title: Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using near infrared light.
abstract: OBJECTIVE
  We evaluated the efficacy and safety of photochemical corneal stiffening by palladium bacteriochlorin 13'-(2-sulfoethyl)amide dipotassium salt (WST11) and near infrared (NIR) illumination, using ex vivo and in vivo rabbit eye models.
  
  
  METHODS
  Corneas of post mortem rabbits and living rabbits were pretreated topically with 2.5 mg/mL WST11 in saline or in 20% dextran T-500 (WST-D), washed and illuminated with an NIR diode laser (755 nm, 10 mW/cm(2). Studies with corneas of untreated fellow eyes served as controls. Tensile strength measurements, histopathology, electron spin resonance, and optical spectroscopy and fluorescence microscopy were used to assess treatment effects. Comparative studies were performed with standard riboflavin/ultraviolet-A light (UVA) treatment.
  
  
  RESULTS
  WST11/NIR treatment significantly increased corneal stiffness following ex vivo or in vivo treatment, compared to untreated contralateral eyes. The incremental ultimate stress and Young's modulus of treated corneas increased by 45, 113, 115%, and 10, 79, and 174% following 10, 20, and 30 minutes of incubation with WST11, respectively. WST-D/NIR had a similar stiffening effect, but markedly reduced post-treatment edema and shorter time of epithelial healing. WST11/NIR and WST-D/NIR generate hydroxyl and superoxide radicals, but no singlet oxygen in the cornea. Histology demonstrated a reduction in the keratocyte population in the anterior half of the corneal stroma, without damage to the endothelium.
  
  
  CONCLUSIONS
  Treatment of rabbit corneas, with either WST11/NIR or WST-D/NIR, increases their biomechanical strength through a mechanism that does not involve singlet oxygen. The WST-D/NIR treatment showed less adverse effects, demonstrating a new potential for clinical use in keratoconus and corneal ectasia after refractive surgery.
authors.affiliation: Departments of Plant Sciences, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Arie L
authors.initials: AL
authors.lastname: Marcovich
authors.forename: Alexander
authors.initials: A
authors.lastname: Brandis
authors.forename: Ofer
authors.initials: O
authors.lastname: Daphna
authors.forename: Ilan
authors.initials: I
authors.lastname: Feine
authors.forename: Iddo
authors.initials: I
authors.lastname: Pinkas
authors.forename: Ruth
authors.initials: R
authors.lastname: Goldschmidt
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Kalchenko
authors.forename: Tamara
authors.initials: T
authors.lastname: Berkutzki
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Wagner
authors.forename: Yoram
authors.initials: Y
authors.lastname: Salomon
authors.forename: Avigdor
authors.initials: A
authors.lastname: Scherz
mesh_terms: D000818:Animals; D001429:Bacteriochlorophylls / Q000493:pharmacokinetics / Q000494:pharmacology*; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D003315:Cornea / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D060527:Corneal Keratocytes / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D003319:Corneal Stroma / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D004728:Endothelium, Corneal / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D007259:Infrared Rays / Q000627:therapeutic use; D054023:Lasers, Semiconductor; D023421:Models, Animal; D038761:Photobleaching / Q000187:drug effects; D017319:Photosensitizing Agents / Q000494:pharmacology; D010789:Phototherapy / Q000379:methods*; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*
chemical_list: D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C503696:padeliporfin