In vivo imaging of therapeutic response in the rat retina by anti-vascular growth factor inhibitors using optical coherence tomography angiography (OCT-A)

Abstract

Purpose : Optical coherence tomography angiography (OCT-A) allows for accurate visualization of the retinal and choroidal vasculature without fluorescent dye injection. Here, we compared OCT-A with conventional fluorescein angiography (FA) and confocal fluorescence microscopy in the rat model of laser-induced choroidal neovascularization (CNV) for analysis of therapeutic response by anti vascular endothelial growth factor (VEGF) inhibitors.

Methods : All animals (dark agouti rats) underwent laser photocoagulation to induce CNV on D0 and aflibercept, AF564 (a rat-specific anti-VEGF antibody, R&D Systems) and NaCl (control) were injected intravitreally. In-vivo imaging by OCT-A and FA was performed at D0, D2, D7, D14 and D21 following initial laser treatment. OCT-A was compared to FA and confocal imaged retinal and choroidal flatmounts. Analysis included measurements of CNV area, vessel density and pixel intensity within/without the laser lesions.

Results : Within laser lesions, new blood vessels were visible by OCT-A especially in the deep vascular plexus, in the avascular zone and the choroid but not by conventional FA. Due to leakage and staining effects, CNV area appeared significantly larger in FA compared to OCT-A images (p<0.0001 for all tested layers, Fig. 1). Overall, CNV area in flatmounts was similar to OCT-A results and smaller compared to area of dye leakage by FA. A decrease in CNV progression was measured following the treatment with aflibercept and AF564 but not with NaCl (Fig. 1).

Conclusions : Therapeutic effects of anti-VEGF inhibitors can be monitored by in-vivo OCT-A imaging in the laser-induced CNV rat model. Overall, OCT-A imaging allows for a more precise, spatial and quantitative analysis of new blood vessel formation and response to therapeutical intervention as compared with conventional FA.

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

 

Fig.1: Analysis of the area of CNV on D14 following the laser treatment and intravitreal injection of Aflibercept (n=11), AF564 (n=10) and NaCl (n=9). The area of new vessels growth was analyze for the superficial vascular plexus (SVP), intermediate vascular plexus (IVP), deep vascular plexus (DVP), outer nuclear layer (ONL), the ellipsoid zone (EZ), inner choroidal (IC) and outer choroidal (OC) layer imaged by OCT-A and FA. The asterisks are indicating a significant difference (p<0.0001) in CNV area calculated by the Mann-Whitney-U-Test.