title: Imaging mass spectrometry by matrix-assisted laser desorption/ionization and stress-strain measurements in iontophoresis transepithelial corneal collagen cross-linking.
abstract: OBJECTIVE
  To compare biomechanical effect, riboflavin penetration and distribution in transepithelial corneal collagen cross-linking with iontophoresis (I-CXL), with standard cross linking (S-CXL) and current transepithelial protocol (TE-CXL).
  
  
  METHODS
  The study was divided into two different sections, considering, respectively, rabbit and human cadaver corneas. In both sections corneas were divided according to imbibition protocols and irradiation power. Imaging mass spectrometry by matrix-assisted laser desorption/ionization (MALDI-IMS) and stress-strain measurements were used. Forty-eight rabbit and twelve human cadaver corneas were evaluated.
  
  
  RESULTS
  MALDI-IMS showed a deep riboflavin penetration throughout the corneal layers with I-CXL, with a roughly lower concentration in the deepest layers when compared to S-CXL, whereas with TE-CXL penetration was considerably less. In rabbits, there was a significant increase (by 71.9% and P = 0.05) in corneal rigidity after I-CXL, when compared to controls. In humans, corneal rigidity increase was not significantly different among the subgroups.
  
  
  CONCLUSIONS
  In rabbits, I-CXL induced a significant increase in corneal stiffness as well as better riboflavin penetration when compared to controls and TE-CXL but not to S-CXL. Stress-strain in human corneas did not show significant differences among techniques, possibly because of the small sample size of groups. In conclusion, I-CXL could be a valid alternative to S-CXL for riboflavin delivery in CXL, preserving the epithelium.
authors.affiliation: Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, Italy.
authors.forename: Paolo
authors.identifier: 0000-0002-3864-8246
authors.initials: P
authors.lastname: Vinciguerra
authors.affiliation: Department of Surgery and Translational Medicine, Eye Clinic, University of Florence, Florence, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Mencucci
authors.affiliation: Department of Ophthalmology, Second University of Naples, Naples, Italy.
authors.forename: Vito
authors.identifier: 0000-0002-5148-7643
authors.initials: V
authors.lastname: Romano
authors.affiliation: University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Eberhard
authors.identifier: 0000-0003-3229-3795
authors.initials: E
authors.lastname: Spoerl
authors.affiliation: Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, Italy.
authors.forename: Fabrizio I
authors.initials: FI
authors.lastname: Camesasca
authors.affiliation: Department of Surgery and Translational Medicine, Eye Clinic, University of Florence, Florence, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Favuzza
authors.affiliation: Department of Surgical and Morphological Sciences, Section of Ophthalmology, School of Medicine, University of Insubria, Via Guicciardini 9, Varese, Italy.
authors.forename: Claudio
authors.identifier: 0000-0002-1334-0974
authors.initials: C
authors.lastname: Azzolini
authors.affiliation: Ophthalmology Unit, Department of Neurological Neuropsychological, Morphological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Rodolfo
authors.identifier: 0000-0003-1541-4735
authors.initials: R
authors.lastname: Mastropasqua
authors.affiliation: Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, Italy ; Department of Surgical and Morphological Sciences, Section of Ophthalmology, School of Medicine, University of Insubria, Via Guicciardini 9, Varese, Italy.
authors.forename: Riccardo
authors.identifier: 0000-0002-2280-9981
authors.initials: R
authors.lastname: Vinciguerra
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007478:Iontophoresis; D011817:Rabbits; D012256:Riboflavin / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013314:Stress, Mechanical; D014019:Tissue Donors
chemical_list: D003432:Cross-Linking Reagents; D003094:Collagen; D012256:Riboflavin