Retinal microvascular network alterations: potential biomarkers of cerebrovascular and neural diseases

Abstract

Increasing evidence suggests that the conditions of retinal microvessels are indicators to a variety of cerebrovascular, neurodegenerative, psychiatric, and developmental diseases. Thus noninvasive visualization of the human retinal microcirculation offers an exceptional opportunity for the investigation of not only the retinal but also cerebral microvasculature. In this review, we show how the conditions of the retinal microvessels could be used to assess the conditions of brain microvessels because the microvascular network of the retina and brain share, in many aspects, standard features in development, morphology, function, and pathophysiology. Recent techniques and imaging modalities, such as optical coherence tomography (OCT), allow more precise visualization of various layers of the retina and its microcirculation, providing a "microscope" to brain microvessels. We also review the potential role of retinal microvessels in the risk identification of cerebrovascular and neurodegenerative diseases. The association between vision problems and cerebrovascular and neurodegenerative diseases, as well as the possible role of retinal microvascular imaging biomarkers in cerebrovascular and neurodegenerative screening, their potentials, and limitations, are also discussed.

Keywords: brain; cerebrovascular and neurodegenerative disorders; optical coherence tomography; optical imaging; retinal imaging biomarkers.

Fig. 1.

Details of the retinal microvasculature. A: fundus photograph of a healthy eye allowing visualization of the entire posterior pole of the ocular fundus, including the optic nerve, the macula, and the major retinal vessels. B: montage of images of the nerve fiber layer obtained by wide-field optical coherence tomography-based microangiography (OMAG) for the same eye. Note the radial pericapillary network within the RNFL. C: the superficial retinal layer slab contains the vascular network within the ganglion cell layer (GCL) and the outer plexiform layer (OPL). Both the arcade vessels and the fine capillaries are shown. D: the deep retinal layer demonstrates deeper capillary network. E: the whole retinal layer slab composed of the superficial retinal layer, the deep retinal layer, and the outer retinal layer allows visualization of the shallow, intermediate, and deep retinal capillary plexuses. Different colors identify various levels of the retina. F: the magnified image of the central macula (identified as in the blue box from E). The cross-sectional flow image of the area is marked with a white dashed line on the magnified OMAG image. Blood flow detected in the superficial retinal layer, the deep retinal layer, and the outer retinal layer (ORL) are in red, green, blue; respectively. Note that flow can be detected in the ORL. [Images adapted from Zhang et al. (143a) with permission.]

Fig. 2.

The advantage of combining multimodal optical imaging approaches: retinal images demonstrating functional and structural signatures of a diabetic patient with proliferative diabetic retinopathy (PDR). Similar signs of capillary dropout and retinal abnormalities are observed in retinal images from patients with cerebrovascular and neurodegenerative diseases with ocular manifestations. Top: noninvasive capillary perfusion map (nCPM) in an eye with extensive retinal ischemia due to the PDR obtained with the Retinal Function Imager (RFI, Optical Imaging Ltd., Rehovot, Israel). The OCT thickness map is overlayed on top of the nCPM. Note how the areas of thinning (represented in blue color) on the OCT map overlap with the capillary dropout. Bottom: focal diabetic macular edema in the temporal part of the macula as seen on the macular thickness map (left) and the horizontal B-scan (right) corresponding to the blue section line on the map. (Images courtesy of William E. Smiddy, MD, Thalmon R. Campagnoli, MD, Jing Tian, Ph.D., and Gabor M. Somfai, MD, Ph.D., University of Miami, Miami, FL.)

Fig. 3.

Quantitative oximetry. Left: fundus image obtained from a healthy eye. Right: oxygen saturation map of the same eye. (Images courtesy of Optical Imaging Ltd., Rehovot, Israel.)