title: Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking.
abstract: The purpose of this study was to investigate the biomechanical stiffening effect induced by nanoplatform-based transepithelial riboflavin/UV-A cross-linking protocol using atomic force microscopy (AFM).
  
  
  
  Twelve eye bank donor human sclerocorneal tissues were investigated using a commercial atomic force microscope operated in force spectroscopy mode. Four specimens underwent transepithelial corneal cross-linking using a hypotonic solution of 0.1% riboflavin with biodegradable polymeric nanoparticles of 2-hydroxypropyl-β-cyclodextrin plus enhancers (trometamol and ethylenediaminetetraacetic acid) and UV-A irradiation with a 10 mW/cm2 device for 9 minutes. After treatment, the corneal epithelium was removed using the Amoils brush, and the Young's modulus of the most anterior stroma was quantified as a function of scan rate by AFM. The results were compared with those collected from four specimens that underwent conventional riboflavin/UV-A corneal cross-linking and four untreated specimens.
  
  
  
  The average Young's modulus of the most anterior stroma after the nanoplatform-based transepithelial and conventional riboflavin/UV-A corneal cross-linking treatments was 2.5 times (P < 0.001) and 1.7 times (P < 0.001) greater than untreated controls respectively. The anterior stromal stiffness was significantly different between the two corneal cross-linking procedures (P < 0.001). The indentation depth decreased after corneal cross-linking treatments, ranging from an average of 2.4 ± 0.3 μm in untreated samples to an average of 1.2 ± 0.1 μm and 1.8 ± 0.1 μm after nanoplatform-based transepithelial and conventional cross-linking, respectively.
  
  
  
  The present nanotechnology-based transepithelial riboflavin/UV-A corneal cross-linking was effective to improve the biomechanical strength of the most anterior stroma of the human cornea.
authors.affiliation: Department of Physics, University of Calabria, Ponte P. Bucci, Rende, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Labate
authors.affiliation: Fondazione G.B. Bietti IRCCS, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lombardo
authors.affiliation: Istituto per i Processi Chimico-Fisici, Consiglio Nazionale delle Ricerche, Messina, Italy 4Vision Engineering Italy Srl, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardo
authors.affiliation: Department of Physics, University of Calabria, Ponte P. Bucci, Rende, Italy.
authors.forename: Maria Penelope
authors.initials: MP
authors.lastname: De Santo
mesh_terms: D000368:Aged; D003094:Collagen / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004548:Elasticity; D019573:Epithelium, Corneal / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007640:Keratoconus / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D017319:Photosensitizing Agents / Q000494:pharmacology; D012256:Riboflavin / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin