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      Hemodynamic Response of the Three Macular Capillary Plexuses in Dark Adaptation and Flicker Stimulation Using Optical Coherence Tomography Angiography

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          Abstract

          Purpose

          To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA).

          Methods

          Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA. Parafoveal vessel density and adjusted flow index (AFI) were calculated for superficial (SCP), middle (MCP), and deep capillary plexuses (DCP), and then compared between conditions after adjusting for age, refractive error, and scan quality. SCP vessel length density (VLD) was also evaluated. Between-condition capillary images were aligned and subtracted to identify differences. We then analyzed images from 10 healthy subjects during the transition from dark adaptation to ambient light.

          Results

          SCP vessel density was significantly higher while SCP VLD was significantly lower during ambient light and flicker compared to dark adaptation. There was a significant positive mean value for DCP “flicker minus dark or light,” suggesting more visible vessels during flicker due to changes in flow, dilation, or vessel recruitment. We found a significant, transient increase in SCP and decrease in both MCP and DCP vessel density during the transition from dark to light.

          Conclusions

          We show evidence suggesting constriction of deeper vessels and dilation of large SCP vessels during the transition from dark to light. This contrasts to redistribution of blood flow to deeper layers during dark adaptation and flicker stimulation.

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          Most cited references43

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          Split-spectrum amplitude-decorrelation angiography with optical coherence tomography

          Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.
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            Energy metabolism of the visual system.

            The visual system is one of the most energetically demanding systems in the brain. The currency of energy is ATP, which is generated most efficiently from oxidative metabolism in the mitochondria. ATP supports multiple neuronal functions. Foremost is repolarization of the membrane potential after depolarization. Neuronal activity, ATP generation, blood flow, oxygen consumption, glucose utilization, and mitochondrial oxidative metabolism are all interrelated. In the retina, phototransduction, neurotransmitter utilization, and protein/organelle transport are energy-dependent, yet repolarization-after-depolarization consumes the bulk of the energy. Repolarization in photoreceptor inner segments maintains the dark current. Repolarization by all neurons along the visual pathway following depolarizing excitatory glutamatergic neurotransmission preserves cellular integrity and permits reactivation. The higher metabolic activity in the magno- versus the parvo-cellular pathway, the ON- versus the OFF-pathway in some (and the reverse in other) species, and in specialized functional representations in the visual cortex all reflect a greater emphasis on the processing of specific visual attributes. Neuronal activity and energy metabolism are tightly coupled processes at the cellular and even at the molecular levels. Deficiencies in energy metabolism, such as in diabetes, mitochondrial DNA mutation, mitochondrial protein malfunction, and oxidative stress can lead to retinopathy, visual deficits, neuronal degeneration, and eventual blindness.
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              Projection-resolved optical coherence tomographic angiography.

              Shadowgraphic projection artifacts from superficial vasculature interfere with the visualization of deeper vascular networks in optical coherence tomography angiography (OCT-A). We developed a novel algorithm to remove this artifact by resolving the ambiguity between in situ and projected flow signals. The algorithm identifies voxels with in situ flow as those where intensity-normalized decorrelation values are higher than all shallower voxels in the same axial scan line. This "projection-resolved" (PR) algorithm effectively suppressed the projection artifact on both en face and cross-sectional angiograms and enhanced depth resolution of vascular networks. In the human macula, the enhanced angiograms show three distinct vascular plexuses in the inner retina and no vessels in the outer retina. We demonstrate that PR OCT-A cleanly removes flow projection from the normally avascular outer retinal slab while preserving the density and continuity of the intermediate and deep retinal capillary plexuses.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                Invest Ophthalmol Vis Sci
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                February 2019
                : 60
                : 2
                : 694-703
                Affiliations
                [1 ]Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
                [2 ]Department of Ophthalmology, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt
                [3 ]Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
                [4 ]Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, Illinois, United States
                [5 ]Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, United States
                Author notes
                Correspondence: Amani Fawzi, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 440, Chicago, IL 60611, USA; afawzimd@ 123456gmail.com .
                Article
                iovs-60-02-12 IOVS-18-25478R2
                10.1167/iovs.18-25478
                6383834
                30786274
                04524b71-80d4-44ac-8ed6-1a196267fb8e
                Copyright 2019 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 8 August 2018
                : 14 January 2019
                Categories
                Retina

                optical coherence tomography angiography,oct,neurovascular coupling,dark adaptation,flicker stimulation

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