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Original Investigation |

Select Features of Diabetic Retinopathy on Swept-Source Optical Coherence Tomographic Angiography Compared With Fluorescein Angiography and Normal Eyes

David A. Salz, MD1; Talisa E. de Carlo, BA1,2,3; Mehreen Adhi, MD1,2,3; Eric Moult, BS2,3; WhooJhon Choi, PhD2,3; Caroline R. Baumal, MD1; Andre J. Witkin, MD1; Jay S. Duker, MD1; James G. Fujimoto, PhD2,3; Nadia K. Waheed, MD, MPH1
[+] Author Affiliations
1New England Eye Center, Tufts Medical Center, Boston, Massachusetts
2Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge
3Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge
JAMA Ophthalmol. 2016;134(6):644-650. doi:10.1001/jamaophthalmol.2016.0600.
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Importance  Optical coherence tomographic angiography (OCTA) is a recently developed noninvasive imaging technique that can visualize the retinal and choroidal microvasculature without the injection of exogenous dyes.

Objective  To evaluate the potential clinical utility of OCTA using a prototype swept-source OCT (SS-OCT) device and compare it with fluorescein angiography (FA) for analysis of the retinal microvasculature in diabetic retinopathy.

Design, Setting, and Participants  Prospective, observational cross-sectional study conducted at a tertiary care academic retina practice from November 2013 through November 2014. A cohort of diabetic and normal control eyes were imaged with a prototype SS-OCT system. The stage of diabetic retinopathy was determined by clinical examination. Imaging was performed using angiographic 3 × 3-mm and 6 × 6-mm SS-OCT scans to generate 3-dimensional en-face OCT angiograms for each eye. Two trained Boston Image Reading Center readers reviewed and graded FA and OCTA images independently.

Main Outcomes and Measures  The size of the foveal nonflow zone and the perifoveal intercapillary area on OCTA were measured in both normal and diabetic eyes using Boston Image Reading Center image analysis software.

Results  The study included 30 patients with diabetes (mean [SD] age, 55.7 [10] years) and 6 control individuals (mean [SD] age, 55.1 [6.4] years). A total of 43 diabetic and 11 normal control eyes were evaluated with OCTA. Fluorescein angiography was performed in 17 of 43 diabetic eyes within 8 weeks of the OCTA. Optical coherence tomographic angiography was able to identify a mean (SD) of 6.4 (4.0) microaneurysms (95% CI, 4.4-8.5), while FA identified a mean (SD) of 10 (6.9) microaneurysms (95% CI, 6.4-13.5). The exact intraretinal depth of microaneurysms on OCTA was localized in all cases (100%). The sensitivity of OCTA in detecting microaneuryms when compared with FA was 85% (95% CI, 53-97), while the specificity was 75% (95% CI, 21-98). The positive predictive value and the negative predictive value were 91% (95% CI, 59-99) and 60% (95% CI, 17-92), respectively.

Conclusions and Relevance  Optical coherence tomographic angiography enables noninvasive visualization of macular microvascular pathology in eyes with diabetic retinopathy. It identified fewer microaneurysms than FA, but located their exact intraretinal depth. Optical coherence tomographic angiography also allowed the precise and reproducible delineation of the foveal nonflow zone and perifoveal intercapillary area. Evaluation of OCTA may be of clinical utility in the evaluation and grading of diabetic eye disease.

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Figure 1.
Foveal Nonflow Zones and Perifoveal Intercapillary Areas

A, The foveal nonflow zone (red line) and perifoveal intercapillary area (yellow line) of a control patient with no history of diabetes. B, The foveal nonflow zone (red line) and perifoveal intercapillary area (yellow line) of a patient with diabetes and proliferative diabetic retinopathy. Note the increased size and irregularity of both the foveal nonflow zone and perifoveal intercapillary area in this patient.

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Figure 2.
Fluorescein Angiography (FA) and Optical Coherence Tomographic Angiography (OCTA) of a Patient With Diabetes

A, Fluorescein angiography of a patient with diabetes. Optical coherence tomographic angiography of a patient with diabetes (B) and an overlay of the FA and OCTA superimposed over one another, allowing for a direct comparison (C). The overlay corroborates microaneurysms as focal areas of whitening that appear on both imaging modalities.

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Figure 3.
Microaneurysms on Optical Coherence Tomographic Angiography (OCTA) and Fluorescein Angiography

Summed optical coherence tomographic angiography image (A) and fluorescein angiography of the same patient (B). C, The outer retinal vascular plexus. D, The inner vascular plexus. The squares show dilation at the end of a capillary (yellow), vascular loops (green and red), and dilation on a string of a capillary (blue).

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Figure 4.
Imaging of Patient 22 With Moderate Nonproliferative Diabetic Retinopathy and Macular Edema

A, The pink arrowheads point to microaneurysms, the yellow arrowhead points to an area of nonperfusion, and the blue arrowhead shows a vascular loop that is not well defined. B, A 3 × 3-mm optical coherence tomographic angiography image showing the same area. The arrowheads point to the corresponding areas on the fluorescein angiography. Note the increased detail of the microvasculature in the optical coherence tomographic angiography.

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Figure 5.
Foveal Nonflow Zones and Perifoveal Intercapillary Areas in Patients With Different Levels of Diabetic Retinopathy
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