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      Quantifying Microvascular Density and Morphology in Diabetic Retinopathy Using Spectral-Domain Optical Coherence Tomography Angiography

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          To quantify changes in retinal microvasculature in diabetic retinopathy (DR) by using spectral-domain optical coherence tomography angiography (SD-OCTA).


          Retrospective, cross-sectional, observational study of healthy and diabetic adult subjects with and without DR. Retinal microvascular changes were assessed by using SD-OCTA images and an intensity-based optical microangiography algorithm. A semiautomated program was used to calculate indices of microvascular density and morphology in nonsegmented and segmented SD-OCTA images. Microvascular density was quantified by using skeleton density (SD) and vessel density (VD), while vessel morphology was quantified as fractal dimension (FD) and vessel diameter index (VDI). Statistical analyses were performed by using the Student's t-test or analysis of variance with post hoc Tukey honest significant difference tests for multiple comparisons.


          Eighty-four eyes with DR and 14 healthy eyes were studied. Spearman's rank test demonstrated a negative correlation between DR severity and SD, VD, and FD, and a positive correlation with VDI ( ρ = −0.767, −0.7166, −0.768, and +0.5051, respectively; P < 0.0001). All parameters showed high reproducibility between graders (ICC = 0.971, 0.962, 0.937, and 0.994 for SD, VD, FD, and VDI, respectively). Repeatability ( κ) was greater than 0.99 for SD, VD, FD, and VDI.


          Vascular changes in DR can be objectively and reliably characterized with SD, VD, FD, and VDI. In general, decreasing capillary density (SD and VD), branching complexity (FD), and increasing average vascular caliber (VDI) were associated with worsening DR. Changes in capillary density and morphology were significantly correlated with diabetic macular edema.

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          Most cited references 39

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          Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales.

          To develop consensus regarding clinical disease severity classification systems for diabetic retinopathy and diabetic macular edema that can be used around the world, and to improve communication and coordination of care among physicians who care for patients with diabetes. Report regarding the development of clinical diabetic retinopathy disease severity scales. A group of 31 individuals from 16 countries, representing comprehensive ophthalmology, retina subspecialties, endocrinology, and epidemiology. An initial clinical classification system, based on the Early Treatment Diabetic Retinopathy Study and the Wisconsin Epidemiologic Study of Diabetic Retinopathy publications, was circulated to the group in advance of a workshop. Each member reviewed this using e-mail, and a modified Delphi system was used to stratify responses. At a later workshop, separate systems for diabetic retinopathy and macular edema were developed. These were then reevaluated by group members, and the modified Delphi system was again used to measure degrees of agreement. Consensus regarding specific classification systems was achieved. A five-stage disease severity classification for diabetic retinopathy includes three stages of low risk, a fourth stage of severe nonproliferative retinopathy, and a fifth stage of proliferative retinopathy. Diabetic macular edema is classified as apparently present or apparently absent. If training and equipment allow the screener to make a valid decision, macular edema is further categorized as a function of its distance from the central macula. There seems to be a genuine need for consistent international clinical classification systems for diabetic retinopathy and diabetic macular edema that are supported with solid evidence. The proposed clinical classification systems provide a means of appropriately categorizing diabetic retinopathy and macular edema. It is hoped that these systems will be valuable in improving both screening of individuals with diabetes and communication and discussion among individuals caring for these patients.
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            Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group.

            The modified Airlie House classification of diabetic retinopathy has been extended for use in the Early Treatment Diabetic Retinopathy Study (ETDRS). The revised classification provides additional steps in the grading scale for some characteristics, separates other characteristics previously combined, expands the section on macular edema, and adds several characteristics not previously graded. The classification is described and illustrated and its reproducibility between graders is assessed by calculating percentages of agreement and kappa statistics for duplicate gradings of baseline color nonsimultaneous stereoscopic fundus photographs. For retinal hemorrhages and/or microaneurysms, hard exudates, new vessels, fibrous proliferations, and macular edema, agreement was substantial (weighted kappa, 0.61 to 0.80). For soft exudates, intraretinal microvascular abnormalities, and venous beading, agreement was moderate (weighted kappa, 0.41 to 0.60). A double grading system, with adjudication of disagreements of two or more steps between duplicate gradings, led to some improvement in reproducibility for most characteristics.
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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.

                Author and article information

                [1 ]Department of Ophthalmology USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States
                [2 ]Departments of Bioengineering and Ophthalmology, University of Washington, Seattle, Washington, United States
                Author notes
                Correspondence: Amir H. Kashani, Department of Ophthalmology, USC Eye Institute, Keck School of Medicine of the University of Southern California, 1450 San Pablo Street, Suite 4700, Los Angeles, CA 90033, USA; ahkashan@ .

                AYK and ZC contributed equally to the work presented here and should therefore be regarded as equivalent authors.

                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                13 July 2016
                July 2016
                : 57
                : 9
                : OCT362-OCT370
                iovs-57-101-20 IOVS-15-18904

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



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