Retinal flow density by optical coherence tomography angiography is useful for detection of nonperfused areas in diabetic retinopathy

  • Yoshihiro Kaizu
  • Shintaro Nakao
  • Haruka Sekiryu
  • Iori Wada
  • Muneo Yamaguchi
  • Toshio Hisatomi
  • Yasuhiro Ikeda
  • Junji Kishimoto
  • Koh-hei Sonoda
Retinal Disorders



Fluorescein angiography (FA) has been conventionally used for detection of retinal nonperfused area (NPA) in diabetic retinopathy (DR) in spite of its qualitative evaluation. Optical coherence tomography angiography (OCTA) has been recently reported to be useful for the quantification of retinal vascular disorder in DR. In this study, we examined whether retinal flow density (FD) measurement in OCTA was useful for NPA detection in DR.


The study included 41 eyes from 29 patients with DR who underwent FA and OCTA. Regions surrounded by arteries or veins were extracted in the OCTA image, and the FDs in each region were measured by Image J. Furthermore, each region was classified as NPA or perfused area (PA) in FA. The receiver operating characteristic (ROC) curve was prepared by logistic regression analysis of the FD. The AUC (area under the ROC curve) and cutoff value of FD were also calculated.


Two hundred fifty-two regions were analyzed and classified into 38 NPA regions and 214 PA regions using FA. FD of each capillary plexus in NPA was significantly smaller than in PA (p < 0.0001). The AUC of total capillary plexus layers (TCP), superficial capillary plexus layer (SCP), and deep capillary plexus layer (DCP) was 0.975, 0.974, and 0.971, respectively. All areas, where the FD was more than the cutoff value (0.07 in TCP), were diagnosed with PA. Three areas with intraretinal microvascular abnormalities (IRMA) were diagnosed as PA despite being below the cutoff value.


FD measurement in OCTA is useful for NPA detection in DR.


Vascular density Vessel density Nonflow area Retinal capillary dropout IRMA 



The authors thank Dr. Shigeo Yoshida for helpful suggestions.


YK and SN did the research of design, data acquisition and analysis, interpretation of data, drafting the manuscript, and critical revision of the manuscript. HS, IW, MY, TH, YI, and K-H S did the data acquisition and analysis, interpretation of data, and critical revision of the manuscript. JK did the analysis, interpretation of data, and critical revision of the manuscript.

Funding information

This study was supported by grants from JSPS KAKENHI, Grant-in-Aid for Scientific Research (C) No. 17K11456 (SN), Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical’s Founder (SN), Novartis Pharma Research Grants (SN), and Alcon Pharma Research Grants (SN).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Patient consent

Informed consent was obtained.

Ethics approval

This study was approved by the Ethics Committee of Kyushu University Hospital.

Supplementary material

417_2018_4122_MOESM1_ESM.jpeg (597 kb)
Supplemental Figure 1 Flow density (FD) distribution of examined regions in all cases. Black circles and white triangles indicate perfused and nonperfused areas, respectively, which were judged using corresponding fluorescein angiography images. The vertical axis shows FD of total capillary plexus layers (TCP), and the horizontal axis shows all 29 cases included in this study. Dotted horizontal line indicates cutoff value of FD in TCP (0.07) with sensitivity (1.0) and specificity (0.95), respectively. (JPEG 597 kb)
417_2018_4122_MOESM2_ESM.jpeg (2.4 mb)
Supplemental Figure 2 Decreased flow density (FD) in OCTA for unclear reasons, Case 4 (right eye). (A) Color fundus photograph shows proliferative diabetic retinopathy. (B) Fluorescein angiography (FA) shows new vessel growth on the disc and some microaneurysms. Yellow dot square indicates the magnified FA images in (C, D) and OCTA image in (E). (C, D) The area with blue dots was classified as perfused area in the early phase (C, 46 s) and the late phase (D, 7 min 55 s) of FA. (E) FD of area with blue dots in OCTA image is 0.002. (F) B scan of blue dots area. (JPEG 2441 kb)
417_2018_4122_MOESM3_ESM.jpeg (2.9 mb)
Supplemental Figure 3 High hierarchical bias ratio of flow density (FD) between surface layer and deep layer, Case 1 (right eye). (A) Color fundus photograph shows proliferative diabetic retinopathy. (B) Fluorescein angiography (FA) shows some IRMA and microaneurysms. Yellow dot square indicates the magnified FA images in (C) and OCTA image in (D, E, F). (C) The area with blue dots was classified as perfused area in the early phase (C, 42 s) of FA. (D, E, F) FD of total capillary plexus (TCP, D), superficial capillary plexus (SCP, E) and deep capillary plexus (DCP, F) of area with blue dots in OCTA image is 0.155, 0.151 and 0.024, respectively. (F) B scan of blue dots area. (JPEG 2949 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Research and Development of Next Generation Medicine, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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