Retinal Microvascular and Neuronal Changes Are Also Present, Even If Differently, in Adolescents with Type 1 Diabetes without Clinical Diabetic Retinopathy

Abstract

The purpose of this study was to evaluate retinal changes in adolescents with childhood-onset, long-lasting type 1 diabetes mellitus (T1D). Patients and healthy controls (HC) underwent optical coherence tomography (OCT) and OCT-angiography (OCTA). Individual macular layers, peripapillary retinal nerve fiber layer (pRNFL), and vascular parameters (vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI)) of macular superficial vascular (SVP), intermediate (ICP), deep (DCP) and radial peripapillary capillary plexuses (RPCP) were quantified. Thirty-nine patients (5 with (DR group) and 34 without (noDR group) diabetic retinopathy) and 20 HC were enrolled. The pRNFL and ganglion cell layer (GCL) were thicker in noDR compared to HC and DR, reaching statistically significant values versus HC for some sectors. At the macular level, VAD and VLF were reduced in DR versus HC in all plexuses, and versus noDR in SVP (p < 0.005 for all). At the RPCP level, VAD and VDI were increased in noDR versus HC, significantly for VDI (p = 0.0067). Glycemic indices correlated to retinal parameters. In conclusion, in T1D adolescents, retinal capillary and neuronal changes are present after long-lasting disease, even in the absence of clinical DR. These changes modify when clinical retinopathy develops. The precocious identification of specific OCT and OCTA changes may be a hallmark of subsequent overt retinopathy.

Early Retinal Microvascular Changes Assessed with Swept-Source OCT Angiography in Type 1 Diabetes Patients without Retinopathy

“…Nevertheless, the literature is conflicting. A few studies showed early modification in the SCP [ 17 , 18 ], whereas others found retinal vessel rarefaction predominantly in the DCP [ 19 , 20 ]. The anatomy of the SCP corresponds with the vascularization lying in the nerve fiber layer and ganglion cell layer [ 21 ].…”

“…The anatomy of the SCP corresponds with the vascularization lying in the nerve fiber layer and ganglion cell layer [ 21 ]. Recent studies have suggested that the neurovascular unit, including endothelial cells, pericytes, retinal neurons, and glial cells, is the primary site of early retinal changes, with a thinning of the nerve fiber and ganglion cell layers in type 1 diabetes even before the development of clinical diabetic retinopathy [ 18 ]. Another hypothesis is that the DCP is more challenging to analyze because of the deeper localization, thereby resulting in projection artifacts from superficial vessels that could lead to a less precise quantitative analysis.…”

Continuous Glucose Monitoring-Derived Metrics and Capillary Vessel Density in Subjects with Type 1 Diabetes without Diabetic Retinopathy

“…However, differences exist in the cohorts of examined patients. For instance, Pilotto et al recruited adolescents with and without DR and found a reduced VD only in patients with clinical signs of DR [ 17 ]. In line with Pilotto, Golebiewska et al found no difference in VD between patients with type 1 diabetes without DR and healthy controls [ 23 ].…”

“…Some methodological differences also emerge by comparing the studies. Indeed, Pilotto et al considered parafoveal and foveal areas when evaluating VD, and Golebiewska et al divided the retinal plexus into three layers [ 17 , 23 ].…”

“…To our knowledge, only one paper by Pilotto et al evaluated the association between retinal changes detected by OCTA and CGM-derived glucose metrics. In a cohort of adolescents with type 1 diabetes, with or without DR, the authors found that vascular density in the intermediate capillary plexus is inversely related to average glucose and SD and directly related to TIR [ 17 ].…”