Abstract
Purpose :
Vascular leakage and aberrant neovascularization in eyes are major causes of blindness affecting diverse patient groups. Current treatments require regular intravitreal injections of anti-VEGF biologics. Here, we demonstrated the therapeutic benefits of a topically administered inhibitor of End-Binding protein 3 (EB3), herein EBIN, in treating leaky choroidal neovessels.
Methods :
The efficacy of topical administration of EBIN was evaluated in a CNV model of AMD in African green monkeys compared to topical vehicle and single IVT administration of aflibercept. Six laser spots were symmetrically placed within the perimacular region employing an Iridex Oculight TX 532 nm laser with laser duration of 100 ms, with a spot size of 50 µm and power of 750 mW. All animals received 30 µL topical instillation of vehicle or 150 µg EBIN twice daily on days 1-7 and once a day on days 8-21. An additional cohort received IVT injections of 2 mg Eylea® per eye. Fluorescein leakage was graded using angiograms of CNV lesions. The CNV complex area was measured using Optical Coherence Tomography images.
Results :
The incidences of clinically relevant grade IV CNV was 23.08% and 16.42% of the total lesions from the vehicle treated group and 11.94% and 7.35% in EBIN treated group at days 14 and 21, respectively. The Fisher’s Exact Probability Test revealed significantly lower incidence of grade IV lesions in EBIN versus vehicle groups at day 14 (p=0.0288). No significant difference was observed between vehicle and EBIN groups on day 21, and EBIN and aflibercept treated groups on days 14 and 21. The mean CNV lesion size was 50,471, 39,512 and 23,838 µm2 at day 14, and 34,621, 33,884 and 19,739 µm2 at day 21 for vehicle, EBIN, and aflibercept groups, respectively. Compared to the vehicle group, the mean CNV complex area was significantly smaller in EBIN-treated eyes at day 14 (p=0.0146), but not at day 21 (p=0.9791). The mean CNV complex area was smaller in the aflibercept group compared to EBIN group at days 14 (p=0.0003) and 21 (p=0.0014).
Conclusions :
Mean CNV complex size was significantly smaller in the EBIN group at day 14 and aflibercept group on days 14 and 21 when compared with the vehicle-treated animals. This was consistent and aligned with observed reduction in incidence of grade IV lesions.
This is a 2021 ARVO Annual Meeting abstract.