Prevention of Ocular Scarring After Glaucoma Filtering Surgery Using the Monoclonal Antibody LT1009 (Sonepcizumab) in a Rabbit Model

• Published in: Journal of glaucoma Vol. 22; no. 2; pp. 145 - 151
• Main Authors: Lukowski, Zachary L, Min, Jeff, Beattie, Ashley R, Meyers, Craig A, Levine, Monica A, Stoller, Glenn, Schultz, Gregory S, Samuelson, Don A, Sherwood, Mark B
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-02-2013
• Subjects: Alkylating Agents - administration & dosage; Animals; Antibodies, Monoclonal, Humanized - therapeutic use; Cicatrix - prevention & control; Conjunctiva - drug effects; Conjunctiva - pathology; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fibrosis - prevention & control; Filtering Surgery; Glaucoma - surgery; Injections; Lysophospholipids - immunology; Mitomycin - administration & dosage; Postoperative Complications - prevention & control; Rabbits; Sphingosine - analogs & derivatives; Sphingosine - immunology; Surgically-Created Structures; Wound Healing
• ISSN: 1057-0829; 1536-481X
• DOI: 10.1097/IJG.0b013e31822e8c83

PURPOSE: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.