title: Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model.
abstract: OBJECTIVE
  Excessive scarring leading to failure of the filtering bleb continues to be a major problem after glaucoma filtration surgery. This study examines the antifibrotic effects of the anti-S1P monoclonal antibody LT1009 (Sonepcizumab) in prolonging bleb survival in a rabbit model of glaucoma filtering surgery.
  
  
  METHODS
  The frequency of LT1009 dosage was determined initially using an enzyme-linked immunosorbent assay assay measuring LT1009 eye tissue retention in 6 New Zealand White rabbits. A further 21 New Zealand White rabbits underwent glaucoma filtering surgery. Bleb tissues were observed and compared clinically and histologically. The duration of bleb elevation was compared among LT1009, balanced saline solution (BSS) negative control, and mitomycin-C (MMC)-positive control.
  
  
  RESULTS
  The mean duration of bleb survival was 28.5±8.5 days for rabbits receiving injections of LT1009, 21.0±5.6 days for those receiving injections of BSS, and 33.8±5.6 days for rabbits receiving MMC. Analysis of variance with post hoc testing suggests a statistically significant trend of improvement in bleb duration for LT1009 when compared with BSS controls. Nonpainful, upper eyelid edema was noted after 5 injections of LT1009, which resolved over a 10-day period. MMC eyes developed avascular conjunctivas with areas of thinning and sparse cellularity, whereas the conjunctiva of LT1009 and BSS eyes remained relatively normal.
  
  
  CONCLUSIONS
  The monoclonal antibody LT1009 demonstrated a longer duration of bleb elevation than BSS control without adverse conjunctival effects associated with MMC. However, after multiple doses LT1009 use was associated with short-term upper eyelid edema.
authors.affiliation: Department of Ophthalmology, COM University of Florida, Gainesville, FL, USA.
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Lukowski
authors.forename: Jeff
authors.initials: J
authors.lastname: Min
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Beattie
authors.forename: Craig A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Monica A
authors.initials: MA
authors.lastname: Levine
authors.forename: Glenn
authors.initials: G
authors.lastname: Stoller
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Schultz
authors.forename: Don A
authors.initials: DA
authors.lastname: Samuelson
authors.forename: Mark B
authors.initials: MB
authors.lastname: Sherwood
mesh_terms: D000477:Alkylating Agents / Q000008:administration & dosage; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002921:Cicatrix / Q000517:prevention & control*; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000517:prevention & control; D018463:Filtering Surgery; D005901:Glaucoma / Q000601:surgery*; D007267:Injections; D008246:Lysophospholipids / Q000276:immunology*; D016685:Mitomycin / Q000008:administration & dosage; D011183:Postoperative Complications / Q000517:prevention & control*; D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology; D019738:Surgically-Created Structures; D014945:Wound Healing
chemical_list: D000477:Alkylating Agents; D061067:Antibodies, Monoclonal, Humanized; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D016685:Mitomycin; D013110:Sphingosine