Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 1: Diabetic Retinopathy

Abstract

Purpose: The purpose of this study was to evaluate specifically in type 1 diabetes mellitus (DM) individuals the relationship between perifoveal superficial capillary plexus (SCP) parameters assessed by optical coherence tomography angiography (OCTA) and diabetic retinopathy (DR) grade.

Methods: Cross-sectional analysis of a large scale prospective OCTA trial cohort (ClinicalTrials.gov NCT03422965). A total of 1186 eyes (593 individuals), 956 type 1 DM eyes (478 patients), and 230 control eyes (115 healthy volunteers) were included in this study. DR stage was graded according to the International Classification. OCTA imaging was performed with a commercially available device (Cirrus HD-OCT). Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) area, perimeter and circularity measurements were quantified in the SCP and receiver operating characteristic (ROC) curves were constructed for each OCTA parameter.

Results: VD and PD (in both 3 × 3 and 6 × 6 mm captures) were inversely associated with DR stage (P < 0.001 in all cases) in a multiple regression analysis after controlling by age, gender, signal strength index, axial length, and DM duration. Greater FAZ area and perimeter and conversely lower circularity measurements were observed as DR severity increased in both scanning protocols (P < 0.05 in all cases).

Conclusions: In type 1 DM individuals, OCTA provides an objective, continuous, and reliable method for accurate quantification of VD, PD, and FAZ parameters in the SCP, which ultimately correlate with DR stages.

Translational relevance: Objective OCTA measurements of the retinal microvasculature could substitute the clinical DR classification in patients with type 1 DM, identify patients at risk of DR progression, and inform treatment decisions to modify the evolution of the disease.

Keywords: diabetic retinopathy; optical coherence tomography angiography; retinal blood flow; retinal imaging; type 1 diabetes mellitus.

Conflict of interest statement

Disclosure: M. Barraso, None; A. Alé-Chilet, None; T. Hernández, None; C. Oliva, None; I. Vinagre, None; E. Ortega, None; M. Figueras-Roca, None; A. Sala-Puigdollers, None; C. Esquinas, None; E. Esmatjes, None; A. Adán, None; J. Zarranz-Ventura, None

Copyright 2020 The Authors.

Figures

Figure 1.

Consolidated standard of reporting trials (CONSORT)-style flow chart describing included and excluded eyes in the study and each individual optical coherence tomography angiography (OCTA) analysis. (*1 eye = ≥ 1 criteria for exclusion; VD = vessel density; PD = perfusion density; FAZ = foveal avascular zone; a = area; p = perimeter; c = circularity; SSI = signal strength index).

Figure 2.

Optical coherence tomography angiography images of the superficial capillary plexus in study eyes. Examples of 3 × 3 mm (top row) and 6 × 6 mm (bottom row) OCTA captures of the control group (left) and different diabetic retinopathy (DR) stages showing progressively lower vessel density (VD) and perfusion density (PD), greater foveal avascular zone (FAZ) area. and perimeter and lower FAZ circularity in greater DR stages.

Figure 3.

Vessel density (VD) and perfusion density (PD) measurements and diabetic retinopathy (DR) grade, after adjusting for age, gender, signal strength index (SSI), axial length and duration of diabetes mellitus disease. Top: VD (left) and PD (right) measurements in the complete scanned area using the 3 × 3 mm scanning protocol. Bottom: VD (left) and PD (right) measurements in the complete scanned area using the 6 × 6 mm scanning protocol. Generalized Estimating Equation (GEE) adjusted for age, gender, signal strength index (SSI), axial length, and duration of diabetes mellitus disease for global P value; pairwise comparisons by Kruskal-Wallis test with Bonferroni correction. P < 0.05: (a) vs. Control; (b) vs. No DR; (c) vs. Mild DR; (d) vs. Moderate DR; (e) vs. Severe DR; (f) vs Proliferative DR (Total number of eyes [3 × 3/6 × 6]: control 189/183, no DR 504/503, mild NPDR 202/198, moderate NPDR 29/30, severe NPDR 4/3, PDR 10/10).

Figure 4.

Foveal Avascular Zone (FAZ) measurements and diabetic retinopathy (DR) grade after adjusting for gender, age, SSI, axial length, and duration of diabetes mellitus disease. Top: FAZ area (left), perimeter (middle), and circularity (right) measurements in the complete scanned area using the 3 × 3 mm scanning protocol. Bottom: FAZ area (left), perimeter (middle), and circularity (right) measurements in the complete scanned area using the 6 × 6 mm scanning protocol. Generalized Estimating Equation (GEE) adjusted for age, gender, signal strength index (SSI), axial length, and duration of diabetes mellitus disease for global P value; pairwise comparisons by Kruskal-Wallis test with Bonferroni correction. P < 0.05: (a) vs. Control; (b) vs. No DR; (c) vs Mild DR; (d) vs Moderate DR; (e) vs Severe DR; (f) vs Proliferative DR. (Total number of eyes [3 × 3/6 × 6]: control 174/169, no DR 470/461, mild NPDR 180/178, moderate NPDR 26/26, severe NPDR 3/2, PDR 8/8).

Figure 5.

Receiver operating curves (ROC) of Optical Coherence Tomography Angiography (OCTA) parameters in 3 × 3 mm scans. Subgroup analysis by controls (left column), patients with type 1 diabetes mellitus with no diabetic retinopathy (middle column) and with diabetic retinopathy (mild, moderate, and severe nonproliferative and proliferative diabetic retinopathy)(right column). Top row: vessel density; Top-middle row: perfusion density; Middle row: Foveal Avascular Zone (FAZ) area; Middle-bottom row: FAZ perimeter; Bottom row: FAZ circularity. AUC, area under the curve; CI, confidence interval.