans Peter Iseli, Christian Koch & Peter Wiedemann

    3. Translational Centre for Regenerative Medicine, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany

      Nicole Körber, Christian Koch, Anett Karl & Mike Francke

    4. Paul-Flechsig-Institute of Brain Research, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany

      Nicole Körber, Anett Karl, Andreas Reichenbach & Mike Francke

    5. Institute of Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, 04107, Leipzig, Germany

      Anja Penk & Daniel Huster

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    1. Hans Peter Iseli
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    Correspondence to Mike Francke.

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    Funding

    Deutsche Forschungsgemeinschaft provided financial support in the form of various research fundings and educational programs: (i) GRK 1097/1 and 1097/2 to AR, (ii) RE849/17-1 to AR, (iii) FR1825/1-1 to MF, (iv) Transregio: TRR 67-A6 to AP and DH. The sponsor had no role in the design or conduct of this research.

    German Federal Ministry of Education and Research provided financial support in the form of research funding: BMBF 1315883 to CK, NK, AK, MF.

    The sponsor had no role in the design or conduct of this research.

    Government of Saxony, Germany: the Ministry for Science and Art and the Sächsische Aufbau-Bank provided financial support in the form of research funding: SAB Project No. 100 175 031, University Leipzig Project No. 5081-7008.

    The sponsor had no role in the design or conduct of this research.

    Medical Faculty of the University of Leipzig provided financial support in the form of research funding: Project No. 984000-176, Admin. No. 78621956 to AK.

    The sponsor had no role in the design or conduct of this research.

    Conflict of interest

    The authors declare that they have no conflict of interest. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

    Animal experiments

    Ethical approval (see also Material and methods): All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

    Additional information

    Hans Peter Iseli and Nicole Körber contributed equally to this work.

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    Iseli, H.P., Körber, N., Koch, C. et al. Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition. Graefes Arch Clin Exp Ophthalmol 254, 109–122 (2016). https://doi.org/10.1007/s00417-015-3213-x

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