title: Staged intrastromal delivery of riboflavin with UVA cross-linking in advanced bullous keratopathy: laboratory investigation and first clinical case.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of staged ultraviolet A (UVA) cross-linking following intrastromal 0.1% riboflavin administration in eyes with advanced corneal edema.
  
  
  METHODS
  Ten eye bank corneas divided in two groups (n = 5) were placed on a pressurized artificial anterior chamber following Descemet's membrane stripping. Two consecutive corneal pockets (350- and 150-microm depth) were sequentially created using a femtosecond laser. Sequential intrastromal injections of 0.1% riboflavin (0.2 mL) followed by either UVA irradiation (15 mW/cm2) for 7 minutes or exposure to air were performed for each pocket. Corneal clarity and central thickness were measured before and after the two UVA cross-linking steps. The same steps were clinically applied in an 84-year-old woman with bullous keratopathy prior to corneal transplantation and followed for 6 months.
  
  
  RESULTS
  The corneal clarity improved in the treated but not the control eyes. The mean central corneal thickness was significantly reduced by 256 microm (ultrasound, P = .0002) and 273 miccrom (Scheimpflug, P = .0004) in treated eyes, but only 100 microm (ultrasound, P = .048) and 107 microm (Scheimpflug, P = .075) in the control eyes. The clinical treatment of corneal edema showed improved clarity and reduced central corneal thickness from 675 to 550 microm (ultrasound) and 696 to 571 microm (Scheimpflug) at 1 month. Best spectacle-corrected visual acuity improved from finger counting to 20/80 at 1 week and beyond, postponing corneal transplantation for > 6 months.
  
  
  CONCLUSIONS
  Staged UVA cross-linking (15 mW/cm2) with femtosecond laser facilitated intrastromal 0.1% riboflavin administration may be a safe (no corneal scarring) and effective (marked reduction of edema) temporizing alternative method for managing bullous keratopathy.
authors.affiliation: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Krueger
authors.forename: Jerome C
authors.initials: JC
authors.lastname: Ramos-Esteban
authors.forename: A John
authors.initials: AJ
authors.lastname: Kanellopoulos
mesh_terms: D000369:Aged, 80 and over; D003094:Collagen / Q000378:metabolism*; D003316:Corneal Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D015715:Corneal Edema / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D003319:Corneal Stroma / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D019781:Corneal Topography; D005260:Female; D006801:Humans; D008954:Models, Biological; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012256:Riboflavin / Q000627:therapeutic use*; D014466:Ultraviolet Rays; D014792:Visual Acuity
chemical_list: D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin