title: Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition.
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/cm(2) (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/cm(2). 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/cm(2) 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.
authors.affiliation: Limmat Eye Center, Hardtturnstraße 133, 8005, Zürich, Switzerland.|Department of Ophthalmology, Leipzig University Hospital, Liebigstraße 10-14, 04103, Leipzig, Germany.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Iseli
authors.affiliation: Translational Centre for Regenerative Medicine, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.|Paul-Flechsig-Institute of Brain Research, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Körber
authors.affiliation: Department of Ophthalmology, Leipzig University Hospital, Liebigstraße 10-14, 04103, Leipzig, Germany.|Translational Centre for Regenerative Medicine, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koch
authors.affiliation: Translational Centre for Regenerative Medicine, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.|Paul-Flechsig-Institute of Brain Research, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
authors.forename: Anett
authors.initials: A
authors.lastname: Karl
authors.affiliation: Institute of Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, 04107, Leipzig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Penk
authors.affiliation: Institute of Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, 04107, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.affiliation: Paul-Flechsig-Institute of Brain Research, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.affiliation: Department of Ophthalmology, Leipzig University Hospital, Liebigstraße 10-14, 04103, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.affiliation: Translational Centre for Regenerative Medicine, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany. Mike.Francke@medizin.uni-leipzig.de.|Paul-Flechsig-Institute of Brain Research, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany. Mike.Francke@medizin.uni-leipzig.de.
authors.forename: Mike
authors.initials: M
authors.lastname: Francke
mesh_terms: D000818:Animals; D058452:Axial Length, Eye / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003432:Cross-Linking Reagents; D005123:Eye / Q000000981:diagnostic imaging / Q000254:growth & development*; D007150:Immunohistochemistry; D008027:Light; D008279:Magnetic Resonance Imaging; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011817:Rabbits; D012256:Riboflavin / Q000494:pharmacology*; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism*; D012684:Sensory Thresholds; D014463:Ultrasonography
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin
keywords: Damage threshold; Eye growth inhibition; Myopia; Rabbit eye; Scleral cross-linking