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

Optical coherence tomography (OCT)-based angiography (OCTA) provides in vivo, three-dimensional vascular information by the use of flowing red blood cells as intrinsic contrast agents, enabling the visualization of functional vessel networks within microcirculatory tissue beds non-invasively, without a need of dye injection. Because of these attributes, OCTA has been rapidly translated to clinical ophthalmology within a short period of time in the development. Various OCTA algorithms have been developed to detect the functional micro-vasculatures in vivo by utilizing different components of OCT signals, including phase-signal-based OCTA, intensity-signal-based OCTA and complex-signal-based OCTA. All these algorithms have shown, in one way or another, their clinical values in revealing micro-vasculatures in biological tissues in vivo, identifying abnormal vascular networks or vessel impairment zones in retinal and skin pathologies, detecting vessel patterns and angiogenesis in eyes with age-related macular degeneration and in skin and brain with tumors, and monitoring responses to hypoxia in the brain tissue. The purpose of this paper is to provide a technical oriented overview of the OCTA developments and their potential pre-clinical and clinical applications, and to shed some lights on its future perspectives. Because of its clinical translation to ophthalmology, this review intentionally places a slightly more weight on ophthalmic OCT angiography.

Optical coherence tomography (OCT)-based angiography is increasingly becoming a clinically useful and important imaging technique due to its ability to provide volumetric microvascular networks innervating tissue beds in vivo without a need for exogenous contrast agent. Numerous OCT angiography algorithms have recently been proposed for the purpose of contrasting microvascular networks. A general literature review is provided on the recent progress of OCT angiography methods and algorithms. The basic physics and mathematics behind each method together with its contrast mechanism are described. Potential directions for future technical development of OCT based angiography is then briefly discussed. Finally, by the use of clinical data captured from normal and pathological subjects, the imaging performance of vascular networks delivered by the most recently reported algorithms is evaluated and compared, including optical microangiography, speckle variance, phase variance, split-spectrum amplitude decorrelation angiography, and correlation mapping. It is found that the method that utilizes complex OCT signal to contrast retinal blood flow delivers the best performance among all the algorithms in terms of image contrast and vessel connectivity. The purpose of this review is to help readers understand and select appropriate OCT angiography algorithm for use in specific applications.