Long-term outcome of aflibercept subconjuctival treatment for chemical induced corneal neovascularization in the rabbit model

Abstract

Purpose : The dynamic course of sulfur mustard (SM) induced ocular insult is characterized by an acute phase, which may be continued to a chronic phase or a quiescent period followed by a late pathology. The aim of this study was to evaluate the efficacy of ziv-aflibercept (Zaltrap) or aflibercept (Eylea) in preventing or ameliorating the corneal insult specifically the late phase induced neovascularization following ocular exposure to SM in the rabbit model.

Methods : Chemical SM burn was induced in the right eyes of NZW rabbits by vapor exposure. Zaltrap (2mg) was applied once by subconjunctival injection at 2h, 9 days or at 4 weeks post exposure. Eylea (2mg), the ocular specific preparation, was administered 4 weeks post SM exposure and following an initial one week treatment with 0.1% dexamethasone.
Non-treated exposed eyes served as controls. A clinical follow-up was performed for up-to 5-12 weeks following exposure and digital photographs of the cornea were taken for measurement of blood vessel length using an image analysis software. Eyes were taken for histological evaluation and extent of NV was determined by using H&E and Masson Trichrome staining.

Results : A single subconjunctival treatment of VEGF-trap 2h or 9 days post exposure presented a slight benefit in reducing the severity of the injury and in postponing the late induced NV growth. However in the group receiving treatment at 4 weeks following exposure, a significant reduced extent of existing NV was already seen at one week following injection, an effect which lasted for at least 8 weeks. The extensive reduction in existing corneal NV in the VEGF-trap treated group was confirmed by histological evaluation. Finally, eyes receiving the steroidal treatment during the first week and the ocular preparation of VEGF-trap following NV detection presented a significant reduction in corneal NV as compared to the steroid only treated group.

Conclusions : Subconjunctival Zaltrap or the combination of dexamethasone followed by Eylea treatment presented a long-term significant benefit in corneal NV reduction following ocular chemical exposure when used against existing NV rather than as a post exposure prophylactic treatment. These findings show the robust anti-angiogenic efficacy of both Eylea and Zaltrap and demonstrate the advantage of this treatment, in ameliorating corneal NV and protecting the ocular surface.

This is a 2021 ARVO Annual Meeting abstract.