OCTA reveals remodeling of the peripheral capillary free zones in normal aging

Abstract

The retinal neurovascular unit consists of blood vessel endothelial cells, pericytes, neurons, astrocytes, and Müller cells that form the inner retinal blood barrier. A peripheral capillary free zone (pCFZ) represents the distance that oxygen and nutrients must diffuse to reach the neural retina, and serves as a metric of retinal tissue oxygenation. The pCFZs are formed based on oxygen saturation in the retinal arterioles and venules. Because retinal arterioles contain a larger concentration of oxygenated blood than venules, there is a reduced need for capillaries to exist closely to arterioles compared to venules. Therefore, in a healthy individual, larger periarteriole CFZs are expected compared to perivenule CFZs. With normal aging, there is atrophy of the inner retinal neurons, and consequently reduced extraction of oxygen and nutrients from the retinal vessels (i.e., increased oxygen saturation). Therefore, we hypothesized that the peripheral CFZ will remodel with normal aging. Using Optical Coherence Tomography Angiography, we showed that the pCFZs do remodel in normal aging with large (perivenule: η2p = 0.56) and moderate (periarteriole: η2p = 0.12) effect sizes, opening the possibility that such changes may be further increased by neurodegenerative diseases that adversely impact the health of the retinal neural cell layers.

Retinal mid-peripheral capillary free zones are enlarged in cognitively unimpaired older adults at high risk for Alzheimer’s disease

“…We obtained 20 × 20°OCTA images consisting of 512 b-scans, 512 A-scans per b-scan, 12 µm spacing between the b-scans, and 5 frames averaged per each b-scan location of the central fovea and of paired major arterioles and venules with their surrounding capillaries inferior to the fovea (Spectralis HRA + OCT; Eye Explorer version 1.10.4.0; Heidelberg Engineering, Germany; Fig. 1 ) as done previously [ 22 , 23 ]. The signal quality values (range for Spectralis = 0–40) of all our OCTA images from the vendor software were at least 20 to ensure good image quality.…”

“…One issue with using the FAZ area as a biomarker for AD is that it is limited to a few or a single layer of capillaries. Moreover, it may become saturated with increasing disease severity and not increase further in size, even with the loss of capillaries [ 22 , 23 ]. FAZ area is highly variable in cognitively unimpaired (CU) older adults [ 23 , 25 – 28 ], and studies have shown that the FAZ area is not consistently significantly larger in an AD cohort than a control cohort [ 29 – 32 ].…”

“…Moreover, it may become saturated with increasing disease severity and not increase further in size, even with the loss of capillaries [ 22 , 23 ]. FAZ area is highly variable in cognitively unimpaired (CU) older adults [ 23 , 25 – 28 ], and studies have shown that the FAZ area is not consistently significantly larger in an AD cohort than a control cohort [ 29 – 32 ]. Also, vessel density measurements in AD patients using optical coherence tomography angiography (OCTA) [ 29 , 33 – 35 ] are influenced by noise in the image, along with variable anatomic features such as vessel diameter [ 20 , 21 , 23 ].…”

“…In previous studies, we characterized and quantified the metrics of tissue oxygenation in the retina of young and older CU participants in the form of periarteriole and perivenule capillary free zones (mid-peripheral CFZs) [ 22 , 23 ]. The mid-peripheral CFZs represent the maximum distance that oxygen and nutrients must diffuse to reach the retinal neurons with larger distances indicating potential ischemia [ 22 , 23 ].…”

“…In previous studies, we characterized and quantified the metrics of tissue oxygenation in the retina of young and older CU participants in the form of periarteriole and perivenule capillary free zones (mid-peripheral CFZs) [ 22 , 23 ]. The mid-peripheral CFZs represent the maximum distance that oxygen and nutrients must diffuse to reach the retinal neurons with larger distances indicating potential ischemia [ 22 , 23 ]. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD [ 36 , 37 ] leading to potential enlargement of the mid-peripheral CFZs around the arterioles and venules in the retina of AD patients.…”