July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Aflibercept in combination with nesvacumab (anti-Ang2) induces vascular remodeling in a rabbit model of pathological neovascularization.
Author Affiliations & Notes
  • Bibiana Iglesias
    Ophthalmology, Regeneron, Tarrytown, New York, United States
  • Thomas MacPherson
    Ophthalmology, Regeneron, Tarrytown, New York, United States
  • Jingtai Cao
    Ophthalmology, Regeneron, Tarrytown, New York, United States
  • Carmelo Romano
    Ophthalmology, Regeneron, Tarrytown, New York, United States
  • Footnotes
    Commercial Relationships   Bibiana Iglesias, Regeneron (E); Thomas MacPherson, Regeneron (E); Jingtai Cao, Regeneron (E); Carmelo Romano, Regeneron (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1447. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Bibiana Iglesias, Thomas MacPherson, Jingtai Cao, Carmelo Romano; Aflibercept in combination with nesvacumab (anti-Ang2) induces vascular remodeling in a rabbit model of pathological neovascularization.
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):1447.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Abnormal VEGF and Angiopoietin 2 (Ang2) mediate pathological retinal neovascularization (RNV) and permeability. Co-administration of the anti-VEGF aflibercept with the anti-Ang2 antibody nesvacumab promotes an extended inhibition of vascular leak in a rabbit model of RNV. Here, we studied the effects of monotherapy and co-formulation on pathological vasculature apoptosis and regression in the days to weeks after intravitreal (IVT) administration and the blood vessel regrowth pattern at 20 weeks post IVT treatment.

Methods : Male New Zealand White rabbits (2.0-2.5 kg) received DL-alpha-aminoadipic acid (AAA) IVT. After 10 weeks, rabbits were divided into six treatment groups: placebo, nesvacumab, aflibercept or different doses of the co-formulation. Red free imaging (RF), fluorescein angiography (FA) and optical coherence tomography (OCT) were performed weekly after treatment (weeks 1 through 20). RF pictures covering the entire fundus at each time point were merged into a single image. Weekly fundus montages were registered to analyze blood vessel morphology over time. In a different study, rabbits were divided into three treatment groups: placebo, aflibercept and co-formulation. All animals received fluorescent AnnexinV in conjunction with treatment. Imaging was performed daily and animals were euthanized on day 3. Retinas were processed for fluorescent staining.

Results : A single intravitreal treatment with aflibercept or co- formulation completely and reversibly suppressed vascular leak for weeks. However, the return of vascular permeability was significantly delayed in eyes that received the co-formulation. AnnexinV positive signal was detected as soon as 24 hours after IVT with aflibercept and co-formulation but not in placebo treated eyes. Apoptosis of pathological vasculature was followed by regrowth several weeks later. The pattern of vessels after aflibercept was superimposable on the pattern seen before aflibercept treatment, whereas there were many de novo paths taken by vessels that re-grew after the combination therapy.

Conclusions : Treatment with aflibercept or co-formulation induces pathological blood vessel apoptosis and regression. However, only treatment with co-formulation with nesvacumab causes blood vessel remodeling.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×