Deep capillary plexus impairment in patients with type1 diabetes mellitus with no signs of diabetic retinopathy revealed using optical coherence tomography angiography.

Abstract

This cross-sectional observational case–control clinical study investigated microvascular retinal changes in type 1 diabetes mellitus (DM1) patients with no signs of diabetic retinopathy (DR) in comparison with healthy controls using optical coherence tomography angiography (OCTA). The local institutional review board approved this study. Enrolment criteria included a diagnosis of DM1 made at least 1 year prior to study enrolment (age ≥ 18 years). Only data from the right eye were analysed. Exclusion criteria included bad metabolic control (HbA1c > 9%) and history of any other retinal disease. Two experienced examiners (MP and MV) classified the eyes as no DR and analysed the optical coherence tomography (OCT) images. We used the AngioVue device (RTVue XR, Optovue, Inc., Fremont, CA), to quantify parafoveal vessel density and foveal avascular zone (FAZ) area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) (Simonett et al. 2017). The split-spectrum amplitude-decorrelation angiography algorithm (Jia et al. 2012) was used to evaluate the blood flow in a 3 × 3 mm scanning area centred on the fovea. En face OCT angiograms were segmented to define the SCP and DCP, using the built-in software segmentation algorithm. Parafoveal vessel density and FAZ were calculated using the automated AngioVue Analytics tool of the OCTA device as shown in details in Fig. 1. This study showed for the first time that DM1 patients with no sign of DR have reduced parafoveal vessel density limited to the DCP when compared to non-diabetic controls. Any difference was found in FAZ area between cohorts. Demographic and clinical data are shown in Fig. 1. In the past, fluorescein angiography was considered a useful tool for revealing incipient retinopathy; indeed, the earlier vascular changes including microaneurysms and leakage are detectable using fluorescein angiography before these latter may seen by means ophthalmoscopy (Dorchy et al. 1979). Today, using OCTA, it is possible to study the complex vascular anatomical architecture of the DCP in DR, which might be more susceptible to diabetic damage because of its complexity. In a previous study using OCTA (Simonett et al. 2017), we found that DM1 patients with no and mild signs of non-proliferative DR showed a reduction in DCP parafoveal vessel density. In this study, by analysing a subgroup of DM1 patients, we demonstrated that patients with no signs of DR also present DCP microvascular impairment. Local retinal acidosis, found in the outer nuclear layer at the early stages of a DR (Dmitriev et al. 2016), could increase leucostasis in small retinal capillaries. Also, diabetic maculopathy seems to be a result of disturbances in retinal vasomotion. (Bek 1999) Therefore, our findings might corroborate the hypothesis that the increased recruitment of microvascular units in the macular area can lead to increased hydrostatic pressure in small capillaries (Bek 1999) with a consequent severely diminished blood flow velocity/rate below the threshold necessary to register as flow in the OCTA system. Finally, the diabetic metabolic disturbances, particularly changes in blood glucose, can influence retinal perfusion and retinal autoregulation, implying that fluctuations in the arterial feeding pressure may be transmitted to the smaller vessels. Limitations are the small sample size and a limited field of view of 3 × 3 mm2 area. Additionally, we cannot exclude that projection from more superficial vasculature may be affecting these findings, particularly in the DCP, for either DM1 patients or control. (Shahlaee et al. 2016) In conclusion, DCP impairment might be harbinger of retinal vascular damage before any sign of DR can be detected by means of ophthalmoscopy, and this finding demonstrated that a decrease in DCP parafoveal capillary density represents an early process in the disease.