Name: retinal vascular reactivity as assessed by optical coherence tomography angiography
Uploaded: 2020-03-26T14:00:00
Description: Watch this Scientific Journal Video about Retinal Vascular Reactivity as Assessed by Optical Coherence Tomography Angiography at JoVE.com

This work was supported by NIH K08EY027006, R01EY030564, UH3NS100614, Research Grants from Carl Zeiss Meditec Inc (Dublin, CA) and Unrestricted Department Funding from Research to Prevent Blindness (New York, NY).

This study was approved by the University of Southern California Institutional Review Board and adhered to the tenets of the Declaration of Helsinki.
1. Setup of Gas Non-rebreathing Apparatus
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60948/60948fig1v2.jpg" /> 
Figure 1: Diagram of the non-rebreathing apparatus.&#160;The full setup has been broken into three separate units according to their functi...

The methodology just described is the complete protocol for a gas breathing provocation experiment that allows for the measurement of a subject&#8217;s RVR in a controlled environment at specific timepoints with no modifications to the OCTA imaging device and minimal discomfort or risk to the subject. This setup is described in a way that allows for easy modifications to fit the needs of the researcher. It can accommodate additional tubing to fit different clinic rooms and certain elements such as the in-house tubing or ...

The metabolic demand of the retina is dependent on an adequate and constant supply of oxygen provided by a well-regulated system of arterioles, capillaries and venules1. Several studies have demonstrated that the function of larger caliber human retinal vessels can be assessed in vivo with various physiologic2,3,4,5 and pharmacologic6,7 stimuli. In addition, abnormal function of this vascular system is common in retinal vascular diseases such as diabetic retinopathy where retinal vascular reactivity (RVR) has been shown to be attenuated even in its earliest stages8,9 through both gas provocation9 and flickering light experiments5,10,11. Retinal vascular risk factors such as smoking have also been correlated with impaired RVR12 and retinal blood flow13. These findings are important since the clinical symptoms of retinal vascular disease occur relatively late in the disease process and proven early clinical markers of disease are lacking14. Thus, assessing RVR can provide useful measures of vascular integrity for the early assessment of abnormalities that can initiate or exacerbate retinal degenerative diseases.
Previous RVR experiments have usually relied upon devices such as a laser blood flowmeter9 or fundus cameras equipped with special filters15 for retinal image acquisition. However, these technologies are optimized for larger diameter vessels such as arterioles16 and venules15, which are not where gas, micronutrient and molecular exchange occur. A more recent study was able to quantify the RVR of capillaries using adaptive optics imaging17, but despite the improved spatial resolution, these images have a smaller field size and are not FDA approved for clinical use18.
The recent advent of optical coherence tomography angiography (OCTA) has provided an FDA approved, noninvasive and dyeless angiographic method of assessing capillary level changes in human patients and subjects in vivo. OCTA is widely accepted in clinical practice as an effective tool for assessing impairment in capillary perfusion in retinal vascular diseases such as diabetic retinopathy19, retinal venous occlusions20, vasculitis21 and many others22. OCTA therefore provides an excellent opportunity for the evaluation of capillary level changes, which can have significant spatial and temporal heterogeneity23 as well as pathologic changes, in a clinical setting. Our group recently demonstrated that OCTA can be used to quantify the responsiveness of retinal vessels at the capillary level2 to physiologic changes in inspired oxygen, which is a retinal vasoconstrictive stimulus16,24, and carbon dioxide, which is a retinal vasodilatory stimulus3,5.
The goal of this article is to describe a protocol that will allow the reader to assess the retinal vascular reactivity of the smaller arterioles and capillary bed using OCTA. The methods are adapted from those presented in Lu et al.25 who described the measurement of cerebrovascular reactivity with magnetic resonance imaging. Although the present methods were developed and used during OCTA imaging2, they are applicable to other retinal imaging devices with relatively simple and obvious modifications.

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retinal vascular reactivity as assessed by optical coherence tomography angiography

The vascular supply to the retina has been shown to dynamically adapt through vasoconstriction and vasodilation to accommodate the metabolic demands of the retina. This process, referred to as retinal vascular reactivity (RVR), is mediated by neurovascular coupling, which is impaired very early in retinal vascular diseases such as diabetic retinopathy. Therefore, a clinically feasible method of assessing vascular function may be of significant interest in both research and clinical settings. Recently, in vivo imaging of the retinal vasculature at the capillary level has been made possible by the FDA approval of optical coherence tomography angiography (OCTA), a noninvasive, minimal risk and dyeless angiography method with capillary level resolution. Concurrently, physiological and pathological changes in RVR have been shown by several investigators. The method shown in this manuscript is designed to investigate RVR using OCTA with no need for alterations to the clinical imaging procedures or device. It demonstrates real time imaging of the retina and retinal vasculature during exposure to hypercapnic or hyperoxic conditions. The exam is easily performed with two personnel in under 30 min with minimal subject discomfort or risk. This method is adaptable to other ophthalmic imaging devices and the applications may vary based on the composition of the gas mixture and patient population. A strength of this method is that it allows for an investigation of retinal vascular function at the capillary level in human subjects in vivo. Limitations of this method are largely those of OCTA and other retinal imaging methods including imaging artifacts and a restricted dynamic range. The results obtained from the method are OCT and OCTA images of the retina. These images are amenable to any analysis that is possible on commercially available OCT or OCTA devices. The general method, however, can be adapted to any form of ophthalmic imaging.

The output from this experiment consists of the manual readings taken from the pulse oximeter, the timing noted for gas exposure or OCTA scanning and the raw OCTA imaging data. An OCTA image consists of the OCT B-scans and the decorrelation signal associated with each B-scan. The data parameters are given by the specifications of the device. A swept source laser platform OCTA machine with a central wavelength of 1040&#8211;1060 nm was used. The images provide a transverse resolution of 20 &#181;m and optical axial resolu...

Watch this Scientific Journal Video about Retinal Vascular Reactivity as Assessed by Optical Coherence Tomography Angiography at JoVE.com

Retinal Vascular Reactivity as Assessed by Optical Coherence Tomography Angiography

This article describes a method for measuring retinal vasculature reactivity in vivo with human subjects using a gas breathing provocation technique to deliver vasoactive stimuli while acquiring retinal images.

The vascular supply to the retina has been shown to dynamically adapt through vasoconstriction and vasodilation to accommodate the metabolic demands of ...

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