Automated Quantification of Capillary Nonperfusion Using Optical Coherence Tomography Angiography in Diabetic Retinopathy.

IMPORTANCE Macular ischemia is a key feature of diabetic retinopathy (DR). Quantification of macular ischemia has potential as a biomarker for DR. OBJECTIVE To assess the feasibility of automated quantification of capillary nonperfusion as a potential sign of macular ischemia using optical coherence tomography (OCT) angiography. DESIGN, SETTING, AND PARTICIPANTS An observational study conducted in a tertiary, subspecialty, academic practice evaluated macular nonperfusion with 6 × 6-mm OCT angiography obtained with commercially available 70-kHz OCT and fluorescein angiography (FA). The study was conducted from January 22 to September 18, 2014. Data analysis was performed from October 1, 2014, to April 7, 2015. Participants included 12 individuals with normal vision serving as controls and 12 patients with various levels of DR. MAIN OUTCOMES AND MEASURES Preplanned primary measures were parafoveal and perifoveal vessel density, total avascular area, and foveal avascular zone as detected with 6 × 6-mm OCT angiography and analyzed using an automated algorithm. Secondary measures included the agreement of the avascular area between the OCT angiogram and FA. RESULTS Compared with the 12 healthy controls (11 women; mean [SD] age, 54.2 [14.2] years), the 12 participants with DR (4 women; mean [SD] age, 55.1 [12.1] years) had reduced parafoveal and perifoveal vessel density by 12.6% (95% CI, 7.7%-17.5%; P < .001) and 10.4% (95% CI, 6.8%-14.1%; P < .001), respectively. Total avascular area and foveal avascular zone area were greater in eyes with DR by 0.82 mm2 (95% CI, 0.65-0.99 mm2; P = .02) and 0.16 mm2 (95% CI, 0.05-0.28 mm2; P < .001). The agreement between the vascular areas in the OCT angiogram and FA had a κ value of 0.45 (95% CI, 0.21-0.70; P < .001). Total avascular area in the central 5.5-mm-diameter area distinguished eyes with DR from control eyes with 100% sensitivity and specificity. CONCLUSIONS AND RELEVANCE Avascular area analysis with an automated algorithm using OCT angiography, although not equivalent to FA, detected DR reliably in this small pilot study. Further study is necessary to determine the usefulness of the automated quantification in clinical practice.

[1]  M. Zweig,et al.  Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. , 1993, Clinical chemistry.

[2]  M Palta,et al.  Abnormalities of the foveal avascular zone in diabetic retinopathy. , 1984, Archives of ophthalmology.

[3]  酒田 久美.  Relationship between macular microcirculation and progression of diabetic macular edema , 2006 .

[4]  Martin F. Kraus,et al.  Split-spectrum amplitude-decorrelation angiography with optical coherence tomography , 2012, Optics express.

[5]  Dawn A Sim,et al.  Quantitative analysis of diabetic macular ischemia using optical coherence tomography. , 2014, Investigative ophthalmology & visual science.

[6]  Jennifer I. Lim,et al.  Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. , 2007, Ophthalmology.

[7]  Yalin Zheng,et al.  Automated segmentation of foveal avascular zone in fundus fluorescein angiography. , 2010, Investigative ophthalmology & visual science.

[8]  Martin F. Kraus,et al.  Optical coherence tomography angiography of optic disc perfusion in glaucoma. , 2014, Ophthalmology.

[9]  Christiane,et al.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. , 2004, Journal international de bioethique = International journal of bioethics.

[10]  Akitoshi Yoshida,et al.  Optical Coherence Tomography Angiography in Diabetic Retinopathy: A Prospective Pilot Study. , 2015, American journal of ophthalmology.

[11]  Y. Yasuno,et al.  Three-dimensional vascular imaging of proliferative diabetic retinopathy by Doppler optical coherence tomography. , 2015, American journal of ophthalmology.

[12]  Robert J Zawadzki,et al.  Phase-variance optical coherence tomography: a technique for noninvasive angiography. , 2014, Ophthalmology.

[13]  James G. Fujimoto,et al.  Quantitative 3D-OCT motion correction with tilt and illumination correction, robust similarity measure and regularization , 2014, Biomedical optics express.

[14]  Matthew D. Davis,et al.  Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. , 2003, Ophthalmology.

[15]  A M Mansour,et al.  FOVEAL AVASCULAR ZONE IN DIABETES MELLITUS , 1993, Retina.

[16]  Barry Cense,et al.  Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics. , 2011, Investigative ophthalmology & visual science.

[17]  David Huang,et al.  Does optic nerve head size variation affect circumpapillary retinal nerve fiber layer thickness measurement by optical coherence tomography? , 2012, Investigative ophthalmology & visual science.

[18]  Ruikang K. Wang,et al.  Simultaneous estimation of bidirectional particle flow and relative flux using MUSIC-OCT: phantom studies , 2014, Physics in medicine and biology.

[19]  Martin F. Kraus,et al.  Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. , 2014, Ophthalmology.

[20]  Jennifer K. Sun,et al.  Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. , 2015, Ophthalmology.

[21]  David J. Wilson,et al.  Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye , 2015, Proceedings of the National Academy of Sciences.

[22]  H Lund-Andersen,et al.  Absence of foveal avascular zone demonstrated by laser scanning fluorescein angiography , 1994, Acta ophthalmologica.

[23]  J Conrath,et al.  Foveal avascular zone in diabetic retinopathy: quantitative vs qualitative assessment , 2005, Eye.

[24]  Robert N. Johnson.  Chapter 1 – Fluorescein Angiography: Basic Principles and Interpretation , 2013 .

[25]  Seiyo Harino,et al.  Relationship of macular microcirculation and retinal thickness with visual acuity in diabetic macular edema. , 2007, Ophthalmology.

[26]  Robert J Zawadzki,et al.  Noninvasive imaging of the foveal avascular zone with high-speed, phase-variance optical coherence tomography. , 2012, Investigative ophthalmology & visual science.

[27]  F Jung,et al.  Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. , 1991, The British journal of ophthalmology.

[28]  Gangjun Liu,et al.  Optimization of the split-spectrum amplitude-decorrelation angiography algorithm on a spectral optical coherence tomography system. , 2015, Optics letters.

[29]  Seiyo Harino,et al.  Relationship between macular microcirculation and progression of diabetic macular edema. , 2006, Ophthalmology.

[30]  A. Harris,et al.  Perifoveal microcirculation with non-insulin-dependent diabetes mellitus , 1994, Graefe's Archive for Clinical and Experimental Ophthalmology.

[31]  Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Early Treatment Diabetic Retinopathy Study Research Group. , 1991, Ophthalmology.

[32]  R A Weale,et al.  On the retinal vasculature of the human fovea. , 1974, Experimental eye research.

[33]  Fluorescein angiographic risk factors for progression of diabetic retinopathy. ETDRS report number 13. Early Treatment Diabetic Retinopathy Study Research Group. , 1991, Ophthalmology.

[34]  M Reim,et al.  Quantification of retinal capillary density and flow velocity in patients with essential hypertension. , 1994, Hypertension.