In vivo optical imaging of human retinal capillary networks using speckle variance optical coherence tomography with quantitative clinico-histological correlation

Abstract

Retinal capillary networks are critically linked to neuronal health and disease. The ability to perform accurate in vivo examination of human retinal capillary networks is therefore valuable for studying mechanisms that govern retinal homeostasis and retinal vascular diseases. Speckle variance optical coherence tomography (svOCT) is a non-invasive imaging technique that has the capacity to provide angiographic information about the retinal circulation. The application of this technology for studying human retinal capillary networks however has not been validated in a quantifiable manner. We use a custom-built svOCT device to qualitatively and quantitatively study the various capillary networks in the human perifovea. Capillary networks corresponding to the nerve fibre layer (NFL), the retinal ganglion cell/superficial inner plexiform layer (RGC/sIPL), the deep inner plexiform layer/superficial inner nuclear layer (dIPL/sINL) and the deep inner nuclear layer (dINL) are imaged in 9 normal human subjects. Measurements of capillary diameter and capillary density are made from each of these networks and results are compared to post-mortem histological data acquired with confocal scanning laser microscopy. Additionally, retinal capillary measurements from high-resolution fundus fluorescein angiogram (FA) are directly compared with svOCT images from 6 eyes. We demonstrate that svOCT images of capillary networks are morphologically comparable to microscopic images of histological specimens. Similar to histological images in svOCT images, the capillaries in the NFL network run parallel to the direction of RGC axons while capillaries in the dINL network comprise a planar configuration with multiple closed loops. Capillaries in remaining networks are convoluted with a complex three-dimensional architecture. We demonstrate that there is no significant difference in capillary density measurements between svOCT and histology images for all networks. Capillary diameter was significantly greater in svOCT images compared to histology for all networks. Capillary density measurements were also higher in svOCT compared to FA. The results of this study suggest that in vivo svOCT imaging allows accurate morphometric assessment of capillary networks in the human perifovea and may provide an improved ability to render microvascular detail compared to FA. Therefore, svOCT may have broad clinical applications in the study of human retinal physiology and disease. The difference in quantitative measurements between svOCT and histology may reflect dynamic variations in the retinal microcirculation and warrants further investigation.