title: Safety outcomes and long-term effectiveness of ex vivo autologous cultured limbal epithelial transplantation for limbal stem cell deficiency.
abstract: OBJECTIVE
  To evaluate the safety and effectiveness of ex vivo autologous cultured limbal stem cell transplantation (CLET).
  
  
  METHODS
  We reviewed the clinical records of 59 consecutive patients treated with 65 CLETs. Efficacy was graded 1 year after surgery as successful, partially successful or failed. A safety analysis was performed considering side effects and complications that were recorded during the first year after CLET and those reported later than 1 year, including the events related to subsequent treatments.
  
  
  RESULTS
  The mean post-CLET follow-up was 6.0±4.1 years. 69% of CLETs had either one or more adverse events (AEs), or adverse drug reactions (ADRs), within 1 year of surgery, with inflammation being the most common (42%), followed by corneal epithelium defects/disepithelialisation (31%), and blood coagula under the fibrin (24%). One year after surgery, 41% of the 59 primary CLET procedures were successful, 39% partially successful and 20% failed. The most common ADRs recorded for the primary unsuccessful CLETs were ulcerative keratitis, melting/perforation, and epithelial defects/disepithelialisation. Six failed CLETs required reconstructive penetrating keratoplasty (PK). Among CLETs with a favourable outcome, 13 underwent corrective PK (mean 4.8±3.4 years), and thereafter seven eyes maintained integrity of the corneal epithelium, five showed corneal surface failure, and one had recurrent epithelial defects. Corneal graft rejection episodes were reported in 71% and 58% of patients following corrective or reconstructive PK, respectively. Seven primary CLETs with a favourable outcome worsened thereafter, and the overall 3-year long-term effectiveness was 68%.
  
  
  CONCLUSIONS
  This study addresses important issues regarding possible risks associated with disarray of the ocular surface homeostasis following autologous CLET in patients with limbal stem cell deficiency, despite the fact that the majority of patients experienced a favourable long-term benefit.
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.|Department of Neurosciences, Biomedicine, and Movement Sciences, Eye Clinic, AOUI-University of Verona, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Fasolo
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, Eye Clinic, AOUI-University of Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Pedrotti
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, Eye Clinic, AOUI-University of Verona, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Passilongo
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, Eye Clinic, AOUI-University of Verona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Marchini
authors.affiliation: Ophthalmology Unit, Ospedale dell'Angelo, ULSS 12 Veneziana, Venezia Zelarino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Monterosso
authors.affiliation: Ophthalmology Unit, Ospedale dell'Angelo, ULSS 12 Veneziana, Venezia Zelarino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zampini
authors.affiliation: Ophthalmology Unit, Ospedale dell'Angelo, ULSS 12 Veneziana, Venezia Zelarino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bohm
authors.affiliation: Ophthalmology Unit, Ospedale SS. Giovanni e Paolo, ULSS 12 Veneziana, Venezia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Birattari
authors.affiliation: Ophthalmology Unit, Ospedale SS. Giovanni e Paolo, ULSS 12 Veneziana, Venezia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Franch
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Barbaro
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bertolin
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Breda
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.|Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Di Iorio
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ferrari
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Meneguzzi
authors.affiliation: Fondazione Banca degli Occhi del Veneto (The Veneto Eye Bank Foundation), Venezia Zelarino, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ponzin
mesh_terms: D000328:Adult; D000368:Aged; D003316:Corneal Diseases / Q000601:surgery*; D004847:Epithelial Cells / Q000637:transplantation*; D019573:Epithelium, Corneal / Q000637:transplantation*; D005126:Eye Burns / Q000601:surgery; D005260:Female; D006801:Humans; D015948:Keratoplasty, Penetrating; D016850:Limbus Corneae / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous; D014792:Visual Acuity; D055815:Young Adult
keywords: Cornea; Ocular surface; Stem Cells