In vivo imaging of anti-vascular growth factor inhibitor induced therapeutic responses in the rat retina by using optical coherence tomography angiography

Abstract

Purpose : Choroidal neovascularization (CNV) is the hallmark of neovascular age-related macular degeneration. New imaging devices including optical coherence tomography angiography (OCTA) may offer a detailed microstructural analysis of the disease progress also allowing for longitudinal review at high resolution. In this study, multimodal in vivo imaging by OCTA, fluorescein angiography (FA) and confocal microscopy was performed in the laser-induced CNV model for analysis of therapeutic response by anti vascular endothelial growth factor (VEGF) inhibitors.

Methods : Rats underwent laser photocoagulation to induce CNV on D0. Immediately following the laser treatment, aflibercept, AF564 (rat anti-VEGF antibody) and NaCl were intravitreal injected. Imaging by OCTA and FA was performed at D0, D2, D7, D14 and D21 following laser treatment. Vascular morphology was validated using confocal immunofluorescent imaging of retinal and choroidal flatmounts. OCTA, FA and flatmount results were compared and analysis included measurements of CNV area, grading score and vessel density within the treatment groups.

Results : Within laser lesions, new blood vessels were visible by OCTA especially in the deep vascular plexus, in the avascular zone and the choroid but not by FA. Overall, a decrease in CNV progression in OCTA, FA and histology was measured following the injection of aflibercept and AF564 compared to NaCl. For ONL, mean area lesion on D21 measured by OCTA was 0.055 mm2 following aflibercept treatment, 0.063 mm2 following AF564 treatment and 0.083 mm2 following NaCL injection (p<0.001 and p<0.0001). Due to leakage effects, CNV area appeared significantly larger in FA compared to OCTA images (p<0.0001 for all layers). Overall, CNV area in flatmounts was similar to OCTA results and smaller compared to leakage by FA.

Conclusions : Detailed and high-contrast images of the retinal and choroidal vasculature can be accurately visualized in vivo by OCTA in the laser-induced CNV rat model. Results from confocal microscopy were comparable with OCTA but not with FA imaging. In vivo OCTA imaging in the rat retina allows to monitor therapeutic effects of pharmacological interventions. Overall, OCTA imaging allows for a more precise, spatial and quantitative analysis of new blood vessel formation and response to therapeutical intervention compared with conventional FA.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.