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      Retinal Oximetry and Vessel Diameter Measurements With a Commercially Available Scanning Laser Ophthalmoscope in Diabetic Retinopathy

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          Abstract

          Purpose

          To test the hypothesis that retinal vascular diameter and hemoglobin oxygen saturation alterations, according to stages of diabetic retinopathy (DR), are discernible with a commercially available scanning laser ophthalmoscope (SLO).

          Methods

          One hundred eighty-one subjects with no diabetes (No DM), diabetes with no DR (No DR), nonproliferative DR (NPDR), or proliferative DR (PDR, all had photocoagulation) underwent imaging with an SLO with dual lasers (532 nm and 633 nm). Customized image analysis software determined the diameters of retinal arteries and veins (D A and D V) and central retinal artery and vein equivalents (CRAE and CRVE). Oxygen saturations of hemoglobin in arteries and veins (SO 2A and SO 2V) were estimated from optical densities of vessels on images at the two wavelengths. Statistical models were generated by adjusting for effects of sex, race, age, eye, and fundus pigmentation.

          Results

          D A, CRAE, and CRVE were reduced in PDR compared to No DM ( P ≤ 0.03). D V and CRVE were similar between No DM and No DR, but they were higher in NPDR than No DR ( P ≤ 0.01). Effect of stage of disease on SO 2A differed by race, being increased relative to No DM in NPDR and PDR in Hispanic participants only ( P ≤ 0.02). Relative to No DM, SO 2V was increased in NPDR and PDR ( P ≤ 0.05).

          Conclusions

          Alterations in retinal vascular diameters and SO 2 by diabetic retinopathy stage can be detected with a widely available SLO, and covariates such as race can influence the results.

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          Most cited references50

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          Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study.

          To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. Population-based, cross-sectional study. Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.
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            Regulation of retinal blood flow in health and disease.

            Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance of retinal structure and function. Retinal blood flow is autoregulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. Autoregulation is achieved by adaptation of the vascular tone of the resistance vessels (arterioles, capillaries) to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting the arteriolar smooth muscle cells and capillary pericytes. Mechanical stretch and increases in arteriolar transmural pressure induce the endothelial cells to release contracting factors affecting the tone of arteriolar smooth muscle cells and pericytes. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy-generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. NO, which plays a central role in neurovascular coupling, may exert its effect, by modulating glial cell function involved in such vasomotor responses. During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Hypoxia-related VEGF expression correlates with the formation of neovessels. The relief from hypoxia results in arteriolar constriction, decreases the hydrostatic pressure in the capillaries and venules, and relieves endothelial stretching. The reestablished oxygenation of the inner retina downregulates VEGF expression and thus inhibits neovascularization and macular edema. Correct control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.
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              Revised formulas for summarizing retinal vessel diameters.

              Background/Purpose. Recent findings suggest that an objective assessment of retinal vessel caliber from fundus photographs provide information about the association of microvascular characteristics with macrovascular disease. Current methods used to quantify retinal vessel caliber, introduced by Parr(1,2) and Hubbard,(3) are not independent of scale and are affected by the number of vessels. To improve upon these methods we introduce revised formulas for quantifying vessel caliber. Methods. Revised formulas were estimated using retinal vessel measurements from 44 young adults free of hypertension and diabetes. Comparisons between the two methods were done using digitized photographs from 4926 participants at the baseline examination of the Beaver Dam Eye Study (BDES), an ongoing population-based cohort study initiated in 1987. Individual arterioles and venules were measured using semi-automated computer software from which summary measures were calculated. Results. Correlation coefficients between the Parr-Hubbard and revised formulas were high (Pearson correlation coefficients ranging from 0.94 to 0.98). Both arteriolar and venular caliber significantly increased with an increasing number of vessels measured using the Parr-Hubbard formulas (p 0.50). Conclusions. We describe revised formulas for summarizing retinal vessel diameters measured from fundus photographs to be used in future studies and analyses. The revised formulas correlate highly with the previously used Parr-Hubbard formulas, but offer the advantages of being more robust against variability in the number of vessels observed, being independent of image scale, and being easier to implement.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                October 2017
                : 58
                : 12
                : 5556-5563
                Affiliations
                [1 ]Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
                [2 ]Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, United States
                [3 ]University of Illinois Cancer Center, Population Health, Behavior, and Outcomes Program, Chicago, Illinois, United States
                [4 ]Department of Ophthalmology, University of Southern California, Los Angeles, California, United States
                Author notes
                Correspondence: Norman P. Blair, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA; npblair@ 123456uic.edu .
                Article
                iovs-58-11-64 IOVS-17-21934
                10.1167/iovs.17-21934
                5656420
                29079858
                2b5b6767-4e68-4a1c-b60d-c6b48f555949
                Copyright 2017 The Authors

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

                History
                : 25 March 2017
                : 7 September 2017
                Categories
                Retina

                diabetic retinopathy,retinal oximetry,retinal vessel diameter,scanning laser ophthalmoscopy

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