Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model

Zachary Lee Lukowski, Jeff Min, Ashley R. Beattie, Craig A. Meyers, Monica A. Levine, Glenn Stoller, Gregory S. Schultz, Don A. Samuelson, Mark B. Sherwood

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalJournal of Glaucoma
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Filtering Surgery
Blister
Glaucoma
Cicatrix
Monoclonal Antibodies
Sodium Chloride
Rabbits
Mitomycin
Conjunctiva
Eyelids
Injections
Edema
Analysis of Variance
Enzyme-Linked Immunosorbent Assay

Keywords

  • Anti-S1P monoclonal antibody
  • Glaucoma
  • Rabbit model
  • Wound healing

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model. / Lukowski, Zachary Lee; Min, Jeff; Beattie, Ashley R.; Meyers, Craig A.; Levine, Monica A.; Stoller, Glenn; Schultz, Gregory S.; Samuelson, Don A.; Sherwood, Mark B.

In: Journal of Glaucoma, Vol. 22, No. 2, 01.02.2013, p. 145-151.

Research output: Contribution to journalArticle

Lukowski, ZL, Min, J, Beattie, AR, Meyers, CA, Levine, MA, Stoller, G, Schultz, GS, Samuelson, DA & Sherwood, MB 2013, 'Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model', Journal of Glaucoma, vol. 22, no. 2, pp. 145-151. https://doi.org/10.1097/IJG.0b013e31822e8c83
Lukowski, Zachary Lee ; Min, Jeff ; Beattie, Ashley R. ; Meyers, Craig A. ; Levine, Monica A. ; Stoller, Glenn ; Schultz, Gregory S. ; Samuelson, Don A. ; Sherwood, Mark B. / Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model. In: Journal of Glaucoma. 2013 ; Vol. 22, No. 2. pp. 145-151.
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AU - Beattie, Ashley R.

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AU - Levine, Monica A.

AU - Stoller, Glenn

AU - Schultz, Gregory S.

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AU - Sherwood, Mark B.

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N2 - 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.

AB - 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.

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