May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Periocular or Intraocular Injection of AL-39324, a Novel Kinase Inhibitor That Blocks VEGF Receptors, Suppresses Choroidal Neovascularization (CNV) in Pigs
Author Affiliations & Notes
  • R. Lima e Silva
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • S. Kachi
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • N. H. Khu
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • S. Hackett
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • D. P. Bingaman
    Alcon Research Laboratories, Fort Worth, Texas
  • C. Romano
    Alcon Research Laboratories, Fort Worth, Texas
  • P. A. Campochiaro
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland
  • Footnotes
    Commercial Relationships R. Lima e Silva, None; S. Kachi, None; N.H. Khu, None; S. Hackett, None; D.P. Bingaman, Alcon Research Laboratories, E; C. Romano, Alcon Research Laboratories, E; P.A. Campochiaro, Alcon, F.
  • Footnotes
    Support Alcon
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1471. doi:https://doi.org/
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      R. Lima e Silva, S. Kachi, N. H. Khu, S. Hackett, D. P. Bingaman, C. Romano, P. A. Campochiaro; Periocular or Intraocular Injection of AL-39324, a Novel Kinase Inhibitor That Blocks VEGF Receptors, Suppresses Choroidal Neovascularization (CNV) in Pigs. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1471. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: The aim of this study was to assess the effect of AL-39324 on CNV in a human-sized eye.

Methods:: Four week-old female Yorkshire pigs had laser-induced rupture of Bruch’s membrane in each eye followed by 3 treatment paradigms: 1) periocular injection of 500µL containing 0, 5 or 10% AL-39324, 2) intraocular injection of 500µL containing 0, 0.3, or 3%, or 3) 100µL l containing 0.06 and 0.3%. The area of CNV at rupture sites was measured 10 days after injections.

Results:: The area of CNV at Bruch’s membrane rupture sites was significantly less in eyes given a periocular injection of 5 or 10% AL-39324 (↓83% and 79%, respectively) compared to eyes injected with vehicle (0.027±0.008 and 0.021±0.003 versus 0.16±0.02 and 0.10±0.016 n=12, p=0.0035 and p=0.0015 by two-tail t-test). Intraocular injections of 0.5 ml of 0.3% or 3% (↓64% and 77%, respectively) (0.036±0.0112 and 0.023±0.0105 versus 0.100±0.0172, n=12, p=0.01 and p=0.0038) or 0.1 ml of 0.06 or 0.3 % of AL-39324 (↓58% and 75%, respectively) (0.046±0.0068 and 0.028±0.0027 versus 0.11±0.0149, n=12, p=0.02 and p=0.00001) also suppressed CNV compared to vehicle.

Conclusions:: AL-39324 strongly suppresses CNV when given by periocular or intraocular injection in a human-sized eye and therefore is a viable candidate for the treatment of exudative AMD.

Keywords: choroid: neovascularization • laser • injection 
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