June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Suprachoroidal administration of aflibercept protects against neovascularization in the mouse CNV model
Author Affiliations & Notes
  • Marc Cerrada-Gimenez
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Maria Vähätupa
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Birgitta Lappeteläinen
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Leena Tähtivaara
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Ville Jokinen
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Anne Mari Haapaniemi
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Olga Vergun
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Nerija Kvietkauskiene
    Research & Development, Experimentica Ltd, Vilnius, Lithuania
  • Simas Bijeikis
    Research & Development, Experimentica Ltd, Vilnius, Lithuania
  • Jonas Jarutis
    Research & Development, Experimentica Ltd, Vilnius, Lithuania
  • Anni Kolehmainen
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Pinja Mertano
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Emmi Sarkola
    Research & Development, Experimentica Ltd., Kuopio, Finland
  • Giedrius Kalesnykas
    Research & Development, Experimentica Ltd., Kuopio, Finland
    Research & Development, Experimentica Ltd, Vilnius, Lithuania
  • Simon Kaja
    Research & Development, Experimentica Ltd, Forest Park, Illinois, United States
    Departments of Ophthalmology and Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
  • Footnotes
    Commercial Relationships   Marc Cerrada-Gimenez None; Maria Vähätupa None; Birgitta Lappeteläinen None; Leena Tähtivaara None; Ville Jokinen None; Anne Mari Haapaniemi None; Olga Vergun None; Nerija Kvietkauskiene None; Simas Bijeikis None; Jonas Jarutis None; Anni Kolehmainen None; Pinja Mertano None; Emmi Sarkola None; Giedrius Kalesnykas None; Simon Kaja None
  • Footnotes
    Support  Experimentica Ltd., Dr John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2233. doi:
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      Marc Cerrada-Gimenez, Maria Vähätupa, Birgitta Lappeteläinen, Leena Tähtivaara, Ville Jokinen, Anne Mari Haapaniemi, Olga Vergun, Nerija Kvietkauskiene, Simas Bijeikis, Jonas Jarutis, Anni Kolehmainen, Pinja Mertano, Emmi Sarkola, Giedrius Kalesnykas, Simon Kaja; Suprachoroidal administration of aflibercept protects against neovascularization in the mouse CNV model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2233.

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

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Abstract

Purpose : Anti-VEGF treatments for exudative AMD are typically delivered by intravitreal injection (ivt). However, advances in gene therapy are exploring alternative ocular delivery modalities, notably suprachoroidal injections (sci). The purpose of this study was to validate sci in the mouse, and to test the efficacy of sci vs. ivt aflibercept in the mouse CNV model.

Methods : For sci a temporal sclerotomy was performed with a 30G needle, and a Hamilton microsyringe with a 33G needle was used to deliver the test article. CNV was induced by perforating the Bruch’s membrane with a 532 nm diode laser (Iridex Corp.), applying stringent exclusion and inclusion criteria (1, “bubble” formation; 2, successful perforation of Bruch’s membrane; 3, presence of leakage after lasering). Mice received either an ivt or sci injection of sterile PBS (vehicle) or aflibercept (Eylea®; 80 µg/eye; 2 µl injection). CNV pathology was assessed by longitudinal in vivo FA and SD-OCT measurements on Days 3 and 7 post-laser. Data were analyzed by a proprietary convolutional neuronal network, and reviewed by a researcher blinded to the study groups.

Results : Injection of blue ink showed distribution throughout the suprachoroidal space, highlighting the feasibility of sci in mice. In the CNV model, aflibercept resulted in a significant suppression of leaky CNV lesions on Day 3 in both delivery methods. FA leakage area was significantly decreased by ivt on Day 3 (58.6%. P < 0.01) and Day 7 (54.2%. P < 0.05). In contrast, sci reduced leakage area significantly on Day 3 (49.8%. P < 0.05), but not on Day 7 (76.8%. P = 0.14).
CNV grading was similar between aflibercept and vehicle groups for both routes of administration on Days 3 and 7.
Presence of leaky lesions on Day 3 was greater following ivt vs. sci delivery of vehicle, with the latter resulting in a faster-resolving pathology more similar to untreated animals.

Conclusions : Sci delivery of test articles is feasible in mice, despite the small size of the eye, and results in delivery of test articles throughout the suprachoroidal space. Sci delivery of aflibercept results in significant suppression of the presence of leaky CNV lesions and leakage area on Day 3. Leakage area was smaller compared to vehicle following ivt, but not sci on Day 7. Our data support the use of the mouse CNV model for testing the delivery of test articles suprachoroidally.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

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