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      Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy

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          Abstract

          Aims/hypothesis

          The aim of this study was to compare retinal oxygen extraction in individuals with diabetes with no or mild non-proliferative diabetic retinopathy and healthy age- and sex-matched volunteers.

          Methods

          A total of 24 participants with type 1 diabetes and 24 healthy age- and sex-matched volunteers were included in this cross-sectional study. Retinal oxygen extraction was measured by combining total retinal blood flow measurements using a custom-built bi-directional Doppler optical coherence tomography system with measurements of oxygen saturation using spectroscopic reflectometry. Based on previously published mathematical modelling, the oxygen content in retinal vessels and total retinal oxygen extraction were calculated.

          Results

          Total retinal blood flow was higher in diabetic participants (46.4 ± 7.4 μl/min) than in healthy volunteers (40.4 ± 5.3 μl/min, p = 0.002 between groups). Oxygen content in retinal arteries was comparable between the two groups, but oxygen content in retinal veins was higher in participants with diabetes (0.15 ± 0.02 ml O 2/ml) compared with healthy control participants (0.13 ± 0.02 ml O 2/ml, p < 0.001). As such, the arteriovenous oxygen difference and total retinal oxygen extraction were reduced in participants with diabetes compared with healthy volunteers (total retinal oxygen extraction 1.40 ± 0.44 vs 1.70 ± 0.47 μl O 2/min, respectively, p = 0.03).

          Conclusions/interpretation

          Our data indicate early retinal hypoxia in individuals with type 1 diabetes with no or mild diabetic retinopathy as compared with healthy control individuals. Further studies are required to fully understand the potential of the technique in risk stratification and treatment monitoring.

          Trial registration:

          ClinicalTrials.gov NCT01843114.

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          Most cited references34

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          Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

          Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.
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            Retinal oxygen saturation is altered in diabetic retinopathy.

            Retinal oxygen metabolism is thought to be affected in diabetic retinopathy. The aim of this study was to test whether retinal vessel oxygen saturation is different in patients with diabetic retinopathy from that in healthy controls. The retinal oximeter is based on a fundus camera. It estimates retinal vessel oxygen saturation from light absorbance at 586 nm and 605 nm. Retinal vessel oxygen saturation was measured in one major temporal retinal arteriole and venule in healthy volunteers and in patients with diabetic retinopathy. Oxygen saturation in the retinal arterioles of healthy volunteers was 93 ± 4% and 58 ± 6% in venules (mean ± SD, n=31). The corresponding values for all diabetic patients (n=20) were 101 ± 5% and 68 ± 7%. The difference between healthy volunteers and diabetic patients was statistically significant (p < 0.001 for arterioles and venules). Three subgroups of diabetic patients (background retinopathy, macular oedema and pre-proliferative/proliferative retinopathy) all had higher saturation values than the healthy volunteers (p < 0.05 for arterioles and venules). Retinal vessel oxygen saturation is higher in patients with diabetic retinopathy than in healthy controls. Possible explanations include shunting of blood through preferential channels, bypassing non-perfused capillaries in the capillary network. Parts of the retinal tissue may be hypoxic while blood in larger vessels has high oxygen saturation.
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              Blood velocity and volumetric flow rate in human retinal vessels.

              The distributions of blood velocity and volumetric flow rate in individual vessels of the normal human retina were determined as a function of vessel diameter. The mean velocity of blood, Vmean, was calculated from the centerline velocity measured by bidirectional laser Doppler velocimetry (LDV). Volumetric flow rate was determined from Vmean and the vessel diameter, D, measured from monochromatic fundus photographs. Diameter of the arteries and veins at the site of the LDV measurements ranged from 39 to 134 microns and 64 to 177 microns, respectively. Flow velocity correlated with D (P less than 0.001 for both arteries and veins). Volumetric flow rate varied with D at a power of 2.76 +/- 0.16 for arteries and 2.84 +/- 0.12 for veins, in close agreement with Murray's law. Calculated from 12 eyes, the average total arterial and venous volumetric flow rates were 33 +/- 9.6 and 34 +/- 6.3 microliters/min, respectively. The good agreement between both flow rates suggests that the technique and the assumptions for calculating flow yield results that satisfy mass conservation. Total arterial and venous volumetric flow rates correlated with total arterial and venous vessel cross-section. Volumetric flow rate in the temporal retina was significantly greater than in the nasal retina, but the difference is likely to be due to the larger area of the temporal retina. No difference in flow rate was observed between the superior and inferior retinal hemispheres. Finally, blood velocity in the major retinal vessels measured under normal experimental conditions appears remarkably constant over short (hours) and long (months) periods of time.
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                Author and article information

                Contributors
                leopold.schmetterer@meduniwien.ac.at
                Journal
                Diabetologia
                Diabetologia
                Diabetologia
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0012-186X
                1432-0428
                25 May 2017
                25 May 2017
                2017
                : 60
                : 8
                : 1534-1540
                Affiliations
                [1 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Department of Clinical Pharmacology, , Medical University of Vienna, ; Währinger Gürtel 18-20, 1090 Vienna, Austria
                [2 ]ISNI 0000000113287408, GRID grid.13339.3b, Department of Ophthalmology, , Medical University of Warsaw, ; Warsaw, Poland
                [3 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Center for Medical Physics and Biomedical Engineering, , Medical University of Vienna, ; Vienna, Austria
                [4 ]ISNI 0000 0000 9828 7548, GRID grid.8194.4, , Carol Davila University of Medicine and Pharmacy, ; Bucharest, Romania
                [5 ]ISNI 0000 0004 0518 8882, GRID grid.412152.1, Department of Ophthalmology, , Emergency University Hospital, ; Bucharest, Romania
                [6 ]Department of Ophthalmology, Sanatorium Hera, Vienna, Austria
                [7 ]ISNI 0000 0001 0706 4670, GRID grid.272555.2, , Singapore Eye Research Institute, ; Singapore, Republic of Singapore
                [8 ]ISNI 0000 0001 2224 0361, GRID grid.59025.3b, Lee Kong Chian School of Medicine, , Nanyang Technological University, ; Singapore, Republic of Singapore
                [9 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, , Imperial College, ; London, UK
                Article
                4309
                10.1007/s00125-017-4309-0
                5491565
                28547132
                4ab7453c-e94f-4ba9-9830-16864ed0b466
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 21 March 2017
                : 20 April 2017
                Funding
                Funded by: Medical University of Vienna
                Categories
                Article
                Custom metadata
                © Springer-Verlag GmbH Germany 2017

                Endocrinology & Diabetes
                diabetes mellitus,diabetic retinopathy,diabetic vascular diseases,retinal blood vessels

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