Abstract

The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of neovascularization is a complex phenomenon under active investigation. Understanding and monitoring retinal neovascularization is critically important in clinical ophthalmology. This study describes a novel multimodal ocular imaging system which combines photoacoustic microscopy (PAM) and a spectral domain optical coherence tomography (SD-OCT) to improve the visualization of retinal neovascularization (RNV), their depth, and the surrounding anatomy in living rabbits. RNV was induced in New Zealand rabbits by intravitreal injection of vascular endothelial growth factor (VEGF). The retinal vasculature before and after injection at various times was monitored and evaluated using multimodal imaging including color fundus photography, fluorescein angiography (FA), OCT, and PAM. In vivo experiments demonstrate that PAM imaging distinctly characterized the location as well as the morphology of individual RNV with high contrast at a safe laser energy of 80 nJ. SD-OCT was used to identify a cross-sectional structure of RNV. In addition, dynamic changes in the retinal morphology and retinal neovascularization were observed at day 4, 5, 6, 7, 9, 11, 14, 28, and day 35 after VEGF injection. PAM demonstrated high-resolution optical absorption of hemoglobin and vascular imaging of the retina and choroid with increased depth of penetration. With the current multimodal imaging system, RNV can be easily visualized in both 2D and 3D angiography. This multimodal ocular imaging system provides improved characterization of the microvasculature in a safe manner in larger rabbit eyes.

Highlights

  • Retinal neovascularization (RNV) is major causes of vision loss and blindness in the United State and around the world [1,2,3]

  • To evaluate the changes in retinal vessels after vascular endothelial growth factor (VEGF) injection, the region of interest (ROI) was imaged, including the RNV and choroidal vessels with a field of view of 3 × 3 mm as shown in optical coherence tomography (OCT), the targeted retinal vessels and the scanning ROI were selected from color fundus camera and fluorescein angiography (FA)

  • The color fundus photograph demonstrates the morphology of the retinal vessels, and choroidal vessels

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Summary

Introduction

Retinal neovascularization (RNV) is major causes of vision loss and blindness in the United State and around the world [1,2,3]. RNV develops when pathologic new blood vessels form in the retina. These RNV vessels lack the normal vascular morphology and can leak fluid, rupture, cause bleeding or scar tissue formation, or cause retinal detachment, leading to vision loss [4,5]. RNV can be treated using several treatment methods, including panretinal photocoagulation, cryotherapy, anti-vascular endothelial growth factor (anti-VEGF), and vitrectomy. Without treatment, vitreous hemorrhage and tractional retinal detachments can develop. Available noninvasive imaging of retinal disease is based on imaging anatomical changes in the retina, including intraretinal and subretinal edema, hemorrhage, microaneurysms, and retinal pigment epithelium (RPE) changes

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