Single Retinal Layer Evaluation in Patients with Type 1 Diabetes with No or Early Signs of Diabetic Retinopathy: The First Hint of Neurovascular Crosstalk Damage between Neurons and Capillaries?

Abstract

Purpose: To analyze the retinal-choroidal changes in type 1 diabetes mellitus (DM1) patients with no or early signs of diabetic retinopathy (DR). Methods: Seventy-six eyes of 38 DM1 patients and 26 control eyes were included. Nine individual retinal layer thickness measurements were obtained using the spectral domain-optical coherence tomography automated segmentation algorithm. Results: The retinal nerve fiber layer was slightly thinner in all explored quadrants, even if the reduction was not significant in DM1 eyes versus control eyes. The inner nuclear layer (INL) thickness was thicker in all DM1 eyes versus control eyes in all quadrants (p < 0.050). Analyses adjusting for inner retinal thickness in all sectors confirmed INL thickening by about 4%, and also found a significant thinning of the ganglion cell layer (GCL) by about 3.5% in all DM1 subjects versus controls (p < 0.050). Conclusion: DM1 patients with no or early signs of DR present retinal changes particularly at the INL and GCL that might be correlated to initial findings of neurodegeneration.

Beyond Hyperglycemia, Evidence for Retinal Neurodegeneration in Metabolic Syndrome

“…5,[20][21][22][23] Thickening of the INL also has been reported in types 1 and 2 DM. 24,25 The activation and swelling of the Müller cells to compensate for extracellular accumulation of fluid with subclinical macular edema was held responsible for the thickening in early DM. The neurodegeneration pattern found in our MetS group was similar to the neurodegeneration pattern described in previous studies done on DM subjects without DRP and no evidence of subclinical macular edema.…”

Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 3-year Pilot Study Evaluating Morpho-Functional Retinal Changes

“…In all patients of the DC and DP groups, SD-OCT and OCTA were conducted three times according to the method described in our previous studies [9,13], and the average values for each parameter (see below) were considered for subsequent analysis (Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany; OCTA AngioVue XR Avanti; Optovue Inc., Fremont, California, USA).…”

“…In SD-OCT, the macular measurements (subfoveal, parafoveal, and total values) were obtained using in-built Spectralis mapping software, and segmentation software [9] was used for individual retinal layer thicknesses: RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), and photoreceptor layer (PR), and central retinal (CRT).…”

“…On the basis of more recent studies, psychophysical [7], morphological [8,9], and electrophysiological [10] abnormalities are involved in the retinal neurodegenerative process; in particular, patients with type 1 diabetes for less than 6 months' duration showed abnormal pattern electroretinogram (PERG) responses, which suggests that functional impairment of RGCs occurs earlier in the course of DR [10]. Moreover, similar dysfunction is observed in glaucoma, in which abnormal PERG responses may precede the onset of visual filed defects [11].…”

“…The morphological changes of single retinal layers including thinning of the RGC layer and retinal fiber nerve layer (RNFL) were detected by spectral domain optical coherence tomography (SD-OCT) [8,9], and these represent potential biomarkers of neurodegeneration in DR. Several studies using optical coherence tomography angiography (OCTA) indicated that parafoveal vessel density is reduced at the level of the deep capillary plexus (DCP) in patients with DM1 and in those with type 2 diabetes with absence of or mild DR [12][13][14][15][16], which suggests that microvascular involvement may be observed before appearance of any vascular alteration on the fundus examination. In addition, adaptive optics (AO) revealed morphological changes of the photoreceptor in patients with mild signs of DR, in particular a reduction of perifoveal photoreceptor density in vivo, increase of distance between the cones, and irregular packing arrangement compared to that of the normal cone [17][18][19].…”